[Federal Register Volume 59, Number 166 (Monday, August 29, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-21278]
[[Page Unknown]]
[Federal Register: August 29, 1994]
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Part IX
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; Proposed Rule
Bovine-Derived Materials; Agenda Letters to Manufacturers of FDA-
Regulated Products; Notice
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 589
[Docket No. 93N-0467]
Substances Prohibited From Use in Animal Food or Feed; Specified
Offal From Adult Sheep and Goats Prohibited in Ruminant Feed; Scrapie
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) proposes to declare
that specified offal from adult (more than 12 months of age) sheep and
goats is not generally recognized as safe (GRAS) for use in ruminant
feed and is an unapproved food additive when added to ruminant feed.
Accordingly, in the absence of an approved food additive regulation or
investigational exemption, the use in ruminant feed of ingredients
containing specified offal from adult sheep or goats will cause the
feeds to be considered adulterated within the meaning of the Federal
Food, Drug, and Cosmetic Act (the act). FDA is proposing this action
because the specified offal may contain the agent that causes scrapie,
a transmissible spongiform encephalopathy (TSE) of sheep and goats. In
the United Kingdom scrapie has been epidemiologically associated with
the occurrence of bovine spongiform encephalopathy (BSE), another TSE.
Because FDA cannot positively rule out a direct association between
scrapie, BSE and human TSE's, FDA is proposing this action to protect
the health of animals and humans.
DATES: Written comments by November 14, 1994. FDA is proposing that any
final rule that may issue based upon this proposal become effective 30
days after its publication in the Federal Register).
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr.,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: John P. Honstead, Center For
Veterinary Medicine (HFV-222), Food and Drug Administration, 7500
Standish Pl., Rockville, MD 20855, 301-594-1728.
SUPPLEMENTARY INFORMATION:
I. Background
Processed tissues from sheep and goats are used as ingredients in
animal feeds. These products are derived from slaughter byproducts
(slaughter inedibles) and dead, dying, diseased, and disabled (4-D)
animals. The slaughter inedibles include certain offal (brain, spinal
cord, spleen, thymus, tonsil, lymph nodes, or intestines) that is
subject of this proposed rule. Four-D animals also contain these
designated materials. Such materials are designated ``specified
offals'' in this proposed rule.
The Association of American Feed Control Officials (AAFCO) has
recognized and defined several animal products as feed ingredients in
its official publication (Ref. 1). Products which are likely to contain
specified offal include, dried meat solubles, glandular meal, meat
meal, meat and bone meal, animal byproduct meal, meat meal tankage,
animal digest, bone ash, bone charcoal, spent bone charcoal, cooked
bone meal, and bone phosphate.
A. Processing Animal Tissues for Feed Ingredients
Generally, feed ingredients from slaughter byproducts and 4-D
animals are processed by rendering. Rendering involves cooking the
slaughter byproducts or the whole carcasses of 4-D animals at 240 to
290 deg.F for 20 minutes to 3 hours to separate oils, fats, and
protein (Ref. 2). These rendered products are used as ingredients to
provide essential nutrients in animal feed. However, there are
processes other than rendering, such as drying, in which slaughter
byproducts are manufactured into feed ingredients.
Because of the prolonged application of heat and the associated
transformation of the tissues, rendering is generally regarded by FDA
as a process that ensures that the ingredients pose no threat of
disease to animals or to the health of humans who consume animal
products such as meat, milk, and eggs. In its role as regulator of
rendering practices, FDA has focused on the efficacy of a facility's
rendering process in the prevention of disease transmission and the
prevention of contamination of the finished products (Ref. 3). FDA has
no previous evidence of a human or animal health TSE hazard or any
other health hazard associated with the feeding of adequately rendered
ingredients to animals. Processed animal byproducts have a long history
of safe use in the United States as a source of nutrients for animals.
However, the agent responsible for the transmission of BSE and
related TSE diseases is not well characterized. It is believed to be a
cattle variant of the sheep scrapie agent (Refs. 4 and 5). As explained
more fully below, epidemiological evidence from the United Kingdom
suggests that a disease agent contained in sheep may have survived the
rendering process to cause BSE in cattle. This is the first reported
instance in which it is suspected that a disease agent survived
rendering.
