97-37. Substances Prohibited From Use in Animal Food or Feed; Animal Proteins Prohibited in Ruminant Feed  

  • [Federal Register Volume 62, Number 2 (Friday, January 3, 1997)]
    [Proposed Rules]
    [Pages 552-583]
    From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
    [FR Doc No: 97-37]
    
    
    
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    Part IV
    
    
    
    
    
    Department of Health and Human Services
    
    
    
    
    
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    Food and Drug Administration
    
    
    
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    21 CFR Part 589
    
    
    
    Substances Prohibited From Use in Animal Food or Feed; Animal Proteins 
    Prohibited in Ruminant Feed; Proposed Rule
    
    Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / 
    Proposed Rules
    
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    DEPARTMENT OF HEALTH AND HUMAN SERVICES
    
    Food and Drug Administration
    
    21 CFR Part 589
    
    [Docket No. 96N-0135]
    RIN 0910-AA91
    
    
    Substances Prohibited From Use in Animal Food or Feed; Animal 
    Proteins Prohibited in Ruminant Feed
    
    AGENCY: Food and Drug Administration, HHS.
    
    ACTION: Proposed rule.
    
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    SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
    the regulations to provide that animal protein derived from ruminant 
    and mink tissues is not generally recognized as safe (GRAS) for use in 
    ruminant feed, and is a food additive subject to certain provisions of 
    the Federal Food, Drug, and Cosmetic Act (the act). The proposed 
    regulations would establish a flexible system of controls, designed to 
    ensure that ruminant feed does not contain animal protein derived from 
    ruminant and mink tissues in a manner that encourages innovation. FDA 
    is also considering alternatives to this proposed ruminant-to-ruminant 
    prohibition, and is requesting comment on the relative merits and 
    disadvantages of the alternatives. FDA is proposing this action because 
    the feeding to ruminants of protein derived from potentially 
    transmissible spongiform encephalopathy (TSE)-infective tissues may 
    cause TSE in animals. TSE's are progressively degenerative central 
    nervous system (CNS) diseases of man and animal that are fatal. 
    Epidemiologic evidence gathered in the United Kingdom (U.K.) suggests 
    an association between an outbreak of a ruminant TSE, specifically 
    bovine spongiform encephalopathy (BSE) and the feeding to cattle of 
    protein derived from sheep infected with scrapie, another TSE. Also, 
    scientists have postulated that there is an epidemiologic association 
    between BSE and a form of human TSE, new variant Creutzfeldt-Jakob 
    disease (nv-CJD) reported recently in England. BSE has not been 
    diagnosed in the United States. However, this proposed rule is intended 
    to prevent the establishment and amplification of BSE in cattle in the 
    United States, and thereby minimize any risk which might be faced by 
    animals and humans.
    
    DATES: Written comments by February 18, 1997. FDA proposes that any 
    final rule that may issue based on this proposal become effective 60 
    days after the date of its publication in the Federal Register.
        Submit written comments on the collection of information 
    requirements by February 18, 1997.
    
    ADDRESSES: Submit written comments to the Dockets Management Branch 
    (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, 
    Rockville, MD 20857. Submit written comments on the information 
    collection requirements to the Office of Information and Regulatory 
    Affairs, Office of Management and Budget (OMB), New Executive Office 
    Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, ATTN: Desk 
    Officer for FDA.
    
    FOR FURTHER INFORMATION CONTACT:
    
    Regarding Scientific and Industry Issues:
        George A. (Bert) Mitchell, Center for Veterinary Medicine (HFV-1), 
    Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 
    301-594-1761.
    Regarding Procedural and Regulatory Issues:
        Richard E. Geyer, Center for Veterinary Medicine (HFV-201), Food 
    and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 301-
    594-1761.
    
    SUPPLEMENTARY INFORMATION
    
    Table of Contents
    
    I. Summary
        A. Introduction
        B. GRAS Status of Ruminant and Mink Tissues
        C. The ``No Action'' Alternative
        D. The Basis for the Agency's Proposed Action
        1. General Discussion
        2. Analysis of Risk Factors
        a. The risk of BSE occurring in the United States
        b. The risk of amplification in the cattle population
        c. The risk of transmission to humans
        E. Enforcement Provisions
        F. Alternatives
    II. Background
        A. TSE's
        1. Scrapie
        2. BSE
        3. Other Animal TSE's
        4. TSE's of Humans
        a. CJD
        b. nv-CJD
        c. Gertsmann-Strausller-Scheinker (GSS) syndrome
        d. Kuru
        e. Fatal familial insomnia (FFI)
        5. Etiology
        6. Pathogenesis
        7. Transmission
        8. Genetics
        9. Diagnostics
        10. Inactivation
        B. The Association Between Scrapie and BSE
        C. The Association Between Animal TSE's and Human TSE's
        D. Infectivity of Specific Tissues
        E. Potential Risk of TSE's to the United States
        1. Overview
        2. Comparison with the U.K. Conditions
        F. Historical Efforts to Control TSE's
        1. U.S. Actions
        a. FDA
        b. USDA
        c. Public Health Service
        i. CDC
        ii. National Institutes of Health (NIH)
        iii. Other actions
        2. International Actions
        a. United Kingdom
        b. WHO
        c. OIE
        d. European Community (EC)
        3. Voluntary Measures by the U.S. Animal Industries
        a. Voluntary ban on rendering adult sheep
        b. Voluntary ban on feeding ruminant proteins to ruminants
        G. Processing Animal Tissues for Feed Ingredients
        1. Current Rendering Practices
        2. Assay Methodologies for Proteins
    III. Statutory Provisions Regarding Food Additives
        A. GRAS Determination
        B. Prior Sanction
        C. Food Additive Status of Ruminant Tissues
    IV. Comments
    V. Analysis of Alternatives
        A. Overview
        B. Ruminant-to-Ruminant Prohibition
        C. Partial Ruminant-to-Ruminant Prohibition
        D. Mammal-to-Ruminant Prohibition
        E. Prohibition of Materials from U.S. Species diagnosed with 
    TSE's (sheep, goats, mink, deer, and elk)
        F. Sheep-Specified Offal Prohibition
        G. No Action
    VI. Description of the Proposed Rule
        A. Introduction
        1. Regulatory Alternatives
        2. The Regulated Industry
        3. Enforcement Consideration
        B. Outline of the Proposed Regulation
    VII. Specific Protein Sources
        A. Milk Proteins
        B. Gelatin Proteins
        C. Blood Meal Proteins
        D. Canine and Feline Derived Proteins
    VIII. Environmental Impact
    IX. Analysis of Impacts
        A. The Need for Regulation
        B. Benefits
        1. Methodology
        2. Reduced Risk to Public Health
        3. Reduced Risk of Direct Livestock Losses
        4. Costs of Future Regulation
        5. Reduced Risk of Losses in Domestic Sales and Exports
        6. Total Losses Averted
        7. Comparison of Alternatives
        C. Industry Impacts
        1. The Proposed Rule
        2. Partial Ruminant-to-Ruminant Prohibition
        3. Mammalian-to-Ruminant Prohibition
        4. Other Regulatory Alternatives
    
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        D. Small Business Impacts
        E. Unfunded Mandates Analysis
    X. The Paperwork Reduction Act of 1995
    XI. Federalism
    XII. References
    XIII. Request for Comments
    
    I. Summary
    
    A. Introduction
    
        In the Federal Register of May 14, 1996 (61 FR 24253), FDA 
    published an advance notice of proposed rulemaking (ANPRM) that 
    solicited information and public comment on the issue of using protein 
    derived from ruminants (cattle, sheep, goats, deer, and elk) in 
    ruminant feed. The agency requested information and comment on a number 
    of issues because it was assessing whether to prohibit the use of 
    ruminant protein in ruminant feed. BSE has not been identified in the 
    United States. The agency issued an ANPRM because of its concern about 
    the possible adverse effect on animal and human health if TSE's were to 
    be spread through animal feed. After reviewing the ANPRM comments and 
    other sources of information, the agency is proposing to prohibit the 
    use of ruminant and mink animal tissue in the feed of ruminants. 
    Because TSE has been found in U.S. mink, the agency is also including 
    mink tissue in the proposed prohibition. The agency is also considering 
    alternatives to the proposed ruminant-to-ruminant prohibition, 
    including the alternative of taking no action.
    
    B. GRAS Status of Ruminant and Mink Tissues
    
        The agency is proposing to declare that protein derived from tissue 
    from ruminant animals and mink is not GRAS, by qualified experts, for 
    use in ruminant feed and is therefore a ``food additive'' under the 
    law. As a result, because neither a food additive regulation nor an 
    exemption is in effect for ruminant and mink tissues intended for 
    feeding to ruminants, such tissues would be deemed adulterated. Milk 
    and gelatin proteins derived from ruminants, and blood from cattle are 
    exempt from the proposed prohibition. The proposed rule does not apply 
    to any nonprotein animal tissues such as tallow or other fats.
        Expert opinion that the tissues are GRAS would need to be supported 
    by scientific literature, and other sources of data and information, 
    establishing that there is a reasonable certainty that the material is 
    not harmful under the intended conditions of use. Expert opinion would 
    need to address topics such as whether it is reasonably certain that 
    BSE does not, or will not, occur in the United States; whether it is 
    reasonably certain that the BSE agent will not be transmitted through 
    animal feed, i.e., that the processed tissues are not infected by the 
    agent, are deactivated by the rendering process or are not transmitted 
    orally; and whether it is reasonably certain that the agent will not be 
    transmitted to humans through consumption of ruminant products. 
    ``General recognition'' cannot be based on an absence of studies that 
    demonstrate that a substance is unsafe; there must be studies to 
    establish that the substance is safe. Also, the burden of establishing 
    that substance is GRAS is on the proponent of the substance. See U.S. 
    v. An Article of Food * * * Co Co Rico, 752 F.2d 11 (1st Cir. 1985).
        Although the ANPRM did not specifically ask for opinion on the GRAS 
    issue, a number of comments from scientific organizations and 
    individual scientists strongly suggest that the comments would support 
    the view that ruminant and mink tissue is not GRAS when fed to 
    ruminants. Some of these comments submitted data and information that 
    would support such opinions. Only a few comments included statements by 
    scientists, or scientific organizations, to the contrary. Similarly, 
    the opinions stated by scientists who spoke during a 1996 symposium on 
    TSE's would, in general, support the ``nonGRAS'' position. The 
    symposium, ``Tissue Distribution, Inactivation and Transmission of 
    Transmissible Spongiform Encephalopathies,'' was cosponsored by FDA and 
    USDA, and was held in Riverdale, MD, on May 13 and 14, 1996.
        FDA has searched for but has not found sufficient literature or 
    other sources of data and information that would, on balance, support 
    expert opinion that ruminant and mink protein is GRAS as a ruminant 
    feed additive. Previous comments on the agency's proposal to prohibit 
    the feeding of specified sheep and goat offal (59 FR 44584, August 29, 
    1994) did not include either written GRAS opinions from qualified 
    experts, or data and information that would support such opinions. The 
    relevant data and information, and lack thereof, are discussed more 
    fully in this section, and in section II. of this document. See Section 
    III.A., of this document, for a further explanation of ``GRAS'' and 
    ``food additive.''
    
    C. The ``No Action'' Alternative
    
        Even when, as in this case, FDA has taken steps leading to a 
    tentative determination that a substance added to food is not GRAS, the 
    agency is not required to issue a proposal declaring that the substance 
    is not GRAS and is a food additive subject to section 409 of the act. 
    Section 570.38 provides that the agency may take such an action. The 
    agency considered the possibility of not issuing a proposal with regard 
    to the feeding of ruminant and mink tissues to ruminants.
        The fact that the data and information do not document an immediate 
    threat to the U.S. public health supports this ``no action'' 
    alternative. Moreover, certain of the available data and information 
    can be used to support the view that the threat, if any, is minimal.
        The evidence suggesting that there is no immediate threat is 
    summarized as follows. First, BSE has not been detected in cattle in 
    the United States despite an extensive surveillance effort that has 
    been in place for several years. Restrictions on the importation of 
    cattle, cattle products and feed ingredients from BSE-affected 
    countries are in place to minimize the possibility of BSE entering into 
    the United States. Surveillance, training of veterinary practitioners 
    and diagnosticians, and other efforts are in place to detect any 
    occurrence of BSE quickly, and to minimize its spread among the cattle 
    population. No empirical scientific evidence is available to establish 
    that BSE will occur from any of the possible sources, such as 
    transmission from another U.S. species in which TSE's have been 
    diagnosed; spontaneous occurrence in cattle; or importation of live 
    animals or animal feed products carrying the BSE agent. For example, 
    transmission between any two species is difficult to predict, based on 
    available data, because of variability in species barriers (Ref. 1).
        Second, even if BSE did develop in the United States there is no 
    conclusive scientific evidence that the disease would be spread through 
    animal feed, the product that provides FDA's jurisdictional nexis. 
    Although there is strong epidemiological evidence that the feeding of 
    processed tissue from sheep containing scrapie to cattle caused the 
    widespread BSE infections in the United Kingdom, many experts believe 
    that the chances that the United States will have a BSE outbreak, 
    similar to the epidemic that took place in the United Kingdom, are low. 
    For example, most of the industry practices and other conditions 
    believed to have been associated with the BSE epidemic in the United 
    Kingdom do not exist in the United States. Further, the U.K. 
    epidemiological evidence of transfer from sheep to cattle has not been 
    confirmed by direct scientific data. This has caused some to question 
    the assumption that the BSE originated from scrapie (Ref. 1). Further, 
    some
    
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    experimental information suggests that the TSE's in general are not 
    readily transferred by the oral route. Experimentally, the oral route 
    has been suggested to be the least efficient means of transmission for 
    TSE's (Ref. 1).
        Third, the postulated connection between BSE and CJD has not been 
    definitively established. Scientists have theorized an association 
    between BSE and the recent appearance of nv-CJD in the United Kingdom. 
    While the epidemiological association, both in time and geography, of 
    these two diseases in the United Kingdom provides suggestive evidence 
    of an association between the two, the available evidence does not 
    establish causation. Although the BSE agent has been transmitted to 
    laboratory animals, the species barrier between cattle and humans may 
    be higher than between cattle and mice (Ref. 1). Epidemiological 
    evidence linking BSE with classical CJD is even less supportive. 
    Although CJD occurs in the United States, nv-CJD has not been reported 
    in this country.
        The FDA's conclusion that there is no immediate threat to the 
    public health in the United States is supported by a statement from the 
    World Health Organization (WHO) that the ``risk, if any, of exposure to 
    the BSE agent in countries other than the U.K. is considered lower than 
    in the U.K.'' (Ref. 2). A number of comments to the ANPRM made a 
    similar assertion, urging that FDA's regulatory decision be made on the 
    basis of scientific information and contending that the available 
    information did not support the contemplated action.
    
    D. The Basis for the Agency's Proposed Action
    
    1. General Discussion
        Even though there is no immediate threat to the U.S. public health 
    and some information that indicates that a threat, if any, is minimal, 
    after careful consideration the agency has tentatively concluded that 
    regulatory action is necessary to protect animal and human health. The 
    agency has reached that tentative conclusion because there is a growing 
    body of data and information that affirmatively raises public health 
    concerns.
        The data and information raise concern that BSE could occur in 
    cattle in the United States; and that if BSE does appear in this 
    country, the causative agent could be transmitted and amplified through 
    the feeding of processed ruminant protein to cattle, and could result 
    in an epidemic. The agency believes that the high cost, in animal and 
    human lives and economics, that could result if this scenario should 
    occur, justifies the preventive measure reflected by the proposed 
    regulation. Although the agency expects some continued voluntary 
    reduction in the feeding of ruminant and mink tissues to ruminants, the 
    reduction is not expected to be extensive enough to obviate the need 
    for mandatory preventive measures.
        Statements from several prominent public and animal health 
    organizations support this proposal to regulate the feeding of ruminant 
    tissues to ruminant animals. For example, the Centers for Disease 
    Control and Prevention (CDC) has urged the agency to adopt a ruminant-
    to-ruminant feed prohibition (Ref. 3), and USDA has recommended the 
    same action. Although WHO considers the risk in countries such as the 
    United States to be minimal, that organization has nevertheless called 
    on all countries to prohibit the use of ruminant tissues in ruminant 
    feed (Ref. 2).
        A number of comments to the ANPRM, including comments by several 
    consumer groups, supported regulatory action by FDA. The Pharmaceutical 
    Research and Manufacturers of America urged FDA to take all necessary 
    steps to prevent an outbreak of BSE, and to prevent the potential 
    spread of BSE should a case occur in the United States. One 
    pharmaceutical firm emphasized the importance of acknowledging public 
    perception, stating that a ruminant-to-ruminant prohibition would 
    ``significantly decrease the concern regarding this perceived risk.'' 
    Another pharmaceutical firm characterized the risk as ``small but 
    real.'' A group of livestock producers, veterinary associations and 
    scientific organizations cited the WHO recommendations to support their 
    call for a voluntary ruminant-to-ruminant prohibition. The group stated 
    that such a prohibition would ``eliminate any risk, no matter how 
    remote [and would] totally prevent BSE from ever occurring in the 
    United States.''
        The agency is concerned about the public health issues raised but 
    not resolved by the available scientific information. The fact that the 
    causative agent or agents for TSE's have not been clearly identified, 
    and their transmissibility has not been fully characterized, adds to 
    the concern. However, certain information that is well documented 
    supports the agency's decision as well. TSE's are 100-percent fatal 
    diseases that have been diagnosed in humans and a number of animal 
    species. The diseases are progressively degenerative CNS diseases that 
    are characterized by a relatively short clinical course of neurological 
    signs. TSE's have a prolonged incubation period, i.e., 2 to 8 years in 
    animals, and scientific evidence supports the view that TSE's can be 
    transmitted in the preclinical stage. There is no practical method to 
    detect the presence of TSE's during the preclinical stage.
    2. Analysis of Risk Factors
        This section describes the evidence that supports the agency's 
    tentative conclusion. The evidence relates to the risks that BSE could 
    occur in cattle in the United States; that the BSE agent or other TSE 
    agents could be amplified in the cattle population by the feeding of 
    ruminant and mink tissues to cattle; and that the agent could 
    potentially be transmitted to humans.
        a. The risk of BSE occurring in the United States. BSE has not been 
    diagnosed in the United States. FDA does not have evidence to support 
    the theory that BSE already exists, undiagnosed, in this country. 
    However, the agency does find plausible the arguments of the theory 
    that BSE could develop in the United States from three possible 
    sources: Transmission of TSE's from other susceptible species, 
    spontaneous occurrence, and importation in live animals or animal 
    products.
        The evidence concerning transmission from other species is 
    summarized as follows. TSE's other than BSE have been diagnosed in 
    animals in the United States. These include scrapie in sheep and goats, 
    transmissible mink encephalopathy (TME), and chronic wasting disease 
    (CWD) in deer and elk. Feline spongiform encephalopathy (FSE) has been 
    diagnosed in cats in other countries. In general, the TSE's have been 
    shown to be naturally transmissible within species and are believed by 
    some scientists to be naturally transmissible (as distinguished from 
    experimentally transmissible), at least to a limited extent, between 
    species. Consumption of meat and bone meal (the predominant animal 
    tissue-containing product fed to animals) which was produced under 
    conditions similar to the meat and bone meal which was implicated in 
    the U.K. BSE epidemic, as well as the feeding of raw bovine tissue, 
    also appeared to cause TSE in exotic cats and various zoo animals. This 
    implies that the species barrier for BSE may be uncharacteristically 
    low. (See e.g., Refs. 3 and 4). In addition to the epidemiological 
    evidence relating to TSE transmission from sheep to cattle in the 
    United Kingdom, there is limited experimental evidence of transmission
    
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    of the BSE agent from cattle to sheep. Many laboratory animal species 
    have also been experimentally infected following the administration of 
    tissues from animals with TSE disease.
        There is some evidence to support the theory that BSE can occur 
    spontaneously in cattle. The leading theory as to the causative agent, 
    e.g., infectious protein or prion, inherently suggests that the BSE 
    could occur spontaneously. Additional support arises from the fact that 
    85 percent of CJD cases are sporadic, and have no familial or 
    identifiable link as to their cause. Recent surveillance information 
    from Northern Ireland and Switzerland also supports the spontaneous 
    theory. In these countries, BSE has occurred in cases in which no 
    exposure to rendered protein can be found, and there is no evidence of 
    BSE in the parental stock or herd mates of affected animals (Ref. 5).
        As described more fully in section II.F.1.b. of this document, 
    USDA-APHIS has implemented import restrictions on live animals and 
    animal products from BSE-affected countries. As a result of the 
    restrictions, the potential risk of BSE occurring in this country as a 
    result of exposure from imported cattle and imported animal protein 
    products appears to be small (Ref. 6). However, the risk from foreign 
    sources of BSE introduction into the United States cannot be dismissed 
    entirely because the USDA import restrictions are unlikely to be 100 
    percent effective even though no cases of BSE have been diagnosed to 
    date in the United States. The USDA regulations are intended to reduce 
    or control risk, not completely eliminate it. See e.g., 56 FR 63866, 
    December 6, 1991.
        b. The risk of amplification in the cattle population. Research has 
    shown that various animal tissues can transmit BSE infectivity. There 
    is also evidence supporting the view that the agent could be 
    transmitted orally (e.g., through animal feed). Although some 
    experimental evidence suggests that the TSE's in general are more 
    readily transmitted by means other that the oral route, research also 
    suggests that the BSE agent is more susceptible to oral transmission. 
    In most cases (e.g., the U.K. epidemic) the natural route of exposure 
    to TSE's including BSE is suspected to be oral. This belief is 
    supported by the dramatic decline in BSE cases in the United Kingdom 
    following implementation of the ruminant-to-ruminant feeding 
    prohibition. In the United Kingdom, where more than 160,000 cases of 
    BSE have been diagnosed, a 1988 ban on the feeding of ruminant-derived 
    protein supplements to other ruminants was associated with a steady 
    decrease in the disease incidence starting in 1993. The 5-year period 
    between the initiation of the ruminant-to-ruminant ban and the decline 
    in the incidence of BSE is consistent with the known incubation period 
    in cattle of 2 to 8 years. Further, preliminary experimental data show 
    that the BSE agent can be transmitted orally to cattle through feeding 
    of material from an infected cow (Ref. 3). Thus, there is a chance that 
    BSE could be spread in animal feed if it developed in the U.S. cattle 
    population, whether spontaneously, from another species or by some 
    other means.
        The greatest risk factor for cattle may not be the single 
    occurrence of a BSE case. Instead, the greatest risk may arise from the 
    potential, given the prolonged incubation period, for unrecognized 
    amplification of BSE in the cattle population, resulting in a potential 
    for greater animal exposure. The possibility of risk from recycling 
    ruminant tissues is enhanced by the fact that current rendering methods 
    have not been shown, and are not expected, to completely deactivate the 
    BSE agent, and that practical tests are not available for detecting 
    either the BSE agent in rendered material or the presence of ruminant 
    material in feed.
        The preliminary experimental cow-to-cow TSE transmission data 
    previously described occurred with as little as a single dose (one-time 
    exposure) of 1 gram of brain material from the infected cow, indicating 
    a low transmitting dose. This means, among other things, that FDA 
    cannot determine the level of feed ingredients from animals tissues, if 
    any, that is considered safe in ruminants.
        c. The risk of transmission of humans. Finally, there exists the 
    theoretical possibility of the transmission of a TSE in animals, such 
    as BSE, to humans. CDC agrees that the link between BSE, and TSE's in 
    humans, has not been fully demonstrated. Some of the ANPRM comments 
    agreed. For example, one pharmaceutical firm stated that the evidence 
    is not entirely conclusive. Nevertheless, a body of epidemiological and 
    experimental evidence is developing to support the postulated 
    association between BSE and nv-CJD. This and other scientific evidence 
    developed more fully in section II leads the agency to propose for 
    comment the prudent risk reduction regulatory action that is 
    incorporated in the proposed rule.
    
    E. Enforcement Provisions
    
        The agency is issuing this proposed rule within the context of 
    comprehensive government-wide efforts to minimize the risks previously 
    described, and within the statutory authority provided to the agency. 
    The proposed rule has two major components. First, the agency proposes 
    to prohibit feeding animal materials derived from ruminant and mink 
    tissues to ruminants, in the absence of a food additive regulation or 
    investigational exemption. Thus, the prohibition would ensure that 
    tissues which could contribute to a TSE epidemic by spreading the 
    causative agent rapidly would not be allowed in ruminant feed.
        The second component of the rule provides for a system of controls 
    to ensure that the proposed rule would achieve its intended purpose. 
    These provisions are necessary because limited controls are in place, 
    or available, to prevent the spread of BSE through animal feed in the 
    United States, should BSE occur. The proposed regulation places two 
    general requirements on persons that manufacture, blend, process and 
    distribute animal protein products, and feeds made from such products. 
    The first requirement is to place cautionary labeling on the protein 
    and feed products. The second is to provide FDA with access to sales 
    and purchase invoices, for compliance purposes.
        Firms that handle animal protein products from both ruminant and 
    nonruminant sources, and that intend to keep the two kinds of products 
    separate, would have certain additional requirements. These 
    requirements would relate to the need for separate facilities or 
    cleanout procedures; the need for standard operating procedures 
    (SOP's); and in the case of renderers, their source of nonruminant 
    material. Similar requirements would be placed on firms that handle 
    animal feed containing animal protein products from both ruminant and 
    nonruminant sources, and intend to keep the two kinds of feed separate. 
    Requirements would be greater for the firms that intend to separate the 
    animal protein products and feeds, because of the greater risk these 
    operations would present for the possibility that ruminant protein 
    might be fed, inadvertently, to ruminants.
        However, the regulatory system would be flexible, allowing the 
    regulated firms to innovate and choose the most cost-effective means of 
    compliance. For example, some or all of the regulatory requirements 
    previously described would not apply if any of the following 
    innovations were developed and validated by FDA: Processing methods 
    that deactivate the agent that causes BSE; test methods to detect the 
    presence of the agent; or methods of marking or otherwise identifying 
    the
    
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    material that contains ruminant protein. Further, the agency will 
    consider modifying or revoking any final rule that is published 
    prohibiting the use of ruminant and mink tissues in ruminant feed, if 
    scientific and technical advances permit even greater flexibility than 
    that offered in the proposed regulation. Conversely, the diagnosis of 
    one or more cases of BSE in the United States, or new scientific 
    findings, could lead to stricter regulatory requirements.
    
    F. Alternatives
    
        The agency is soliciting comments on several alternative means of 
    minimizing the risk of transmitting TSE's in ruminant feed, in addition 
    to the proposed ruminant-to-ruminant prohibition. These alternatives 
    include:
        (1) A partial ruminant-to-ruminant prohibition which would exclude 
    all ruminant and mink tissues from ruminant feed except those bovine 
    tissues that have not been found to present a risk of transmitting 
    spongiform encephalopathy. Possible exclusions include slaughter 
    byproducts from cattle that have been inspected and passed in inspected 
    slaughter facilities, except tissues that have been shown through 
    experimental trials and bioassays to transmit spongiform 
    encephalopathy. Examples of the latter might include the brain, eyes, 
    spinal cord and distal ileum. The agency solicits comments on the scope 
    of this alternative;
        (2) A prohibition on the feeding of all mammalian tissues to 
    ruminants;
        (3) A prohibition on the feeding of rendered material from those 
    animal species in which TSE's have been diagnosed in the United States 
    (sheep, goats, mink, elk, and deer);
        (4) A prohibition on the feeding of specified offal from adult 
    sheep and goats as proposed in 1994;
        (5) Other alternative approaches that meet the agency's regulatory 
    objectives and that might be suggested in comments to the proposed 
    rule. The agency may in any final rule issued adopt such alternative 
    approaches. Such alternatives may be more or less stringent than this 
    proposal or may be a combination of provisions from this proposal and 
    other alternatives. For example, one such option might be a proposal to 
    exclude from the scope of any regulation certain facilities that apply 
    specified risk-reduction measures in addition to, or in place of, those 
    included in the regulation FDA is proposing in this publication. 
    Therefore, the agency specifically requests comments on other 
    approaches that would achieve the agency's regulatory objectives. Any 
    proposed alternative approaches should be explained in detail, and 
    their justification should be well documented. To the extent possible, 
    please include information on costs and benefits of the proposals; and
        (6) The ``no action'' alternative as it relates to this proposed 
    rule. Again, detailed explanation and well-documented justification 
    should be presented.
        The agency's views on the advantages and disadvantages of these 
    options appears in section V of this document. The agency invites 
    comments on the relative merits and disadvantages of all these 
    alternative concepts.
        FDA has estimated that the annualized costs of the proposal, 
    comprised of both the direct compliance costs and various indirect 
    gains and losses, would range from $21.4 to $48.2 million. The agency 
    also estimated that the annualized costs could range from $45.0 to 
    $56.5 million for the mammalian-to-ruminant option; from $28.5 to $37.3 
    million for the partial ruminant-to-ruminant option; and would total 
    less than $10 million for each of the remaining options. On the other 
    hand, if the agency chooses the ``no action'' option and a BSE epidemic 
    occurs, the above costs could be expanded by a great magnitude.
        Because the body of scientific research related to TSE's is growing 
    rapidly, the agency will place in the Docket copies of relevant 
    scientific literature published after the agency completes work on this 
    proposal, and before the agency completes work on any final regulation. 
    The agency will add to the Docket, as appropriate, a brief statement of 
    its assessment of the significance of the literature, and will invite 
    comments. However, substantive changes from the proposed rule would be 
    made in accordance with the discussions in the preceding paragraphs and 
    the Administrative Procedure Act.
    
    II. Background
    
    A. TSE's
    
    1. Scrapie
        Scrapie is a slowly progressive, transmissible disease of the CNS 
    in sheep and goats. Scrapie is characterized by a prolonged incubation 
    period averaging 2 years, followed by a clinical course of 2 to 6 
    months when the animal exhibits sensory and motor malfunction, 
    hyperexcitability, and death. The agent presumably moves from infected 
    to susceptible animals by direct or indirect contact and enters through 
    the gastrointestinal tract. Consequently, its spread appears to be both 
    vertical (mother to offspring in utero) (Ref. 7) and horizontal (direct 
    contact) between sheep (Ref. 8). Early signs of scrapie include subtle 
    changes in behavior or temperament which may be followed by scratching 
    and rubbing against fixed objects. Other signs include loss of 
    coordination, weight loss despite a good appetite, biting of feet and 
    limbs, tremor around head and neck, and unusual walking habits (Ref. 
    9).
        The scrapie agent is found in lymphatic tissue (spleen, thymus, 
    tonsil, and lymph nodes) in sheep with preclinical infections; however, 
    in clinically affected sheep, the agent is identified in the 
    intestines, nervous tissues (brain and spinal cord), and lymphatic 
    tissues as determined by experimental infectivity studies in a 
    susceptible animal model (Ref. 8). The brain has been demonstrated to 
    have the highest level of infectivity of all tissues (Ref. 10).
        Scrapie is known to have existed in Britain, Ireland, France, and 
    Germany for over 200 years. It has been observed in the United States 
    and Canada for about 50 years. The first case of scrapie in the United 
    States was diagnosed in Michigan in 1947. From 1947 through January 
    1993, approximately 653 flocks have been diagnosed with scrapie (Ref. 
    11). At the present time, there are 67 known scrapie-infected flocks 
    (flocks with sheep diagnosed with scrapie), and there are 8 known 
    scrapie-source flocks (flocks to which scrapie-infected sheep were 
    traced) (Ref. 12). In the absence of an antemortem diagnostic test, it 
    is not possible to establish with absolute certainty that a flock is 
    free of scrapie. Moreover, lack of reporting, the long incubation 
    period, and open range husbandry practices in the western United States 
    make it difficult to detect classical clinical signs and completely 
    monitor scrapie in the United States.
    2. BSE
        BSE is a transmissible, slowly progressive, degenerative disease of 
    the CNS of adult cattle. This disease has a prolonged incubation period 
    in cattle following oral exposure (2 to 8 years) and is always fatal. 
    BSE is characterized by abnormalities of behavior, sensation, posture, 
    and gait. These signs are similar to those seen in sheep that are 
    infected with scrapie. BSE is associated with spongiform lesions in the 
    gray matter neuropil of the brainstem and neuronal vacuolization (Ref. 
    13). The clinical signs usually begin with changes in animal behavior, 
    and may include separation from the rest of the herd while at pasture, 
    disorientation, or excessive licking of the nose or flanks (Ref. 14). 
    The most common history given by the herdsman was nervousness
    
    [[Page 557]]
    
    or altered behavior or temperament, weakness associated with pelvic 
    limb ataxia, paresis, and loss of body weight (Ref. 15). In some 
    animals there are few gross pathological changes at necropsy associated 
    with BSE other than the loss of body weight. However, postmortem 
    histopathology of BSE distinguish it from other neurological disorders 
    (Refs. 16 and 17). Neither vertical nor horizontal transmission has 
    been documented for BSE.
        BSE was first recognized as a new cattle disease by researchers at 
    the Central Veterinary Laboratory of the British Ministry of 
    Agriculture, Fisheries, and Foods at Weybridge, England in November 
    1986. As of November 15, 1996, BSE had been diagnosed in Great Britain 
    in more than 165,000 head of cattle from more than 31,000 herds. Cases 
    have been confirmed in 59.2 percent of the dairy herds and 15.3 percent 
    of the beef herds (Ref. 18). The BSE epidemic curve for Great Britain 
    peaked in January 1993 and is decreasing steadily, concomitantly with 
    changes in rendering and feeding practices. BSE has also been reported 
    in native cattle of Northern Ireland, Guernsey, Jersey, Isle of Man, 
    the Republic of Ireland, Switzerland, France, and Portugal. BSE has 
    been confirmed in cattle exported from Great Britain to Oman, the 
    Falkland Islands, Germany, Denmark, Canada, and Italy.
        There have been no cases of BSE in cattle in the United States. 
    There has been one case of BSE in a cow imported into Canada from Great 
    Britain. That cow was destroyed, along with its herdmates and other 
    nearby cattle considered by animal health authorities in Canada to have 
    possibly been exposed to the cow with BSE (Ref. 19).
    3. Other Animal TSE's
        Other animals have TSE's with typical characteristics of long 
    incubation, neurological degeneration, and a 100-percent death rate. 
    These animals include: Mink, elk and deer, zoo ruminants, and exotic 
    and domestic cats.
        TME is a mink disease with clinical signs and brain lesions similar 
    to those of sheep infected with scrapie. TME is a rare disease in the 
    United States. Since the disease was first recognized in 1947, in 
    Wisconsin, four additional outbreaks have occurred in the United 
    States. The last outbreak occurred in 1985 and was limited to a single 
    mink ranch in Wisconsin (Ref. 20).
        CWD of deer and elk is characterized by emaciation, changes in 
    behavior and excessive salivation, polydipsia, and polyuria. The 
    clinical course is from several weeks to 8 months, and the disease is 
    invariably fatal (Ref. 20). From 1967 to 1979, CWD was observed in 53 
    captive mule deer in Colorado and Wyoming. Clinical signs were seen in 
    adult deer and included behavioral alterations, progressive weight loss 
    and death in 2 weeks to 8 months. Consistent histopathologic change was 
    limited to the CNS and characterized by widespread spongiform 
    transformation of the neuropil. The disease is a specific, 
    spontaneously occurring form of spongiform encephalopathy (Ref. 21). 
    Topographic distribution and lesion severity were most similar to those 
    of scrapie and BSE. The duration of the clinical disease did not 
    significantly influence lesion distribution or severity in either 
    species (Ref. 22).
        Scrapie-like encephalopathies have been described in certain zoo 
    ruminants, i.e., a nyala, an Arabian oryx, and a greater kudu. Clinical 
    signs included ataxia and loss of coordination with a short, 
    progressive clinical course. Histopathological examination of the 
    brains revealed spongiform encephalopathy characteristic of that 
    observed in scrapie and BSE (Refs. 23, 24, and 25). Strain typing of 
    the agent suggests that all of the cases are directly related to BSE.
        Seventy domestic cats in the United Kingdom have developed FSE, a 
    spongiform encephalopathy that was never previously reported. The cats 
    all had progressive, neurological disease involving locomotor 
    disturbances, abnormal behavior and, in most cases, altered sensory 
    responses. Histopathological examination of the central nervous system 
    revealed changes pathognomonic of spongiform encephalopathy; this 
    included widespread vacuolization of the gray matter neuropil and 
    neuronal perikarya (Refs. 26 and 27). Infective tissue from several of 
    these cases, when injected into mice, resulted in brain lesions with a 
    distribution and morphology that is undistinguishable from the lesions 
    produced by BSE infective tissue injected into mice.
    4. TSE's of Humans
        The TSE's of humans are divided into specific clinical types, which 
    may appear similar histopathologically but are either transmitted 
    differently or demonstrate different patterns of distribution and 
    prevalence.
        a. CJD. CJD was first described in 1920 and 1921 when it was known 
    as ``spastic pseudosclerosis'' or ``subacute spongiform 
    encephalopathy'' (Ref. 28). The illness exists throughout the world and 
    is claimed to have a similar prevalence in each of the countries tested 
    with an annual incidence of approximately one case per million of the 
    population. Autopsies are sometimes not performed on persons who may 
    have died of CJD and many older people dying of a dementing illness do 
    not have autopsies performed. There is an increased incidence among 
    Libyan Jews (26 cases per million) and spatial or temporal clusters in 
    areas of Slovakia, Hungary, England, the United States, and Chile. The 
    average age of a typical CJD victim is 56 years of age, and only a few 
    cases involving persons between 4 and 29 years have been reported prior 
    to 1993. Between 4 and 15 percent of cases have a familial connection 
    with other cases. There is a slightly higher incidence of CJD in women 
    compared to men. Clinical prodromal symptoms start with changes in 
    sleeping and eating patterns, and often include confusion, 
    inappropriate behavior, vague visual complaints and/or ataxia. Those 
    symptoms progress over a few weeks to a clearly neurological syndrome. 
    A rapid onset of neurological symptoms appears in 20 percent of cases, 
    most commonly myoclonic jerks and dementia with loss of higher brain 
    function and behavioral abnormalities. The disease progresses with 
    continued deterioration in cerebral and cerebellar function, and the 
    onset of seizures. Ninety percent of the cases end in death within 1 
    year of onset. Diagnosis is by clinical assessment of patients and by 
    examination of electroencephalogram patterns. Post mortem diagnosis is 
    currently carried out by histological examination of cerebral tissue 
    under the light microscope, although this is not always reliable. 
    Research techniques that have been used to demonstrate CJD (and other 
    TSE's) include electron microscopic examination of brain tissue 
    extracts for scrapie-associated fibrils (SAF), immuno-staining of the 
    tissue for prion-protein (PrP) antigens, western blotting of extracted 
    PrP antigens and the intracerebral injection of tissue suspensions into 
    test animals.
        In some patients, the source of CJD has been claimed to be an 
    infection transferred from other patients with the condition. For 
    example, in one case, cerebral electrodes that had been sterilized with 
    alcohol and formalin vapor after use in a patient with CJD, were used 
    in the brains of two young epileptic patients, both of whom contracted 
    CJD after a short incubation. The transfer of CJD by corneal transplant 
    in 1 patient, by cadaveric dura mater grafts in several patients and by 
    pituitary-derived human growth hormone injections in over 80 patients 
    has also been reported.
    