The occurrence of BSE in cattle has not been shown to cause a TSE
disease in humans (Ref. 6). On the other hand, the possibility of a
causal relationship has not been disproved. BSE has not been diagnosed
in cattle in the United States (Ref. 7). However, sheep scrapie is
present in the United States. Accordingly, the agency believes that the
potential implications for humans as well as animal health require
regulatory action to minimize the possibility for the introduction of
the disease into U.S. cattle. For reasons described more fully below,
FDA is proposing that any feed ingredient that contains specified offal
from adult sheep or goats is a food additive when added to the feed of
ruminants.
B. Transmissible Spongiform Encephalopathies (TSE's)
TSE's are progressively degenerative central nervous system (CNS)
diseases of man and animals that are characterized by a long incubation
period, a relatively short clinical course of neurological signs, and a
100-percent mortality (Ref. 8). TSE's are believed to be caused by
abnormal isoform neuronal membrane proteins which contain no detectable
nucleic acids, are resistant to most methods of sterilization, and
survive severe environmental conditions such as 360 deg.C dry heat
(Refs. 6 and 9). The agent, however, is not generally believed to be a
virus, but rather a protein devoid of nucleic acid components. Nucleic
acid components are characteristic of other living microorganisms.
These proteins have been termed prions, and are abnormal forms of
proteins already present in all animals (Refs. 10 and 11). 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 some
cases of sheep scrapie and human TSE diseases including Creutzfeldt-
Jakob disease, and Gerstmann-Straussler Syndrome (Ref. 12).
Antemortem diagnostic tests for the detection of TSE do not exist.
Postmortem tests are required to confirm suspected TSE cases. The
observation of histopathological changes in the brain, such as
vacuolization of the brainstem, are positive indicators (Ref. 13).
Other diagnostic tests available are immunohistochemical staining and
immunoblotting the abnormal protein (Ref. 14). 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. 15).
1. Sheep 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,
depression, 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 is both vertical
(mother to offspring in utero) (Ref. 16) and horizontal (direct
contact) between sheep (Ref. 15). 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.
17). Since there is no detectable immune response to scrapie, diagnosis
of scrapie in live sheep is possible only when clinical signs are
evident and must be confirmed by histopathology at postmortem (Ref.
14).
The scrapie agent may be identified in lymphatic tissue (spleen,
thymus, tonsil, and lymph nodes) in sheep with preclinical infections;
however, in clinically affected adult sheep, the agent is identified in
the intestines, nervous tissues (brain and spinal cord), and lymphatic
tissues (Ref. 15). The brain has been shown to contain by far the
highest scrapie infectivity of any body tissue.
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.
18).
In 1993, there were estimated to be a total of 11 million sheep in
112,000 flocks in the United States. At the present time, there are 108
known scrapie-infected flocks (flocks with sheep diagnosed with
scrapie) containing a total of 7,430 sheep, and there are 13 known
scrapie-source flocks (flocks to which scrapie-infected sheep were
traced) containing a total of 3,418 sheep (Ref. 19).
In the absence of an antemortem diagnostic test, it is not possible
to establish with absolute certainty that a flock is free of scrapie
infection. 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 accurately monitor
scrapie in the United States.
2. Bovine Spongiform Encephalopathy (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. In retrospect, the literature indicates that the first clinical
case of BSE may have been observed as early as April 1985 (Ref. 20). As
of September 1993, there have been more than 100,000 confirmed cases of
BSE in England, Scotland, and Wales. In the United Kingdom, 44 percent
of the dairy herds and 9 percent of the beef herds are infected (Ref.
21). BSE has also been reported in Northern Ireland, the Republic of
Ireland, Switzerland, France, Oman, and the Falkland Islands (Ref. 22).
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.
21). The clinical signs usually begin with changes in animal behavior
that are suggestive of apprehension, anxiety, and fear. There is
increased reaction to sound and touch. A swaying gait is sometimes
coupled with high stepping of the feet and is most evident in the hind
limbs. Changes in the normal behavior of the individual cow may also
include separation from the rest of the herd while at pasture,
disorientation, or excessive licking of the nose or flanks (Ref. 23).