    [[Page 558]]
    
        Only the medical procedures described previously have been 
    conclusively linked to transmission. The transmission of the disease 
    from animal sources has been suggested; see further discussion in 
    section II.C. of this document.
        b. nv-CJD. A previously undetected new variant of CJD (nv-CJD) was 
    reported by British scientists at a meeting of international experts 
    convened by WHO on April 2 and 3, 1996 (Ref. 29), and published 3 days 
    later (Ref. 30).
        The major evidence for the existence of nv-CJD is the recognition 
    of a new neuropathologic profile and the unusually young ages of 10 
    U.K. patients. Although all the cases had evidence of the pathognomonic 
    spongiform changes characteristic of classic CJD, and therefore were 
    appropriately classified as a form of CJD, the clinical course of the 
    disease was atypical of classic CJD. The most striking and consistent 
    neuropathologic feature of nv-CJD was the formation of amyloid plaques 
    surrounded by halos of spongiform change. Plaques were extensively 
    distributed throughout the cerebrum and cerebellum. Many of these 
    plaques resembled those in kuru and were visible when examined by 
    routine staining methods.
        The temporal cluster of cases of nv-CJD in young patients (three 
    were teenagers, five were in their twenties, and two were in their 
    thirties at onset of disease) is highly unusual. Five of the eight 
    deceased patients died before 30 years of age. (The expected annual 
    mortality rate for CJD in persons under 30 years of age is less than 
    five per billion.) The characteristic clinical features of the nv-CJD 
    cases were: (1) A psychiatric presentation, (2) onset of a progressive 
    cerebellum syndrome with ataxia within weeks or months of the initial 
    presentation, (3) memory impairment with dementia in the late stages, 
    (4) myoclonus, and (5) the absence of electroencephalographic changes 
    typical of classic CJD.
        Review of the patients' medical histories and consideration of 
    various risk factors for CJD yielded no adequate clues as to the cause 
    of this disease. The PrP genotype was determined for eight cases. The 
    researchers noted that all genotypes were methionine homozygotes at 
    codon 129 of the PrP gene. The research did not identify any of the 
    known mutations associated with the inherited forms of CJD (Ref. 30).
        Although scientists have stated that exposure to the BSE agent 
    prior to the U.K. bans described in section II.F. of this document is 
    the most plausible explanation for these findings, no clear 
    epidemiologic link to BSE was identified. (See further discussion in 
    section II.C. of this document.) Another potential explanation is 
    exposure to TSE agents from animals other than cattle. Because the 
    United Kingdom reinstituted epidemiological surveillance for CJD in 
    1990, increased surveillance is still another potential reason for the 
    identification of this cluster of 10 cases of nv-CJD.
        c. Gertsmann-Strausller-Scheinker (GSS) syndrome. GSS syndrome is 
    an autosomal dominant condition in about 50 percent of siblings of 
    reference cases (Ref. 28). The disease is similar to CJD except that it 
    has a more extended onset and duration, a tendency towards cerebellar 
    ataxia as the initial predominant neurological sign, and a large number 
    of amyloid plaques present among the spongiform encephalopathic changes 
    of the brain. The extensive distribution of amyloid plaques in the 
    patient's brain is an observation shared by GSS syndrome and v-CJD. It 
    has been transmitted to monkeys and rodents by intracerebral 
    inoculation.
        d. Kuru. Kuru is a condition of the Fore people of the Okapa 
    district of the Eastern Highland in Papua New Guinea, in which a 
    practice of ritual cannibalism of fellow tribesmen took place until 
    approximately 1956 (Ref. 28). This TSE disease, which affected mainly 
    adult women and children of both sexes, caused an annual disease 
    specific mortality of approximately 3 percent. Most deaths of women in 
    the tribe occurred through this disease. Some men who died from this 
    disease were thought to have contracted it when they were young. Kuru 
    may be transmitted by eating infected tissue or through open wounds. 
    The brains of dead tribal members were eaten by women and children and 
    the muscle tissue by men. The cohort of children born since 1957 have 
    not suffered from kuru at all.
        Clinically the disease causes a progressive cerebellar ataxia, 
    uncoordinated movements, neurological weakness, palsies, and decay in 
    brain stem function. Most patients dying of kuru are not demented, a 
    major clinical difference between kuru and CJD.
        e. Fatal familial insomnia (FFI). FFI is another inherited TSE-
    linked disease (Ref. 31). FFI is characterized clinically by 
    untreatable progressive insomnia, dysautonomia, and motor dysfunctions. 
    The disease often starts between 35 and 60 years of age and leads to 
    death within 7 to 32 months. FFI is characterized pathologically by 
    atrophy, neuronal loss, and gliosis in the anterior and dorsomedial 
    nuclei of the thalamus (Ref. 32). FFI has been successfully transmitted 
    to mice (Ref. 33), but not to primates.
    5. Etiology
        The cause of TSE's is controversial. The TSE agent: (1) Is 
    presumably smaller than most viral particles and is highly resistant to 
    heat, ultraviolet light, ionizing radiation, and common disinfectants 
    that normally inactivate viruses or bacteria; (2) causes little 
    detectable immune or inflammatory response in the host; and (3) has not 
    been observed microscopically.
        Resistance of the TSE agent to physical and chemical methods that 
    destroy nucleic acid have essentially ruled out conventional 
    microbiological agents as the cause. Currently, the infectious protein 
    or prion theory is favored. Other proposed causes are an unconventional 
    virus, consisting of virus-coded protein and virus-specific nucleic 
    acid with unconventional properties, and a ``virino'' consisting of a 
    core of nontranslated nucleic acid associated with host cell proteins 
    (Ref. 34). Proposed causes of TSE's with less supporting evidence are: 
    (1) Retroviruses (Ref. 35), (2) a spiroplasma (Refs. 36 and 37), (3) 
    organophosphates (Ref. 38), and (4) peptide hormones (Ref. 39).
        The prion theory suggests that the causative agent is a normal host 
    protein (PrP or PrP-C) that is posttranslationally transformed into the 
    causative agent or PrP-Sc. Transformation of the PrP can occur from 
    rare somatic mutation of the prion gene, spontaneously or from contact 
    with extraneous PrP-Sc. The spread of BSE in the United Kingdom is 
    postulated to have occurred through the feeding of ruminant protein 
    that contained the PrP-Sc protein and thus follows the portion of the 
    theory that involves contact with extraneous PrP-Sc. This explanation 
    requires that one accept that abnormal prion protein from sheep crossed 
    the species barrier and resulted in BSE in cattle. An alternate 
    explanation is that a spontaneous mutation or transformation or other 
    nonorally induced event, occurred and resulted in undetected disease in 
    a bovine. These explanations are not mutually exclusive and it is 
    possible that both occurred.
        Recent surveillance information from Northern Ireland and 
    Switzerland tend to support the spontaneous mutation as a method by 
    which BSE can occur. Northern Ireland has had more than 10 cows produce 
    offspring, after the feeding ban, that developed BSE. Thus, 10+ cases 
    are theorized to be spontaneous because there is no evidence of feeding 
    meat and bone meal to the offspring and the dams are alive
    
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    and show no signs of BSE (Ref. 5). Switzerland, which has one of the 
    most aggressive BSE investigational surveillance of any European Union 
    (EU) country, has reported 205 cases of BSE. Some of these cases are in 
    animals that were fed only grass and hay (Ref. 5). Regardless of how 
    the initial cases occurred, however, the resulting unrecognized disease 
    was amplified by the feeding of ruminant protein to ruminants.
        Additional support for the feasibility of the TSE spontaneous 
    mutation explanation is the fact that 85 percent of all CJD cases are 
    sporadic and have no familial or identifiable link as to their cause. 
    It is these cases that give rise to the very stable, 1 in a million per 
    year, world wide incidence of the disease. DeArmond and Prusiner (Ref. 
    40), and Lansbury and Caughey (Ref. 41) have postulated that a 
    noninduced somatic cell mutation or the spontaneous conversion of PrP-C 
    into PrP-Sc are plausible explanations for the sporadic cases of CJD. 
    DeArmond and Prusiner theorized that the 1 in a million
    
        * * * may represent the combined probabilities that a mutation 
    occurs in the PRNP gene, the probability that the mutation leads to 
    the synthesis of the PrP-cjd (the abnormal protein), and the 
    probability that the resultant PrP-cjd targets other neurons for the 
    synthesis of more PrP-cjd at a rate fast enough to cause clinical 
    disease in the patient's lifetime.
    
        The etiology of human and animal TSE's are similar. Therefore the 
    spontaneous mutation explanation cannot be dismissed with regard to 
    BSE.
    6. Pathogenesis
        Following oral exposure of goats or sheep to the scrapie agent, the 
    agent first accumulates in gut-associated lymphoid organs (tonsils and 
    Peyers patches of terminal ileum) and later in other lymphoid organs, 
    such as spleen and thymus, and finally in the spinal cord and brain 
    (Ref. 8).
        Likewise, in mice inoculated intra-peritoneally with the CJD agent, 
    the agent localizes first in Peyer's patches and spleen, followed by 
    the central nervous system (Ref. 42). The agent may enter the body 
    through macrophages in the tonsils and domes over Peyer's patches in 
    the intestine (distal ileum). The proposed routes of spread from the 
    point of entry to other tissues and central nervous system are blood 
    stream or nerve trunks. In experimentally inoculated animals, spread 
    from the inoculation site in the eye of monkeys and peritoneum of mice 
    has been shown to be by optic and splanchnic nerves respectively (Ref. 
    43).
        Other investigators have demonstrated transient infectivity in the 
    blood of experimentally infected laboratory animals, and naturally 
    occurring infections of humans and mink, causing speculation that the 
    agent is carried in the blood (Refs. 45 to 49). With one exception in 
    serum (Ref. 50), all attempts to isolate TSE agents from the blood or 
    milk of sheep or cattle have failed (Refs. 51 to 54). When TSE agents 
    are injected intravenously into mice, the rate of clearance from the 
    blood is extremely rapid (Ref. 55). In natural cases of BSE, 
    infectivity has been found only in the brain, spinal cord, and eye; in 
    experimental cases the agent has also been identified in the ileum 
    (Ref. 56).
        The question of disease mechanism remains open. Candidate 
    mechanisms are the storage or accumulation of a large amount of 
    abnormal PrP in the brain (Refs. 57 to 60), or insufficient amounts of 
    normal PrP.
    7. Transmission
        There is little information about the natural transmission of TSE's 
    of animals. In most cases the natural route of exposure to the TSE 
    agent is suspected to be oral, although genetic disposition is known to 
    play a role in sheep scrapie (Ref. 61). Investigators have suspected 
    transmission of scrapie in sheep and goats by ingestion of placenta and 
    have been successful in experimentally transmitting scrapie by feeding 
    placenta to sheep (Ref. 62); however, genotyping of the PrP gene was 
    not conducted.
        In 1993, a study by Foster, et al., (Ref. 63) using a line of sheep 
    in which natural scrapie does not occur demonstrated that sheep can be 
    experimentally infected with BSE by intracerebral or oral 
    administration. The intracerebral challenge resulted in five of six 
    sheep developing the disease. The oral challenge resulted in one of six 
    sheep developing the disease. Brain and spleen were recovered from the 
    orally infected sheep and from one of the intracerebrally injected 
    sheep. Goldmann, et al. (Ref. 64), confirmed that both sheep had the 
    same PrP genotype. In 1996, Foster, et al. (Ref. 65) reported the 
    results of injecting homogenized tissue harvested from these infected 
    animals into a panel of mice. Transmission from the brains and spleen 
    of both sheep gave incubation periods and pathology in mice similar to 
    those seen in direct BSE transmissions from cattle to mice. Foster's 
    work supports the position that BSE can cross species barriers by the 
    oral route and that, when judged by the mouse bioassay, the disease 
    manifested in sheep retains the incubation time and pathology 
    characteristic of BSE rather than scrapie. However, the manifestation 
    of BSE in the sheep is histopathologically and clinically 
    indistinguishable from natural scrapie.
        Information regarding the interaction of the TSE agents and the 
    environment is limited. In 1964, Gordon reported the transmission of 
    scrapie among bands of unrelated sheep on pasture. The mode of 
    transmission was unknown (Ref. 66). In an effort to eradicate scrapie 
    from Iceland a large area was depopulated of sheep and restocked with 
    new sheep following a period of 3 years. Despite this effort, a few 
    flocks of the new sheep developed scrapie; the origin was believed to 
    be from scrapie that survived in the environment and not from 
    reintroduction of the agent with the new sheep or through contaminated 
    hay remaining on farms. However, a 1996 report suggests that six 
    species of hay mites may be potential vectors associated with 
    transmission of TSE's in Iceland (Ref. 67).
    8. Genetics
        There is a genetic component associated with several of the human 
    TSE diseases. A specific point mutation at codon 178 is associated with 
    fatal familial insomnia (Ref. 68). Point mutations at codons 102, 105, 
    117, 145, 198, and 217 are associated with GSS syndrome (Ref. 69). 
    Point mutations at codons 178, 180, 200, 210, and 232 are associated 
    with CJD (Refs. 68 and 70). Various insertions into the octapeptide 
    repeat region of the PrP gene have also been associated with human 
    TSE's (Ref. 71). It appears that the methionine/valine polymorphism at 
    codon 129 may modify the phenotype and the transmission rate from GSS 
    syndrome patients to mice (Ref. 72). No abnormalities in the sequence 
    of the PrP gene in kuru patients were found.
        There is also a genetic component associated with sheep scrapie. 
    Point mutations at codon 171 of the sheep PrP gene are linked to the 
    disease in the Corriedale, Lacaune, Romanov, Suffolk, and Texel breeds 
    (Refs. 73 to 76).
        An analysis of 370 cattle from Scotland revealed no difference 
    between healthy cattle and cattle with BSE in the number of octapeptide 
    repeat sequences (either five or six) and in a silent HindII 
    restriction site polymorphism on the PrP gene (Ref. 77). No data were 
    found that compared the sequence of the PrP gene of healthy deer, elk, 
    mink, and goats with those afflicted by TSE's.
    9. Diagnostics
        Because of the long incubation period, the ability to diagnose the 
    presence of a BSE infection prior to the onset of the
    
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    clinical disease would enhance the efficacy of surveillance and 
    prevention programs. Because there is no fully characterized immune 
    response to BSE or scrapie, diagnosis in live animals has been thought 
    to be possible only when clinical signs are evident and must be 
    confirmed by histopathology at post mortem (Ref. 10), or brain biopsy 
    of moribund patients. Recently published research suggests antemortem 
    tests for the TSE agent may be possible.
        The observation of histopathological changes in the brain, such as 
    vacuolization of the brainstem in BSE are positive indicators of 
    disease (Ref. 78). Other available diagnostic tests are 
    immunohistochemical staining and immunoblotting of the abnormal protein 
    (Ref. 10). Detection and titration of the TSE agent can also be 
    accomplished by intracerebral inoculation in mice or hamsters with a 
    brain homogenate from a suspected animal. After an appropriate 
    incubation period, the brain of the laboratory animal is examined for 
    histopathological changes characteristic of TSE (Ref. 8).
        The potential antemortem tests that have been published are 
    described as follows: (1) Tests specific for PrP: (a) A capillary 
    electrophoresis test (Ref. 79), and (b) a western blot test with 
    increased sensitivity (Ref. 80); and (2) tests which identify 
    metabolites of infected animals or humans: (a) A cyclic voltametric 
    method which describes metabolites in urine (Ref. 81), and (b) an 
    immunoblot test describing metabolites in cerebral spinal fluid (Ref. 
    82). Antemortem tests have not yet been validated for practical use.
        Recent research has shown some promise for antemortem testing. 
    Research by Shreuder et al. (Ref. 83), detected scrapie-associated 
    PrPsc protein in tonsils from scrapie susceptible sheep about a year 
    before the expected onset of the clinical disease. The research holds 
    promise for preclinical detection in sheep, but needs further 
    development. With regard to cattle, the researchers concluded that the 
    technique may not work but is worth investigating. Research by Hsich et 
    al. (Ref. 84), describes an experimental assay in humans and animals. 
    The research found that a positive immunoassay in human dementia 
    patients supports a diagnosis of CJD. The authors concluded that the 
    assay may be helpful in premortem diagnosis of TSE in humans and 
    animals showing clinical signs associated with TSE's. The validity of 
    the test as a preclinical screen has not been established.
    10. Inactivation
        The agency considered requiring procedures for the manufacture of 
    animal-derived proteins that would inactivate TSE infectivity. There 
    have been several studies on the inactivation of TSE agents. The only 
    broad generalization that can be drawn is that agents that denature 
    protein can diminish the infectivity of the TSE agents. TSE infectivity 
    does not appear to be markedly diminished by radiation or UV-light.
        Recent research (Ref. 85) showed that 11 of the 15 rendering 
    procedures tested produced meat and bone meal with no detectable BSE 
    infectivity in a mouse bioassay. Only limited conclusions can be drawn 
    about safety from these 11 procedures because the infectivity titer of 
    the spiked starting material (which consisted of 10 percent brain) was 
    several logs lower than that typically found in brain that is not 
    minced and not stored at -20  deg.C. Also, the question of the adequacy 
    of the mouse bioassay as the regulatory test which acceptably assures 
    the absence of TSE infectivity to animals or man remains to be answered 
    through future research investigations.
        The four procedures that failed included two protocols using 
    continuous vacuum rendering of high fat material and two protocols 
    using continuous atmospheric rendering of natural fat material. The 
    continuous vacuum rendering processes that failed were 120  deg.C for 
    20 minutes at a vacuum of 0.38 bar and 121  deg.C for 57 minutes at a 
    vacuum of 0.4 bar. The continuous atmospheric rendering processes of 
    natural fat material that failed were end temperatures of 112 and 122 
    deg.C after 50 minutes; however, end temperatures of 123 and 139  deg.C 
    after 125 minutes both inactivated the BSE agent. Unexpectedly, the BSE 
    agent was inactivated by three wet rendering processes that only 
    reached a maximum temperature of 119  deg.C with a cooking time of 240 
    minutes, a maximum temperature of 101  deg.C with a cooking time of 120 
    minutes, and a maximum temperature of 72  deg.C with a cooking time of 
    240 minutes under a vacuum of 0.85 bar.
        Preliminary, unpublished results indicate that the only rendering 
    process which completely inactivates the scrapie agent (which was 
    spiked with higher infectivity than that in the BSE experiments 
    described in this section) is batch rendering under pressure (Ref. 86). 
    The agency encourages more research in this area.
    
    B. The Association Between Scrapie and BSE
    
        Epidemiological studies of the outbreak of BSE in the United 
    Kingdom, including a computer simulation of the BSE epidemic, have 
    characterized it as an extended common-source epidemic. Each case has 
    been considered a primary case resulting from exposure to a single 
    common source of infection. It is believed in the United Kingdom that 
    rendered feed ingredients contaminated with scrapie infected sheep, or 
    cattle with a previously unidentified TSE, served as the common source 
    of infection. One study demonstrated that meat and bone meal could be 
    incorporated into cattle feed in sufficient quantity to transmit BSE to 
    some of the animals that consumed the feed (Ref. 87). Thus far, other 
    research including research by USDA has not confirmed that the feeding 
    of U.S.-origin scrapie-infected feed ingredients to cattle produces 
    BSE. Therefore, the theory that BSE evolved naturally in cattle has not 
    been ruled out (Ref. 88). See also the discussion in II.A.5. of this 
    document.
        Furthermore, the U.K. studies suggest that the spread of BSE 
    appeared to have been exacerbated by the practice of feeding 
    ingredients from rendered BSE-infected cattle to cattle, including 
    young calves, a practice that was subsequently banned. Incomplete 
    immediate compliance with the feeding ban may account for the fact that 
    some cattle born after the ban continue to be infected with BSE and has 
    complicated any theory of vertical transmission of the disease. The 
    research findings of maternal transmission of BSE are inconclusive, but 
    if it occurs, it does so at a rate insufficient to maintain the 
    epidemic (Ref. 89).
    
    C. The Association Between Animal TSE's and Human TSE's
    
        All the animal and human TSE's have been shown to be transmissible 
    experimentally to laboratory animals. The human and animal diseases are 
    pathologically similar and share some etiological similarities. TSE's 
    are not officially considered zoonotic diseases, i.e., known to be 
    naturally transmissible from animals to humans. The distribution of CJD 
    in the world does not coincide with that of scrapie in sheep or of BSE 
    in cattle. Human exposure to sheep or cattle has a low correlation with 
    CJD. However, the recent report from the United Kingdom of nv-CJD, and 
    its possible relationship to BSE, is causing scientists around the 
    world including those at CDC to
    
    [[Page 561]]
    
    reevaluate whether BSE may be a zoonotic disease.
        This concern is further supported by the recent report of 
    experimental BSE transmission to macaques, with the development of nv-
    CJD-like plaques in these monkeys (see the following discussion in this 
    section).
        The possibility of transmission of TSE's from animals to humans has 
    been suggested, most recently in connection with the identification of 
    nv-CJD in the United Kingdom. Scientists in the United Kingdom 
    concluded that the nv-CJD cases may be unique to the United Kingdom, 
    raising the possibility that they are causally linked to BSE. The 
    scientists stated that ``the common neuropathological picture may 
    indicate infection by a common strain of the causative agent, as in 
    sheep scrapie in which strains of the disease have been identified * * 
    * '' (Ref. 30). The United Kingdom Spongiform Encephalopathy Advisory 
    Committee (SEAC) stated that ``although there is no direct evidence of 
    a link, on current data and in absence of any credible alternative the 
    most likely explanation at present is that these cases are linked to 
    exposure to BSE before introduction of the SBO [specified bovine offal] 
    ban in 1989'' (Ref. 90). A WHO consultation in April 1996 concluded 
    that ``a link has not yet been proven between v-CJD in the U.K. and the 
    effect of exposure to the BSE agent. The most likely hypothesis for v-
    CJD is the exposure of the United Kingdom population to BSE'' (Ref. 2). 
    However, a second WHO consultation, in May 1996 concluded that ``the 
    clinical and neuropathological features of the newly recognized CJD 
    variant do not provide information which could be used to prove the 
    possible link between this disease and BSE in cattle'' (Ref. 91).
        The recent finding of florid amyloid plaques in the brains of 
    macaques inoculated with suspensions of BSE-infected cow brains 
    increases suspicion that exposure to the BSE agent may be the source of 
    nv-CJD. Amyloid plaques have never before been seen in monkeys with 
    TSE's, and the florid plaques resembled those in nv-CJD patients (Ref. 
    92). In a recent paper by Collinge, et al. (Ref. 93), it is stated that 
    ``strains of transmissible encephalopathies are distinguished by 
    differing physicochemical properties of PrPsc, the disease-related 
    isoform of prion protein, which can be maintained on transmission to 
    transgenic mice. 'New variant' CJD has a strain characteristic distinct 
    from other types of CJD and which resembles those of BSE transmitted to 
    mice, domestic cat and macaque, and is consistent with BSE being the 
    source of this new disease. Strain characteristics revealed here 
    suggest that the prion protein may itself encode disease phenotypes.''
        The possible association between BSE and nv-CJD may be further 
    clarified by results from studies that are under way (e.g., 
    experimental inoculation of brain tissue from the nv-CJD patients into 
    mice).
    
    D. Infectivity of Specific Tissues
    
        The WHO in a recent publication has summarized the infectivity of 
    various tissues from sheep, goat, and cattle (Ref. 94). Scientific 
    studies are currently being conducted in which calves are fed 
    homogenized brain tissue from United Kingdom cattle confirmed to have 
    BSE, and then various tissues are collected from the calves at 4-month 
    intervals (Refs. 56 and 95). The tissues from these calves are being 
    analyzed for the presence of the BSE agent. The study has been in 
    progress for 18 months and only brain, spinal cord, and retina have 
    been shown to be highly infectious. Distal ileum has been shown to be 
    infectious, but much less than the previously mentioned tissues. No 
    other tissues, most notably, muscle meat, milk, or blood have been 
    shown to be infectious. The results of these current experiments 
    parallel the previous research as summarized by WHO. However, the 
    agency notes that infectivity of other tissues that might be fed to 
    ruminants has not been definitively determined. This is, in part, 
    because of the lack of desired sensitivity in the available assay 
    methods.
        In summary, meat, milk, milk products, and blood have not been 
    shown to transmit BSE infectivity. These products are considered safe 
    for human consumption by health authorities including the WHO.
    
    E. Potential Risk of TSE's to the United States
    
    1. Overview
        This proposed FDA action is designed to reduce the risk of a BSE 
    epidemic in the United States and thereby protect the health of animals 
    and possibly of people if there is, in fact, a zoonotic relationship 
    between BSE and CJD. Risk is defined as the probability of an adverse 
    effect to an individual or a population. The four steps that are 
    typically involved in risk analysis are hazard identification, hazard 
    exposure, dose response, and risk characterization.
        While BSE has not been found in the United States, the agency 
    believes it presents a potential risk to the health of animals and 
    people. There are incubational and symptomatic similarities (as well as 
    several differences) among the TSE's. The scientific characterization 
    of these diseases is incomplete. However, interspecies cross-infections 
    have been scientifically demonstrated by parenteral injection and oral 
    routes of exposure.
        The typically long incubation period and the potentially 
    devastating effect that a BSE outbreak would have on animal health and 
    U.S. agribusiness also supports a conservative regulatory approach 
    aimed at prevention. While the current level of exposure to products 
    derived from animals with a TSE is extremely low or absent, the 
    potential consequences of such exposure and the apparent small intake 
    of the agent needed to achieve infection in some animals further 
    encourage a conservative regulatory policy.
        Dose response assessments will be difficult because of the lack of 
    good exposure data and the possibility of different susceptibilities, 
    e.g., age or genetic factors, in different subpopulations. Although the 
    TSE's are generally transmissible to laboratory animals following 
    intraperitoneal (ip) or intracerebral (ic) routes of administration, 
    the limited data that are available following the oral route of 
    administration suggests that this route is much less efficient than ip 
    or ic. Currently, it is quite difficult to make an accurate dose 
    response assessment for a TSE agent following oral administration.
        A number of actions, in addition to this proposed rule, have been 
    taken to manage a reduction in risk that BSE will enter the United 
    States cattle population. Restrictions have been placed on the 
    importation of live cattle (July 1989) and ruminant products (e.g., 
    meat and bone meal, bone meal, blood meal, offal, fat, and glands) from 
    countries which have BSE. Live animals imported prior to the 
    restrictions on imports have been regularly monitored by Animal and 
    Plant Health Inspection Service (APHIS) veterinarians, and APHIS is 
    currently in the process of purchasing the remaining live cattle for 
    diagnostic research purposes. Histopathological examination of brain 
    tissues has been carried out on more than 5,000 specimens from cattle 
    that were disabled or that demonstrated neurological signs prior to 
    slaughter or on the farm, e.g., nonambulatory or rabies-negative 
    cattle. Histopathological and immunohistochemical examination of the 
    nonambulatory or ``downer'' cows has been carried out since 1993. There 
    has been no finding of BSE in tissues from these animals. These animals 
    represent the highest BSE risk in the country, however, they also 
    represent an extremely small percentage of the cattle
    
    [[Page 562]]
    
    slaughtered in the United States. This active surveillance program is 
    continuing and may be expanded. The expansion of this program was 
    indirectly supported by a comment to the ANPRM that all ``downer'' cows 
    should be examined for BSE.
        Voluntary actions by industry have reduced the feeding of rendered 
    sheep proteins to ruminants and the rendering of adult sheep. A 
    voluntary Scrapie Flock Certification Program was implemented in 1992. 
    The program, a cooperative effort among industry, State animal health 
    officials and APHIS, seeks to reduce the prevalence of scrapie in U.S. 
    sheep. A considerable educational effort continues to increase the 
    awareness of veterinarians, veterinary laboratory diagnosticians, 
    livestock and related industry businesses, and producers to the early 
    clinical signs of BSE. Videos of United Kingdom BSE affected animals 
    have been distributed to USDA veterinarians to enhance their ability to 
    clinically diagnose BSE in suspect live animals. CDC has recently 
    published an update (Ref. 96) of its previous review of national CJD 
    mortality and the results of active CJD surveillance in five sites in 
    the United States. These reviews did not detect evidence of the 
    occurrence of the newly described variant form of CJD in the United 
    States. As an important complement to these other public health 
    efforts, this proposed rule would declare that animal protein derived 
    from ruminant and mink tissues is an unapproved food additive for use 
    in ruminant feeds, and would establish enforcement procedures. These 
    actions, individually and collectively, contribute to a greatly reduced 
    risk of a BSE epidemic ever occurring in the United States.
    2. Comparison With the U.K. Conditions
        Investigators have identified several major risk factors that 
    apparently contributed to the emergence of the disease and the 
    resultant epidemic in the United Kingdom. These are: (1) A large sheep 
    population relative to the cattle population, (2) a large, 
    uncontrolled, scrapie incidence rate, (3) the production of 
    ``greaves,'' an incompletely processed intermediate product in the 
    rendering process, (4) changes in rendering processes, such as the 
    reduced use of solvent extraction, and (5) the feeding of significant 
    amounts, up to 4 percent of the diet, of meat and bone meal to young 
    dairy calves.
        In addition to the risk factors described in section II.E.2. of 
    this document, the practice of processing dead sheep and cattle in the 
    United Kingdom likely contributed to the amplification of the TSE 
    agent. In the United Kingdom, sheep which may have died of scrapie and 
    cattle with BSE, were picked up by ``knackers'' for rendering into 
    animal feed. This material was partially rendered into ``greaves,'' 
    which might have contained large amounts of the scrapie/BSE agent, and 
    was fed to dairy calves in large amounts. The spread of BSE appeared to 
    be facilitated by the feeding of rendered BSE-infected cattle back to 
    calves. The BSE agent is postulated to have recycled from cows to 
    calves through ruminant-to-ruminant feeding until the practice ceased 
    following the 1989 ban on the practice.
        In the United States, the cattle population is much larger than the 
    sheep population, the incidence of scrapie is much lower and a scrapie 
    control program is in place; renderers in the United States do not 
    manufacture greaves; and the rendering processes used in the United 
    States are thought to reduce the titre (level) of TSE agents if any. 
    The lack of a practice of feeding large amounts of meat and bone meal 
    to calves in the United States, and the comparatively younger average 
    age of U.S. dairy cattle are also differences that are believed to be 
    important in protecting the United States against a U.K.-type BSE 
    epidemic. Nevertheless, scrapie does exist in the United States, sheep 
    are rendered and included in ruminant feed, the rendering process does 
    not totally inactivate TSE agents, and calves are fed meat and bone 
    meal. Therefore the risk of a BSE epidemic in the United States, while 
    much less, cannot be completely discounted.
    
    F. Historical Efforts to Control TSE's
    
    1. U.S. Actions
        a. FDA. FDA is the Federal agency responsible for the safety and 
    effectiveness of a large number of products and commodities. Briefly, 
    these include, drugs for use in people and animals, human biological 
    products, medical devices, food, dietary supplements, cosmetics, and 
    animal feeds. Each of these product groups provides the potential for 
    the transmission of spongiform encephalopathies in man or animals. FDA 
    formed a Working Group composed of the Deputy Commissioner for 
    Operations and representatives from the Centers to consider TSE's in 
    relation to FDA regulated products. As a result of the Working Group's 
    deliberations, FDA has taken the following actions:
         In 1992, letters were sent to manufacturers of dietary 
    supplements asking those manufacturers to reformulate their products to 
    be certain they do not contain materials from BSE or scrapie infected 
    animals;
         In 1993, letters were sent to manufacturers of drugs, 
    biologics, and devices asking them not to use bovine-derived materials 
    from countries with BSE; and
         In 1996, letters were sent to manufacturers of drugs, 
    biologics, devices, and animal feeds noting a possible relationship 
    between BSE and nv-CJD and asking that they not use materials from BSE 
    countries.
        In 1992, FDA conducted a survey of major sheep rendering plants to 
    determine compliance with a 1989 voluntary industry ban on the use of 
    adult sheep offal in ruminant feeds. The voluntary ban and results of 
    the survey are described in section I.F.3. of this document. In the 
    Federal Register of August 29, 1994 (59 FR 44584), FDA published a 
    proposed rule proposing to declare that specified offal from adult 
    sheep and goats is an unapproved feed additive in ruminant feed 
    (hereinafter referred to as the August 1994 proposed rule). In the 
    Federal Register of May 14, 1996, FDA published an ANPRM stating that 
    FDA was considering whether to provide that the use of protein derived 
    from ruminants in ruminant feed be prohibited.
        An international symposium entitled ``Tissue Distribution, 
    Inactivation, and Transmission of Transmissible Spongiform 
    Encephalopathies'' and cohosted by APHIS and FDA's Center for 
    Veterinary Medicine (CVM) was held on May 13 and 14, 1996, in 
    Riverdale, MD. The symposium participants engaged in discussion of 
    findings from unpublished, recently completed, and in-progress 
    scientific investigations on TSE's, and optimal approaches to managing 
    any risk of TSE's to animal health.
        b. USDA. USDA policy has been both proactive and preventive. The 
    Food Safety and Inspection Service (FSIS) and APHIS have been active in 
    taking measures in surveillance, prevention, and education about TSE's. 
    In 1990, APHIS created a BSE Issues Management Team to analyze risks of 
    BSE to the United States, disseminate accurate information about the 
    disease, and act as a reference source for responding to questions 
    about BSE. APHIS has also collaborated in the education of veterinary 
    practitioners, veterinary laboratory diagnosticians, industry and 
    producers on the clinical signs and pathology of BSE.
        APHIS has increased its surveillance efforts to verify that the 
    United States is free of BSE and to detect the disease should it be 
    introduced into the United
    
    [[Page 563]]
    