The most common history given by the herdsman was nervousness or
altered behavior or temperament, weakness associated with pelvic limb
ataxia, paresis, and loss of body weight (Ref. 24).
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. 25 and 26).
3. Other Animal TSE's
Transmissible mink encephalopathy (TME) is a mink disease with
clinical signs and brain lesions similar to those of sheep infected
with scrapie. The development of TME on a mink farm that reportedly fed
only cattle byproducts has led some to believe that BSE exists at a low
level in the United States (Ref. 27). TME is a rare disease in the
United States, with only 5 outbreaks (involving 11 mink farms) reported
in the last 50 years. Based on available evidence, the U.S. Department
of Agriculture (USDA) has concluded that the byproducts from United
States cattle are unlikely to have caused the TME outbreak on the mink
farm (Ref. 28).
Other animals have TSE's with typical characteristics of long
incubation, neurological degeneration, and a 100-percent death rate.
These include elk and deer (Refs. 29 and 30), zoo ruminants (Refs. 31,
32, and 33), and domestic cats (Refs. 34 and 35).
C. 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 that rendered feed
ingredients contaminated with sheep scrapie and BSE agents served as
the common source of infection. One study demonstrated that meat and
bone meal could be incorporated into the cattle feed in sufficient
quantity to initiate clinical BSE in some of the animals that consumed
the feed (Ref. 36). Thus far, other research has not confirmed that the
feeding of scrapie-infected feed ingredients to cattle produces BSE.
Therefore, the theory that BSE evolved naturally in cattle has not been
ruled out (Ref. 37). Furthermore, the United Kingdom studies suggest
that the spread of BSE appeared to have been exacerbated by the
practice of feeding ingredients from rendered BSE-infected cattle to
calves, a practice that was subsequently banned. Incomplete immediate
compliance with the feeding ban may account for the fact that some
calves born after the ban continue to be infected with BSE has
complicated any theory of vertical transmission of the disease.
Maternal transmission has been documented, but at a rate insufficient
to maintain the epidemic (Ref. 38).
Investigators have identified major risk factors that apparently
contributed to the emergence of BSE epidemic in the United Kingdom
(Refs. 39 to 42). These include:
(1) A large sheep population, relative to cattle population;
(2) A high scrapie incidence rate;
(3) The practice of feeding rendered products from BSE-infected
cattle to young cattle at high amounts (up to 4 percent of the diet);
(4) The feeding of greaves. In the United Kingdom, whole dead
animals were processed as a source of tallow. The remaining unextracted
bone and protein solids, termed ``greaves,'' were used as dairy calf
feed. The greaves may have contained the BSE agent. This practice is
not followed in the United States and has stopped in the United
Kingdom; and
(5) Changes in the rendering process. In 1981-1982, the rendering
industry in the United Kingdom reduced the use of hydrocarbon solvent
extraction in the rendering process (Ref. 43). The United States
rendering industry had taken this step in the 1970's. The appearance of
BSE in the United Kingdom approximately 3 years after the change in the
rendering process is consistent with the 2- to 8-year incubation period
of BSE. The epidemiological evidence has suggested that changes in the
solvent extraction process was the major factor responsible for
initiating a BSE epidemic in the United Kingdom. Furthermore,
laboratory tests based on intracerebral injection studies in rodents
indicated that the hydrocarbon extraction method inactivated the
causative agent while the heat method did not inactivate the scrapie-
like agent present in rendered animal byproducts (Refs. 13 and 40). The
heat extraction method is the most common rendering process currently
in use world wide.
D. Historical Efforts To Control BSE
1. United Kingdom Regulatory Actions
Regulatory controls taken to manage the BSE epidemic in the United
Kingdom and to address public health concern 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 1988 on the human
consumption of specified offals (including brain, spinal cord, thymus,
spleen, tonsils, and intestines) of ruminants; and (5) a ban in
September 1990 of feeding any ingredient containing specified offals to
all pet and farm animals.