    States. As part of an ongoing active surveillance program, more than 60 
    veterinary diagnostic laboratories across the United States, and the 
    National Veterinary Service Laboratories (NVSL) of APHIS, continue to 
    examine bovine brains from the following sources: (1) APHIS 
    investigations in the United States where suspected encephalitic 
    conditions in cattle are reported under the foreign animal disease 
    investigation program; (2) CDC and State public health laboratories 
    (specimens from bovine that were found negative for rabies); and (3) 
    FSIS (specimens from ``downer'' cows or those exhibiting CNS 
    abnormalities). More than 5,000 bovine brains have been examined, and 
    none of these specimens contained lesions with the characteristics and 
    distribution typical for BSE (Refs. 12 and 97). APHIS is currently in 
    the process of purchasing the 69 living cattle (from a total of 496 
    cattle) imported from the United Kingdom between 1981 and 1989. In July 
    1989, the importation of live ruminants and ruminant products from all 
    countries known to have BSE in native animals was banned.
        USDA continues to analyze and report epidemiologic findings and 
    potential risks to the United States. In 1991, USDA issued two reports 
    analyzing risk factors associated with BSE in the United Kingdom based 
    on the British hypothesis of the disease occurring as a result of 
    feeding scrapie-contaminated meat and bone meal (Refs. 98 and 84). 
    Because of some similarities in the animal industries between the two 
    countries, the possibility of BSE occurring in the United States could 
    not be eliminated. However, the probability of occurrence was 
    determined to be very low as the amount of sheep offal was found to be 
    0.6 percent of all U.S. rendered product compared to the estimate of 14 
    percent of all U.K. rendered product. Furthermore, the incidence of 
    scrapie in the United States is much lower than in Great Britain; a 
    scrapie eradication or control program has been in effect in the United 
    States and rendered products are not routinely incorporated into calf 
    diets as was the practice in the United Kingdom.
        Since 1991, USDA has closely followed scientific findings and has 
    updated the BSE risk factor analysis, first in 1993 (Ref. 99) and as 
    recently as February 1996 (Ref. 4). Changes within each of the risk 
    factors have been evaluated, and because there has either been no 
    change or a decrease in the magnitude of risk factors, the overall risk 
    of BSE in the United States is believed to have decreased. The 
    February, 1996 report estimated the maximum potential 1-year period 
    prevalence of BSE to range from 2.3 to 12 cases per 1 million adult 
    cattle. In other words, under the worst case scenario between 
    approximately 115 and 600 adult cattle would become infected with BSE 
    each year, in a U.S. population of nearly 50 million adult cattle.
        APHIS has had a scrapie control program in effect since 1952. 
    Flocks that have been enrolled in the voluntary certification program 
    for sheep for 5 years, and have not had a diagnosed case of scrapie 
    within 5 years or a case traced back to the flock during that period, 
    may apply for APHIS certification and be officially identified as such. 
    This new control effort provides a mechanism to recognize flocks as 
    scrapie-free in the absence of a live animal diagnostic test.
        There is no official USDA program on TME or CWD. Although the last 
    TME case detected in the United States was in 1985, monitoring for this 
    disease continues. APHIS cooperates with State wildlife and diagnostic 
    officials in Colorado and Wyoming in the limited areas where CWD has 
    been reported.
        In December 1991, APHIS placed a ban on importation of certain 
    products of ruminant origin from countries known to have BSE (56 FR 
    63865, December 6, 1991). These products include: Meat and bone meal, 
    bone meal, blood meal, offal, fat, and glands. In addition to 
    prohibiting the materials listed previously, the regulation requires 
    that imported meat for human or animal consumption from bovines be 
    deboned, with visible lymphatic and nervous tissue removed; that it be 
    obtained from animals which have undergone a veterinary examination 
    prior to slaughter; and that it be obtained from ruminants which have 
    not been in any country in which BSE has been reported during a period 
    of time when that country permitted the use of ruminant protein in 
    ruminant feed. APHIS may allow the importation of the banned products 
    under a special permit for scientific or research purposes, or under 
    special conditions to be used in cosmetics. No bovine meat from the 
    United Kingdom has been allowed to be imported into the United States 
    by FSIS for human consumption since before the BSE epidemic occurred in 
    the United Kingdom. The network of private veterinary practitioners 
    that refers unusual cases to veterinary schools or State diagnostic 
    laboratories around the United States provides an extensive 
    surveillance system. FSIS performs both antemortem and post mortem 
    inspections at all federally-inspected slaughter establishments, and 
    inspectors condemn all animals with central nervous system disorders. 
    State-inspected slaughter operations follow the same procedures.
        USDA also maintains a database on these and other conditions. The 
    Veterinary Diagnostic Laboratory Reporting System (VDLRS) is a database 
    of selected disease conditions submitted by 29 State and university 
    veterinary diagnostic laboratories throughout the United States, and 
    includes the results of histologic examinations for BSE. The VDLRS is a 
    cooperative effort of the American Association of Veterinary Laboratory 
    Diagnosticians (AAVLD), the U.S. Animal Health Association (USAHA), 
    APHIS' Veterinary Service Centers for Epidemiology and Animal Health, 
    and the 29 laboratories mentioned previously.
        c. Public Health Service (PHS). i. CDC. CDC conducts surveillance 
    for CJD through examination of death certificate data compiled by the 
    National Center for Health Statistics, CDC, for U.S. residents for whom 
    CJD was listed as one of the multiple causes of death (Ref. 100). These 
    data indicate that the annual CJD mortality rates in the United States 
    between 1979 and 1993 have been relatively stable, ranging between only 
    0.8 case per million in both 1979 and 1990 and 1.1 cases per million in 
    1987. In addition, CJD deaths in persons younger than 30 years of age 
    in the United States remain extremely rare (<5 cases="" per="" billion="" per="" year)="" (ref.="" 101).="" cdc="" is="" working="" with="" the="" council="" of="" state="" and="" territorial="" epidemiologists="" to="" consider="" expansion="" of="" current="" cjd="" surveillance.="" cdc="" is="" also="" working="" with="" its="" four="" established="" emerging="" infections="" programs="" (minnesota,="" oregon,="" connecticut,="" and="" the="" san="" francisco="" bay="" area,="" california),="" the="" georgia="" department="" of="" human="" resources,="" and="" the="" atlanta="" metropolitan="" active="" surveillance="" program="" to="" pilot="" enhanced="" surveillance="" efforts="" for="" cjd="" (ref.="" 101).="" this="" effort="" includes="" an="" active="" search="" for="" v-cjd="" as="" described="" in="" the="" united="" kingdom="" (ref.="" 30).="" on="" august="" 9,="" 1996,="" the="" results="" of="" this="" enhanced="" cjd="" surveillance="" effort="" was="" published;="" no="" evidence="" of="" the="" occurrence="" of="" the="" newly="" described="" variant="" form="" of="" cjd="" was="" found="" in="" the="" united="" states.="" no="" evidence="" of="" v-cjd="" has="" been="" found="" in="" the="" united="" states.="" ii.="" national="" institutes="" of="" health="" (nih).="" a="" project="" of="" the="" laboratory="" of="" central="" nervous="" system="" studies="" of="" the="" national="" institute="" of="" neurological="" diseases="" and="" stroke="" is="" conducting="" investigations="" on="" slow,="" latent,="" and="" temperate="" viral="" infections="" associated="" with="" chronic="" degenerative="" neurological="" diseases.="" important="" areas="" of="" study="" are="" the="" pathogenesis="" of="" slow="" infections="" and="" mechanisms="" of="" persistence="" in="" kuru="" and="" [[page="" 564]]="" cjd.="" also="" intensive="" molecular,="" biological,="" genetic,="" and="" immunological="" studies="" are="" being="" conducted="" on="" amyloid="" formation="" in="" the="" brain="" in="" alzheimer's="" disease,="" normal="" aging,="" down's="" syndrome,="" and="" slow="" viral="" infections,="" and="" the="" elucidation="" of="" the="" de="" novo="" generation="" of="" infectious="" amyloid="" proteins="" from="" normal="" host="" precursor="" proteins="" in="" kuru,="" cjd,="" gss="" syndrome,="" scrapie="" and="" bse.="" research="" on="" tse's="" has="" also="" been="" conducted="" by="" the="" nih="" laboratory="" of="" persistent="" viral="" disease.="" fda="" maintains="" close="" contact="" with="" scientists="" in="" the="" laboratories="" and="" expects="" to="" use="" their="" expertise="" in="" the="" evaluation="" of="" inactivation="" methods="" and="" transmission="" studies.="" iii.="" other="" actions.="" on="" april="" 8,="" 1996,="" an="" interagency="" meeting="" at="" cdc="" including="" representatives="" from="" cdc,="" nih,="" fda,="" usda,="" and="" the="" u.s.="" department="" of="" defense="" was="" held="" to="" disseminate="" conclusions="" from="" the="" who="" consultation="" regarding="" v-cjd="" and="" to="" coordinate="" preventive="" activities="" among="" these="" agencies="" to="" address="" the="" bse="" and="" cjd="" issues.="" 2.="" international="" actions="" a.="" united="" kingdom.="" regulatory="" controls="" taken="" to="" manage="" the="" bse="" epidemic="" in="" the="" united="" kingdom="" and="" to="" address="" public="" health="" concerns="" include:="" (1)="" an="" action="" in="" june="" 1988="" to="" make="" the="" disease="" reportable;="" (2)="" a="" ban="" in="" july="" 1988="" on="" the="" feeding="" of="" ruminant-derived="" protein="" supplements="" to="" other="" ruminants;="" (3)="" an="" order="" in="" august="" 1988="" for="" the="" compulsory="" slaughter="" and="" incineration="" of="" bse="" suspect="" cattle;="" (4)="" a="" ban="" in="" november="" 1989="" on="" the="" inclusion="" of="" specified="" bovine="" offal="" (brain,="" spinal="" cord,="" thymus,="" spleen,="" tonsils,="" and="" intestines)="" for="" human="" consumption;="" and="" (5)="" a="" ban="" in="" september="" 1990="" on="" use="" of="" specified="" bovine="" offal="" in="" any="" animal="" feed.="" a="" cjd="" surveillance="" unit="" was="" established="" to="" monitor="" cjd="" numbers="" in="" the="" united="" kingdom.="" seac,="" consisting="" of="" experts="" in="" neurology,="" epidemiology,="" and="" microbiology="" from="" outside="" the="" british="" government,="" was="" established="" in="" 1990="" to="" oversee="" all="" aspects="" of="" tse's="" and="" human="" and="" animal="" health.="" usda="" has="" a="" representative="" on="" this="" committee.="" major="" regulatory="" actions="" occurring="" after="" the="" seac="" report="" on="" nv-cjd="" (ref.="" 90)="" include="" legislation="" to="" ban="" the="" feeding="" of="" mammalian="" meat="" and="" bone="" meal="" to="" any="" farmed="" animal,="" and="" legislation="" to="" ban="" the="" use="" of="" cattle="" head="" meat="" for="" human="" consumption.="" b.="" who.="" who="" has="" held="" meetings="" on="" the="" spongiform="" encephalopathies="" in="" 1991,="" 1993,="" 1995,="" and="" 1996,="" and="" a="" meeting="" in="" collaboration="" with="" the="" office="" international="" des="" epizooties="" (oie)="" in="" 1994.="" the="" general="" purposes="" of="" these="" meetings="" were="" to="" review="" the="" existing="" state="" of="" knowledge="" on="" spongiform="" encephalopathies="" including="" bse,="" to="" evaluate="" possible="" means="" of="" transmission,="" and="" to="" identify="" risk="" factors="" for="" infection.="" a="" specific="" purpose="" was="" to="" review="" the="" possible="" human="" public="" health="" implications="" of="" animal="" spongiform="" encephalopathies,="" with="" special="" emphasis="" on="" bse.="" the="" group="" of="" international="" experts="" convened="" in="" april="" 1996="" by="" who="" recommended="" that="" all="" countries="" should="" ban="" the="" use="" of="" ruminant="" tissues="" in="" ruminant="" feed.="" the="" who="" group="" also="" declared="" that="" milk="" and="" milk="" products,="" including="" such="" products="" from="" the="" united="" kingdom,="" are="" safe="" for="" human="" consumption="" and="" that="" gelatin="" in="" the="" food="" chain="" is="" considered="" safe="" because="" its="" preparation="" effectively="" destroys="" bse.="" finally,="" the="" group="" concluded="" that="" tallow="" could="" be="" safe="" if="" effective="" rendering="" procedures="" are="" in="" place="" (i.e.,="" rendered="" as="" protein-free)="" (ref.="" 2).="" c.="" oie.="" oie="" has="" supported="" the="" u.k.="" ban="" on="" the="" use="" of="" specified="" offals="" and="" has="" recommended="" that="" the="" same="" action="" be="" taken="" in="" other="" countries="" with="" a="" high="" incidence="" of="" the="" disease="" (ref.="" 102).="" oie="" has="" held="" meetings="" in="" 1990,="" 1991,="" 1992,="" 1995,="" and="" 1996,="" and="" has="" developed="" guidelines="" concerning="" animals="" and="" animal="" products="" to="" prevent="" movement="" to="" unaffected="" countries.="" d.="" european="" community="" (ec).="" the="" ec="" has="" held="" a="" series="" of="" meetings="" related="" to="" bse.="" following="" issuance="" of="" the="" u.k.="" seac="" statement="" suggesting="" a="" possible="" link="" between="" nv-cjd="" and="" bse,="" the="" ec="" imposed="" a="" ban="" on="" british="" cattle,="" beef="" and="" bovine="" derivatives="" (ref.="" 103).="" 3.="" voluntary="" measures="" by="" the="" u.s.="" animal="" industries="" a.="" voluntary="" ban="" on="" rendering="" adult="" sheep.="" in="" 1989,="" the="" national="" renderers="" association="" (nra)="" and="" the="" animal="" protein="" producers="" industry="" (appi)="" recommended="" to="" their="" members="" that="" they="" stop="" rendering="" adult="" sheep="" or="" providing="" sheep="" offal="" for="" sale="" as="" meat="" and="" bone="" meal="" for="" inclusion="" in="" cattle="" feed="" (ref.="" 104).="" following="" the="" recommendation="" of="" the="" voluntary="" ban,="" fda="" carried="" out="" a="" survey="" of="" current="" practices="" in="" the="" united="" states="" for="" rendering="" or="" otherwise="" disposing="" of="" adult="" sheep="" carcasses="" and="" parts,="" specifically="" head,="" brain,="" and="" spinal="" cord.="" limited="" inspections="" of="" rendering="" plants="" were="" conducted="" in="" 1992="" to:="" (1)="" assess="" compliance="" by="" u.s.="" renderers="" with="" the="" voluntary="" ban;="" (2)="" identify="" rendering="" plant="" practices="" concerning="" adult="" sheep;="" and="" (3)="" determine="" if="" rendered="" adult="" sheep="" protein="" byproducts="" were="" being="" sold="" or="" labeled="" for="" use="" as="" feed="" or="" feed="" components="" for="" cattle.="" of="" the="" 19="" plants="" surveyed,="" 15="" rendered="" carcasses="" or="" offal="" of="" adult="" sheep.="" these="" 15="" plants="" processed="" more="" than="" 85="" percent="" of="" the="" adult="" sheep="" rendered="" in="" the="" united="" states.="" eleven="" of="" the="" 15="" plants="" rendered="" carcasses="" of="" adult="" sheep="" with="" heads,="" 7="" of="" the="" 15="" rendered="" sheep="" carcasses="" separately="" from="" other="" species,="" 6="" of="" the="" 15="" maintained="" meat="" and="" bone="" meal="" from="" adult="" sheep="" separate="" from="" meat="" and="" bone="" meal="" from="" other="" species,="" and="" 4="" of="" the="" 15="" rendered="" sheep="" that="" had="" died="" of="" causes="" other="" than="" slaughter.="" six="" of="" the="" 11="" renderers="" processing="" adult="" sheep="" with="" heads="" had="" sold="" meat="" and="" bone="" meal="" to="" manufacturers="" of="" cattle="" feed.="" thus,="" the="" rendering="" industry's="" voluntary="" ban="" on="" the="" rendering="" of="" adult="" sheep="" or="" providing="" sheep="" offal="" for="" use="" in="" cattle="" feed="" was="" not="" fully="" implemented="" at="" the="" time="" of="" the="" survey="" (ref.="" 105).="" b.="" voluntary="" ban="" on="" feeding="" ruminant="" proteins="" to="" ruminants.="" on="" march="" 29,="" 1996,="" the="" national="" cattlemen's="" beef="" association="" (ncba),="" the="" national="" milk="" producers="" federation,="" the="" american="" sheep="" association,="" the="" american="" veterinary="" medical="" association,="" the="" american="" association="" of="" veterinary="" medical="" colleges,="" and="" the="" american="" association="" of="" bovine="" practitioners="" announced="" the="" recommendation="" of="" a="" voluntary="" ban="" on="" the="" feeding="" of="" ruminant-derived="" proteins="" to="" ruminant="" animals="" (ref.="" 106).="" usda,="" phs,="" the="" american="" society="" of="" animal="" science,="" and="" other="" organizations="" announced="" support="" for="" the="" voluntary="" ban="" (refs.="" 107="" and="" 108).="" according="" to="" the="" ncba="" (ref.="" 109),="" a="" comprehensive="" communication="" strategy,="" seeking="" removal="" of="" ruminant-derived="" proteins="" from="" the="" rations="" of="" ruminants,="" was="" implemented="" in="" may="" 1996="" by="" the="" feed="" industry,="" nutritionists,="" veterinarians,="" extension="" specialists,="" and="" dairy="" and="" beef="" producers.="" ncba="" has="" not="" conducted="" a="" survey="" to="" assess="" the="" impact="" of="" its="" communication="" strategy;="" however,="" ncba="" did="" point="" out="" that="" past="" requests="" for="" voluntary="" action="" by="" the="" cattle="" industry="" have="" been="" quite="" successful,="" approaching="" 90="" percent="" compliance.="" in="" contrast,="" an="" anonymous="" comment="" to="" the="" anprm="" suggested="" a="" compliance="" level="" of="" less="" than="" 5="" percent="" (ref.="" 110).="" fda="" has="" not="" conducted="" a="" survey="" to="" ascertain="" the="" level="" of="" compliance="" with="" the="" voluntary="" ban.="" g.="" processing="" animal="" tissues="" for="" feed="" ingredients="" 1.="" current="" rendering="" practices="" the="" following="" discussion="" on="" current="" rendering="" practices="" comes="" directly="" from="" comments="" supplied="" to="" fda="" in="" response="" to="" the="" anprm="" from="" representatives="" of="" [[page="" 565]]="" appi="" and="" nra.="" knowledge="" about="" the="" four="" basic="" types="" of="" rendering="" systems="" that="" are="" most="" commonly="" used="" in="" the="" united="" states="" today="" may="" be="" crucial="" in="" dealing="" with="" the="" tse="" issue="" in="" this="" country.="" data="" on="" the="" inactivation="" of="" the="" bse="" and="" scrapie="" agents="" following="" simulation="" of="" the="" most="" commonly="" used="" basic="" types="" of="" rendering="" systems="" in="" the="" united="" states="" could="" be="" quite="" useful,="" especially="" because="" some="" of="" these="" systems="" do="" not="" appear="" to="" have="" been="" used="" in="" the="" only="" published="" rendering="" study="" on="" bse="" inactivation="" (ref.="" 85).="" rendering,="" the="" process="" of="" cooking="" raw="" material="" to="" remove="" the="" moisture="" and="" fat="" from="" the="" solid="" protein="" portion="" of="" animal="" tissues,="" has="" been="" practiced="" by="" humans="" for="" more="" than="" 2,000="" years.="" the="" united="" states="" rendering="" industry="" has="" developed="" over="" the="" last="" 160="" years.="" modern="" rendering="" systems="" are="" high-technology="" recycling="" processes="" that="" efficiently="" convert="" animal="" byproducts="" (shop="" fat="" and="" bone,="" beef="" and="" pork="" slaughterhouse="" materials,="" poultry="" offal,="" fish,="" etc.)="" to="" stable="" protein="" and="" fat="" supplements="" for="" feed.="" current="" technology="" consists="" of="" four="" basic="" types="" of="" rendering="" systems--batch="" cooker,="" continuous="" cooker,="" continuous="" multi-stage="" evaporator,="" and="" continuous="" preheat/press/evaporator.="" all="" systems="" consist="" of="" three="" basic="" steps:="" grinding="" the="" raw="" material,="" cooking="" it="" to="" remove="" moisture,="" and="" separating="" the="" melted="" fat="" from="" the="" protein="" solids.="" batch="" cookers="" are="" multiple="" units,="" each="" consisting="" of="" a="" horizontal,="" steam-jacketed="" cylindrical="" vessel="" with="" an="" agitator.="" batch="" cookers="" are="" operated="" at="" atmospheric="" pressure.="" the="" cooked="" material="" is="" discharged="" to="" the="" percolator="" drain="" pan,="" which="" contains="" a="" perforated="" screen="" that="" allows="" the="" free-run="" fat="" to="" drain="" and="" be="" separated="" from="" the="" protein="" solids="" known="" as="" ``tankage.''="" because="" ``tankage''="" contains="" considerable="" fat,="" it="" is="" processed="" through="" a="" screw="" press="" to="" complete="" the="" separation="" of="" fat="" from="" solids.="" the="" fat="" discharged="" from="" the="" screw="" press="" usually="" contains="" fine="" solid="" particles="" that="" are="" removed="" by="" either="" centrifuging="" or="" filtration.="" the="" protein="" solids="" discharged="" from="" the="" screw="" press="" are="" known="" as="" ``cracklings,''="" which="" normally="" are="" screened="" and="" ground="" with="" a="" hammer="" mill="" to="" produce="" protein="" meal.="" the="" continuous="" cooker="" rendering="" system="" normally="" consists="" of="" a="" single="" continuous="" cooker,="" operating="" at="" atmospheric="" pressure.="" the="" discharge="" from="" the="" continuous="" cooker="" usually="" passes="" across="" either="" a="" vibrating="" screen="" or="" stationary="" perforated="" screen="" to="" allow="" the="" free-run="" fat="" to="" drain.="" the="" subsequent="" steps="" in="" the="" continuous="" cooker="" rendering="" process="" are="" similar="" to="" those="" described="" before="" for="" the="" batch="" cooker.="" in="" the="" continuous="" multi-stage="" evaporator="" rendering="" system,="" crushing="" is="" used="" as="" the="" first="" stage="" of="" size="" reduction="" of="" the="" raw="" material.="" a="" fat="" recycle="" stream="" is="" then="" used="" to="" deliver="" the="" material="" as="" a="" pumpable="" slurry="" through="" the="" secondary="" grinding="" step="" to="" reduce="" further="" the="" particle="" size.="" particle="" size="" and="" fat="" ratios="" are="" important="" components="" of="" this="" system.="" the="" slurry="" discharge="" from="" the="" final="" stage="" of="" evaporation="" is="" pumped="" to="" a="" centrifuge="" which="" removes="" most="" of="" the="" fat="" and="" part="" of="" it="" is="" recycled="" back="" to="" the="" second="" stage="" of="" size="" reduction.="" the="" solids="" discharged="" from="" the="" centrifuge="" are="" conveyed="" to="" screw="" presses="" which="" complete="" the="" separation="" of="" fat="" from="" the="" protein="" solids.="" the="" continuous="" preheat/press/evaporator="" rendering="" system="" is="" known="" by="" a="" variety="" of="" names="" including="" the="" stord="" dewatering="" rendering="" system="" and="" the="" atlas="" low="" temperature="" wet="" rendering="" system.="" in="" either="" case,="" raw="" material="" is="" ground="" in="" two="" stages="" and="" passes="" through="" the="" preheater="" to="" raise="" the="" temperature="" to="" 180="" to="" 190="" deg.ef="" before="" entry="" to="" the="" twin="" screw="" press.="" the="" press="" separates="" this="" material="" into="" two="" phases:="" a="" presscake="" of="" solids="" containing="" moisture="" and="" a="" low="" fat="" concentration,="" and="" a="" liquid="" containing="" mostly="" water="" (stickwater)="" with="" fine="" solids,="" soluble="" protein,="" insoluble="" protein="" and="" melted="" fat.="" the="" press="" liquid="" is="" processed="" either="" by="" passing="" through="" a="" multistage="" evaporator="" system="" to="" remove="" the="" water="" before="" centrifuging="" to="" remove="" the="" fine="" solids="" from="" the="" fat,="" or="" by="" passing="" through="" a="" centrifuge="" to="" separate="" the="" fat="" before="" multistage="" evaporation="" of="" the="" remaining="" water/fine="" solids="" fraction.="" the="" liquid="" separation="" system="" consisting="" of="" two="" stages="" of="" centrifuges="" completes="" the="" separation="" of="" the="" melted="" fat="" from="" the="" solids="" and="" water.="" in="" this="" system,="" the="" screw="" press="" normally="" used="" to="" process="" the="" ``tankage''="" is="" no="" longer="" needed.="" longer="" drying="" times="" are="" needed="" with="" this="" system="" as="" compared="" to="" previous="" systems="" because="" of="" the="" early="" fat="" removal="" (less="" fat="" means="" less="" effective="" heat="" transfer).="" the="" agency="" encourages="" further="" research="" into="" methods="" of="" deactivation="" of="" the="" bse="" agent="" during="" the="" rendering="" process.="" 2.="" assay="" methodologies="" for="" proteins="" enforcement="" of="" the="" proposed="" regulation="" would="" be="" facilitated="" if="" a="" test="" to="" detect="" and="" distinguish="" ruminant="" from="" nonruminant="" materials="" in="" feeds="" or="" feed="" ingredients="" was="" available.="" however,="" practical="" assays="" that="" could="" be="" used="" to="" enforce="" the="" proposed="" regulation="" are="" not="" available="" at="" this="" time.="" the="" test="" procedure="" would="" need="" to="" exhibit="" a="" high="" degree="" of="" sensitivity="" and="" selectivity;="" that="" is,="" the="" test="" must="" be="" able="" to="" detect="" the="" analyte="" of="" interest="" to="" the="" exclusion="" of="" other="" components.="" a="" test="" for="" acceptable="" rendered="" products="" in="" animal="" feed="" must="" therefore="" be="" able="" to="" discriminate="" and="" differentiate="" between="" permitted="" and="" prohibited="" animal="" derived="" proteins.="" other="" factors="" of="" importance="" are="" the="" ruggedness="" of="" the="" test="" method,="" speed,="" and="" simplicity="" of="" design.="" an="" enzyme-linked="" immunosorbant="" assay="" (elisa)="" based="" analytic="" method="" that="" is="" both="" sensitive="" (detects="" low="" levels="" of="" analyte)="" and="" specific="" (detects="" primarily="" the="" analyte="" of="" interest)="" is="" one="" possibility.="" elisa="" is="" a="" relatively="" straightforward="" methodology.="" there="" are="" numerous="" commercial="" sources="" for="" antisera="" capable="" of="" binding="" to="" bovine,="" ovine,="" porcine,="" and="" caprine="" proteins.="" antisera="" have="" also="" been="" generated="" from="" muscle="" extracts="" and="" validated="" for="" use="" in="" usda-approved="" elisa="" methods="" to="" determine="" the="" identity="" of="" raw="" and="" cooked="" meats="" (refs.="" 111="" and="" 112).="" however,="" rendered="" products="" present="" a="" unique="" problem="" because="" rendering="" causes="" the="" destruction="" of="" most="" of="" the="" antibody="" binding="" epitopes="" needed="" for="" an="" elisa="" test.="" therefore,="" detection="" of="" rendered="" proteins="" by="" a="" given="" antibody="" cannot="" be="" automatically="" assumed.="" other="" potential="" methodologies="" include="" western="" blot="" analysis,="" capillary="" electrophoresis,="" and="" high="" pressure="" liquid="" chromatography.="" the="" applicability="" of="" these="" three="" methods="" to="" this="" issue="" has="" not="" been="" addressed.="" furthermore,="" they="" require="" expensive,="" specialized="" equipment="" and="" a="" high="" degree="" of="" technical="" competence.="" the="" agency="" encourages="" research="" to="" detect="" and="" distinguish="" ruminant="" from="" nonruminant="" materials="" in="" rendered="" products="" and="" animal="" feeds.="" iii.="" statutory="" provisions="" regarding="" food="" additives="" the="" term="" ``food''="" as="" defined="" in="" the="" act="" includes="" animal="" feed.="" section="" 201(f)="" of="" the="" act="" (21="" u.s.c.="" 321(f))="" defines="" food="" as="" ``articles="" used="" for="" food="" or="" drink="" for="" man="" or="" other="" animals''="" and="" ``articles="" used="" for="" components="" of="" any="" such="" article.''="" furthermore,="" any="" substance="" whose="" intended="" use="" results="" or="" may="" reasonably="" be="" expected="" to="" result="" in="" its="" becoming="" a="" component="" of="" food="" is="" a="" food="" additive="" unless,="" among="" other="" things,="" it="" is="" gras="" or="" is="" the="" subject="" of="" a="" prior="" sanction.="" section="" 402(a)(2)(c)="" of="" the="" act="" (21="" u.s.c.="" 342(a)(2)(c))="" deems="" food="" adulterated="" ``if="" it="" is,="" or="" it="" bears="" or="" contains,="" any="" food="" additive="" which="" is="" unsafe="" within="" the="" meaning="" of="" section="" 409="" *="" *="" *.''="" under="" section="" 409(a)="" of="" the="" act="" (21="" u.s.c="" 348(a)),="" a="" food="" additive="" is="" unsafe="" unless="" [[page="" 566]]="" a="" food="" additive="" regulation="" or="" an="" exemption="" is="" in="" effect="" with="" respect="" to="" its="" use="" or="" its="" intended="" use.="" a="" food="" additive="" regulation="" is="" established="" by="" the="" submission="" and="" approval="" of="" a="" food="" additive="" petition,="" as="" provided="" in="" 21="" cfr="" 571.1,="" or="" on="" fda's="" initiative="" as="" provided="" in="" 21="" cfr="" 570.15.="" fda="" on="" its="" own="" initiative="" or="" at="" the="" request="" of="" an="" interested="" party,="" also="" may="" propose="" to="" determine="" that="" a="" substance="" intended="" for="" use="" in="" animal="" feed="" is="" not="" gras="" and="" is="" a="" food="" additive="" subject="" to="" section="" 409="" of="" the="" act="" as="" provided="" in="" sec.="" 570.38="" (21="" cfr="" 570.38).="" subsequent="" to="" the="" publication="" of="" such="" a="" proposal="" and="" after="" consideration="" of="" public="" comments,="" fda="" may="" issue="" a="" final="" rule="" declaring="" the="" substance="" to="" be="" a="" food="" additive="" and="" require="" discontinuation="" of="" its="" use="" except="" when="" used="" in="" compliance="" with="" a="" food="" additive="" regulation.="" a.="" gras="" determination="" a="" determination="" that="" a="" substance="" added="" directly="" or="" indirectly="" to="" a="" food="" is="" gras,="" is="" generally="" based="" on="" specific="" information="" regarding="" the="" composition="" of="" the="" substance,="" its="" use,="" method="" of="" preparation,="" methods="" for="" detecting="" its="" presence="" in="" food,="" and="" information="" about="" its="" functionality="" in="" food="" (21="" cfr="" 570.35)="" as="" determined="" by="" experts="" qualified="" by="" scientific="" training="" and="" experience="" to="" evaluate="" the="" safety="" of="" such="" a="" substance.="" a="" substance="" added="" to="" food="" becomes="" gras="" as="" the="" result="" of="" a="" common="" understanding="" about="" the="" substance="" throughout="" the="" scientific="" community="" familiar="" with="" safety="" of="" such="" substances.="" the="" basis="" of="" expert="" views="" may="" be="" either="" scientific="" procedures,="" or,="" in="" the="" case="" of="" a="" substance="" used="" in="" food="" prior="" to="" january="" 1,="" 1958,="" experience="" based="" on="" common="" use="" in="" food="" (sec.="" 570.30(a))="" (21="" cfr="" 570.30(a)).="" general="" recognition="" of="" safety="" through="" experience="" based="" on="" common="" use="" in="" food="" prior="" to="" january="" 1,="" 1958,="" may="" be="" determined="" without="" the="" quantity="" or="" quality="" of="" scientific="" studies="" required="" for="" the="" approval="" of="" a="" food="" additive="" regulation.="" however,="" substances="" that="" are="" gras="" based="" on="" such="" use="" must="" be="" currently="" recognized="" as="" safe="" based="" on="" their="" pre-1958="" use.="" (see="" united="" states="" v.="" naremco,="" 553="" f.2d="" 1138="" (8th="" cir.="" 1977);="" compare="" united="" states="" v.="" western="" serum,="" 666="" f.2d="" 335="" (9th="" cir.="" 1982).)="" a="" recognition="" of="" safety="" through="" common="" use="" is="" ordinarily="" to="" be="" based="" on="" generally="" available="" data="" and="" information="" (sec.="" 570.30(c)).="" an="" ingredient="" that="" was="" not="" in="" common="" use="" in="" food="" prior="" to="" january="" 1,="" 1958,="" may="" achieve="" general="" recognition="" of="" safety="" only="" through="" scientific="" procedures.="" general="" recognition="" of="" safety="" based="" upon="" scientific="" procedures="" requires="" the="" same="" quantity="" and="" quality="" of="" scientific="" evidence="" as="" is="" required="" to="" obtain="" approval="" of="" a="" food="" additive="" regulation="" for="" the="" ingredient="" (sec.="" 570.30(b)).="" (see="" united="" states="" v.="" naremco,="" 553="" f.2d="" at="" 1143.)="" a="" substance="" is="" not="" gras="" if="" there="" is="" a="" genuine="" dispute="" among="" experts="" as="" to="" its="" recognition="" (an="" article="" of="" drug="" *="" *="" *="" furestrol="" vaginal="" suppositories,="" 251="" f.="" supp.="" 1307="" (n.d.="" ga.="" 1968),="" aff'd="" 415="" f.2d="" 390="" (5th="" cir.="" 1969).)="" further,="" general="" recognition="" of="" safety="" through="" scientific="" procedures="" must="" be="" based="" upon="" published="" studies="" (united="" states="" v.="" articles="" of="" food="" and="" drug="" colitrol="" 80="" medicated,="" 372="" f.="" supp.="" 915="" (n.d.="" ga.="" 1974),="" aff'd,="" 518="" f.2d="" 743,="" 747="" (5th="" cir.="" 1975)),="" so="" that="" the="" results="" are="" generally="" available="" to="" experts.="" it="" is="" not="" enough,="" in="" attempting="" to="" establish="" that="" a="" substance="" is="" gras,="" to="" establish="" that="" there="" is="" an="" absence="" of="" scientific="" studies="" that="" demonstrate="" the="" substance="" to="" be="" unsafe;="" there="" must="" be="" studies="" that="" show="" the="" substance="" to="" be="" safe="" (united="" states="" v.="" an="" article="" of="" food="" *="" *="" *="" co="" co="" rico,="" supra.)="" conversely,="" a="" substance="" may="" be="" ineligible="" for="" gras="" status="" if="" studies="" show="" that="" the="" substance="" is,="" or="" may="" be,="" unsafe.="" this="" is="" true="" whether="" the="" studies="" are="" published="" or="" unpublished="" (50="" fr="" 27294="" at="" 27296,="" july="" 2,="" 1985).="" if="" there="" are="" studies="" that="" tend="" to="" support="" a="" finding="" that="" a="" particular="" substance="" is="" gras,="" but="" also="" studies="" that="" tend="" to="" support="" a="" contrary="" position,="" the="" conflict="" in="" the="" studies,="" just="" as="" a="" conflict="" in="" expert="" opinion,="" may="" prevent="" the="" general="" recognition="" of="" the="" safe="" use="" of="" the="" substance.="" b.="" prior="" sanction="" under="" section="" 201(s)="" of="" the="" act,="" the="" term="" ``food="" additive''="" does="" not="" apply="" to="" any="" substance="" used="" in="" accordance="" with="" a="" sanction="" or="" approval="" granted="" prior="" to="" enactment="" of="" section="" 201(s)="" of="" the="" act="" and="" granted="" under="" the="" act,="" the="" poultry="" products="" inspection="" act="" (21="" u.s.c.="" 451="" et="" seq.),="" or="" the="" federal="" meat="" inspection="" act="" (21="" u.s.c.="" 601="" et="" seq.).="" section="" 570.38(d)="" provides="" that="" if="" the="" commissioner="" of="" food="" and="" drugs="" is="" aware="" of="" any="" prior="" sanction="" for="" use="" of="" a="" substance,="" he="" will,="" concurrently="" with="" a="" notice="" determining="" that="" a="" substance="" is="" not="" gras="" and="" is="" a="" food="" additive="" subject="" to="" section="" 409="" of="" the="" act,="" propose="" a="" separate="" regulation="" covering="" such="" use="" of="" the="" substance.="" in="" the="" case="" of="" the="" materials="" subject="" to="" this="" proposed="" rule,="" fda="" has="" determined="" that="" it="" is="" unaware="" of="" any="" applicable="" prior="" sanction.="" any="" person="" who="" intends="" to="" assert="" or="" rely="" on="" such="" sanction="" is="" required="" to="" submit="" proof="" of="" the="" existence="" of="" the="" applicable="" prior="" sanction.="" the="" failure="" of="" any="" person="" to="" come="" forward="" with="" proof="" of="" such="" an="" applicable="" prior="" sanction="" in="" response="" to="" this="" notice="" will="" constitute="" a="" waiver="" of="" the="" right="" to="" assert="" or="" rely="" on="" such="" sanction="" at="" any="" later="" time.="" c.="" food="" additive="" status="" of="" ruminant="" tissues="" the="" agency="" recognizes="" that="" processed="" ruminant="" byproducts="" have="" a="" long="" history="" of="" use="" in="" animal="" feeds="" without="" known="" adverse="" effects.="" however,="" the="" evidence="" as="" discussed="" in="" sections="" i="" and="" ii.a.="" through="" ii.d.="" of="" this="" document,="" for="" the="" development="" of="" a="" new="" pattern="" of="" disease="" transmission,="" now="" indicates="" that="" these="" ingredients="" can="" no="" longer="" be="" categorically="" regarded="" as="" safe.="" the="" agency="" tentatively="" concludes="" that,="" based="" on="" this="" evidence,="" use="" of="" such="" products="" in="" ruminant="" feed="" is="" not="" gras.="" the="" agency="" is="" proposing="" this="" regulation="" in="" light="" of="" the="" findings="" and="" conclusions="" described="" in="" sections="" i="" and="" ii="" in="" this="" notice.="" nor="" is="" the="" agency="" aware="" of="" a="" prior="" sanction="" for="" any="" feed="" products="" that="" contain="" these="" tissues.="" therefore,="" fda="" is="" proposing="" that="" the="" addition="" of="" protein="" derived="" from="" ruminant="" tissues="" to="" ruminant="" feed="" would="" constitute="" the="" use="" of="" an="" unapproved="" food="" additive="" because="" no="" regulation="" is="" in="" effect="" providing="" for="" such="" use.="" any="" ruminant="" feed="" that="" contains="" protein="" derived="" from="" ruminant="" and="" mink="" tissues="" would="" be="" adulterated.="" accordingly,="" fda="" is="" proposing="" to="" list="" protein="" derived="" from="" ruminant="" tissues="" in="" part="" 589.="" iv.="" comments="" fda's="" may="" 1996="" anprm="" requested="" public="" comment="" and="" information="" on="" all="" aspects="" of="" tse's,="" including="" bse,="" and="" the="" potential="" consequences="" of="" a="" prohibition="" on="" the="" feeding="" of="" ruminant="" protein="" to="" ruminants.="" the="" agency="" received="" nearly="" 600="" comments,="" including="" many="" that="" were="" submitted="" long="" after="" the="" comment="" period="" ended.="" the="" agency="" has="" attempted="" to="" address="" the="" comments="" in="" this="" proposal.="" if="" there="" are="" any="" significant="" concerns="" that="" the="" agency="" has="" not="" addressed,="" these="" concerns="" should="" be="" brought="" to="" the="" agency's="" attention="" in="" timely="" comments="" on="" this="" proposal.="" comments="" that="" were="" specific="" to="" the="" topics="" covered="" by="" the="" other="" sections="" of="" this="" preamble="" were="" considered="" in="" the="" preamble="" as="" written.="" comments="" are="" discussed="" in="" the="" text="" of="" some="" of="" these="" sections.="" the="" following="" is="" a="" general="" discussion="" of="" the="" comments="" received.="" many="" comments,="" especially="" from="" renderers,="" meat="" packers,="" feed="" companies="" and="" farmers,="" opposed="" the="" prohibition="" of="" ruminant="" protein="" being="" fed="" to="" ruminants.="" the="" main="" reasons="" offered="" were="" the="" lack="" of="" evidence="" of="" bse="" in="" the="" united="" states,="" lack="" of="" scientific="" data="" to="" support="" the="" proposal="" in="" the="" absence="" of="" [[page="" 567]]="" bse,="" environmental="" concerns,="" lack="" of="" an="" assay="" or="" other="" practical="" means="" to="" support="" enforcement,="" and="" the="" economic="" hardship="" that="" would="" fall="" upon="" the="" animal="" producers,="" slaughter="" facilities,="" renderers,="" feed="" manufacturers,="" and="" packers.="" support="" for="" such="" a="" prohibition="" from="" consumer="" groups,="" pharmaceutical="" firms,="" scientists="" and="" veterinarians,="" and="" some="" livestock="" organizations,="" emphasized="" a="" potential="" effect="" on="" human="" health,="" the="" experience="" and="" data="" from="" the="" united="" kingdom,="" and="" significant="" economic="" detriment="" if="" a="" bse="" epidemic="" were="" to="" occur="" in="" this="" country.="" other="" comments="" described="" a="" need="" to="" ensure="" that="" exported="" u.s.="" bovine-derived="" products="" met="" international="" standards="" and="" guidelines,="" and="" to="" maintain="" consumer="" confidence="" in="" the="" beef="" and="" dairy="" industries="" even="" though="" those="" comments="" acknowledged="" that="" there="" is="" a="" minimal="" potential="" risk="" of="" infectivity="" to="" animals="" and="" humans.="" the="" agency="" requested="" scientific="" information="" regarding="" the="" occurrence,="" transmission,="" etiology,="" pathogenesis,="" epidemiology,="" and="" inactivation="" of="" tse="" agents.="" many="" comments="" were="" received="" that="" contained="" useful="" scientific="" information="" that="" was="" considered="" in="" the="" preparation="" of="" this="" proposed="" rule,="" as="" described="" in="" this="" preamble="" and="" supporting="" documents.="" three="" comments="" suggested="" that="" the="" documented="" existence="" of="" nonbse="" tse's,="" and="" the="" presence="" of="" ``downer''="" cows="" (cows="" unable="" to="" walk)="" in="" the="" united="" states="" is="" evidence="" that="" bse="" is="" present="" in="" this="" country.="" three="" comments="" stated="" that="" the="" bse="" surveillance="" in="" the="" united="" states="" provides="" sufficient="" assurance="" that="" bse="" does="" not="" exist="" in="" this="" country.="" a="" number="" of="" persons="" commented="" on="" whether="" specific="" tissues,="" such="" as="" milk,="" blood,="" and="" gelatin,="" should="" be="" excluded="" from="" any="" prohibition,="" with="" nearly="" all="" supporting="" such="" exclusion.="" the="" agency="" requested="" information="" on="" the="" economic="" impact="" of="" the="" described="" action.="" numerous="" comments="" provided="" data="" on="" volume="" of="" product="" impacted,="" potential="" economic="" benefits,="" and="" cost="" of="" compliance="" to="" affected="" persons.="" the="" data="" were="" used="" to="" develop="" the="" preliminary="" economic="" assessment="" supporting="" this="" proposed="" rule.="" the="" agency="" requested="" information="" on="" the="" environmental="" impact="" and="" potential="" mitigating="" factors="" of="" the="" described="" action.="" many="" comments="" stated="" that="" alternative="" disposal="" of="" the="" prohibited="" carcasses="" would="" be="" less="" environmentally="" safe="" than="" rendering.="" these="" and="" other="" comments="" were="" considered="" in="" the="" development="" of="" the="" environmental="" assessment.="" numerous="" comments="" were="" received="" regarding="" the="" need="" to="" prohibit="" only="" tissues="" that="" have="" been="" demonstrated="" to="" be="" infective.="" generally,="" the="" comments="" stated="" that="" tissues="" that="" have="" been="" proven="" to="" be="" noninfective="" should="" be="" exempted.="" although="" the="" agency="" is="" proposing="" a="" rule="" that="" would="" prohibit="" the="" use="" of="" all="" ruminant-derived="" protein="" in="" ruminant="" feeds,="" the="" agency="" will,="" as="" explained="" elsewhere="" in="" this="" document,="" consider="" a="" partial="" ruminant-to-ruminant="" prohibition="" as="" well="" as="" a="" mammalian-to-="" ruminant="" prohibition.="" many="" comments="" supported="" establishment="" of="" hazard="" analysis="" critical="" control="" points="" (haccp)="" for="" the="" rendering="" industry,="" often="" with="" concurrent="" support="" for="" current="" good="" manufacturing="" practices="" (cgmp's)="" for="" animal-derived="" proteins.="" for="" example,="" the="" american="" feed="" industry="" association="" proposed="" a="" specific="" set="" of="" good="" manufacturing="" practices="" for="" the="" producers="" of="" animal="" protein="" products,="" and="" the="" national="" renderers="" association="" proposed="" a="" specific="" haccp="" regulation="" for="" rendering="" operations.="" the="" agency="" agrees="" that="" the="" need="" for="" haccp,="" perhaps="" supported="" by="" cgmp's,="" for="" animal-derived="" proteins="" could="" be="" considered="" in="" future="" rulemaking.="" several="" comments="" were="" received="" regarding="" labeling="" requirements="" for="" animal-derived="" proteins.="" the="" majority="" of="" the="" comments="" supported="" a="" statement="" of="" the="" origin="" of="" animal-derived="" protein.="" the="" agency="" has="" included="" a="" labeling="" requirement="" in="" the="" proposed="" rule.="" v.="" analysis="" of="" alternatives="" a.="" overview="" in="" addition="" to="" the="" proposed="" ruminant-to-ruminant="" rule,="" the="" agency="" is="" considering="" alternative="" approaches.="" the="" alternatives="" include:="" (1)="" excluding="" from="" ruminant="" feed="" all="" ruminant="" and="" mink="" materials="" except="" those="" that="" have="" not="" been="" found="" to="" present="" a="" risk="" of="" transmitting="" spongiform="" encephalopathy="" (partial="" ruminant-to-ruminant="" prohibition);="" (2)="" prohibiting="" the="" use="" in="" ruminant="" feed="" of="" all="" mammalian="" protein="" (mammalian-to-ruminant="" prohibition);="" (3)="" prohibiting="" the="" feeding="" of="" materials="" from="" species="" in="" which="" tse's="" have="" been="" diagnosed="" in="" the="" united="" states="" (sheep,="" goats,="" mink,="" deer,="" and="" elk);="" (4)="" prohibiting="" the="" feeding="" of="" specified="" sheep="" and="" goat="" offal,="" as="" proposed="" by="" the="" agency="" in="" 1994;="" (5)="" other="" alternatives="" that="" might="" be="" proposed="" by="" the="" comments;="" and="" (6)="" no="" action.="" analysis="" of="" the="" advantages="" and="" disadvantages="" of="" the="" options="" follows.="" analysis="" of="" costs="" and="" benefits,="" including="" detailed="" economic="" analysis,="" also="" appears="" in="" section="" ix.="" of="" this="" document.="" environmental="" consequences="" are="" discussed="" in="" section="" viii.="" of="" this="" document.="" in="" determining="" the="" scope="" of="" the="" final="" rule,="" the="" agency="" will="" weigh="" carefully="" the="" comments="" received,="" along="" with="" material="" contained="" in="" the="" administrative="" record="" for="" this="" proposal="" and="" the="" comments="" submitted="" in="" response="" to="" the="" anprm.="" comments="" regarding="" the="" scope="" of="" the="" rule,="" including="" those="" comments="" supporting="" other="" options="" other="" than="" the="" proposed="" option,="" should="" be="" addressed="" accordingly.="" b.="" ruminant-to-ruminant="" prohibition="" advantages="" of="" this="" option,="" compared="" with="" the="" ``no="" action''="" option,="" are="" discussed="" in="" detail="" in="" section="" i.="" of="" this="" document.="" the="" advantages="" of="" this="" option="" that="" are="" discussed="" in="" that="" section="" would="" apply="" if="" bse="" were="" to="" occur="" in="" this="" country.="" as="" discussed="" in="" separate="" sections="" that="" follow,="" there="" would="" also="" be="" environmental="" and="" economic="" advantages="" to="" the="" ruminant-to-ruminant="" option,="" if="" bse="" were="" to="" occur="" in="" this="" country.="" disadvantages="" of="" the="" ruminant-to-ruminant="" option,="" compared="" to="" the="" ``no="" action''="" option,="" would="" be="" relevant="" primarily="" if="" bse="" did="" not="" occur="" in="" the="" united="" states.="" these="" disadvantages="" would="" include="" the="" time="" and="" expense="" required="" to="" comply="" with="" the="" provisions="" of="" the="" regulation,="" and="" the="" limited,="" short="" term="" environmental="" effects="" described="" in="" section="" viii.="" of="" this="" document.="" compared="" with="" the="" mammalian-to-ruminant="" option,="" the="" ruminant-to-="" ruminant="" option="" has="" the="" advantages="" of="" being="" tailored="" more="" precisely="" to="" the="" identified="" scientific="" concerns,="" and="" less="" burdensome="" on="" the="" affected="" industries.="" economic="" and="" environmental="" costs="" would="" be="" less.="" the="" major="" disadvantage="" is="" that="" the="" ruminant-to-ruminant="" option="" results="" in="" more="" complexity="" for="" the="" regulated="" industries,="" and="" thereby="" provides="" less="" assurance="" of="" compliance.="" this="" is="" explained="" further="" in="" the="" discussion="" of="" the="" mammalian-to-ruminant="" option,="" in="" section="" v.d.="" of="" this="" document.="" compared="" to="" the="" other="" remaining="" options,="" which="" are="" less="" restrictive,="" the="" ruminant-to-ruminant="" option="" provides="" greater="" assurance="" of="" protection="" of="" the="" public="" health="" and,="" if="" bse="" were="" to="" occur="" in="" the="" united="" states,="" lower="" economic="" and="" environmental="" costs.="" the="" disadvantages="" relate="" generally="" to="" the="" greater="" economic="" and="" environmental="" costs="" that="" would="" be="" incurred="" if="" bse="" did="" not="" occur="" in="" the="" united="" states.="" c.="" partial="" ruminant-to-ruminant="" prohibition="" as="" an="" alternative="" to="" the="" proposed="" ruminant-to-ruminant="" prohibition,="" the="" agency="" is="" considering="" a="" partial="" [[page="" 568]]="" ruminant-to-ruminant="" prohibition="" which="" would="" exclude="" from="" ruminant="" feed="" all="" ruminant="" and="" mink="" materials="" except="" those="" that="" have="" not="" been="" found="" to="" present="" a="" risk="" of="" transmitting="" spongiform="" encephalopathy.="" the="" exclusions="" would="" be="" in="" addition="" to="" milk="" products,="" gelatin="" and="" bovine="" blood,="" which="" are="" excluded="" in="" the="" proposed="" rule.="" possible="" exclusions="" include="" slaughter="" byproducts="" from="" bovine="" that="" have="" been="" inspected="" and="" passed="" in="" inspected="" slaughter="" facilities,="" except="" the="" brain,="" eyes,="" spinal="" cord,="" and="" distal="" ileum.="" the="" four="" named="" tissues="" would="" be="" prohibited="" because="" they="" have="" been="" shown="" through="" experimental="" trials="" and="" bioassays="" to="" transmit="" spongiform="" encephalopathy.="" the="" remaining="" tissues="" have="" not="" been="" demonstrated="" to="" transmit="" spongiform="" encephalopathy.="" this="" option="" has="" the="" advantage="" of="" having="" its="" prohibitions="" based="" primarily="" on="" scientific="" information="" related="" to="" infectivity="" of="" specific="" tissues.="" a="" number="" of="" persons="" who="" commented="" on="" the="" anprm="" urged="" the="" agency="" to="" base="" its="" regulation="" entirely="" on="" such="" scientific="" information.="" in="" addition,="" this="" option="" would="" likely="" involve="" lower="" lost="" sales="" revenues="" to="" the="" affected="" industries,="" and="" could="" have="" fewer="" adverse="" economic="" effects,="" than="" would="" the="" other="" options.="" however,="" the="" agency="" has="" three="" concerns="" with="" regard="" to="" the="" adequacy="" of="" this="" option="" in="" providing="" sufficient="" protection="" for="" the="" public="" health.="" first,="" fda="" recognizes="" that="" it="" may="" be="" impractical="" in="" the="" slaughter="" and="" rendering="" processes="" to="" segregate="" and="" exclude="" the="" bovine="" tissues="" that="" have="" not="" been="" found="" to="" present="" a="" risk.="" for="" example,="" usda="" has="" expressed="" reservations="" that="" separating="" the="" distal="" ileum="" from="" the="" other="" intestinal="" offal="" could="" jeopardize="" a="" slaughter="" plant's="" ability="" to="" meet="" pathogen="" reduction="" goals="" required="" under="" usda's="" haccp="" regulations.="" furthermore,="" regulatory="" enforcement="" of="" a="" prohibition="" affecting="" only="" specified="" bovine="" tissues="" may="" be="" impractical="" in="" the="" absence="" of="" specific="" diagnostic="" methods="" for="" identifying="" protein="" derived="" from="" such="" tissues.="" if="" a="" partial="" prohibition="" were="" adopted,="" it="" would="" be="" based="" on="" a="" finding="" that="" practical="" methods="" can="" be="" implemented="" for="" segregating,="" processing,="" storing,="" and="" identifying="" feed="" materials="" derived="" from="" tissues="" that="" have="" not="" been="" found="" to="" present="" a="" risk.="" second,="" this="" option="" would="" be="" inconsistent="" with="" actions="" taken="" in="" a="" number="" of="" other="" nations.="" for="" example,="" cdc="" has="" commented="" that="" any="" prohibition="" of="" lesser="" scope="" than="" a="" ruminant-to-ruminant="" prohibition="" would="" place="" the="" united="" states="" out="" of="" step="" with="" the="" international="" public="" health="" community.="" third,="" limiting="" the="" prohibition="" of="" tissues="" to="" those="" that="" have="" been="" shown="" to="" be="" infective="" would="" not="" address="" the="" risk="" that="" may="" be="" presented="" by="" other="" tissues.="" definitive="" assays="" using="" methods="" more="" sensitive="" than="" currently="" available="" methods="" might="" identify="" such="" additional="" tissues="" as="" infective.="" the="" possibility="" of="" undetected="" low="" dose="" exposure="" cannot="" be="" eliminated,="" particularly="" for="" tissues="" such="" as="" lymph="" nodes="" and="" spleens="" which="" would="" be="" expected="" to="" be="" infective="" (ref.="" 1).="" these="" issues="" raise="" a="" substantial="" question="" as="" to="" whether="" the="" tissues="" could="" be="" gras.="" to="" achieve="" the="" highest="" level="" of="" public="" health="" protection,="" the="" agency="" believes="" that="" it="" may="" be="" reasonable="" to="" assume="" that,="" in="" the="" absence="" of="" scientific="" data="" definitively="" establishing="" that="" each="" tissue="" does="" not="" transmit="" spongiform="" encephalopathy,="" all="" ruminant="" tissues="" present="" a="" risk="" of="" infectivity.="" the="" agency="" nevertheless="" welcomes="" comments="" on="" this="" alternative="" to="" the="" proposed="" ruminant-to-ruminant="" prohibition="" and="" especially="" invites="" comments="" on="" possible="" practical="" means="" of="" separating="" the="" distal="" ileum="" in="" compliance="" with="" usda="" and="" industry="" standards,="" as="" well="" as="" the="" practicality="" of="" the="" removal="" of="" brain,="" spinal="" cord,="" and="" eye="" and="" the="" segregation="" of="" these="" tissues="" from="" others="" in="" the="" slaughter="" plant.="" d.="" mammal-to-ruminant="" prohibition="" the="" agency="" received="" comments="" in="" support="" of="" a="" rule="" that="" would="" prohibit="" the="" use="" in="" ruminant="" feed="" of="" all="" mammalian-derived="" protein.="" for="" instance,="" the="" american="" feed="" industry="" association,="" nra,="" and="" appi="" expressed="" concerns="" that="" segregating="" certain="" mammalian="" derived="" proteins="" from="" others="" would="" not="" be="" feasible="" because="" of="" regular="" commingling="" of="" protein="" products="" at="" feed="" mills="" and="" rendering="" facilities.="" a="" mammalian-="" to-ruminant="" prohibition="" would="" provide="" greater="" assurance="" of="" industry="" compliance="" than="" either="" a="" partial="" or="" total="" ruminant-to-ruminant="" prohibition="" because="" practical="" analytical="" methods="" exist="" for="" distinguishing="" mammalian="" from="" nonmammalian="" proteins.="" implementation="" of="" a="" mammal-to-ruminant="" prohibition="" by="" the="" regulated="" industries="" would="" be="" less="" complex,="" and="" would="" reduce="" the="" potential="" for="" contamination="" of="" cattle="" feeds="" with="" material="" intended="" for="" feeding="" monogastric="" animals.="" contamination="" of="" cattle="" feeds="" with="" material="" intended="" for="" feeding="" nonruminants="" was="" the="" primary="" reason="" that="" the="" united="" kingdom="" has="" prohibited="" mammalian="" proteins="" in="" the="" rations="" of="" cattle.="" a="" mammal-to-="" ruminant="" prohibition="" would="" enable="" the="" continued="" use="" of="" association="" of="" american="" feed="" control="" officials="" definitions="" for="" the="" purpose="" of="" identifying="" and="" labeling="" products="" covered="" by="" the="" prohibition,="" and="" would="" not="" require="" additional="" or="" new="" labeling.="" finally,="" concerns="" were="" expressed="" that="" allowing="" certain="" products="" containing="" meat="" and="" bone="" meal="" to="" be="" used="" in="" ruminant="" feeds="" while="" prohibiting="" others="" would="" lead="" to="" instability="" in="" financially="" sensitive="" commodity="" markets="" for="" animal="" protein.="" on="" the="" other="" hand,="" the="" agency="" is="" not="" aware="" of="" any="" scientific="" data="" that="" establish="" or="" suggest="" tse="" infectivity="" in="" nonruminant="" mammals="" except="" in="" mink.="" thus,="" excluding="" nonruminant="" tissues="" from="" ruminant="" feed="" would="" be="" based="" primarily="" on="" the="" view="" that="" the="" possibility="" of="" infection="" of="" nonruminant="" tissue="" through="" cross-contamination="" or="" commingling="" with="" ruminant="" tissue="" is="" sufficient="" to="" preclude="" gras="" status="" for="" the="" nonruminant="" tissue.="" however,="" fda="" is="" aware="" that="" some="" portions="" of="" the="" affected="" industries="" would="" prefer="" to="" segregate="" ruminant="" from="" nonruminant="" tissues,="" and="" believe="" that="" such="" separation="" is="" practical.="" accordingly,="" the="" agency="" invites="" comments="" on="" the="" relative="" merits="" and="" disadvantages="" of="" a="" mammal-to-ruminant="" prohibition="" compared="" with="" a="" total="" or="" partial="" ruminant-to-ruminant="" prohibition.="" e.="" prohibition="" of="" materials="" from="" u.s.="" species="" diagnosed="" with="" tse's="" (sheep,="" goats,="" mink,="" deer,="" and="" elk)="" this="" option="" would="" involve="" requiring="" that="" ruminants="" not="" be="" fed="" any="" proteins="" derived="" from="" any="" u.s.="" animal="" species="" in="" which="" a="" tse="" has="" been="" diagnosed.="" this="" includes="" sheep,="" goats,="" mink,="" deer,="" and="" elk.="" this="" approach="" would="" eliminate="" the="" scrapie="" agent,="" along="" with="" tme="" and="" cwd,="" from="" ruminant="" feed,="" and="" thereby="" reduce="" the="" risk="" of="" bse="" in="" cattle="" caused="" by="" tse="" transmission="" from="" other="" species.="" however,="" it="" would="" not="" prevent="" the="" spread="" of="" bse="" among="" cattle="" if="" bse="" occurred="" for="" some="" other="" reasons,="" e.g.,="" by="" a="" spontaneous="" mutation="" in="" cattle="" or="" importation="" of="" animals="" with="" bse,="" and="" the="" animals="" were="" processed="" and="" subsequently="" included="" in="" ruminant="" feed.="" as="" explained="" in="" section="" ix.="" of="" this="" document,="" this="" option="" involves="" lower="" economic="" costs="" than="" the="" three="" options="" previously="" described,="" in="" the="" absence="" of="" a="" bse="" outbreak.="" f.="" sheep-specified="" offal="" prohibition="" the="" option="" of="" prohibiting="" only="" protein="" from="" specified="" offal="" from="" sheep="" and="" goats="" for="" use="" in="" ruminant="" feed="" would="" eliminate="" the="" scrapie="" agent="" from="" bovine="" feed.="" however,="" it="" would="" not="" prevent="" the="" spread="" of="" bse="" among="" cattle="" if="" bse="" occurred="" for="" some="" other="" reason,="" e.g.,="" by="" [[page="" 569]]="" a="" spontaneous="" mutation="" in="" cattle="" or="" importation="" of="" animals="" with="" bse,="" and="" the="" animals="" were="" processed="" and="" subsequently="" included="" in="" ruminant="" feed.="" the="" agency="" notes="" that="" if="" it="" were="" to="" select="" this="" option,="" it="" would="" reconsider="" its="" statement="" in="" the="" 1994="" proposed="" rule="" that="" sheep="" less="" than="" 12="" months="" of="" age="" presented="" a="" minimal="" risk.="" cases="" of="" scrapie="" in="" sheep="" as="" young="" as="" 7="" months="" have="" been="" reported="" (ref.="" 113).="" although="" the="" risk="" presented="" by="" young="" animals="" may="" be="" minimal,="" excluding="" them="" may="" provide="" inadequate="" protection="" to="" the="" public="" health.="" as="" explained="" in="" section="" ix.="" of="" this="" document,="" this="" option="" involves="" lower="" economic="" costs="" than="" the="" options="" described="" previously,="" in="" the="" absence="" of="" a="" bse="" outbreak.="" g.="" no="" action="" the="" advantages="" and="" disadvantages="" of="" this="" option,="" in="" relation="" to="" the="" other="" options,="" are="" discussed="" in="" detail="" in="" section="" i.="" of="" this="" document="" and="" in="" the="" preceding="" subsections="" of="" this="" section,="" as="" well="" as="" the="" environmental="" and="" economic="" sections.="" in="" general,="" this="" option="" offers="" lower="" economic="" and="" environmental="" costs="" if="" bse="" does="" not="" occur="" in="" the="" united="" states,="" and="" higher="" such="" costs="" (in="" addition="" to="" public="" health="" implications)="" if="" bse="" does="" occur.="" vi.="" description="" of="" the="" proposed="" rule="" a.="" introduction="" 1.="" regulatory="" alternatives="" typically,="" fda="" regulates="" products="" that="" are="" of="" public="" health="" concern="" through="" a="" combination="" of="" regulatory="" tools="" including:="" labeling="" for="" appropriate="" use;="" cgmp="" regulations="" and,="" recently,="" haccp="" regulations;="" specifications="" for="" the="" product="" or="" its="" manufacture;="" and="" testing="" to="" determine="" the="" presence="" or="" level="" of="" the="" agent="" of="" concern.="" use="" of="" two="" or="" more="" of="" these="" means="" provides="" for="" appropriate="" reinforcement="" to="" ensure="" that="" the="" public="" is="" protected.="" the="" agency's="" choice="" of="" readily="" available="" approaches="" for="" regulating="" animal="" protein="" products="" derived="" from="" ruminant="" and="" mink="" tissues="" is="" limited.="" for="" example,="" there="" are="" no="" practical="" tests="" for="" the="" presence="" of="" the="" tse="" agent="" or="" of="" ruminant="" protein="" in="" animal="" feed.="" no="" commercial="" method="" of="" deactivating="" the="" tse="" agent="" in="" animal="" protein="" products="" has="" been="" scientifically="" validated="" as="" effective.="" none="" of="" the="" agency's="" cgmp="" or="" haccp="" regulations="" apply="" to="" this="" situation.="" labeling="" requirements="" can="" be="" used="" but,="" by="" themselves,="" do="" not="" meet="" the="" agency's="" regulatory="" objectives.="" 2.="" the="" regulated="" industry="" often,="" the="" industry="" that="" manufactures="" and="" distributes="" an="" fda-="" regulated="" product="" is="" fairly="" easily="" characterized.="" this="" facilitates="" regulation.="" that="" is="" not="" the="" case="" for="" animal="" protein="" products,="" as="" the="" following="" brief="" overview="" makes="" clear.="" renderers="" collect="" animal="" tissues="" from="" a="" variety="" of="" sources,="" and="" process="" these="" tissues="" into="" both="" protein="" and="" nonprotein="" products.="" the="" renderers="" may="" be="" specialized="" (packer/renderer)="" or="" independent.="" the="" packer/renderer,="" which="" involves="" a="" renderer="" associated="" with="" a="" large="" slaughter="" operation,="" specializes="" in="" one="" species--primarily="" cattle,="" swine,="" or="" poultry.="" thus,="" whether="" the="" packer/renderer="" handles="" ruminant="" materials="" is="" fairly="" easily="" determined.="" the="" independent="" renderer,="" on="" the="" other="" hand,="" obtains="" a="" variety="" of="" raw="" materials="" ranging="" from="" restaurant="" scraps="" to="" byproducts="" from="" multi-species="" slaughtering="" operations="" to="" dead="" animals="" obtained="" from="" farmers.="" typically,="" the="" independent="" renderer="" does="" not="" have="" a="" practical="" method="" to="" separate="" incoming="" ruminant="" from="" nonruminant="" materials,="" and="" thus="" commingles="" both="" ruminant="" and="" nonruminant="" materials="" in="" the="" rendering="" process.="" the="" rendered="" product="" is="" typically="" designated="" ``meat="" and="" bone="" meal,''="" but="" rendering="" operations="" produce="" a="" variety="" of="" other="" products.="" renderers="" sell="" their="" products="" to="" animal="" protein="" blenders,="" animal="" feed="" manufacturers="" or="" pet="" food="" manufacturers.="" virtually="" all="" rendered="" material="" at="" present="" is="" used="" ultimately="" for="" pet="" food="" or="" the="" feed="" of="" livestock="" or="" poultry.="" animal="" protein="" blenders="" mix="" animal="" and="" plant="" protein="" materials="" to="" meet="" a="" protein="" guarantee="" stated="" on="" the="" label,="" and="" to="" make="" a="" balanced="" nutritional="" product.="" typically,="" the="" blender="" does="" not="" separate="" ruminant="" from="" nonruminant="" animal="" protein="" in="" its="" blending="" operation,="" although="" it="" may="" keep="" mammalian,="" poultry,="" fish="" and="" soybean="" meal="" protein="" separate="" at="" least="" in="" the="" initial="" stages.="" the="" blender="" sells="" its="" products="" to="" feed="" or="" pet="" food="" manufacturers.="" some="" renderers="" also="" blend="" animal="" protein="" products.="" feed="" manufacturers="" use="" the="" protein="" material="" to="" make="" a="" complete="" feed="" (ready="" to="" be="" feed="" to="" animals),="" or="" a="" concentrated="" feed="" that="" needs="" to="" be="" further="" diluted="" (blended)="" before="" it="" can="" be="" fed="" to="" animals.="" the="" feed="" may="" be="" manufactured="" by="" an="" off-farm="" miller,="" or="" on="" the="" farm.="" feed="" that="" is="" manufactured="" off-farm="" may="" be="" sold="" to="" one="" or="" more="" persons="" (for="" blending="" and/or="" further="" distribution)="" before="" reaching="" the="" farm.="" farmers="" that="" feed="" animals="" typically="" raise="" one="" species,="" but="" may="" have="" more="" than="" one="" (including="" both="" ruminants="" and="" nonruminants).="" only="" about="" 10="" percent="" of="" all="" animal="" protein="" products="" are="" fed="" to="" ruminants="" (mainly="" cattle)="" but="" approximately="" half="" of="" all="" animal="" protein="" products="" comes="" from="" ruminants.="" 3.="" enforcement="" considerations="" the="" industry="" scenario="" described="" in="" the="" preceding="" section="" presents="" unique="" enforcement="" challenges.="" the="" agency="" is="" aware,="" from="" the="" comments="" to="" the="" anprm="" and="" other="" sources,="" of="" concerns="" that="" the="" regulatory="" impact="" be="" minimized.="" the="" agency="" is="" also="" aware="" of="" the="" need="" to="" provide="" incentive="" for="" innovation,="" e.g.,="" in="" testing="" methodology="" and="" manufacturing="" technology,="" that="" would="" reduce="" the="" need="" for="" regulation.="" finally,="" the="" agency="" is="" aware="" of="" the="" need,="" in="" designing="" a="" regulatory="" program,="" to="" acknowledge="" the="" different="" circumstances="" that="" exist="" in="" the="" industries="" previously="" described.="" therefore,="" the="" agency="" has="" designed="" a="" proposed="" regulatory="" scheme="" using="" the="" following="" principles.="" first,="" the="" agency="" has="" identified="" minimally="" necessary="" requirements="" to="" meet="" its="" regulatory="" objectives.="" the="" agency's="" goal="" is="" to="" apply="" risk="" management="" principles="" that="" minimize="" risk.="" second,="" the="" proposed="" regulation="" applies="" greater="" restriction="" where="" the="" risk="" is="" greater--for="" example,="" where="" a="" firm="" handles="" both="" ruminant="" and="" nonruminant="" materials="" and="" intends="" to="" keep="" them="" separated.="" third,="" the="" agency="" intends="" to="" rely="" on="" normal="" business="" records="" for="" much="" of="" the="" documentation="" it="" needs.="" a="" fourth="" and="" most="" important="" principle="" concerns="" the="" related="" objectives="" of="" flexibility="" and="" providing="" incentives="" to="" reduce="" recordkeeping="" and="" labeling="" requirements.="" the="" proposed="" regulation="" provides="" for="" the="" reduction="" or="" elimination="" of="" recordkeeping="" and="" labeling="" requirements,="" upon="" the="" development="" of="" methods="" for="" detection,="" deactivation,="" or="" verification="" of="" product="" identity.="" these="" provisions="" are="" described="" further="" in="" the="" discussion="" that="" follows.="" industry-wide="" adoption="" of="" scientific="" advances="" including,="" or="" in="" addition="" to,="" those="" specified="" in="" the="" regulation,="" could="" ultimately="" lead="" to="" amendment="" or="" revocation="" of="" any="" final="" regulation.="" an="" example="" of="" an="" additional="" method="" would="" be="" the="" development="" of="" a="" practical="" method="" to="" detect="" the="" presence="" of="" ruminant="" protein="" in="" animal="" protein="" products="" or="" feed,="" which="" could="" be="" used="" for="" quality="" control="" by="" firms="" that="" separate="" ruminant="" from="" nonruminant="" protein,="" and="" by="" firms="" downstream="" from="" renderers.="" similarly,="" research="" leading="" to="" identification="" of="" the="" tse="" causative="" agent="" and="" the="" etiology="" of="" bse,="" and="" the="" characterization="" of="" the="" zoonotic="" nature="" of="" animal="" tse's,="" could="" also="" lead="" to="" amendment="" or="" revocation="" of="" any="" final="" regulation.="" [[page="" 570]]="" the="" agency="" has="" tentatively="" decided="" not="" to="" place="" any="" record="" keeping,="" labeling="" or="" other="" specific="" requirement="" on="" firms="" that="" handle="" only="" protein="" materials="" from="" nonruminant="" sources.="" an="" example="" would="" be="" a="" rendering="" operation="" that="" is="" part="" of="" a="" swine="" slaughter="" operation.="" however,="" if="" these="" firms="" would="" use="" or="" intend="" to="" use="" animal="" protein="" products="" containing="" ruminant="" tissues="" in="" ruminant="" feed,="" or="" caused="" such="" use="" or="" intended="" use,="" the="" feed="" would="" be="" adulterated="" under="" the="" act.="" the="" agency="" has="" also="" tentatively="" decided="" to="" require="" farmers="" (those="" responsible="" for="" feeding="" ruminant="" animals)="" only="" to="" make="" available="" copies="" of="" invoices="" and="" labeling="" for="" feed="" purchases.="" farmers="" would="" not="" be="" required="" to="" maintain="" written="" procedures="" for="" handling="" animal="" protein="" products.="" these="" minimal="" requirements="" would="" apply="" even="" if="" the="" farmers="" were="" feeding="" both="" ruminant="" and="" nonruminant="" animals.="" purchase="" records="" would="" be="" used="" primarily="" for="" traceback="" purposes.="" because="" only="" minimal="" requirements="" would="" be="" placed="" on="" farmers,="" the="" proposed="" rules="" require="" that="" labeling="" for="" the="" animal="" protein="" and="" feed="" products="" caution="" against="" feeding="" the="" products="" to="" ruminants.="" comments="" on="" these="" two="" tentative="" decisions="" are="" encouraged.="" b.="" outline="" of="" the="" proposed="" regulation="" the="" proposed="" regulation="" places="" two="" general="" requirements="" on="" persons="" that="" manufacture,="" blend,="" process,="" and="" distribute="" animal="" protein="" products="" and="" feeds="" made="" from="" such="" products.="" the="" first="" requirement="" is="" to="" place="" cautionary="" labeling="" on="" the="" protein="" and="" feed="" products.="" the="" second="" is="" a="" requirement="" to="" provide="" fda="" with="" access="" to="" sales="" and="" purchase="" invoices,="" for="" compliance="" purposes.="" for="" example,="" an="" invoice="" obtained="" from="" a="" feed="" manufacturer="" for="" a="" protein="" product="" not="" labeled="" with="" the="" cautionary="" statement="" could="" be="" used="" to="" trace="" back="" to="" the="" supplying="" renderer="" to="" ensure="" that="" it="" manufactures="" and="" distributes="" animal="" protein="" product="" from="" nonruminant="" sources.="" firms="" (renderers,="" blenders,="" and="" feed="" manufacturers="" and="" distributors)="" that="" handle="" animal="" protein="" products="" from="" both="" ruminant="" and="" nonruminant="" sources,="" and="" that="" intend="" to="" keep="" the="" products="" separate,="" would="" have="" certain="" additional="" requirements="" related="" to="" their="" source="" of="" nonruminant="" material;="" the="" need="" for="" separate="" facilities="" or="" cleanout="" procedures;="" and="" the="" need="" for="" sop's.="" the="" same="" requirements="" would="" apply="" to="" firms="" that="" handle="" feeds="" containing="" animal="" protein="" products="" from="" both="" ruminant="" and="" nonruminant="" sources,="" and="" that="" intend="" to="" keep="" the="" feeds="" separate.="" requirements="" would="" be="" greater="" for="" these="" operations="" because="" of="" the="" greater="" risk="" they="" would="" present="" for="" the="" possibility="" of="" ruminant="" protein="" being="" fed="" to="" ruminants.="" the="" proposed="" rule="" provides="" that="" some="" or="" all="" of="" the="" regulatory="" requirements="" would="" not="" apply="" if="" innovations="" such="" as="" development="" of="" test="" methods="" and="" deactivation="" processes="" for="" tse="" agents="" were="" scientifically="" validated="" and="" put="" into="" commercial="" use.="" provisions="" for="" use="" of="" such="" methods="" do="" not="" imply="" that="" the="" agency="" believes="" that="" such="" agents="" are="" or="" will="" be="" in="" the="" animal="" protein="" products.="" the="" objective="" is="" to="" minimize="" the="" risk="" that="" the="" agent="" would="" occur="" in="" the="" products,="" regardless="" of="" the="" level="" of="" risk.="" certain="" minimal="" but="" additional="" requirements="" would="" be="" imposed="" in="" such="" circumstances.="" for="" example,="" because="" the="" innovations="" likely="" would="" be="" applied="" by="" renderers,="" the="" renderers="" would="" need="" to="" certify="" to="" downstream="" customers="" that="" the="" methods="" were="" being="" utilized.="" section="" 589.2000(a)="" presents="" definitions="" of="" certain="" words="" used="" in="" the="" regulation.="" the="" definition="" of="" ``protein="" derived="" from="" ruminant="" and="" mink="" tissues''="" excludes="" blood="" from="" bovines,="" milk="" proteins,="" and="" gelatins.="" thus,="" those="" products="" are="" not="" subject="" to="" the="" regulatory="" provisions="" of="" the="" regulation.="" the="" proposed="" rule="" does="" not="" apply="" to="" any="" nonprotein="" animal="" tissues="" such="" as="" tallow="" or="" other="" fats.="" ``renderer''="" includes="" firms,="" not="" traditionally="" considered="" to="" be="" included="" within="" the="" definition="" of="" that="" term,="" but="" that="" collect="" animal="" tissues="" from="" various="" sources="" and="" subject="" them="" to="" minimal="" processing="" before="" offering="" the="" materials="" for="" use="" in="" animal="" feed.="" also,="" ``feed="" manufacturers''="" is="" defined="" to="" include="" both="" off-farm="" and="" on-farm="" feed="" manufacturing="" operations.="" section="" 589.2000(b)="" declares="" that="" protein="" derived="" from="" ruminant="" and="" mink="" tissues="" is="" not="" gras="" when="" intended="" for="" use="" in="" the="" feed="" of="" ruminant="" animals.="" the="" use="" or="" intended="" use="" of="" such="" material="" in="" ruminant="" animal="" feed="" causes="" the="" feed="" to="" be="" adulterated.="" section="" 589.2000(c)="" establishes="" regulatory="" requirements="" for="" renderers="" that="" manufacture="" products="" that="" contain="" or="" may="" contain="" protein="" derived="" from="" ruminant="" and="" mink="" tissues.="" (``may="" contain''="" allows="" for="" the="" fact="" that="" the="" renderer="" may="" not="" be="" able="" to="" determine="" the="" species="" of="" some="" incoming="" material).="" these="" renderers="" typically="" process="" both="" ruminant="" and="" nonruminant="" materials,="" but="" do="" not="" attempt="" to="" separate="" ruminant="" from="" nonruminant="" materials.="" section="" 589.2000(e)="" covers="" renderers="" that="" intend="" to="" separate="" such="" materials.="" as="" mentioned,="" renderers="" that="" process="" exclusively="" nonruminant="" materials="" are="" not="" covered="" by="" the="" specific="" requirements="" of="" the="" regulation.="" section="" 589.2000(c)="" applies="" to="" animal="" protein="" products="" intended="" for="" use="" in="" animal="" feeds,="" as="" well="" as="" animal="" feeds="" containing="" such="" products.="" two="" requirements="" would="" be="" placed="" on="" renderers="" covered="" by="" sec.="" 589.2000(c).="" first,="" they="" would="" be="" required="" to="" label="" their="" products="" to="" indicate="" that="" they="" contain="" (or="" may="" contain)="" protein="" derived="" from="" ruminant="" and="" mink="" tissues,="" and="" that="" the="" materials="" should="" not="" be="" fed="" to="" ruminant="" animals="" or="" used="" to="" manufacture="" feed="" for="" ruminants.="" second,="" the="" renderers="" would="" be="" required="" to="" maintain="" copies="" of="" sales="" invoices="" for="" all="" their="" animal="" protein="" products,="" and="" to="" make="" those="" copies="" readily="" available="" for="" inspection.="" as="" an="" example,="" fda="" would="" use="" the="" invoices="" to="" follow="" up="" with="" customers="" to="" verify="" that="" the="" customers="" are="" not="" using="" the="" products="" to="" manufacture="" ruminant="" feed.="" because="" sales="" invoices="" are="" normal="" business="" records,="" the="" agency="" believes="" that="" the="" additional="" burden="" imposed="" by="" this="" requirement="" would="" be="" minimal.="" section="" 589.2000(c)="" renderers="" would="" be="" exempted="" from="" the="" labeling="" and="" record="" requirements="" if="" they="" used="" a="" manufacturing="" method="" that="" deactivates="" the="" agent="" that="" causes="" tse's,="" or="" a="" test="" method="" that="" detects="" the="" presence="" of="" the="" agent="" that="" causes="" tse's.="" both="" methods="" would="" have="" to="" be="" validated="" by="" fda,="" and="" made="" available="" to="" the="" public.="" the="" regulation="" would="" require="" ``routine''="" use.="" that="" is,="" renderers="" would="" be="" required="" to="" use="" the="" test="" method="" on="" all="" incoming="" material="" or="" in="" each="" batch="" it="" manufactures.="" section="" 589.2000(c)="" renderers="" would="" be="" exempted="" from="" the="" record="" requirements="" (but="" not="" the="" labeling="" requirement)="" if="" they="" used="" a="" safe="" method="" to="" mark="" the="" presence="" of="" the="" materials.="" the="" marking="" could="" be="" visible="" to="" the="" naked="" eye,="" e.g.,="" through="" use="" of="" a="" dye,="" or="" by="" a="" nonvisual="" means.="" one="" anprm="" comment="" recommended="" use="" of="" a="" colored="" uniform="" fine="" iron="" product="" to="" identify="" specific="" feed="" ingredients.="" if="" the="" marking="" is="" not="" visible,="" the="" marking="" agent="" must="" be="" detectable="" by="" a="" method="" that="" has="" been="" validated="" by="" fda,="" and="" made="" available="" to="" the="" public.="" the="" mark="" must="" be="" permanent,="" i.e.,="" it="" must="" be="" visible="" in="" mixed="" feed="" as="" used="" on="" the="" farm.="" section="" 589.2000(d)="" establishes="" regulatory="" requirements="" for="" persons="" other="" than="" renderers="" and="" persons="" responsible="" for="" feeding="" ruminants="" that="" handle="" animal="" protein="" products="" or="" feeds="" containing="" such="" products.="" this="" includes="" protein="" blenders,="" and="" feed="" manufacturers="" and="" distributors.="" however,="" as="" in="" the="" case="" of="" renderers,="" those="" firms="" that="" would="" otherwise="" be="" included="" in="" sec.="" 589.2000(d)="" but="" that="" handle="" both="" ruminant="" and="" nonruminant="" [[page="" 571]]="" materials="" and="" intend="" to="" separate="" the="" materials="" would="" be="" covered="" by="" sec.="" 589.2000(e)="" instead.="" protein="" blenders,="" and="" feed="" manufacturers="" and="" distributors,="" that="" handle="" only="" nonruminant="" materials="" are="" excluded="" from="" the="" regulatory="" requirements="" of="" the="" proposed="" rule.="" persons="" covered="" by="" sec.="" 589.2000(d)="" would="" be="" subject="" to="" the="" same="" requirements="" as="" renderers,="" i.e.,="" labeling="" and="" records.="" the="" records="" would="" include="" invoices="" both="" to="" cover="" purchases="" and="" sales="" of="" animal="" protein="" products="" and="" feeds="" containing="" those="" products.="" for="" on-farm="" mixers,="" production="" records="" could="" be="" substituted="" for="" sales="" invoices.="" section="" 589.2000(d)="" firms="" would="" be="" exempt="" from="" the="" labeling="" and="" record="" requirements="" if="" they="" purchased="" materials="" from="" renderers="" that="" certified="" the="" use="" of="" deactivation="" or="" detection="" methods="" as="" described="" in="" sec.="" 589.2000(c).="" they="" would="" also="" be="" exempt="" from="" the="" labeling="" and="" record="" requirements="" if="" they="" purchased="" materials="" from="" persons="" other="" than="" renderers="" who="" certified="" that="" they="" purchased="" materials="" from="" renderers="" who="" certified="" the="" use="" of="" deactivation="" and="" detection="" methods="" as="" described="" in="" sec.="" 589.2000(c).="" paragraph="" (d)="" firms="" would="" also="" be="" exempt="" if="" they="" used="" the="" deactivation="" or="" detection="" methods="" described="" in="" sec.="" 589.2000(c),="" where="" use="" of="" such="" method="" is="" appropriate="" for="" the="" particular="" firm.="" paragraph="" (d)="" firms="" would="" be="" exempt="" from="" the="" record="" requirements="" if="" they="" purchased="" visibly-marked="" materials,="" or="" purchased="" from="" renderers="" that="" certified="" the="" use="" of="" marking="" methods="" as="" described="" in="" sec.="" 589.2000(c).="" they="" would="" also="" be="" exempt="" from="" the="" record="" requirements="" if="" they="" used="" the="" marking="" methods="" as="" described="" in="" sec.="" 589.2000(c).="" section="" 589.2000(e)="" establishes="" regulatory="" requirements="" for="" renderers,="" protein="" blenders,="" feed="" manufacturers="" and="" distributors,="" and="" independent="" haulers="" that="" handle="" both="" ruminant="" and="" nonruminant="" materials,="" and="" intend="" to="" keep="" the="" products="" separate.="" section="" 589.2000(e)="" establishes="" four="" kinds="" of="" requirements.="" first,="" the="" firms="" would="" have="" the="" same="" labeling="" and="" recordkeeping="" requirements="" as="" specified="" in="" paragraphs="" (c)="" and="" (d)="" of="" sec.="" 589.2000,="" except="" that="" the="" labeling="" requirement="" would="" apply="" only="" to="" the="" ruminant="" and="" mink="" materials.="" second,="" a="" renderer's="" source="" of="" nonruminant="" protein="" materials="" would="" be="" limited="" to="" single-species="" facilities,="" i.e.,="" facilities="" slaughtering="" only="" swine.="" a="" renderer="" could="" purchase="" nonruminant="" protein="" from="" more="" than="" one="" single-species="" facility.="" the="" agency="" believes="" that="" this="" restriction="" is="" necessary="" because="" of="" its="" understanding="" that="" it="" is="" not="" likely="" to="" be="" feasible="" for="" mixed="" species="" slaughterhouses="" to="" undertake="" the="" additional="" compliance="" costs,="" and="" possibly="" additional="" facility="" costs,="" that="" would="" be="" required="" to="" assure="" separation="" of="" ruminant="" and="" nonruminant="" materials.="" the="" restriction="" would="" therefore="" help="" assure="" that="" enforcement="" of="" sec.="" 589.2000(e)="" would="" be="" practicable.="" however,="" the="" agency="" specifically="" requests="" comments="" on="" this="" provision.="" third,="" the="" firms="" would="" be="" required="" to="" establish="" separate="" equipment="" and="" facilities="" for="" the="" two="" kinds="" of="" materials,="" or="" cleanout="" procedures="" to="" prevent="" cross="" contamination.="" fourth,="" the="" firms="" would="" need="" to="" establish="" written="" sop's="" specifying="" the="" cleanout="" procedures,="" if="" used,="" and="" specifying="" procedures="" for="" separating="" the="" materials="" from="" the="" time="" of="" receipt="" until="" the="" time="" of="" shipment.="" although="" sec.="" 589.2000(e)="" applies="" to="" several="" different="" kinds="" of="" firms,="" the="" agency's="" preliminary="" expectation="" is="" that="" only="" feed="" manufacturers="" and="" distributors="" will="" find="" it="" feasible="" to="" separate="" ruminant="" and="" nonruminant="" materials.="" as="" an="" example,="" a="" feed="" manufacturer="" might="" obtain="" ruminant="" materials="" from="" an="" independent="" renderer="" and="" swine="" materials="" from="" a="" packer/renderer,="" and="" use="" these="" materials="" to="" manufacture="" feed="" both="" for="" ruminants="" and="" nonruminants.="" the="" feed="" manufacturer="" would="" be="" required="" to="" meet="" the="" criteria="" listed="" previously,="" including="" the="" use="" of="" separate="" equipment="" and="" facilities="" or="" cleanout="" procedures,="" and="" the="" establishment="" of="" sop's.="" the="" requirements="" of="" sec.="" 589.2000(e)="" would="" be="" applicable="" in="" the="" transportation="" process,="" whether="" the="" material="" is="" hauled="" by="" the="" feed="" manufacturer="" or="" another="" party="" such="" as="" an="" independent="" hauler.="" the="" requirement="" for="" separate="" facilities,="" procedures="" or="" sop's="" would="" not="" apply="" to="" a="" firm,="" e.g.,="" a="" feed="" mill="" or="" hauler,="" that="" handles="" only="" nonruminant="" materials,="" or="" only="" ruminant="" materials.="" nor="" would="" it="" apply="" to="" a="" firm="" that="" handles="" both="" ruminant="" and="" nonruminant="" materials="" but="" does="" not="" attempt="" to="" separate="" the="" two="" kinds="" of="" materials.="" the="" paragraph="" (e)="" firms="" would="" be="" exempted="" from="" the="" labeling="" and/or="" record="" keeping="" requirements,="" and="" the="" requirements="" related="" to="" sourcing,="" facilities="" and="" sop's,="" if="" they="" meet="" the="" appropriate="" criteria="" for="" exemption.="" that="" is,="" renderers="" covered="" by="" sec.="" 589.2000(e)="" would="" be="" exempt="" from="" the="" labeling="" and="" recordkeeping="" requirements="" if="" they="" used="" deactivation="" or="" detection="" methods,="" and="" from="" the="" recordkeeping="" requirements="" if="" they="" used="" marking="" methods.="" blenders="" and="" feed="" manufacturers="" and="" distributors="" would="" be="" exempt="" in="" a="" similar="" manner.="" section="" 589.2000(f)="" establishes="" requirements="" for="" those="" who="" are="" responsible="" for="" feeding="" ruminant="" animals.="" the="" only="" requirement="" contained="" in="" this="" paragraph="" is="" that="" those="" persons="" make="" available="" to="" fda="" copies="" of="" purchase="" invoices="" and="" labeling="" for="" all="" incoming="" feeds.="" however,="" sec.="" 589.2000(f)="" does="" not="" apply="" to="" the="" feed="" manufacturing="" portion="" of="" farms="" and="" feedlots="" that="" have="" on-farm="" feed="" manufacturing="" operations.="" section="" 589.2000="" (d)="" and="" (e)="" would="" apply="" in="" those="" instances.="" furthermore,="" persons="" who="" feed="" or="" intend="" to="" feed="" ruminant="" protein="" to="" ruminant="" animals="" would="" be="" subject="" to="" regulatory="" action="" for="" using="" or="" intending="" to="" use="" an="" unapproved="" feed="" additive="" as="" established="" in="" sec.="" 589.2000="" (b).="" section="" 589.2000(g)="" establishes="" that="" violations="" of="" sec.="" 589.2000="" (c)="" through="" (f)="" would="" cause="" animal="" protein="" products="" or="" feed="" containing="" animal="" protein="" products="" to="" be="" adulterated="" under="" sections="" 402(a)(4)="" or="" 402(a)(2)(d)="" of="" the="" act,="" or="" misbranded="" under="" section="" 403(a)(1).="" section="" 589.2000(h)="" establishes="" inspection="" and="" records="" retention="" requirements="" for="" persons="" covered="" by="" section="" 589.2000="" (c)="" through="" (f).="" records="" that="" are="" required="" under="" those="" paragraphs="" would="" need="" to="" be="" kept="" for="" a="" minimum="" of="" 2="" years.="" the="" agency="" believes="" that="" this="" time="" period="" is="" adequate="" for="" purposes="" of="" verifying="" compliance="" with="" the="" regulation's="" procedural="" requirements.="" the="" agency="" invites="" comments="" on="" the="" need="" for="" a="" longer="" retention="" period="" related="" to="" the="" bse="" incubation="" period,="" especially="" the="" practicality="" of="" using="" such="" records="" for="" epidemiologic="" investigation.="" section="" 589.2000(h)="" also="" requires="" that="" written="" procedures="" required="" by="" the="" regulation="" be="" made="" available="" for="" inspection="" and="" copying="" by="" fda.="" the="" written="" procedures="" referred="" to="" are="" those="" specified="" in="" sec.="" 589.2000(e)(3).="" affected="" firms="" would="" be="" required="" to="" have="" a="" copy="" of="" the="" current="" procedures="" available="" at="" all="" times.="" vii.="" specific="" protein="" sources="" a="" number="" of="" comments="" discussed="" the="" exemption="" of="" certain="" tissues,="" including="" fluids,="" from="" any="" prohibitory="" rule.="" most="" commentors="" favored="" the="" exemption="" of="" one="" or="" more="" tissues,="" including="" milk="" products;="" blood="" products;="" skeletal="" muscle="" and="" gelatin;="" and="" a="" variety="" of="" other="" tissues="" including="" both="" protein="" and="" nonprotein="" materials.="" most="" of="" the="" comments="" cited="" published="" studies="" as="" well="" as="" positions="" taken="" by="" the="" european="" union,="" european="" commission,="" who="" and="" the="" government="" of="" france.="" the="" agency's="" comments="" on="" the="" status="" of="" milk,="" gelatin="" and="" blood="" follow.="" in="" addition,="" we="" discuss="" a="" comment="" on="" the="" use="" of="" canine="" and="" feline="" derived="" protein.="" [[page="" 572]]="" a.="" milk="" proteins="" data="" available="" to="" the="" agency="" suggests="" that="" milk="" proteins="" do="" not="" transmit="" the="" tse="" agent.="" research="" with="" oral="" exposure,="" intracerebral,="" and="" intraperitoneal="" administration="" of="" milk="" or="" mammary="" glands="" from="" bse-="" infected="" bovine="" to="" normal="" and="" bse-sensitive="" mice="" has="" not="" demonstrated="" the="" development="" of="" tse's="" (refs.="" 42="" and="" 52).="" an="" expert="" group="" under="" the="" auspices="" of="" who="" recommended="" that="" all="" countries="" prohibit="" the="" use="" of="" ruminant="" tissues="" in="" ruminant="" feed.="" the="" who="" expert="" group="" also="" declared="" that="" milk="" and="" milk="" products,="" including="" such="" products="" from="" the="" united="" kingdom,="" are="" safe="" for="" human="" consumption.="" in="" addition,="" oie="" has="" recommended,="" because="" of="" lack="" of="" infectivity,="" that="" restriction="" of="" import="" or="" transit="" of="" milk="" products="" from="" healthy="" animals="" from="" bse="" countries="" need="" not="" be="" instituted.="" therefore,="" the="" proposed="" rules="" provide="" that="" protein="" derived="" from="" ruminant="" tissues="" does="" not="" include="" milk="" proteins="" derived="" from="" bovine,="" ovine,="" caprine,="" and="" cervine.="" b.="" gelatin="" proteins="" data="" available="" to="" the="" agency="" suggest="" that="" gelatin="" does="" not="" transmit="" the="" tse="" agent.="" the="" who="" has="" concluded="" that="" gelatin="" in="" the="" food="" chain="" is="" considered="" to="" be="" safe,="" as="" the="" conventional="" manufacturing="" process="" for="" gelatin="" has="" been="" demonstrated="" to="" significantly="" inactivate="" any="" residual="" infective="" activity="" that="" may="" have="" been="" present="" in="" source="" tissues="" (ref.="" 2).="" fda="" concurs="" with="" this="" statement="" and="" the="" scientific="" information="" on="" which="" it="" is="" based.="" thus,="" the="" proposed="" rule="" excludes="" gelatin="" from="" protein="" derived="" from="" ruminant="" tissues.="" c.="" blood="" meal="" proteins="" data="" available="" to="" the="" agency="" suggests="" that="" bovine="" blood="" components="" do="" not="" transmit="" the="" tse="" agent="" (refs.="" 56,="" 78,="" and="" 94).="" therefore,="" the="" proposed="" rule="" does="" not="" include="" blood="" meal="" from="" bovine="" as="" a="" protein="" derived="" from="" ruminant="" tissues.="" d.="" canine="" and="" feline="" derived="" proteins="" one="" comment="" suggesting="" that="" canine-="" and="" feline-derived="" proteins="" should="" not="" be="" fed="" to="" ruminants="" because="" of="" the="" finding="" of="" fse="" in="" domestic="" cats="" in="" the="" united="" kingdom.="" the="" agency="" is="" also="" aware="" of="" an="" ethically-based="" objection="" by="" some="" to="" the="" rendering="" of="" the="" carcasses="" of="" pet="" animals.="" tse="" has="" not="" been="" diagnosed="" in="" dogs="" or="" other="" canines.="" fse="" has="" not="" been="" diagnosed="" in="" the="" united="" states.="" the="" agency="" has="" considered="" the="" information="" provided="" by="" the="" comments="" and="" the="" published="" scientific="" literature="" (refs.="" 26="" and="" 27),="" and="" has="" preliminarily="" determined="" that="" there="" is="" no="" measurable="" risk="" of="" the="" spread="" of="" tse's="" from="" canine-="" or="" feline-derived="" proteins="" to="" ruminants="" in="" the="" united="" states.="" however,="" the="" agency="" is="" inviting="" further="" comment="" on="" this="" issue.="" viii.="" environmental="" impact="" fda="" has="" carefully="" considered="" the="" potential="" environmental="" effects="" of="" this="" proposed="" rule="" and="" of="" five="" possible="" alternative="" actions.="" in="" doing="" so,="" the="" agency="" reviewed="" anprm="" comments="" submitted="" by="" a="" number="" of="" organizations="" and="" individuals.="" the="" comments="" were="" mostly="" concerned="" with="" the="" volume="" of="" material="" (e.g.,="" dead="" animals="" and="" slaughter="" byproducts)="" that="" would="" be="" affected,="" and="" the="" nonrendering="" or="" rendering="" alternative="" means="" by="" which="" these="" materials="" could="" be="" disposed="" of,="" or="" utilized,="" safely.="" comments="" suggested="" a="" number="" of="" uses="" for="" the="" processed="" materials,="" other="" than="" ruminant="" feed,="" including="" use="" in="" nonruminant="" animal="" feed="" and="" fertilizers,="" and="" disposal="" methods="" such="" as="" on-farm="" burial,="" landfilling,="" and="" incineration.="" in="" the="" environmental="" assessment="" that="" accompanies="" this="" proposed="" rule,="" fda="" evaluated="" the="" environmental="" consequences="" of="" six="" different="" options.="" these="" included:="" no="" action;="" ruminant="" and="" mink-to-ruminant="" prohibition="" (the="" proposed="" action);="" partial="" ruminant="" and="" mink-to-="" ruminant="" prohibition;="" mammalian-to-ruminant="" prohibition;="" prohibition="" of="" feeding="" tissues="" from="" any="" animal="" species="" in="" which="" tse="" has="" been="" detected="" in="" the="" united="" states;="" and="" sheep="" and="" goat="" specified="" offal="" prohibition.="" the="" environmental="" assessment="" considered="" each="" of="" the="" alternatives="" in="" the="" context="" of="" two="" scenarios.="" the="" first="" assumes="" that="" bse="" does="" not="" occur="" in="" the="" united="" states,="" regardless="" of="" the="" alternative="" selected.="" the="" second="" scenario="" assumes="" that="" bse="" does="" occur="" in="" the="" united="" states,="" again="" regardless="" of="" the="" alternative="" selected.="" in="" the="" first="" scenario,="" the="" assessment="" considered="" environmental="" impacts="" related="" to="" on-farm="" disposal,="" landfill,="" incineration,="" and="" industry="" wastes="" produced.="" the="" second="" scenario="" considered="" environmental="" impacts="" related="" to="" production="" losses="" and="" impacts,="" wildlife="" exposure,="" on-farm="" disposal,="" landfill,="" and="" incineration.="" in="" the="" first="" scenario="" (no="" bse),="" the="" ``no="" action''="" alternative="" does="" not="" have="" environmental="" consequences="" because="" it="" is="" the="" ``status="" quo''="" or="" baseline="" alternative.="" environmental="" impacts="" for="" the="" other="" alternatives="" ranged="" from="" slight="" to="" moderate="" increases="" in="" environmental="" effects.="" for="" the="" proposed="" option="" (ruminant-to-ruminant)="" there="" would="" be="" moderate="" increases="" in="" environmental="" effects="" from="" on-farm="" disposal="" and="" landfill="" use,="" and="" slight="" increases="" in="" the="" other="" effects.="" increases="" in="" waste="" disposal="" (on-farm,="" landfill,="" etc.)="" are="" anticipated="" to="" be="" temporary,="" however,="" as="" the="" markets="" are="" expected="" to="" adjust="" quickly="" to="" the="" more="" restricted="" uses="" of="" the="" ruminant="" materials.="" in="" the="" second="" scenario="" (occurrence="" of="" bse),="" the="" greatest="" negative="" environmental="" effect="" would="" occur="" in="" the="" case="" of="" the="" ``no="" action''="" alternative.="" this="" is="" because="" the="" likely="" spread="" of="" the="" bse="" agent="" through="" animal="" feed="" before="" the="" first="" bse="" case="" is="" diagnosed="" would="" result="" in="" disposal="" of="" large="" numbers="" of="" animals="" by="" means="" other="" than="" rendering.="" similar="" large="" impacts="" would="" occur="" with="" the="" sheep="" and="" goat,="" and="" tse="" animal,="" options.="" minimum="" environmental="" consequences="" would="" occur="" with="" the="" proposed="" option="" (ruminant-to-ruminant),="" because="" the="" spread="" of="" the="" bse="" agent="" would="" have="" been="" controlled.="" minimum="" to="" small="" effects="" would="" result="" from="" the="" remaining="" two="" options,="" partial="" ruminant="" prohibition="" and="" mammalian-to-ruminant="" prohibition.="" the="" agency="" has="" concluded="" that="" the="" proposed="" rule="" will="" not="" have="" a="" significant="" impact="" on="" the="" human="" environment,="" and="" that="" an="" environmental="" impact="" statement="" is="" not="" required.="" fda's="" finding="" of="" no="" significant="" impact="" (fonsi)="" and="" the="" evidence="" supporting="" that="" finding,="" contained="" in="" an="" environmental="" assessment="" (ea)="" prepared="" under="" 21="" cfr="" 25.31,="" may="" be="" seen="" in="" the="" dockets="" management="" branch="" (address="" above)="" between="" 9="" a.m.="" and="" 4="" p.m.,="" monday="" through="" friday.="" fda="" invites="" comments="" and="" submission="" of="" data="" concerning="" the="" ea="" and="" fonsi.="" ix.="" analysis="" of="" impacts="" fda="" has="" examined="" the="" impacts="" of="" the="" proposed="" rule="" under="" executive="" order="" 12866,="" under="" the="" regulatory="" flexibility="" act="" (5="" u.s.c.="" 601-612),="" and="" under="" the="" unfunded="" mandates="" reform="" act="" (pub.="" l.="" 104-4).="" executive="" order="" 12866="" directs="" agencies="" to="" assess="" all="" costs="" and="" benefits="" of="" available="" regulatory="" alternatives="" and,="" when="" regulation="" is="" necessary,="" to="" select="" regulatory="" approaches="" that="" maximize="" net="" benefits="" (including="" potential="" economic,="" environmental,="" public="" health="" and="" safety,="" and="" other="" advantages;="" and="" distributive="" impacts="" and="" equity).="" the="" regulatory="" flexibility="" act="" requires="" agencies="" to="" analyze="" regulatory="" options="" that="" would="" minimize="" any="" significant="" impact="" of="" a="" rule="" on="" small="" entities.="" the="" unfunded="" mandates="" reform="" act="" requires="" that="" agencies="" prepare="" an="" assessment="" of="" anticipated="" costs="" and="" benefits="" before="" proposing="" any="" rule="" that="" may="" result="" in="" an="" annual="" expenditure="" by="" state,="" local,="" and="" tribal="" governments,="" in="" the="" aggregate,="" or="" by="" the="" private="" sector,="" of="" $100,000,000="" (adjusted="" annually="" for="" inflation).="" fda="" [[page="" 573]]="" concludes="" that="" this="" proposed="" rule="" is="" consistent="" with="" the="" principles="" set="" forth="" in="" the="" executive="" order="" and="" in="" these="" two="" statutes.="" a="" study="" of="" the="" impacts="" on="" industry="" of="" the="" proposed="" rule="" (on="" file="" with="" the="" docket="" management="" branch="" (ref.="" 114))="" conducted="" for="" fda="" by="" the="" eastern="" research="" group="" (erg),="" a="" private="" consulting="" firm,="" and="" the="" discussion="" in="" the="" remainder="" of="" this="" section,="" demonstrate="" that="" the="" proposed="" rule="" constitutes="" an="" economically="" significant="" rule="" as="" described="" in="" the="" executive="" order.="" the="" agency="" has="" further="" determined="" that="" the="" proposed="" rule="" will="" have="" a="" significant="" impact="" on="" a="" substantial="" number="" of="" small="" entities.="" the="" proposal="" makes="" no="" mandates="" on="" government="" entities="" and="" is="" estimated="" to="" result="" in="" aggregate="" net="" annual="" costs="" ranging="" from="" $21.4="" to="" $48.2="" million="" to="" the="" private="" sector.="" a.="" the="" need="" for="" regulation="" although="" bse="" has="" not="" been="" diagnosed="" in="" the="" united="" states,="" the="" need="" for="" regulatory="" action="" is="" based="" on="" a="" need="" to="" protect="" u.s.="" livestock="" from="" the="" risk="" of="" contracting="" bse.="" in="" its="" guidelines="" for="" the="" preparation="" of="" economic="" impact="" analyses,="" the="" office="" of="" management="" and="" budget="" (omb)="" directs="" federal="" regulatory="" agencies="" to="" determine="" whether="" a="" market="" failure="" exists,="" and="" if="" so,="" whether="" that="" market="" failure="" could="" be="" resolved="" by="" measures="" other="" than="" new="" federal="" regulation.="" in="" this="" instance,="" private="" incentive="" systems="" for="" both="" suppliers="" and="" purchasers="" may="" fail="" in="" markets="" for="" cattle,="" rendering,="" and="" ruminant="" feed.="" the="" potential="" for="" market="" failure="" among="" the="" suppliers="" in="" these="" sectors="" results="" from="" the="" externality="" that="" could="" be="" created="" by="" individual="" suppliers="" imposing="" economic="" hardships="" on="" other="" suppliers="" within="" the="" industry.="" the="" potential="" for="" market="" failure="" among="" the="" purchasers="" results="" from="" the="" inadequate="" information="" that="" would="" be="" available="" to="" purchasers="" of="" potentially="" infective="" products.="" any="" renderer,="" feed="" manufacturer,="" or="" cattle="" producer="" that="" permits="" animal="" protein="" derived="" from="" ruminants="" and="" mink="" to="" be="" placed="" in="" ruminant="" feed="" increases="" the="" risk="" that="" other="" renderers,="" feed="" manufacturers,="" or="" cattle="" producers="" will="" suffer="" the="" severe="" economic="" consequences="" that="" would="" follow="" an="" outbreak="" of="" bse="" in="" the="" united="" states.="" the="" industry="" is="" aware="" of="" this="" risk,="" as="" evidenced="" by="" the="" existence="" of="" voluntary="" programs="" aimed="" at="" reducing="" the="" transmission="" of="" the="" infectious="" agent.="" these="" include="" an="" adult="" sheep="" rendering="" ban="" recommended="" by="" the="" nra,="" a="" recommended="" ban="" on="" the="" feeding="" of="" rendered="" ruminant="" protein="" to="" ruminants="" by="" the="" ncba="" and="" others,="" and="" scrapie-free="" certification="" programs="" by="" individual="" sheep="" producers.="" although="" the="" benefits="" of="" such="" programs--the="" reduction="" or="" elimination="" of="" the="" risk="" of="" an="" outbreak="" of="" bse="" and="" the="" increased="" consumer="" confidence="" in="" the="" safety="" of="" the="" industries'="" products--accrue="" to="" all="" members="" of="" these="" industries,="" compliance="" with="" these="" measures="" is="" incomplete,="" because="" individual="" noncomplying="" members="" can="" avoid="" the="" costs="" of="" risk="" reduction="" measures="" while="" still="" enjoying="" the="" benefits="" of="" compliance="" by="" others="" in="" the="" industry.="" if="" purchasers="" could="" easily="" identify="" the="" risks="" of="" infective="" agent="" contamination="" associated="" with="" products="" from="" specific="" suppliers,="" they="" could="" more="" easily="" take="" defensive="" actions="" to="" reduce="" these="" risks="" (e.g.,="" refusing="" products="" from="" cattle="" known="" to="" have="" consumed="" specified="" ruminant="" proteins).="" purchasers="" are="" unlikely="" to="" obtain="" the="" information="" they="" need,="" however,="" for="" several="" reasons.="" first,="" the="" long="" incubation="" period="" for="" bse="" creates="" a="" lag="" between="" the="" actual="" onset="" and="" the="" recognition="" of="" the="" disease="" and="" could="" lead="" to="" a="" suboptimal="" level="" of="" risk="" prevention="" by="" the="" concerned="" parties="" during="" the="" incubation="" period.="" by="" the="" time="" the="" first="" signs="" of="" disease="" are="" observed,="" many="" animals="" may="" have="" been="" already="" exposed.="" moreover,="" renderers="" sell="" their="" product="" to="" feed="" manufacturers="" who="" frequently="" combine="" proteins="" from="" many="" different="" plant="" sources="" and="" animal="" species="" to="" produce="" cattle="" feed.="" ruminant="" producers,="" therefore,="" have="" no="" sure="" way="" of="" knowing="" whether="" a="" particular="" batch="" of="" feed="" is="" free="" from="" potentially="" infective="" proteins="" and="" cannot="" easily="" avoid="" purchasing="" risky="" feed.="" finally,="" if="" renderers="" or="" feed="" manufacturers="" do="" not="" believe="" that="" bse="" is="" an="" important="" threat="" they="" may="" choose="" not="" to="" take="" preventive="" action,="" regardless="" of="" the="" risk="" levels="" perceived="" by="" epidemiological="" experts="" or="" consumers.="" b.="" benefits="" the="" proposed="" rule="" would="" reduce="" the="" risk="" of="" an="" outbreak="" and="" subsequent="" proliferation="" of="" bse="" disease="" in="" the="" united="" states.="" it="" may="" also="" forestall="" the="" loss="" of="" consumer="" confidence="" in="" the="" u.s.="" beef="" market="" due="" to="" concerns="" about="" bse="" and="" its="" implications.="" thus,="" the="" benefits="" of="" this="" proposal="" would="" include="" the="" value="" of="" reduced="" risks="" to="" human="" and="" animal="" health="" and="" to="" the="" economic="" stability="" of="" the="" u.s.="" livestock="" and="" livestock="" dependent="" industries="" compared="" to="" the="" ``no="" action''="" option.="" in="" technical="" terms,="" these="" benefits="" measure="" the="" expected="" value="" of="" the="" future="" disease-related="" costs="" that="" might="" be="" averted="" by="" the="" proposed="" rule.="" specifically,="" they="" are="" calculated="" as="" a="" product="" of="" three="" factors:="" (1)="" the="" probability="" that,="" in="" the="" absence="" of="" this="" rule,="" bse="" would="" be="" introduced="" and="" proliferate="" in="" the="" united="" states,="" (2)="" the="" costs,="" both="" direct="" and="" indirect,="" that="" would="" be="" associated="" with="" the="" spread="" of="" bse="" in="" the="" united="" states,="" and="" (3)="" the="" extent="" to="" which="" the="" proposed="" rule="" would="" reduce="" the="" likelihood="" of="" bse="" proliferation.="" bse="" has="" not="" been="" detected="" in="" the="" united="" states="" and="" the="" probability="" that="" it="" currently="" exists="" is="" remote.="" nevertheless,="" it="" is="" possible="" that="" bse="" could="" develop="" in="" the="" future.="" once="" developed,="" bse="" could="" remain="" undetected="" for="" several="" years="" because="" of="" its="" long="" incubation="" period="" and="" because,="" at="" present,="" it="" can="" be="" diagnosed="" reliably="" only="" by="" microscopic="" brain="" examination="" after="" death.="" during="" the="" period="" between="" introduction="" and="" diagnosis,="" the="" disease="" could="" spread="" as="" it="" apparently="" did="" in="" the="" u.k.="" via="" intake="" of="" infective="" feed.="" if="" regulation="" was="" delayed="" until="" after="" discovery,="" the="" costs="" would="" be="" substantial.="" by="" addressing="" the="" central="" risk="" factors="" associated="" with="" bse,="" fda="" believes="" that="" the="" proposed="" rule="" would="" eliminate="" the="" vast="" majority="" of="" the="" bse-related="" risks="" and="" costs.="" bse="" was="" first="" detected="" in="" the="" u.k.="" in="" november="" 1986,="" and="" a="" ban="" on="" ruminant="" offal="" in="" ruminant="" feed="" was="" imposed="" in="" the="" u.k.="" in="" july="" 1988="" (ref.="" 115).="" an="" analysis="" of="" cattle="" born="" before="" and="" after="" the="" feed="" ban="" went="" into="" effect="" suggests="" that="" the="" feed="" ban="" significantly="" decreased="" disease="" transmission="" (ref.="" 116).="" this="" analysis="" found="" that="" the="" incidence="" of="" confirmed="" bse="" roughly="" doubled="" each="" year="" for="" animals="" born="" between="" july="" 1985="" and="" july="" 1988,="" but="" declined="" precipitously="" in="" animals="" born="" in="" august="" 1988="" compared="" to="" the="" previous="" year="" and="" continued="" to="" fall="" thereafter.="" because="" bse="" has="" a="" long="" incubation="" period,="" however,="" a="" decrease="" in="" the="" incidence="" was="" not="" evident="" until="" several="" years="" after="" the="" initial="" feed="" ban="" was="" implemented.="" the="" incidence="" of="" bse="" peaked="" in="" 1992="" at="" 36,681="" detected="" cases,="" or="" approximately="" 0.3="" percent="" of="" the="" uk's="" 11.5="" million="" cattle.="" despite="" a="" sharp="" decrease="" in="" the="" incidence="" rate="" since="" then,="" by="" the="" end="" of="" 1996,="" more="" than="" 165,000="" cases="" of="" bse="" will="" have="" been="" detected,="" with="" one-third="" of="" all="" u.k.="" cattle="" herds="" infected="" (refs.="" 115="" and="" 117).="" the="" likelihood="" that="" bse="" will="" someday="" be="" developed="" in="" the="" united="" states="" cannot="" be="" estimated="" with="" any="" confidence,="" although="" u.s.="" risk="" factors="" are="" believed="" to="" be="" significantly="" smaller="" than="" existed="" in="" the="" united="" kingdom="" of="" the="" early="" 1980's.="" as="" described="" previously,="" the="" various="" remaining="" modes="" include="" transmission="" from="" scrapie-infected="" sheep="" or="" other="" animals="" with="" tse,="" e.g.,="" through="" meat="" and="" bone="" meal;="" introduction="" via="" imported="" [[page="" 574]]="" animals;="" and="" spontaneous="" introduction="" (which="" in="" some="" tse's="" has="" been="" hypothesized="" to="" occur="" at="" a="" rate="" of="" about="" 1="" case="" per="" million="" per="" year).="" usda="" import="" controls="" and="" the="" voluntary="" bans="" on="" sheep="" offal="" and="" ruminant="" tissues="" in="" ruminant="" foods="" reduce="" the="" risk="" of="" disease="" introduction="" but="" cannot="" completely="" eliminate="" it.="" although="" fda="" cannot="" quantitatively="" estimate="" the="" risk="" of="" a="" significant="" bse="" outbreak="" in="" the="" united="" states,="" the="" agency="" has="" used="" the="" u.k.="" experience,="" modified="" to="" account="" for="" major="" differences="" in="" circumstances,="" to="" assess="" the="" consequences="" of="" the="" potential="" spread="" of="" the="" disease="" within="" the="" united="" states.="" if="" bse="" were="" introduced="" in="" this="" country,="" the="" pattern="" of="" disease="" spread="" would="" presumably="" be="" similar="" to="" that="" in="" the="" united="" kingdom,="" with="" most="" symptomatic="" disease="" appearing="" in="" older="" cattle="" (the="" average="" time="" for="" bse="" symptoms="" is="" approximately="" 5="" years="" after="" infection="" (ref.="" 115)).="" the="" rate="" of="" spread="" of="" symptomatic="" disease="" would="" probably="" differ,="" however,="" because="" compared="" with="" the="" pre-="" bse="" u.k.="" dairy="" industry,="" u.s.="" dairy="" cows="" are="" younger="" and="" are="" exposed="" to="" meat="" and="" bone="" meal="" in="" feed="" later="" in="" life="" than="" was="" true="" in="" the="" united="" kingdom="" (ref.="" 118).="" united="" kingdom="" dairy="" animals="" were="" historically="" fed="" meat="" and="" bone="" meal="" as="" calves,="" whereas="" u.s.="" dairy="" cows="" ingest="" meat="" and="" bone="" meal="" primarily="" as="" adults.="" 1.="" methodology="" to="" develop="" an="" illustrative="" estimate="" of="" the="" number="" of="" cattle="" that="" might="" be="" lost="" to="" bse="" infection="" if="" the="" disease="" were="" to="" occur="" in="" the="" united="" states="" in="" the="" absence="" of="" regulation,="" fda="" extrapolated="" from="" the="" experience="" in="" the="" united="" kingdom,="" but="" adjusted="" for="" the="" differences="" in="" cattle="" age="" and="" potential="" age="" of="" exposure="" to="" meat="" and="" bone="" meal.="" this="" extrapolation="" assumes="" that="" the="" detection="" of="" bse="" in="" this="" country="" would="" quickly="" lead="" to="" a="" ruminant-to-ruminant="" feed="" prohibition="" but="" that,="" as="" in="" the="" united="" kingdom,="" bse="" incidence="" would="" nonetheless="" continue="" to="" increase="" for="" 6="" years="" due="" to="" the="" disease's="" long="" incubation="" time="" (hence="" several="" years="" of="" disease="" spread="" before="" the="" diagnosis="" of="" the="" first="" case).="" to="" account="" for="" the="" difference="" in="" cattle="" age-related="" risk="" factors,="" fda="" assumed="" that,="" if="" bse="" occurred="" in="" the="" united="" states,="" the="" affected="" animals="" would="" be="" predominately="" dairy="" cows="" of="" age="" 4="" or="" more,="" rather="" than="" age="" 3="" and="" up="" as="" in="" the="" u.k.="" (due="" to="" the="" differences="" in="" age="" of="" exposure.)="" the="" difference="" of="" 1="" year="" is="" based="" on="" the="" agency's="" estimate="" that="" u.s.="" cattle="" are="" first="" exposed="" to="" meat="" and="" bone="" meal="" 1="" year="" later="" than="" u.k.="" cattle.="" therefore,="" the="" onset="" of="" the="" clinical="" disease="" is="" estimated="" to="" start="" 1="" year="" later.="" accordingly,="" only="" 47="" percent="" of="" u.s.="" dairy="" cows="" are="" age="" 4="" and="" up="" (about="" 4.8="" million="" cows),="" while="" 90="" percent="" of="" united="" kingdom="" cows="" are="" age="" 3="" and="" up="" (about="" 2.6="" million="" cows).="" thus,="" a="" lower="" percentage="" of="" u.s.="" cattle="" were="" assumed="" to="" be="" at="" risk="" of="" symptomatic="" bse,="" and="" the="" projected="" rate="" of="" death="" was="" proportionately="" lower.="" based="" on="" the="" relative="" size="" of="" the="" u.s.="" and="" u.k.="" dairy="" cattle="" populations,="" these="" projections="" suggest="" that="" if="" bse="" were="" introduced="" in="" the="" united="" states="" and="" spread="" in="" a="" similar="" manner,="" the="" disease="" would="" destroy="" 299,000="" u.s.="" cattle="" over="" 11="" years="" (4.8="" x="" 2.6="" x="" 162,000="" u.k.="" bse="" deaths).="" (these="" calculations="" assume="" that="" a="" feed="" prohibition="" would="" be="" implemented="" very="" soon="" after="" the="" first="" case="" is="" diagnosed,="" and="" that="" the="" prohibition="" would="" immediately="" begin="" to="" affect="" the="" underlying="" rate="" of="" new="" infection.="" if="" a="" feed="" prohibition="" were="" not="" implemented="" at="" that="" time,="" the="" number="" of="" cattle="" deaths="" would="" be="" much="" higher.)="" other="" adjustments="" could="" be="" made="" to="" this="" estimate,="" but="" their="" effect="" on="" the="" direction="" of="" the="" results="" would="" be="" uncertain.="" for="" example,="" compared="" with="" u.k.="" practices="" before="" 1988,="" u.s.="" dairy="" cattle="" consume="" a="" higher="" proportion="" of="" concentrated="" feed="" that="" contains="" meat="" and="" bone="" meal.="" on="" the="" other="" hand,="" most="" u.s.="" concentrate="" contains="" a="" lower="" percentage="" of="" meat="" and="" bone="" meal="" (and="" a="" higher="" percentage="" of="" vegetable-="" based="" proteins).="" if="" bse="" infectivity="" in="" feed="" is="" highly="" dose-dependent,="" these="" factors="" could="" cause="" fda's="" cost="" estimate="" to="" be="" either="" too="" high="" or="" too="" low,="" if="" one="" of="" the="" factors="" is="" dominant="" over="" the="" other.="" the="" risks="" and="" costs="" associated="" with="" bse="" when="" it="" occurs="" are="" primarily="" of="" three="" types.="" first,="" there="" is="" the="" possible="" risk="" and="" associated="" cost="" of="" ruminant-to-human="" transmission="" of="" tse="" disease.="" the="" proposed="" rule="" would="" reduce="" this="" risk="" by="" eliminating="" the="" main="" routes="" by="" which="" ruminants="" might="" acquire="" transmissible="" tse,="" greatly="" reducing="" any="" risk="" incurred="" by="" the="" human="" consumption="" of="" ruminant-derived="" products.="" thus,="" the="" proposed="" rule="" would="" reduce="" the="" risk="" of="" future="" mortality,="" morbidity,="" and="" health="" care="" costs="" due="" to="" human="" tse.="" second,="" there="" is="" the="" risk="" of="" livestock="" losses.="" these="" losses="" include="" not="" only="" the="" deaths="" of="" bse-infected="" animals,="" but="" also="" the="" loss="" and="" disposal="" costs="" of="" other="" animals="" that="" would="" be="" destroyed,="" either="" to="" contain="" the="" immediate="" spread="" of="" disease="" or="" to="" restore="" consumer="" confidence="" in="" the="" safety="" of="" beef="" and="" dairy="" products.="" third,="" there="" are="" the="" costs="" associated="" with="" decreased="" domestic="" sales="" and="" exports="" of="" beef="" and="" other="" bovine-derived="" products="" until="" consumer="" and="" international="" confidence="" could="" be="" restored.="" 2.="" reduced="" risk="" to="" public="" health="" as="" discussed="" earlier,="" scientists="" believe="" that="" the="" nv-cjd="" cases="" identified="" in="" the="" u.k.="" may="" have="" been="" associated="" with="" the="" bse="" epidemic.="" if="" indeed="" there="" were="" such="" an="" association,="" and="" if="" bse="" were="" to="" occur="" in="" this="" country,="" there="" would="" be="" a="" risk="" of="" spreading="" bse-related="" human="" tse="" in="" the="" united="" states="" the="" proposed="" rule="" therefore="" might="" avert="" human="" deaths="" in="" the="" united="" states,="" although="" the="" number="" of="" deaths="" cannot="" be="" estimated.="" the="" proposed="" rule="" would="" also="" save="" the="" health="" care="" and="" other="" costs="" associated="" with="" treating="" individuals="" with="" the="" disease.="" 3.="" reduced="" risk="" of="" direct="" livestock="" losses="" for="" estimating="" the="" present="" value="" of="" livestock="" losses="" if="" bse="" occurred="" in="" the="" united="" states,="" fda="" assumed="" that="" the="" first="" case="" of="" bse="" would="" not="" be="" detected--even="" in="" the="" absence="" of="" the="" proposed="" rule--for="" 4="" years.="" based="" on="" an="" estimated="" value="" of="" $502="" per="" animal="" (ref.="" 119)="" and="" disposal="" costs="" of="" $4="" per="" animal,="" direct="" losses="" from="" the="" death="" of="" 299,000="" bse-infected="" cattle="" would="" reach="" $151="" million="" over="" 11="" years="" (starting="" 4="" years="" from="" now).="" at="" a="" discount="" rate="" of="" 7="" percent,="" the="" total="" present="" value="" of="" these="" losses="" is="" $75="" million.="" in="" addition="" to="" the="" animal="" losses="" from="" direct="" infection,="" a="" significant="" outbreak="" would="" probably="" lead="" to="" the="" eradication="" of="" high-="" risk="" animals="" to="" restore="" consumer="" confidence.="" switzerland,="" for="" example,="" has="" proposed="" slaughtering="" all="" cattle="" born="" before="" that="" country="" implemented="" a="" feed="" ban,="" or="" approximately="" one-eighth="" of="" its="" national="" herd="" (ref.="" 120).="" the="" united="" kingdom="" has="" begun="" a="" program="" to="" destroy="" and="" incinerate="" all="" animals="" over="" age="" 30="" months="" as="" they="" reach="" the="" end="" of="" their="" useful="" life,="" or="" about="" 1="" million="" animals="" in="" 1996="" and="" a="" total="" of="" 4.7="" million="" over="" 6="" years.="" in="" addition,="" the="" united="" kingdom="" has="" a="" program="" to="" slaughter="" some="" unmarketable="" male="" dairy="" calves="" (126,000="" had="" been="" slaughtered="" as="" of="" august="" 1996)="" and="" up="" to="" 147,000="" additional="" ``high-="" risk''="" animals="" (refs.="" 115="" and="" 121).="" even="" if="" the="" u.k.="" eradication="" of="" animals="" were="" limited="" to="" a="" one-time="" total="" of="" 1="" million="" cattle="" (about="" 8.7="" percent="" of="" their="" cattle="" stock),="" similar="" measures="" in="" the="" united="" states,="" if="" they="" occurred="" immediately="" upon="" detection="" of="" the="" disease,="" would="" result="" in="" the="" one-time="" destruction="" of="" $4.58="" billion="" worth="" of="" cattle,="" with="" a="" present="" value="" of="" $3.49="" billion.="" 4.="" costs="" of="" future="" regulation="" moreover,="" the="" ability="" to="" control="" a="" bse="" outbreak="" once="" it="" occurred="" would="" require="" putting="" in="" place="" restrictions="" on="" the="" use="" [[page="" 575]]="" of="" ruminant="" proteins="" in="" ruminant="" feeds="" that="" would="" be="" at="" least="" as="" restrictive="" as="" the="" measure="" under="" this="" proposed="" rule.="" presumably,="" the="" total="" costs="" of="" implementing="" a="" ruminant-to-ruminant="" feed="" prohibition="" at="" that="" point="" would="" be="" at="" least="" as="" great="" as="" the="" low="" estimates="" for="" this="" proposed="" rule,="" or="" $21.4="" million="" per="" year.="" the="" present="" value="" of="" these="" future="" regulatory="" costs="" would="" total="" approximately="" $240="" million.="" moreover,="" this="" estimate="" may="" vastly="" understate="" the="" economic="" impact="" because="" the="" market="" value="" of="" ruminant-derived="" proteins="" could="" disappear="" if="" there="" were="" an="" actual="" outbreak.="" 5.="" reduced="" risk="" of="" losses="" in="" domestic="" sales="" and="" exports="" if="" bse="" were="" to="" emerge="" in="" the="" united="" states,="" the="" news="" could="" greatly="" reduce="" both="" domestic="" sales="" and="" exports="" of="" bovine="" products.="" in="" the="" united="" kingdom,="" domestic="" consumption="" fell="" by="" more="" than="" 20="" percent="" between="" 1988="" and="" 1990="" and="" has="" not="" yet="" fully="" recovered="" (ref.="" 122),="" presumably="" due="" to="" continuing="" concerns="" about="" possible="" links="" between="" bse="" and="" cjd.="" if="" u.s.="" consumers="" acted="" similarly,="" u.s.="" producers="" of="" beef="" products="" could="" lose="" over="" $9="" billion="" in="" annual="" sales="" (ref.="" 123).="" alternatively,="" u.s.="" consumers="" might="" demonstrate="" considerably="" less="" concern,="" as="" the="" u.k.="" experience="" may="" have="" improved="" the="" ability="" of="" u.s.="" risk="" managers="" to="" communicate="" both="" the="" extent="" of="" the="" risk="" of="" contracting="" cjd="" from="" the="" consumption="" of="" beef="" and="" the="" responsiveness="" of="" the="" government's="" safety="" policies.="" nonetheless,="" it="" remains="" probable="" that="" the="" uncertainty="" surrounding="" a="" serious="" bse="" outbreak="" would="" lead="" u.s.="" consumers="" to="" reduce="" their="" consumption="" and="" spending="" on="" beef="" by="" a="" significant="" amount.="" also,="" at="" the="" same="" time="" that="" u.k.="" domestic="" sales="" of="" beef="" were="" declining="" due="" to="" the="" fear="" of="" bse,="" the="" volume="" of="" u.k.="" exported="" beef="" fell="" by="" nearly="" 16="" percent="" (ref.="" 122).="" based="" on="" u.s.="" beef="" exports="" in="" 1994="" of="" approximately="" $2.2="" billion="" (ref.="" 109),="" a="" proportional="" decline="" of="" this="" magnitude="" would="" reduce="" u.s.="" exports="" by="" up="" to="" $0.3="" billion="" per="" year.="" while="" the="" values="" of="" such="" lost="" domestic="" and="" international="" sales="" would="" reduce="" the="" profits="" of="" the="" u.s.="" beef="" industry="" and="" the="" enjoyment="" of="" some="" u.s.="" consumers="" of="" beef,="" they="" do="" not="" provide="" an="" accurate="" measure="" of="" societal="" costs,="" because="" competitor="" industries,="" such="" as="" poultry,="" pork,="" and="" seafood,="" would="" gain="" new="" profits.="" thus,="" the="" net="" costs="" that="" would="" result="" from="" such="" potential="" shifts="" in="" consumer="" spending="" cannot="" be="" precisely="" discerned="" without="" extensive="" economic="" modeling.="" while="" fda="" examined="" a="" partial="" equilibrium="" model="" for="" projecting="" the="" approximate="" losses="" of="" consumer="" and="" producer="" surplus="" within="" the="" market="" for="" beef="" products,="" the="" agency="" could="" not="" adequately="" quantify="" the="" likely="" effects="" on="" the="" markets="" for="" substitutes="" of="" beef.="" consequently,="" fda="" could="" not="" estimate="" the="" net="" economic="" cost="" of="" these="" lost="" sales.="" nevertheless,="" the="" magnitude="" of="" these="" potential="" costs="" could="" be="" substantial="" and="" the="" agency="" requests="" public="" comment="" on="" how="" the="" appropriate="" measurement="" methodologies="" could="" be="" developed="" and="" applied.="" finally,="" even="" in="" the="" absence="" of="" evidence="" of="" bse="" in="" the="" united="" states,="" consumer="" concern="" about="" bse="" could="" affect="" beef="" consumption="" and="" expenditures.="" thus,="" one="" benefit="" of="" implementing="" the="" proposed="" rule="" now="" is="" that="" it="" might="" prevent="" a="" loss="" of="" consumer="" confidence="" in="" the="" beef="" market,="" irrespective="" of="" the="" actual="" risk="" of="" bse.="" fda="" did="" not="" attempt="" to="" quantify="" this="" potential="" loss,="" but="" believes="" that="" it="" also="" may="" be="" substantial,="" particularly="" in="" light="" of="" the="" recent="" increased="" u.s.="" publicity="" of="" bse="" and="" its="" hypothesized="" links="" to="" cjd.="" 6.="" total="" losses="" averted="" in="" summary,="" the="" losses="" averted="" by="" the="" proposed="" rule="" include="" the="" expected="" value="" of="" the="" costs="" associated="" with="" bse="" itself,="" and="" the="" potential="" value="" of="" forestalling="" a="" drop="" in="" domestic="" and="" international="" demand="" for="" u.s.="" beef="" due="" to="" bse-related="" causes.="" the="" first="" component="" largely="" reflects="" the="" statistical="" probability="" that="" bse="" could="" occur="" and="" spread="" within="" the="" united="" states="" and="" the="" potential="" $3.7="" billion="" cost="" of="" destroying="" bse-exposed="" livestock.="" the="" second="" primarily="" measures="" the="" expected="" loss="" to="" u.s.="" consumers="" and="" producers="" that="" would="" result="" from="" reduced="" sales.="" while="" fda="" has="" not="" quantified="" these="" latter="" costs,="" plausible="" scenarios="" indicate="" that="" they="" could="" reach="" billions="" of="" dollars.="" moreover,="" these="" figures="" have="" not="" included="" the="" possibility="" of="" lost="" lives="" and="" treatment="" costs="" associated="" with="" treating="" human="" tse.="" finally,="" the="" expected="" benefits="" of="" the="" proposed="" rule="" are="" slightly="" lower="" than="" the="" sum="" of="" the="" expected="" value="" of="" all="" the="" costs="" associated="" with="" bse,="" because="" the="" rule="" would="" not="" totally="" eliminate="" all="" of="" the="" related="" risk="" (e.g.,="" due="" to="" the="" possibility="" of="" spontaneous="" introduction="" of="" disease="" and="" the="" possible="" incomplete="" compliance="" with="" the="" rule).="" fda="" believes,="" however,="" that="" any="" remaining="" risk="" would="" be="" extremely="" small.="" in="" addition,="" because="" the="" rate="" of="" bse="" infection="" and="" the="" associated="" costs="" would="" probably="" vary="" geographically="" (as="" scrapie="" does="" now)="" (ref.="" 98)="" ,="" the="" benefits="" would="" vary="" across="" regions="" of="" the="" country.="" 7.="" comparison="" of="" alternatives="" as="" described="" elsewhere="" in="" this="" document,="" fda="" is="" considering="" five="" alternatives="" to="" the="" proposed="" rule,="" in="" addition="" to="" other="" options="" that="" might="" be="" offered="" in="" the="" comments.="" the="" first="" three="" of="" these="" alternatives="" are:="" (1)="" no="" action="" (relying="" on="" voluntary="" industry="" activities),="" (2)="" prohibit="" only="" materials="" from="" u.s.="" species="" in="" which="" tse="" has="" been="" diagnosed,="" and="" (3)="" a="" prohibition="" on="" proteins="" from="" specified="" sheep="" and="" goat="" offal="" in="" ruminant="" feed.="" compared="" with="" the="" proposed="" action,="" prohibiting="" proteins="" from="" all="" u.s.="" tse="" species="" provides="" similar="" reductions="" in="" the="" risk="" that="" bse="" might="" be="" introduced,="" with="" a="" sheep/goat="" specified="" offal="" protein="" ban="" and="" no="" action="" providing="" progressively="" less="" risk="" reduction.="" the="" tse="" species="" alternative,="" however,="" would="" be="" significantly="" less="" effective="" in="" limiting="" the="" spread="" of="" bse="" (e.g.,="" after="" spontaneous="" introduction)="" until="" bse="" was="" diagnosed="" and="" cattle="" were="" added="" to="" the="" list="" of="" tse="" species.="" likewise,="" the="" two="" other="" alternatives="" would="" be="" significantly="" less="" effective="" in="" inhibiting="" the="" spread="" of="" ruminant-="" to-ruminant="" transmission="" of="" disease="" once="" bse="" is="" introduced.="" thus,="" the="" expected="" value="" of="" the="" benefits="" of="" each="" of="" the="" three="" rejected="" options="" is="" substantially="" lower="" than="" the="" proposed="" rule,="" although="" the="" amount="" of="" difference="" cannot="" be="" estimated="" precisely.="" the="" agency="" is="" also="" considering="" two="" other="" alternatives:="" (1)="" a="" mammalian-protein-to-ruminant="" prohibition,="" and="" (2)="" a="" partial="" ruminant-="" to-ruminant="" prohibition="" which="" would="" exclude="" all="" ruminant="" and="" mink="" tissues="" except="" certain="" bovine="" tissues.="" compared="" with="" the="" proposed="" rule,="" both="" alternatives="" offer="" similar="" benefits="" in="" substantially="" inhibiting="" the="" initial="" introduction="" of="" bse.="" the="" extent="" of="" inhibition="" of="" the="" spread="" of="" disease="" (and="" associated="" costs),="" however,="" would="" be="" different.="" the="" mammalian="" protein="" alternative="" would="" further="" reduce="" the="" spread="" of="" disease="" compared="" with="" the="" proposed="" rule,="" by="" reducing="" the="" risk="" of="" cross-contamination="" within="" rendering="" and="" processing="" plants.="" thus,="" this="" alternative="" would="" bring="" the="" expected="" value="" of="" the="" bse-related="" costs="" even="" closer="" to="" zero="" than="" would="" the="" proposed="" measure.="" however,="" the="" incremental="" benefit="" is="" small="" if="" cross-="" contamination="" under="" the="" proposed="" measure="" does="" not="" pose="" a="" substantial="" risk.="" the="" partial="" ruminant-to-ruminant="" prohibition="" would="" be="" less="" effective="" than="" the="" proposed="" measure,="" because="" it="" would="" be="" more="" administratively="" difficult="" to="" enforce.="" thus,="" this="" alternative="" would="" not="" reduce="" the="" expected="" value="" of="" the="" [[page="" 576]]="" bse-related="" costs="" as="" much="" as="" the="" proposal.="" again,="" however,="" the="" exact="" difference="" cannot="" be="" estimated,="" but="" would="" vary="" depending="" on="" the="" likely="" level="" of="" compliance="" under="" the="" alternative.="" c.="" industry="" impacts="" the="" erg="" study="" examines="" the="" composition,="" size,="" and="" scale="" of="" economic="" activity="" for="" the="" various="" affected="" industry="" sectors="" and="" provides="" estimates="" of="" the="" cost="" and="" high="" and="" low="" market="" impacts="" (depending="" on="" the="" size="" of="" the="" price="" change="" for="" restricted="" meat="" and="" bone="" meal="" of="" five="" regulatory="" options="" (see="" table="" 1).="" table="" 1.--estimated="" costs="" of="" alternative="" regulatory="" prohibitions="" \1\="" ruminant-to-="" partial="" mammalian-="" ruminant="" ruminant-to-="" sheep/mink-="" sheep/goat-="" to-ruminant="" (proposal)="" ruminant="" to-ruminant="" to-ruminant="" annualized="" impacts----------------------------------------------------------------------------------------------="" (4)="" ($="" million)="" ----------------------------------------------------------------------------------------------------------------="" low="" market="" impact="" scenario="" ($25/ton)="" ----------------------------------------------------------------------------------------------------------------="" capital="" costs..................................="" 8.8="" 1.0="" 3.2="" 0.0="" 0.0="" operating/disposal="" costs.......................="" 10.1="" 0.1="" 14.4="" 5.1="" 0.2="" transportation.................................="" 10.7="" 7.6="" 5.3="" 0.0="" 0.0="" documentation..................................="" 1.9="" 1.5="" 0.5="" 0.0="" 0.0="" substitution="" costs.............................="" 9.7="" 8.0="" 3.7="" 0.0="" 0.0="" renderer="" revenue="" losses........................="" 76.4="" 63.2="" 28.8="" 4.2="" 0.1="" nonruminant="" gains..............................="" (72.6)="" (60.0)="" (27.4)="" 0.0="" 0.0="" ----------------------------------------------------------------="" totals...................................="" 45.0="" 21.4="" 28.5="" 9.3="" 0.3="" ----------------------------------------------------------------------------------------------------------------="" high="" market="" impact="" scenario="" ($100/ton)="" ----------------------------------------------------------------------------------------------------------------="" capital="" costs..................................="" 8.8="" 8.2="" 4.9="" 0.0="" 0.0="" operating/disposal="" costs.......................="" 10.1="" 10.1="" 16.9="" 5.1="" 0.2="" transportation.................................="" 10.7="" 7.6="" 5.3="" 0.0="" 0.0="" documentation..................................="" 1.9="" 1.8="" 0.7="" 0.0="" 0.0="" substitution="" costs.............................="" 9.7="" 8.0="" 3.7="" 0.0="" 0.0="" renderer="" revenue="" losses........................="" 305.6="" 252.8="" 115.4="" 4.2="" 0.1="" nonruminant="" gains..............................="" (290.3)="" (240.2)="" (109.6)="" 0.0="" 0.0="" totals...................................="" 56.5="" 48.3="" 37.3="" 9.3="" 0.3="" ----------------------------------------------------------------------------------------------------------------="" \1\="" totals="" may="" not="" match="" text="" due="" to="" rounding="" error.="" 1.="" the="" proposed="" rule="" the="" proposed="" alternative="" would="" prohibit="" the="" use="" of="" ruminant="" and="" mink="" protein="" in="" ruminant="" feeds.="" currently,="" only="" about="" 10="" percent="" of="" the="" meat="" and="" bone="" meal="" supply="" is="" used="" in="" ruminant="" feed,="" but="" over="" 80="" percent="" of="" the="" meat="" and="" bone="" meal="" contains="" some="" ruminant="" material.="" erg="" forecast="" that="" because="" no="" mixed-species="" slaughtering="" or="" rendering="" establishments="" would="" find="" it="" profitable="" to="" separate="" ruminant="" from="" nonruminant="" offal,="" most="" would="" continue="" to="" contain="" ruminant="" material.="" erg="" estimated="" that="" affected="" renderers="" and="" feedmills="" would="" incur="" total="" direct="" compliance="" costs="" ranging="" from="" $10.2="" to="" $27.6="" million="" per="" year.="" renderers="" would="" bear="" annual="" costs="" of="" about="" $6.3="" million="" and="" feed="" mills="" would="" bear="" annual="" costs="" of="" from="" $3.8="" to="" $21.3="" million.="" arrayed="" by="" compliance="" category,="" transportation="" costs="" were="" estimated="" at="" $7.6="" million;="" documentation="" costs="" for="" activities="" to="" ensure="" control="" of="" ruminant="" feed="" constituents="" ranged="" from="" $1.5="" to="" $1.8="" million;="" and="" capital="" costs="" and="" operating="" costs="" ranged="" from="" $1.0="" to="" $8.2="" million="" and="" $0.1="" to="" $10.1="" million,="" respectively,="" due="" primarily="" to="" the="" need="" for="" some="" feedmills="" to="" expand="" their="" capacity="" to="" offer="" both="" ruminant="" and="" nonruminant="" feed="" products="" under="" a="" high="" market="" impact="" scenario.="" because="" consumer="" response="" to="" the="" rule="" is="" uncertain,="" erg="" could="" not="" develop="" a="" precise="" projection="" of="" future="" meat="" and="" bone="" meal="" prices.="" erg="" estimated,="" however,="" that="" the="" regulatory="" prohibition="" of="" marketing="" ruminant="" meat="" and="" bone="" meal="" to="" ruminants="" would="" lower="" the="" price="" of="" this="" product="" by="" from="" $25="" to="" $100="" per="" ton,="" decreasing="" rendering="" industry="" revenues="" by="" from="" $63.2="" to="" $252.8="" million="" per="" year.="" in="" contrast,="" a="" lower="" mbm="" price="" would="" increase="" sales="" of="" meat="" and="" bone="" meal="" to="" the="" nonruminant="" sector="" and="" the="" resulting="" increased="" profits="" for="" that="" sector="" would="" offset,="" at="" an="" aggregate="" level,="" most="" revenue="" losses.="" although="" erg="" did="" not="" quantify="" this="" effect,="" fda="" determined="" that="" the="" assumption="" of="" a="" fixed="" supply="" of="" meat="" and="" bone="" meal="" and="" a="" linear="" demand="" for="" nonruminant="" feed="" implies="" that="" purchasers="" of="" mixed-species="" meat="" and="" bone="" meal="" for="" nonruminant="" uses="" would="" save="" from="" $60.0="" to="" $240.2="" million="" annually,="" because="" of="" the="" lower="" meat="" and="" bone="" meal="" costs.="" this="" estimate="" assumes="" a="" total="" meat="" and="" bone="" meal="" supply="" of="" 2.5="" million="" tons,="" changes="" in="" price="" ranging="" from="" $25="" to="" $100="" per="" ton,="" and="" an="" increase="" in="" nonruminant="" consumption="" of="" meat="" and="" bone="" meal="" of="" about="" 250,000="" tons.="" in="" addition,="" manufacturers="" of="" ruminant="" feed="" would="" incur="" higher="" costs="" if="" they="" could="" not="" use="" ruminant="" proteins.="" in="" an="" analysis="" prepared="" for="" the="" feed="" industry,="" protein="" substitutes,="" such="" as="" soybean="" meal="" and="" other="" minerals="" necessary="" to="" provide="" the="" same="" nutritional="" level="" as="" that="" provided="" by="" the="" meat="" and="" bone="" meal,="" were="" estimated="" to="" cost="" approximately="" $31.75="" per="" ton="" more="" than="" meat="" and="" bone="" meal="" (ref.="" 125).="" fda="" believes="" that="" this="" estimate="" is="" overstated,="" because="" it="" assumes="" that="" soybean="" meal="" alone="" sells="" for="" $20="" per="" ton="" more="" than="" meat="" and="" bone="" meal.="" in="" fact,="" their="" respective="" market="" prices="" are="" currently="" similar.="" nevertheless,="" fda="" used="" the="" reported="" $31.75="" per="" ton="" differential="" to="" estimate="" that="" the="" higher="" price="" of="" alternative="" proteins="" would="" increase="" ruminant="" feed="" costs="" by="" about="" $8.0="" million="" per="" year.="" as="" a="" result,="" fda="" estimates="" that="" the="" aggregated="" annualized="" costs="" of="" this="" proposal,="" comprised="" of="" both="" the="" direct="" compliance="" costs="" and="" the="" various="" indirect="" gains="" and="" losses,="" would="" total="" [[page="" 577]]="" from="" $21.4="" to="" $48.2="" million.="" although="" the="" greatest="" initial="" burden="" would="" fall="" on="" the="" rendering="" and="" feed="" manufacturing="" sectors,="" erg="" noted="" that="" the="" final="" distribution="" of="" these="" impacts="" would="" shift;="" renderers="" would="" pass="" back="" the="" economic="" impacts="" to="" slaughterers,="" who,="" in="" turn,="" would="" pass="" them="" back="" to="" cattle="" producers.="" fda="" judged,="" however,="" that="" of="" the="" small="" renderers="" dependent="" upon="" farmers'="" and="" ranchers'="" dead="" stock="" for="" their="" raw="" materials,="" 20="" to="" 25="" would="" be="" likely="" to="" close.="" erg="" also="" forecast="" that="" these="" impacts="" would="" cause="" a="" decline="" in="" prices="" for="" slaughter-weight="" cattle="" of="" $1="" to="" $5="" per="" head.="" in="" the="" long="" run,="" erg="" foresaw="" a="" modest="" reduction="" in="" the="" size="" of="" the="" u.s.="" cattle="" herd.="" in="" response="" to="" its="" anprm,="" fda="" received="" comments="" on="" the="" possible="" impacts="" of="" the="" proposal="" from="" both="" individuals="" and="" industry.="" the="" submission="" from="" the="" american="" feed="" industry="" association="" (afia)="" contained="" an="" analysis="" of="" the="" animal="" feed="" market="" that="" was="" based="" on="" the="" assumption="" that="" the="" proposal="" would="" taint="" the="" safety="" of="" all="" meat="" and="" bone="" meal="" (both="" ruminant="" and="" nonruminant),="" to="" the="" extent="" that="" even="" nonruminant="" animal="" producers="" would="" refuse="" to="" purchase="" the="" product.="" this="" loss="" of="" wholesale="" value="" was="" estimated="" at="" $523="" million.="" further,="" the="" afia="" comment="" estimated="" the="" cost="" for="" disposing="" of="" this="" meat="" and="" bone="" meal="" at="" $349="" million="" and="" for="" substituting="" to="" higher="" priced="" feeds="" at="" $74="" million="" annually.="" fda="" questions="" the="" conclusions="" of="" the="" afia="" report,="" largely="" because="" the="" proposed="" rule="" does="" not="" prohibit="" the="" use="" of="" ruminant="" proteins="" in="" nonruminant="" feeds="" and="" there="" is="" no="" evidence="" that="" this="" market="" would="" disappear.="" as="" noted="" earlier,="" nonruminant="" feed="" use="" currently="" constitutes="" about="" 90="" percent="" of="" the="" meat="" and="" bone="" meal="" market.="" while="" some="" nonruminant="" producers="" may="" be="" wary="" of="" ruminant="" mbm="" after="" the="" proposal="" becomes="" final,="" the="" broad="" media="" coverage="" of="" bse="" in="" the="" united="" kingdom="" and="" the="" voluntary="" prohibition="" of="" ruminant="" mbm="" in="" ruminant="" feeds="" have="" already="" provided="" nonruminant="" producers="" with="" substantial="" information="" on="" the="" relevant="" risks.="" the="" implications="" of="" the="" erg="" study="" are="" that="" most="" of="" the="" major="" nonruminant="" sectors="" that="" use="" ruminant="" meat="" and="" bone="" meal="" in="" their="" feeds="" would="" continue="" this="" practice,="" particularly="" at="" sharply="" lower="" mbm="" prices.="" because="" erg="" believed="" that="" all="" stocks="" of="" meat="" and="" bone="" meal="" would="" find="" a="" commercial="" outlet="" within="" the="" nonruminant="" feed="" sector,="" they="" projected="" no="" additional="" disposal="" costs="" and="" far="" smaller="" revenue="" losses="" than="" afia.="" 2.="" partial="" ruminant-to-ruminant="" prohibition="" erg="" also="" estimated="" the="" economic="" impact="" of="" a="" partial="" ruminant-to-="" ruminant="" prohibition,="" which="" would="" prohibit="" only="" the="" use="" of="" proteins="" from="" designated="" ruminant="" tissues="" in="" ruminant="" feeds.="" erg="" projected="" that="" cattle="" packer/renderers="" and="" approximately="" one-half="" of="" the="" large="" cattle="" packers="" would="" choose="" to="" separate="" the="" designated="" and="" nondesignated="" tissues.="" as="" shown="" in="" table="" 1,="" this="" change="" in="" processing="" would="" lead="" to="" increased="" costs="" from="" capital="" investments,="" increases="" in="" operating="" and="" transportation="" expenses,="" training,="" and="" documentation="" activities.="" further,="" erg="" projected,="" under="" the="" high="" market="" impact="" scenario,="" that="" some="" feedmills="" would="" expand="" their="" facilities="" to="" offer="" both="" restricted="" and="" nonrestricted="" meat="" and="" bone="" meal.="" they="" estimated="" the="" annualized="" direct="" compliance="" costs="" for="" this="" option="" at="" from="" $23.5="" to="" $27.9="" million.="" in="" addition,="" erg="" projected="" that="" this="" option="" would="" cause="" price="" declines="" of="" from="" $25="" to="" $100="" per="" ton="" for="" the="" meat="" and="" bone="" meal="" derived="" from="" designated="" tissues,="" leading="" to="" decreases="" in="" renderer="" revenues="" of="" from="" $28.8="" to="" $115.4="" million="" per="" year.="" as="" discussed="" previously,="" fda="" again="" assumed="" a="" fixed="" supply="" of="" meat="" and="" bone="" meal="" and="" a="" linear="" demand="" for="" nonruminant="" feed="" to="" calculate="" that="" purchasers="" of="" mixed-species="" meat="" and="" bone="" meal="" for="" nonruminant="" uses="" would="" save="" from="" $27.4="" million="" to="" $109.6="" million="" annually="" because="" of="" the="" lower="" meat="" and="" bone="" meal="" costs.="" adding="" additional="" protein="" substitution="" costs="" of="" $3.7="" million="" and="" other="" indirect="" costs="" raises="" the="" estimated="" net="" aggregate="" costs="" for="" this="" alternative="" to="" $28.6="" to="" $37.4="" million.="" 3.="" mammalian-to-ruminant="" prohibition="" the="" third="" option="" assessed="" was="" the="" prohibition="" of="" mammalian="" protein="" in="" ruminant="" feeds.="" erg="" projected="" that="" slaughtering="" and="" rendering="" establishments="" would="" have="" no="" reason="" to="" separate="" offal="" because="" very="" few="" of="" these="" establishments="" process="" both="" mammals="" and="" nonmammals.="" they="" estimated="" annualized="" direct="" compliance="" costs="" for="" this="" option="" at="" $31.6="" million.="" erg="" forecast="" that,="" regardless="" of="" the="" size="" of="" the="" price="" decline="" for="" restricted="" meat="" and="" bone="" meal,="" some="" feedmills="" would="" expand="" their="" capacity="" to="" offer="" both="" restricted="" and="" nonrestricted="" meat="" and="" bone="" meal,="" resulting="" in="" increased="" capital="" and="" plant="" operating="" costs.="" the="" majority="" of="" the="" remaining="" regulatory="" costs="" are="" composed="" of="" documentation="" costs.="" assuming="" that="" a="" regulatory="" prohibition="" on="" marketing="" restricted="" meat="" and="" bone="" meal="" to="" ruminants="" would="" cause="" the="" price="" of="" the="" restricted="" meat="" and="" bone="" meal="" to="" fall="" by="" from="" $25="" to="" $100="" per="" ton,="" erg="" projected="" that="" this="" option="" would="" reduce="" renderer="" revenues="" by="" from="" $76.4="" to="" $305.6="" million="" per="" year.="" alternatively,="" under="" the="" same="" assumptions="" as="" applied="" above,="" fda="" found="" that="" purchasers="" of="" mixed-species="" meat="" and="" bone="" meal="" for="" nonruminant="" uses="" would="" save="" from="" $72.6="" million="" to="" $290.3="" million="" annually,="" because="" of="" the="" lower="" meat="" and="" bone="" meal="" costs.="" adding="" additional="" protein="" substitution="" costs="" of="" $9.7="" million="" and="" other="" indirect="" costs="" raises="" the="" estimated="" net="" aggregate="" costs="" for="" this="" third="" option="" to="" from="" $45.1="" to="" $56.6="" million.="" 4.="" other="" regulatory="" alternatives="" fda="" also="" considered="" two="" less="" restrictive="" options="" for="" controlling="" the="" spread="" of="" an="" outbreak="" of="" bse="" in="" the="" united="" states:="" a="" prohibition="" of="" all="" sheep,="" goat,="" mink,="" deer,="" and="" elk="" proteins="" in="" ruminant="" feed;="" and="" a="" prohibition="" of="" sheep="" and="" goat="" proteins="" in="" ruminant="" feed.="" the="" first="" of="" these="" alternatives="" would="" require="" that="" ruminants="" not="" be="" fed="" proteins="" from="" any="" species="" in="" which="" a="" tse="" was="" diagnosed="" in="" the="" united="" states,="" which="" includes="" sheep,="" goats,="" mink,="" deer,="" and="" elk.="" erg="" anticipated="" minimal="" regulatory="" impacts="" for="" sheep,="" lamb,="" and="" goat="" producers="" because="" most="" renderers="" already="" require="" that="" sheep,="" lamb,="" and="" goat="" offal="" be="" excluded="" from="" mixed="" species="" meat="" and="" bone="" meal.="" erg="" estimated="" that="" this="" alternative="" could="" restrict="" the="" use="" of="" up="" to="" 34,150="" tons="" of="" offal="" annually="" from="" the="" various="" species,="" or="" about="" 0.3="" percent="" of="" all="" mammalian="" offal="" rendered.="" using="" an="" estimated="" cost="" of="" $150/ton="" for="" landfill="" disposal,="" erg="" calculated="" that="" the="" disposal="" costs="" for="" this="" alternative="" could="" equal="" $5.1="" million.="" furthermore,="" erg="" estimated="" that="" the="" meat="" and="" bone="" meal="" and="" tallow="" manufactured="" from="" offal="" generates="" revenues="" of="" about="" $500/ton="" of="" processed="" material.="" under="" this="" option,="" meat="" and="" bone="" meal="" production="" would="" fall="" by="" 8,450="" tons="" per="" year,="" reducing="" industry="" revenues="" by="" an="" estimated="" $4.2="" million="" annually.="" the="" final="" alternative="" would="" restrict="" only="" sheep="" and="" goat="" protein="" from="" use="" in="" ruminant="" feed.="" this="" alternative="" is="" similar="" to="" the="" agency's="" 1994="" proposal,="" which="" pertained="" only="" to="" adult="" sheep="" and="" goats.="" most="" sheep="" and="" goats="" are="" currently="" excluded="" by="" renderers="" from="" being="" rendered="" into="" mixed="" species="" meat="" and="" bone="" meal.="" erg="" estimated="" that="" this="" alternative="" would="" restrict="" the="" use="" of="" up="" to="" 1,200="" tons="" of="" offal,="" or="" about="" 0.01="" percent="" of="" all="" mammalian="" offal="" rendered.="" at="" $150/ton="" for="" landfill="" disposal,="" the="" disposal="" costs="" would="" equal="" $0.2="" million.="" erg="" calculated="" that="" [[page="" 578]]="" production="" of="" meat="" and="" bone="" meal="" under="" this="" option="" would="" be="" restricted="" by="" only="" 300="" tons="" per="" year,="" leading="" to="" revenue="" losses="" of="" about="" $0.1="" million.="" erg="" noted="" that="" the="" disposal="" costs="" presented="" for="" the="" latter="" two="" alternatives="" are="" high-end="" estimates="" because="" of="" the="" likelihood="" of="" onsite="" disposal="" for="" deer="" and="" elk="" taken="" by="" hunters.="" further,="" these="" alternatives="" were="" not="" expected="" to="" have="" a="" measurable="" effect="" on="" the="" price="" of="" meat="" and="" bone="" meal="" because="" they="" would="" affect="" only="" 0.3="" percent="" and="" 0.01="" percent="" of="" the="" meat="" and="" bone="" meal="" markets,="" respectively.="" in="" contrast="" to="" the="" first="" three="" options,="" these="" rules="" would="" not="" change="" the="" demand="" for="" meat="" and="" bone="" meal,="" but="" would="" restrict="" the="" supply="" of="" meat="" and="" bone="" meal.="" any="" postregulation="" increase="" in="" price,="" therefore,="" would="" increase="" revenues="" of="" renderers="" and="" costs="" of="" purchasers="" of="" meat="" and="" bone="" meal="" by="" an="" almost="" equal="" amount.="" erg="" reported="" that="" this="" decrease="" in="" supply="" would="" have="" a="" negligible="" effect="" on="" meat="" and="" bone="" meal="" prices.="" d.="" small="" business="" impacts="" the="" regulatory="" flexibility="" act="" requires="" agencies="" to="" prepare="" a="" regulatory="" flexibility="" analysis="" if="" a="" rule="" would="" have="" a="" significant="" impact="" on="" a="" substantial="" number="" of="" small="" entities.="" the="" discussion="" in="" this="" section,="" as="" well="" as="" in="" other="" sections="" of="" this="" document,="" and="" the="" erg="" report,="" constitute="" the="" agency's="" compliance="" with="" this="" requirement.="" the="" regulatory="" flexibility="" act="" asks="" for="" a="" succinct="" statement="" of="" the="" purpose="" and="" objectives="" of="" the="" rule.="" as="" explained="" previously="" in="" this="" document,="" fda="" is="" proposing="" this="" measure="" to="" address="" the="" risk="" to="" u.s.="" livestock="" associated="" with="" feeding="" ruminant="" proteins="" to="" ruminants.="" existing="" epidemiological="" evidence="" suggests="" a="" link="" between="" an="" outbreak="" of="" bse="" in="" the="" united="" kingdom="" and="" the="" practice="" of="" feeding="" products="" to="" cattle="" that="" included="" ruminant="" proteins.="" this="" rule="" would="" prohibit="" that="" practice.="" thus,="" the="" need="" for="" regulatory="" action="" is="" based="" on="" the="" need="" to="" prevent="" the="" spread="" of="" bse="" and="" thereby="" to="" protect="" the="" health="" of="" animals="" and="" to="" minimize="" any="" risk="" that="" might="" be="" posed="" to="" humans="" from="" bse.="" the="" regulatory="" flexibility="" act="" also="" requires="" a="" description="" of="" the="" affected="" small="" entities.="" the="" erg="" study="" includes="" counts="" of="" entities="" in="" each="" class="" of="" industry="" that="" are="" involved="" in="" ruminant="" production="" and="" meat="" preparation.="" the="" vast="" majority="" of="" all="" of="" these="" firms="" are="" considered="" small="" businesses="" according="" to="" size="" standards="" set="" by="" the="" small="" business="" administration.="" there="" are="" 282="" rendering="" plants,="" of="" which="" 204="" have="" fewer="" than="" 500="" employees,="" including="" all="" of="" the="" 152="" independent="" renderers.="" erg="" also="" estimated="" that="" 30,000="" feedmills,="" all="" with="" fewer="" than="" 500="" employees,="" could="" be="" affected="" by="" this="" rule.="" an="" estimated="" 1.4="" million="" enterprises="" are="" engaged="" in="" ruminant="" production.="" these="" include="" businesses="" engaged="" in="" the="" production="" of="" beef="" and="" dairy="" cattle,="" including="" farmers="" and="" ranchers,="" stocker="" operators,="" and="" cattle="" feeders,="" and="" other="" ruminant="" producers.="" the="" slaughtering="" industry="" contains="" more="" than="" 4,000="" establishments.="" of="" this="" total,="" however,="" only="" 130="" are="" packer/="" renderers="" that="" could="" have="" compliance="" requirements="" and="" about="" 52="" of="" these="" establishments="" have="" fewer="" than="" 500="" employees.="" erg="" estimated="" that="" almost="" 300,000="" small="" establishments="" are="" engaged="" in="" meat="" processing.="" these="" businesses="" would="" have="" no="" direct="" compliance="" activities,="" but="" could="" be="" affected="" indirectly="" by="" altered="" renderer="" practices.="" also,="" about="" 150,000="" small="" producers="" of="" nonruminant="" animals="" could="" gain="" from="" lower="" feed="" costs.="" the="" rfa="" also="" requires="" a="" description="" of="" the="" recordkeeping="" requirements="" of="" the="" proposed="" rule.="" the="" erg="" report="" presents="" detailed="" estimates="" of="" these="" costs.="" erg="" found="" that="" the="" rule="" would="" require="" certain="" feed="" manufacturers="" to="" develop="" new="" written="" operating="" procedures.="" in="" addition,="" affected="" firms="" would="" have="" to="" retain="" invoices="" but="" fda="" believes="" this="" activity="" is="" already="" generally="" accepted="" business="" practice.="" finally,="" the="" regulatory="" flexibility="" act="" asks="" for="" an="" evaluation="" of="" any="" regulatory="" overlaps="" and="" regulatory="" alternatives="" that="" would="" minimize="" costs="" to="" small="" entities.="" fda="" is="" unaware="" of="" any="" significant="" regulatory="" conflicts="" with="" other="" federal="" rules.="" fda="" examined="" five="" regulatory="" alternatives="" in="" addition="" to="" no="" action:="" (1)="" the="" ruminant-to-ruminant="" prohibition;="" (2)="" the="" partial="" ruminant-to-ruminant="" prohibition;="" (3)="" the="" mammalian-to-="" ruminant="" prohibition;="" (4)="" the="" prohibition="" of="" all="" sheep,="" goat,="" mink,="" deer,="" and="" elk="" proteins="" in="" ruminant="" feed;="" and="" (5)="" the="" prohibition="" of="" specified="" sheep="" and="" goat="" proteins="" in="" ruminant="" feed.="" the="" erg="" report="" provides="" a="" detailed="" comparison="" of="" the="" respective="" impacts="" of="" these="" alternatives="" and="" found="" that="" the="" estimated="" direct="" compliance="" costs="" are="" lower="" under="" the="" proposed="" rule="" ($10.2="" to="" $27.6="" million)="" than="" under="" two="" of="" the="" alternative="" rules="" ($23.5="" to="" $27.9="" million="" for="" the="" partial="" ruminant-to-ruminant="" option,="" $31.6="" million="" for="" the="" mammalian-to-="" ruminant="" option).="" the="" other="" alternatives="" would="" not="" be="" nearly="" as="" effective="" at="" reducing="" the="" risk="" of="" an="" outbreak="" and="" spread="" of="" bse,="" but="" are="" considerably="" less="" costly.="" as="" many="" of="" the="" above="" projections="" are="" uncertain,="" fda="" particularly="" invites="" additional="" data="" or="" comment="" on="" the="" effects="" of="" the="" proposed="" and="" alternative="" rules="" on="" any="" group="" of="" small="" businesses.="" e.="" unfunded="" mandates="" analysis="" based="" on="" the="" erg="" study,="" fda="" estimated="" that="" aggregate="" expenditures="" by="" the="" private="" sector="" that="" result="" from="" the="" proposed="" rule,="" issued="" under="" 21="" cfr="" 589.2000,="" will="" range="" from="" $10.2="" to="" $27.6="" million="" per="" year.="" as="" described="" in="" section="" ix.b.="" of="" this="" document,="" the="" benefits="" of="" this="" measure="" accrue="" both="" to="" the="" general="" public="" (through="" decreased="" risks="" to="" health)="" and="" to="" the="" livestock="" and="" associated="" industries.="" the="" costs="" of="" the="" measure="" are="" borne="" by="" the="" private="" sector,="" primarily="" the="" rendering="" and="" animal="" feed="" industries.="" because="" fda="" anticipates="" no="" significant="" additional="" costs="" to="" state,="" local,="" or="" tribal="" governments,="" this="" regulatory="" action="" does="" not="" require="" an="" assessment="" under="" the="" unfunded="" mandates="" reform="" act.="" x.="" the="" paperwork="" reduction="" act="" of="" 1995="" this="" proposed="" rule="" contains="" recordkeeping="" requirements="" that="" are="" subject="" to="" public="" comment="" and="" review="" by="" omb="" under="" the="" paperwork="" reduction="" act="" of="" 1995="" (pub.="" l.="" 104-13).="" therefore,="" in="" accordance="" with="" 5="" cfr="" part="" 1320,="" a="" description="" of="" reporting="" requirements="" is="" given="" in="" table="" 2="" of="" this="" document,="" with="" an="" estimate="" of="" the="" annual="" collection="" of="" information="" burden.="" included="" in="" the="" estimate="" is="" the="" time="" for="" reviewing="" instructions,="" gathering="" and="" maintaining="" the="" data="" needed,="" and="" completing="" and="" reviewing="" the="" collection="" of="" information.="" with="" respect="" to="" the="" following="" collection="" of="" information,="" fda="" is="" soliciting="" comments="" on:="" (1)="" whether="" the="" proposed="" collection="" of="" information="" is="" necessary="" for="" proper="" performance="" of="" fda's="" functions,="" including="" whether="" the="" information="" will="" have="" practical="" utility;="" (2)="" the="" accuracy="" of="" fda's="" estimate="" of="" the="" burden="" of="" the="" proposed="" collection="" of="" information,="" including="" the="" validity="" of="" the="" methodology="" and="" assumptions="" used;="" (3)="" ways="" to="" enhance="" the="" quality,="" utility,="" and="" clarity="" of="" the="" information="" to="" be="" collected;="" and="" (4)="" ways="" to="" minimize="" the="" burden="" of="" the="" collection="" of="" information="" on="" those="" who="" are="" to="" respond,="" including="" through="" the="" use="" of="" automated="" collection="" techniques="" or="" other="" forms="" of="" information="" technology,="" when="" appropriate.="" title:="" substances="" prohibited="" from="" use="" in="" animal="" food="" or="" feed;="" animal="" proteins="" prohibited="" in="" ruminant="" feed.="" description:="" the="" proposed="" rule="" (sec.="" 589.2000)="" provides="" that="" protein="" derived="" from="" ruminant="" and="" mink="" tissues="" is="" not="" gras="" for="" use="" in="" ruminant="" feed="" and="" is="" a="" food="" additive="" subject="" to="" section="" 409="" of="" the="" act.="" proteins="" derived="" from="" [[page="" 579]]="" animal="" tissues="" contained="" in="" such="" feed="" ingredients="" in="" distribution="" cannot="" be="" readily="" determined="" by="" recipients="" engaged="" in="" the="" manufacture,="" processing="" and="" distribution,="" and="" use="" of="" animal="" feeds="" and="" feed="" ingredients.="" to="" achieve="" the="" public="" and="" animal="" health="" objectives="" of="" this="" proposed="" rule,="" the="" agency="" believes="" that="" manufacturers,="" processors,="" distributors,="" and="" users="" must="" be="" responsible="" for="" ensuring="" and="" appropriately="" maintaining="" the="" identity="" of="" the="" specific="" nature="" of="" the="" components="" of="" animal="" protein="" products="" and="" animal="" feeds="" containing="" these="" products.="" thus,="" under="" the="" agency's="" authority="" in="" section="" 701(a)="" (21="" u.s.c.="" 371(a))="" of="" the="" act="" to="" issue="" regulations="" for="" the="" efficient="" enforcement="" of="" the="" act,="" this="" proposed="" rule="" places="" three="" general="" requirements="" on="" persons="" that="" manufacture,="" blend,="" process="" and="" distribute="" products="" that="" contain="" or="" may="" contain="" protein="" derived="" from="" ruminant="" and="" mink="" tissues,="" and="" feeds="" made="" from="" such="" products.="" the="" first="" requirement="" is="" for="" cautionary="" labeling="" of="" these="" products="" with="" direct="" language="" developed="" by="" fda.="" the="" second="" requirement="" is="" for="" these="" establishments="" to="" provide="" fda="" with="" access="" to="" their="" purchase="" and="" sales="" invoices="" for="" compliance="" purposes.="" fda="" believes="" that="" maintenance="" of="" such="" records="" is="" a="" usual="" and="" customary="" part="" of="" normal="" business="" activities="" for="" such="" firms.="" these="" two="" requirements="" are="" not="" within="" the="" scope="" of="" the="" paperwork="" reduction="" act.="" the="" third="" requirement="" is="" recordkeeping="" which="" requires="" that="" the="" firms="" develop="" standard="" operating="" procedures="" if="" they="" intend="" to="" keep="" ruminant="" and="" mink="" material="" separate="" from="" nonruminant="" material.="" the="" agency="" is="" aware="" that="" the="" certification="" procedures="" provided="" in="" sec.="" 589.2000(d)="" of="" the="" regulation="" could="" be="" interpreted="" as="" imposing="" a="" paperwork="" burden="" on="" certain="" industry="" segments.="" however,="" the="" agency="" notes="" that="" the="" certification="" procedures="" apply="" only="" where="" new="" technology="" (e.g.,="" a="" deactivation="" method)="" is="" developed.="" the="" agency="" was="" unable="" to="" estimate="" when="" such="" technology="" might="" be="" developed,="" what="" its="" characteristics="" and="" costs="" would="" be,="" and="" other="" essential="" information="" needed="" to="" make="" realistic="" estimates="" of="" any="" paperwork="" burden.="" therefore,="" such="" costs="" are="" not="" included="" in="" this="" proposed="" rule.="" however,="" the="" agency="" specifically="" requests="" comments="" and="" information="" related="" to="" the="" factors="" that="" would="" determine="" the="" extent="" of="" any="" paperwork="" burden.="" the="" recordkeeping="" burden="" in="" table="" 2="" has="" been="" estimated="" using="" the="" typical="" average="" size="" establishment="" that="" is="" expected="" to="" handle="" animal="" protein="" from="" both="" ruminant="" and="" nonruminant="" sources,="" or="" feeds="" containing="" these="" products,="" and="" intend="" to="" keep="" them="" separate.="" fda's="" preliminary="" estimate="" is="" that="" only="" a="" fraction="" of="" feed="" manufacturers="" and="" distributors="" will="" separate="" their="" products.="" independent="" renderers="" were="" excluded="" from="" the="" burden="" estimates="" based="" on="" information="" provided="" for="" the="" economic="" estimate.="" packer/renderers="" were="" excluded="" because="" they="" are="" single="" species="" processors.="" under="" these="" recordkeeping="" requirements,="" for="" which="" records="" must="" be="" made="" available="" for="" fda="" inspection,="" an="" estimated="" 2,000="" feed="" mills="" would="" handle="" both="" restricted="" and="" nonrestricted="" products="" and="" would="" develop="" standard="" operating="" procedures="" for="" keeping="" ruminant="" and="" mink="" material="" separate="" from="" nonruminant="" material="" from="" the="" time="" of="" receipt="" to="" time="" of="" shipment.="" the="" estimate="" in="" the="" burden="" chart="" is="" based="" on="" the="" time="" required="" to="" develop="" and="" establish="" the="" written="" procedures="" and="" is="" a="" one="" time="" requirement.="" the="" 2,000="" firms="" will="" also="" incur="" annual="" operating="" cost="" estimated="" at="" $10="" million,="" because="" of="" the="" flushing,="" sequencing="" and="" other="" procedures="" that="" will="" be="" required.="" it="" is="" estimated="" that="" 1,000="" of="" the="" firms="" may="" incur="" capital="" cost="" for="" the="" construction="" of="" separate="" facilities.="" these="" costs="" have="" been="" annualized="" for="" 10="" years,="" at="" $7.119="" million="" per="" year.="" the="" remaining="" firms="" are="" expected="" to="" be="" able="" to="" meet="" the="" regulation's="" requirements="" without="" incurring="" capital="" cost.="" the="" agency="" has="" submitted="" copies="" of="" the="" proposed="" rule="" to="" omb="" for="" its="" review="" of="" these="" requirements.="" interested="" persons="" are="" requested="" to="" send="" comments="" regarding="" this="" collection="" of="" information="" by="" february="" 18,="" 1997,="" but="" not="" later="" than="" march="" 4,="" 1997="" to="" the="" office="" of="" information="" and="" regulatory="" affairs,="" omb="" (address="" above),="" attn:="" desk="" officer="" for="" fda.="" description="" of="" respondents:="" distributors,="" feed="" manufacturers,="" blenders="" and="" renderers.="" table="" 2.--estimated="" annual="" recordkeeping="" burden="" \1\="" --------------------------------------------------------------------------------------------------------------------------------------------------------="" no.="" of="" record="" total="" hours="" per="" capital="" cost="" operating="" cost="" 21="" cfr="" section="" keepers/="" frequency="" annual="" record="" total="" hours="" (annualized)="" (yearly)="" firms="" records="" --------------------------------------------------------------------------------------------------------------------------------------------------------="" 589.2000="" (e)(1)(iv)....................................="" 2,000="" 1="" 2,000="" 14="" 28,000="" $7,119,000="" $10,000,000="" --------------------------------------------------------------------------------------------------------------------------------------------------------="" \1\="" costs="" are="" only="" incurred="" under="" the="" high-impact="" scenario.="" xi.="" federalism="" fda="" has="" analyzed="" this="" proposal="" in="" accordance="" with="" the="" principles="" and="" criteria="" set="" forth="" in="" executive="" order="" 12612="" and="" has="" determined="" that="" this="" proposal="" does="" not="" warrant="" the="" preparation="" of="" a="" federalism="" assessment.="" xii.="" references="" the="" following="" references="" have="" been="" placed="" on="" display="" in="" the="" dockets="" management="" branch="" (address="" above)="" and="" may="" be="" seen="" by="" interested="" persons="" between="" 9="" a.m.="" and="" 4="" p.m.,="" monday="" through="" friday.="" 1.="" transcript,="" fda="" and="" usda="" symposium,="" ``tissue="" distribution,="" inactivation="" and="" transmission="" of="" transmissible="" spongiform="" encephalopathies,''="" riverdale,="" md,="" 1996.="" 2.="" who,="" ``report="" of="" a="" who="" consultation="" on="" public="" issues="" related="" to="" human="" and="" animal="" transmissible="" spongiform="" encephalopathies,''="" with="" the="" participation="" of="" fao="" and="" oie,="" geneva,="" switzerland,="" who/emc/="" dis/96.147,="" 2-3="" april="" 1996.="" 3.="" centers="" for="" disease="" control="" and="" prevention,="" memorandum,="" july="" 25,="" 1996.="" 4.="" usda,="" aphis,="" ``bovine="" spongiform="" encephalopathy:="" implications="" for="" the="" united="" states,="" a="" 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experimentally="" infected="" sheep,''="" veterinary="" record,="" 138:546,="" 1996.="" 66.="" gordon,="" w.="" s.,="" ``transmission="" of="" scrapie="" and="" evidence="" of="" spread="" of="" infection="" in="" sheep="" at="" pasture,''="" report="" at="" scrapie="" seminar,="" washington,="" dc,="" january="" 27-30,="" 1964;="" ars="" 91--53:8-18,="" 1966.="" 67.="" wisniewski,="" h.,="" et="" al.,="" ``mites="" as="" vectors="" for="" scrapie,''="" lancet,="" 347:1114,="" 1996.="" [[page="" 581]]="" 68.="" goldfarb,="" l.="" g.,="" r.="" b.="" petersen,="" m.="" tabaton,="" p.="" brown,="" a.="" c.="" leblanc,="" p.="" montagna,="" p.="" cortelli,="" j.="" julien,="" c.="" vital,="" and="" w.="" w.="" pendelbury,="" et="" al.,="" ``fatal="" familial="" insomnia="" and="" familial="" creutzfeldt-jakob="" disease:="" disease="" phenotype="" determined="" by="" a="" dna="" polymorphism,''="" science,="" 258(5083):="" 806-808,="" 1992.="" 69.="" ghetti,="" b.,="" s.="" r.="" dlouhy,="" g.="" giaccone,="" o.="" bugiani,="" b.="" frangione,="" m.="" r.="" farlow,="" and="" f.="" tagliavini,="" gerstmann-straussler-="" scheinker="" disease="" and="" the="" indiana="" kindred,="" brain="" pathology,="" 5:61-75,="" 1995.="" 70.="" kitamoto,="" t.,="" m.="" ohta,="" k.="" doh-ura,="" s.="" hitoshi,="" y.="" terao,="" and="" j.="" tateishi,="" ``novel="" missense="" variants="" of="" prion="" protein="" in="" creutzfeldt-jakob="" disease="" or="" gerstmann-straussler="" syndrome,''="" biochemical="" and="" biophysical="" research="" communication,="" 191:="" 709-714,="" 1993.="" 71.="" oda,="" t.,="" t.="" kitamoto,="" j.="" tateishi,="" t.="" mitsuhashi,="" k.="" iwabuchi,="" c.="" haga,="" e.="" oguni,="" y.="" kato,="" i.="" tominaga,="" and="" k.="" yanai,="" et="" al.,="" ``prion="" disease="" with="" 144="" base="" pair="" insertion="" in="" a="" japanese="" family="" line,''="" acta="" neuropathologica,="" 90:80-86,="" 1995.="" 72.="" tateishi,="" j.,="" and="" t.="" kitamoto,="" ``inherited="" prion="" diseases="" and="" transmission="" to="" rodents,''="" brain="" pathology,="" 5:53-59,="" 1995.="" 73.="" ikeda,="" t.,="" m.="" horiuchi,="" n.="" ishiguro,="" y.="" muramatsu,="" g.="" d.="" kai-uwe,="" and="" m.="" shinagaw,="" ``amino="" acid="" polymorphisms="" of="" prp="" with="" reference="" to="" onset="" of="" scrapie="" in="" suffolk="" and="" corriedale="" sheep="" in="" japan,''="" journal="" of="" genetic="" virology,="" 76:2577-2581,="" 1995.="" 74.="" belt,="" p.="" b.,="" i.="" h.="" muileman,="" b.="" e.="" schreuder,="" j.="" bos-de-="" ruijter,="" a.="" l.="" gielkens,="" and="" m.="" a.="" smits,="" ``identification="" of="" five="" allelic="" variants="" of="" the="" sheep="" prp="" gene="" and="" their="" association="" with="" natural="" scrapie,''="" journal="" of="" genetic="" virology,="" 76:509-517,="" 1995.="" 75.="" westaway,="" d.,="" v.="" zuliani,="" c.="" m.="" cooper,="" m.="" da-costa,="" s.="" neuman,="" a.="" l.="" jenny,="" l.="" detwiler,="" and="" s.="" b.="" prusiner,="" ``homozygosity="" for="" prion="" protein="" alleles="" encoding="" glutamine-171="" renders="" sheep="" susceptible="" to="" natural="" scrapie,''="" genes="" and="" development,="" 8:959-969,="" 1994.="" 76.="" clouscard,="" c.,="" p.="" beaudry,="" j.="" m.="" elsen,="" d.="" milan,="" m.="" dussaucy,="" c.="" bounneau,="" f.="" schelcher,="" j.="" chatelain,="" j.="" m.="" launay,="" and="" j.="" l.="" laplanche,="" ``different="" allelic="" effects="" of="" the="" codons="" 136="" and="" 171="" of="" the="" prion="" protein="" gene="" in="" sheep="" with="" natural="" scrapie,''="" journal="" of="" genetic="" virology,="" 76:2097-2101,="" 1995.="" 77.="" hunter,="" n.,="" w.="" goldmann,="" g.="" smith="" and="" j.="" hope,="" ``frequencies="" of="" prp="" gene="" variants="" in="" healthy="" cattle="" and="" cattle="" with="" bse="" in="" scotland,''="" veterinary="" record,="" 135:400-403,="" 1994.="" 78.="" kimberlin,="" r.="" h.,="" ``bovine="" spongiform="" encephalopathy,''="" scientific="" and="" technical="" review,="" 11:347-390,="" 1992.="" 79.="" schmerr,="" et="" al.,="" journal="" of="" chromatography,="" in="" press.="" 80.="" beekes,="" m.,="" et="" al.,="" ``western="" blot="" mapping="" of="" disease-="" specific="" amyloid="" in="" various="" animal="" species="" and="" humans="" with="" transmissible="" spongiform="" encephalopathies="" using="" a="" high-yield="" purification="" method,''="" journal="" of="" general="" virology,="" 76:2567-2576,="" 1995.="" 81.="" banissi-sabourdy,="" c.,="" et="" al.,="" ``electroanalytical="" characterization="" of="" alzheimer's="" disease="" and="" ovine="" spongiform="" encephalopathy="" by="" repeated="" cyclic="" volummetry="" at="" a="" capillary="" graphite="" paste="" electrode,''="" bioelectrochemistry="" and="" bioenergetics,="" 28:127-="" 147,="" 1996.="" 82.="" gibbs,="" c.="" j.,="" et="" al.,="" personal="" communications,="" 1996.="" 83.="" schreuder,="" b.="" e.="" c.,="" et="" al,="" ``preclinical="" test="" for="" prion="" diseases,''="" nature,="" 381:563,="" 1996.="" 84.="" hsich,="" g.,="" et="" al,="" ``the="" 14-3-3="" brain="" protein="" in="" cerebrospinal="" fluid="" as="" a="" marker="" for="" transmissible="" spongiform="" encephalopathies,''="" nejm,="" 335:924,="" 1996.="" 85.="" taylor,="" d.="" m.,="" s.="" l.="" woodgate,="" and="" m.="" j.="" atkinson,="" ``inactivation="" of="" the="" bovine="" spongiform="" encephalopathy="" agent="" by="" rendering="" procedures,''="" veterinary="" record,="" 9(137):605-610,="" 1995.="" 86.="" taylor,="" d.="" m.="" and="" r.="" bradley,="" personal="" communication,="" 1996.="" 87.="" collee,="" j.="" g.,="" ``food="" borne="" illness-bovine="" spongiform="" encephalopathy,''="" lancet,="" 336:1300-1303,="" 1990.="" 88.="" fraser,="" h.,="" et="" al.,="" ``transmission="" of="" bovine="" spongiform="" encephalopathy="" and="" scrapie="" to="" mice,''="" journal="" of="" general="" virology,="" 73:1891-1897,="" 1992.="" 89.="" robinson,="" m.="" m.,="" ``bovine="" spongiform="" encephalopathy,''="" foreign="" animal="" disease,="" pp.="" 134-138,="" 1992.="" 90.="" spongiform="" encephalopathy="" advisory="" committee,="" united="" kingdom,="" statement,="" march="" 20,="" 1996.="" 91.="" who,="" ``scientific="" consultation="" on="" human="" and="" animal="" spongiform="" encephalopathies,''="" geneva,="" switzerland,="" 16-="" 17="" may="" 1996,="" press="" release="" who/38.="" 92.="" lasmezas,="" c.="" i.,="" et="" al,="" ``bse="" transmission="" to="" macaques,''="" nature,="" 381:743,="" 1996.="" 93.="" collinge,="" j.,="" et="" al.,="" ``molecular="" analysis="" of="" prion="" strain="" variation="" and="" the="" aetiology="" of="" `new="" variant'="" cjd,''="" nature,="" 383:685,="" 1996.="" 94.="" world="" health="" organization,="" ``report="" of="" a="" who="" consultation="" on="" public="" health="" issues="" related="" to="" human="" and="" animal="" transmissible="" spongiform="" encephalopathies,''="" who/cds/ph/95.145,="" 1995.="" 95.="" hueston,="" will,="" usda,="" personal="" communication,="" 1996.="" 96.="" centers="" for="" disease="" control="" and="" prevention,="" ``surveillance="" for="" creutzfeld-jakob="" disease--united="" states,''="" morbidity="" and="" mortality="" weekly="" report,="" 45(31):665,="" 1996.="" 97.="" usda,="" ``animal="" and="" plant="" health="" inspection="" service,="" emergency="" programs="" activities,="" bovine="" spongiform="" encephalopathy="" (bse)="" surveillance="" program,''="" in="" foreign="" animal="" disease="" report,="" no.="" 20-3/4,="" pp.="" 1-2,="" 1992,="" and="" poster="" display="" at="" u.s.="" animal="" health="" association="" annual="" meeting,="" october="" 30,="" 1993.="" 98.="" usda,="" aphis,="" ``qualitative="" analysis="" of="" bse="" risk="" factors="" in="" the="" united="" states,''="" 1991.="" 99.="" usda,="" aphis,="" ``bovine="" spongiform="" encephalopathy:="" implications="" for="" the="" united="" states,''="" 1993.="" 100.="" holman,="" r.="" c.,="" a.="" s.="" khan,="" j.="" kent,="" t.="" w.="" strine,="" and="" l.="" b.="" schonberger,="" ``epidemiology="" of="" creutzfeldt-jakob="" diseases="" in="" the="" united="" states,''="" 1979-1990:="" analysis="" of="" national="" mortality="" data,="" neuroepidemiology,="" 14:174-181,="" 1995.="" 101.="" cdc,="" ``world="" health="" organization="" consultation="" on="" public="" health="" issues="" related="" to="" bovine="" spongiform="" encephalopathy="" and="" the="" emergence="" of="" a="" new="" variant="" of="" creutzfeldt-jakob="" disease,''="" morbidity="" and="" mortality="" weekly="" report,="" 45/(14):295-303,="" 1996.="" 102.="" office="" internationale="" epizootics,="" international="" animal="" health="" code,="" chapter="" 3.2.13="" on="" bse,="" pp.="" 231-235,="" july="" 1993.="" 103.="" european="" community="" decisions,="" 96/362/ec.="" 104.="" bisplinghoff,="" f.="" d.,="" national="" renderers="" association="" letter="" to="" animal="" protein="" producers,="" 1989.="" 105.="" fda,="" ``report="" of="" findings="" of="" directed="" inspections="" of="" sheep="" rendering="" facilities,''="" january="" 1993.="" 106.="" a="" joint="" statement="" by="" national="" livestock="" and="" professional="" animal="" health="" organizations="" regarding="" a="" voluntary="" ban="" on="" ruminant="" derived="" protein="" in="" ruminant="" feed="" recommendations,="" press="" release="" march="" 29,="" 1996.="" 107.="" usda="" news="" release="" no.="" 0159.96,="" ``usda,="" u.s.="" public="" health="" service="" announce="" additional="" steps,="" support="" for="" industry="" efforts="" to="" keep="" u.s.="" free="" of="" bse,''="" march="" 29,="" 1996.="" 108.="" zimbleman,="" robert="" g.="" (representing="" the="" american="" society="" of="" animal="" science),="" april="" 8,="" 1996,="" letter="" to="" gary="" weber,="" national="" cattleman's="" beef="" association.="" 109.="" weber,="" g.="" m.,="" national="" cattlemen's="" beef="" association,="" comment="" no.="" 280,="" june="" 13,="" 1996.="" 110.="" anonymous,="" comment="" no.="" 279,="" june="" 13,="" 1996.="" 111.="" andrews,="" c.="" d.,="" et="" al.,="" ``detection="" of="" beef,="" sheep,="" deer,="" and="" horse="" meat="" in="" cooked="" meat="" products="" by="" enzyme-linked="" immunosorbent="" assay,''="" journal="" of="" association="" of="" analytical="" chemist="" international,="" 75:572-576,="" 1992.="" 112.="" berger,="" r.="" g.,="" et="" al.,="" ``detection="" of="" poultry="" and="" pork="" in="" cooked="" and="" canned="" meat="" foods="" by="" enzyme-linked="" immunosorbent="" assays,''="" journal="" of="" association="" of="" analytical="" chemist="" international,="" 71:406-410,="" 1988.="" 113.="" lamming,="" e.,="" ``bovine="" spongiform="" encephalopathy="" and="" other="" spongiform="" encephalopathies,''="" in="" ``the="" report="" of="" the="" expert="" group="" on="" animal="" feedingstuffs="" to="" the="" minister="" of="" agriculture,="" fisheries,="" and="" food,="" the="" secretary="" of="" state="" for="" health="" and="" the="" secretaries="" of="" state="" for="" wales,="" scotland,="" and="" northern="" ireland,''="" 1992.="" 114.="" eastern="" research="" group,="" ``cost="" analysis="" of="" regulatory="" options="" to="" reduce="" the="" risk="" of="" an="" outbreak="" of="" bovine="" spongiform="" encephalopathy="" (bse),''="" july="" 1996.="" 115.="" ministries="" of="" agriculture,="" fisheries="" and="" foods,="" ``programme="" to="" eradicate="" bse="" in="" the="" united="" kingdom,''="" may="" 1996.="" 116.="" hoinville,="" l.="" j.,="" ``decline="" in="" the="" incidence="" of="" bse="" in="" cattle="" born="" after="" the="" introduction="" of="" the="" 'feed="" ban',''="" veterinary="" record,="" 134:274-275,="" 1994.="" 117.="" united="" kingdom,="" ministries="" of="" agriculture,="" fisheries="" and="" foods,="" animal="" pharm,="" march="" 1994.="" 118.="" mathews="" jr.,="" k.h.,="" et="" al.,="" bovine="" spongiform="" encephalopathy:="" a="" qualitative="" economic="" assessment,="" usda="" livestock="" marketing="" information="" center,="" may="" 10,="" 1996.="" 119.="" usda,="" agricultural="" statistics,="" 1996.="" 120.="" ``swiss="" plan="" mass="" cattle="" slaughter,''="" animal="" pharm,="" no.="" 357:p.6,="" sept.="" 20,="" 1996.="" [[page="" 582]]="" 121.="" united="" kingdom,="" ministries="" of="" agriculture,="" fisheries="" and="" foods,="" bse:="" government="" measures="" to="" assist="" the="" beef="" industry,="" aug.="" 19,="" 1996.="" 122.="" ashworth,="" s.="" w.,="" and="" d.="" d.="" mainland,="" ``the="" economic="" impact="" of="" bse="" on="" the="" united="" kingdom="" beef="" industry,''="" outlook="" on="" agriculture,="" vol.="" 24,3,="" pp.="" 151-154,="" 1995.="" 123.="" duewer,="" l.a.,="" usda,="" economic="" research="" service,="" personal="" communication,="" october="" 31,="" 1996;="" putnam,="" judith="" j.,="" and="" j.="" e.="" allshouse,="" food="" consumption="" prices="" and="" expenditures,="" 1970-94,="" usda,="" economic="" research="" service,="" statistical="" bulletin="" no.="" 928,="" table="" 45,="" 1996.="" 124.="" marsh,="" j.="" m.,="" derived="" demand="" elasticities:="" marketing="" margin="" methods="" versus="" an="" inverse="" demand="" model="" for="" choice="" beef,="" western="" journal="" of="" agricultural="" economics,="" vol.16="" no.2,="" pp.382-391,="" 1991.="" 125.="" lenard,="" thomas="" m.,="" preliminary="" economic="" analysis="" of="" a="" ruminant-to-ruminant="" feeding="" ban,="" prepared="" for="" american="" feed="" industry="" association.="" comments="" submitted="" to="" fda="" docket="" no.="" 96n-0135.="" xiii.="" request="" for="" comments="" interested="" persons="" may,="" on="" or="" before="" february="" 18,="" 1997,="" submit="" to="" the="" dockets="" management="" branch="" (address="" above)="" written="" comments="" regarding="" this="" proposal.="" two="" copies="" of="" any="" comments="" are="" to="" be="" submitted,="" except="" that="" individuals="" may="" submit="" one="" copy.="" comments="" are="" to="" be="" identified="" with="" the="" docket="" number="" found="" in="" brackets="" in="" the="" heading="" of="" this="" document.="" received="" comments="" may="" be="" seen="" in="" the="" office="" above="" between="" 9="" a.m.="" and="" 4="" p.m.,="" monday="" through="" friday.="" list="" of="" subjects="" in="" 21="" cfr="" part="" 589="" animal="" feeds,="" animal="" foods,="" food="" additives.="" therefore,="" under="" the="" federal="" food,="" drug,="" and="" cosmetic="" act="" and="" under="" authority="" delegated="" to="" the="" commissioner="" of="" food="" and="" drugs,="" it="" is="" proposed="" that="" 21="" cfr="" part="" 589="" be="" amended="" as="" follows:="" part="" 589--substances="" prohibited="" from="" use="" in="" animal="" food="" or="" feed="" 1.="" the="" authority="" citation="" for="" 21="" cfr="" part="" 589="" continues="" to="" read="" as="" follows:="" authority:="" secs.="" 201,="" 402,="" 409,="" 701="" of="" the="" federal="" food,="" drug,="" and="" cosmetic="" act="" (21="" u.s.c.="" 321,="" 342,="" 348,="" 371).="" 2.="" new="" sec.="" 589.2000="" is="" added="" to="" subpart="" b="" to="" read="" as="" follows:="" sec.="" 589.2000="" animal="" proteins="" prohibited="" in="" ruminant="" feed.="" (a)="" definitions.="" (1)="" protein="" derived="" from="" ruminant="" and="" mink="" tissues="" means="" any="" protein-containing="" portion="" of="" ruminant="" animals="" or="" mink,="" excluding="" blood="" from="" bovines,="" milk="" proteins="" and="" gelatin.="" (2)="" renderer="" means="" any="" firm="" or="" individual="" that="" processes="" slaughter="" byproducts,="" animals="" unfit="" for="" human="" consumption,="" meat="" scraps="" or="" food="" waste.="" the="" term="" includes="" persons="" who="" collect="" such="" materials="" and="" subject="" them="" to="" minimal="" processing,="" or="" distribute="" them="" to="" firms="" other="" than="" renderers="" whose="" intended="" use="" for="" the="" products="" may="" include="" animal="" feed.="" the="" term="" includes="" renderers="" that="" also="" blend="" animal="" protein="" products.="" (3)="" blender="" means="" any="" firm="" or="" individual="" which="" obtains="" processed="" animal="" protein="" from="" more="" than="" one="" source="" or="" from="" more="" than="" one="" species,="" and="" subsequently="" mixes="" (blends)="" or="" redistributes="" an="" animal="" protein="" product.="" (4)="" feed="" manufacturer="" and="" distributor="" includes="" manufacturers="" and="" distributors="" of="" complete="" and="" intermediate="" feeds="" intended="" for="" animals,="" and="" includes="" on-farm="" in="" addition="" to="" off-farm="" feed="" manufacturing="" and="" mixing="" operations.="" (5)="" nonruminant="" protein="" includes="" protein="" from="" nonruminant="" animals="" and="" from="" vegetable="" sources.="" (b)="" food="" additive="" status.="" the="" food="" and="" drug="" administration="" has="" determined="" that="" protein="" derived="" from="" ruminant="" and="" mink="" tissues="" is="" not="" generally="" recognized="" as="" safe="" for="" use="" in="" ruminant="" feed="" because="" it="" may="" contain="" transmissible="" spongiform="" encephalopathy="" (tse)-infective="" material,="" and="" is="" a="" food="" additive="" subject="" to="" section="" 409="" of="" the="" federal="" food,="" drug,="" and="" cosmetic="" act="" (the="" act).="" in="" the="" absence="" of="" a="" regulation="" providing="" for="" its="" safe="" use="" as="" a="" food="" additive="" under="" section="" 409="" of="" the="" act,="" the="" use="" or="" intended="" use="" in="" ruminant="" feed="" of="" any="" material="" that="" contains="" protein="" derived="" from="" ruminant="" and="" mink="" tissues="" causes="" the="" feed="" to="" be="" adulterated="" and="" in="" violation="" of="" the="" act,="" unless="" it="" is="" the="" subject="" of="" an="" effective="" notice="" of="" claimed="" investigational="" exemption="" for="" a="" food="" additive="" under="" sec.="" 570.17="" of="" this="" chapter.="" the="" food="" and="" drug="" administration="" has="" determined="" that="" ruminant="" and="" mink="" derived="" protein="" is="" not="" prior="" sanctioned="" for="" use="" in="" ruminant="" feeds.="" (c)="" requirements="" for="" renderers="" that="" are="" not="" included="" in="" paragraph="" (e)="" of="" this="" section.="" (1)="" renderers="" that="" manufacture="" products="" that="" contain="" or="" may="" contain="" protein="" derived="" from="" ruminant="" and="" mink="" tissues="" and="" that="" are="" intended="" for="" use="" in="" animal="" feed="" shall="" take="" the="" following="" measures="" to="" ensure="" that="" materials="" identified="" in="" paragraph="" (b)="" of="" this="" section="" are="" not="" used="" in="" the="" feed="" of="" ruminants:="" (i)="" label="" the="" materials="" as="" follows:="" ``contains="" (or="" may="" contain)="" protein="" derived="" from="" ruminant="" and="" mink="" tissues.="" do="" not="" feed="" to="" ruminant="" animals,="" and="" do="" not="" use="" to="" manufacture="" feed="" intended="" for="" ruminant="" animals'';="" and="" (ii)="" maintain="" copies="" of="" sales="" invoices="" for="" the="" materials,="" and="" make="" the="" copies="" available="" for="" inspection="" and="" copying="" by="" the="" food="" and="" drug="" administration.="" (2)="" renderers="" described="" in="" paragraph="" (c)(1)="" of="" this="" section="" will="" be="" exempted="" from="" the="" requirements="" of="" paragraphs="" (c)(1)(i)="" and="" (c)(1)(ii)="" of="" this="" section="" if="" they:="" (i)="" use="" exclusively="" a="" manufacturing="" method="" that="" has="" been="" validated="" by="" the="" food="" and="" drug="" administration="" to="" deactivate="" the="" agent="" that="" causes="" tse's="" and="" whose="" design="" has="" been="" made="" available="" to="" the="" public;="" or="" (ii)="" use="" routinely="" a="" test="" method="" that="" has="" been="" validated="" by="" the="" food="" and="" drug="" administration="" to="" detect="" the="" presence="" of="" the="" agent="" that="" causes="" tse's="" and="" whose="" design="" has="" been="" made="" available="" to="" the="" public.="" products="" found="" to="" contain="" the="" agent="" that="" causes="" tse's="" shall="" be="" labeled="" ``not="" for="" use="" in="" animal="" feed.''="" records="" of="" the="" test="" results="" shall="" be="" made="" available="" for="" inspection="" by="" the="" food="" and="" drug="" administration.="" (3)="" renderers="" described="" in="" paragraph="" (c)(1)="" of="" this="" section="" who="" are="" not="" exempted="" under="" paragraph="" (c)(2)(i)="" or="" paragraph="" (c)(2)(ii)="" of="" this="" section="" will="" be="" exempted="" from="" the="" requirements="" of="" paragraph="" (c)(1)(ii)="" of="" this="" section="" if="" they="" use="" a="" permanent="" method,="" approved="" by="" fda,="" to="" mark="" the="" presence="" of="" the="" materials.="" if="" the="" marking="" is="" by="" the="" use="" of="" an="" agent="" that="" cannot="" be="" detected="" on="" visual="" inspection,="" the="" renderer="" must="" use="" an="" agent="" whose="" presence="" can="" be="" detected="" by="" a="" method="" that="" has="" been="" validated="" by="" the="" food="" and="" drug="" administration="" and="" whose="" design="" has="" been="" made="" available="" to="" the="" public.="" (d)="" requirements="" for="" protein="" blenders,="" and="" feed="" manufacturers="" and="" distributors,="" that="" are="" not="" included="" in="" paragraph="" (e)="" of="" this="" section.="" (1)="" protein="" blenders,="" and="" feed="" manufacturers="" and="" distributors,="" that="" manufacture,="" blend,="" process="" and="" distribute="" products="" that="" contain="" or="" may="" contain="" protein="" derived="" from="" ruminant="" and="" mink="" tissues="" shall:="" (i)="" comply="" with="" paragraph="" (c)(1)="" of="" this="" section,="" and="" (ii)="" maintain="" copies="" of="" invoices="" for="" purchase="" of="" animal="" protein="" products="" or="" feeds="" containing="" such="" products,="" and="" make="" copies="" available="" for="" inspection="" and="" copying="" by="" the="" food="" and="" drug="" administration.="" (2)="" protein="" blenders,="" and="" feed="" manufacturers="" and="" distributors,="" shall="" be="" exempt="" from="" paragraphs="" (d)(1)(i)="" and="" (d)(1)(ii)="" of="" this="" section="" if="" they:="" (i)="" purchase="" animal="" protein="" products="" from="" renderers="" that="" certified="" compliance="" with="" paragraph="" (c)(2)="" of="" this="" section="" or="" purchase="" such="" materials="" from="" parties="" [[page="" 583]]="" that="" certify="" that="" the="" materials="" were="" purchased="" from="" renderers="" that="" certified="" compliance="" with="" paragraph="" (c)(2);="" or="" (ii)="" comply="" with="" the="" requirements="" of="" paragraph="" (c)(2)="" of="" this="" section="" where="" appropriate.="" (3)="" protein="" blenders,="" and="" feed="" manufacturers="" and="" distributors,="" shall="" be="" exempt="" from="" paragraph="" (c)(1)(ii)="" of="" this="" section="" if="" they:="" (i)="" purchase="" animal="" protein="" products="" that="" are="" marked="" or="" purchase="" such="" materials="" from="" renderers="" that="" certified="" compliance="" with="" paragraph="" (c)(3)="" of="" this="" section,="" or="" purchase="" such="" materials="" from="" parties="" that="" certify="" that="" the="" materials="" were="" purchased="" from="" renderers="" that="" certified="" compliance="" with="" paragraph="" (c)(3)="" of="" this="" section;="" or="" (ii)="" comply="" with="" the="" requirements="" of="" paragraph="" (c)(3)="" of="" this="" section="" where="" appropriate.="" (4)="" copies="" of="" certifications="" as="" described="" in="" paragraphs="" (d)(2)="" and="" (d)(3)="" of="" this="" section,="" shall="" be="" made="" available="" for="" inspection="" and="" copying="" by="" the="" food="" and="" drug="" administration.="" (e)="" requirements="" for="" persons="" that="" intend="" to="" separate="" ruminant/mink="" and="" nonruminant/mink="" materials.="" (1)="" renderers,="" protein="" blenders,="" feed="" manufacturers="" and="" distributors,="" haulers="" and="" others="" that="" manufacture,="" process,="" blend="" and="" distribute="" both="" protein="" products="" derived="" from="" ruminant="" and="" mink="" tissues="" or="" feeds="" containing="" such="" products,="" and="" protein="" products="" from="" other="" animal="" tissues="" or="" feeds="" containing="" such="" products,="" and="" that="" intend="" to="" keep="" those="" products="" separate="" shall:="" (i)="" comply="" with="" paragraphs="" (c)(1)="" or="" (d)(1)="" of="" this="" section="" as="" appropriate="" except="" that="" the="" labeling="" requirement="" shall="" apply="" only="" to="" products="" derived="" from="" ruminant="" and="" mink="" tissues="" or="" feeds="" containing="" such="" products;="" (ii)="" in="" the="" case="" of="" a="" renderer,="" obtain="" nonruminant="" (excluding="" mink)="" materials="" only="" from="" single-species="" facilities;="" (iii)="" provide="" for="" measures="" to="" avoid="" commingling="" or="" cross-="" contamination:="" (a)="" maintain="" separate="" equipment="" or="" facilities="" for="" the="" manufacture,="" processing,="" or="" blending="" of="" such="" materials;="" or="" (b)="" use="" clean-out="" procedures="" or="" other="" means="" adequate="" to="" prevent="" carry-over="" of="" ruminant="" and="" mink="" derived="" protein="" into="" animal="" protein="" products="" or="" feeds="" that="" may="" be="" used="" for="" ruminants;="" and="" (iv)="" maintain="" written="" procedures="" specifying="" the="" clean-out="" procedures="" or="" other="" means,="" and="" specifying="" the="" procedures="" for="" separating="" ruminant="" and="" mink="" materials="" from="" nonruminant="" materials="" (excluding="" mink)="" from="" the="" time="" of="" receipt="" until="" the="" time="" of="" shipment.="" (2)="" renderers,="" blenders,="" and="" feed="" manufacturers="" and="" distributors="" will="" be="" exempted="" from="" appropriate="" requirements="" of="" paragraph="" (e)(1)="" of="" this="" section,="" if="" they="" meet="" the="" appropriate="" criteria="" for="" exemption="" under="" paragraphs="" (c)(2)="" or="" (c)(3),="" and="" (d)(2)="" or="" (d)(3)="" of="" this="" section.="" (f)="" requirements="" for="" establishments="" and="" individuals="" that="" are="" responsible="" for="" feeding="" ruminant="" animals.="" establishments="" and="" individuals="" that="" are="" responsible="" for="" feeding="" ruminant="" animals="" shall="" maintain="" copies="" of="" purchase="" invoices="" and="" labeling="" for="" all="" feeds="" received,="" and="" make="" the="" copies="" available="" for="" inspection="" and="" copying="" by="" the="" food="" and="" drug="" administration.="" (g)="" adulteration="" and="" misbranding.="" (1)="" animal="" protein="" products,="" and="" feeds="" containing="" such="" products,="" that="" are="" not="" in="" compliance="" with="" paragraphs="" (c)="" through="" (f)="" of="" this="" section,="" excluding="" labeling="" requirements,="" will="" be="" deemed="" adulterated="" under="" section="" 402(a)(2)(c)="" or="" 402(a)(4)="" of="" the="" act.="" (2)="" animal="" protein="" products,="" and="" feeds="" containing="" such="" products,="" that="" are="" not="" in="" compliance="" with="" the="" labeling="" requirements="" of="" paragraphs="" (c)="" through="" (f)="" of="" this="" section="" will="" be="" deemed="" misbranded="" under="" section="" 403(a)(1)="" of="" the="" act.="" (h)="" inspection;="" records="" retention.="" (1)="" records="" that="" are="" to="" be="" made="" available="" for="" inspection="" and="" copying,="" as="" required="" by="" this="" section,="" shall="" be="" kept="" for="" a="" minimum="" of="" 2="" years.="" (2)="" written="" procedures="" required="" by="" this="" section="" shall="" be="" made="" available="" for="" inspection="" and="" copying="" by="" the="" food="" and="" drug="" administration.="" dated:="" december="" 27,="" 1996.="" david="" a.="" kessler,="" commissioner="" of="" food="" and="" drugs.="" donna="" e.="" shalala,="" secretary="" of="" health="" and="" human="" services.="" [fr="" doc.="" 97-37="" filed="" 1-2-97;="" 8:45="" am]="" billing="" code="" 4160-01-f="">

Document Information

Published:
01/03/1997
Department:
Food and Drug Administration
Entry Type:
Proposed Rule
Action:
Proposed rule.
Document Number:
97-37
Dates:
Written comments by February 18, 1997. FDA proposes that any final rule that may issue based on this proposal become effective 60 days after the date of its publication in the Federal Register.
Pages:
552-583 (32 pages)
Docket Numbers:
Docket No. 96N-0135
RINs:
0910-AA91: Substances Prohibited From Use in Animal Food or Feed; Protein Derived From Ruminants Prohibited in Ruminant Feed
RIN Links:
https://www.federalregister.gov/regulations/0910-AA91/substances-prohibited-from-use-in-animal-food-or-feed-protein-derived-from-ruminants-prohibited-in-r
PDF File:
97-37.pdf
CFR: (4)
21 CFR 589.2000(c)
21 CFR 589.2000(e)
21 CFR 589.2000(e)(3)
21 CFR 589.2000