The Office Internationale Epizootics (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. 44). OIE has recommended that British manufacturers of human and
animal drugs and biologics not use source material from BSE-positive
countries.
2. United States Regulatory Actions
The USDA Animal and Plant Health Inspection Service (APHIS) has had
a scrapie control program in effect since 1952. This program has been
responsible for the relatively low incidence of the disease in the
United States. 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 above, the regulation requires that
imported meat for human or animal consumption from the ruminants in the
Bovidae family (e.g., cattle) 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.
In addition to these import restrictions, 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
States. APHIS is tracing the movement and current health status of 459
cattle that were imported from United Kingdom between 1981 and 1989.
Due to concerns about BSE in the United States, USDA has
implemented several programs to monitor United States cattle.
Pathologists at Iowa State University and the National Veterinary
Service Laboratories (NVSL) of APHIS, USDA, are examining bovine brains
submitted to NVSL from the following sources: (1) Foreign animal
disease investigations where suspected encephalitic conditions in
cattle are reported; (2) Centers for Disease Control laboratories
(specimens that were found negative for rabies); (3) the USDA Food
Safety and Inspection Service (specimens from nonambulatory, commonly
called downer cows); and (4) veterinary diagnostic laboratories in the
United States. Between 1989 and October 1993, a total of 1,153 bovine
brains have been examined and none of these specimens contained lesions
with the characteristics and distribution typical for BSE (Ref. 45).
This program is ongoing. Data on the incidence of cattle in the United
States showing clinical symptoms of CNS disease that are similar to
clinical symptoms of BSE have shown no increase during the past 5 years
(Ref. 46).
To decrease further the incidence of scrapie and the threat of BSE
in the United States, APHIS, in 1992, initiated a voluntary
certification program for sheep (57 FR 58132, December 9, 1992). Flocks
that have not had a diagnosed case of scrapie within 5 years, or a case
traced back to the flock in 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.
3. Voluntary Ban by Renderers
In 1989, the National Renderers Association (NRA) and the Animal
Protein Producers Industry (APPI) recommended to its members that they
stop rendering adult sheep or sheep offal for sale as meat and bone
meal for inclusion in cattle feed (Ref. 47). Following adoption of the
voluntary ban, the 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 to: (1) Assess
compliance by United States renderers with the industry imposed
voluntary ban on rendering adult sheep for cattle feed; (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 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 was not fully implemented at the time of the survey (Ref.
48).
II. The Regulatory Issues
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)(2) of
the act (21 U.S.C. 348(a)(2)), a food additive is unsafe unless 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 Sec. 570.38 (21 CFR 570.38). The
Commissioner of Food and Drugs (the Commissioner), on his own
initiative or at the request of an interested party, 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 and
Sec. 570.38. Subsequent to the publication of such a proposal and after
consideration of public comments, the Commissioner 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); United States v. Naremco, supra, 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, 752 F.2d
11, 15 (1st Cir. 1985)).
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. Food Additive Status of Specified Offal From Adult Sheep and Goats
The agency recognizes that the processed slaughter byproducts and
4-D adult sheep and goats have a long history of use in animal feeds
without known adverse effects. However, the evidence 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 believes that the epidemiological evidence linking the
occurrence of BSE in ruminants with the feed ingredients containing
specified offal from adult sheep and goats precludes any claim of
reliance upon a general recognition of safety as a sufficient basis for
the continued use of these specified offals in food.
The agency reached this conclusion in light of the findings
regarding a possible mechanism for the transmission of BSE to ruminants
as a result of feed ingredients containing specified offal from
scrapie-infected adult sheep and goats, as discussed in section I.B. of
this document. FDA cannot determine what level of feed ingredients from
processed adult sheep and goat products, if any, is safe in ruminant
feed.
A search of the scientific literature did not reveal information
that would provide a basis for the GRAS status of feed ingredients
derived from processed adult sheep or goat slaughter byproducts. Nor is
the agency aware of a prior sanction for any feed products that contain
these products.
In view of the above, FDA has preliminarily concluded that the
addition of specified offal to ruminant feed constitutes, in light of
the epidemiological evidence about BSE, the use of an unapproved food
additive. A regulation for the use of processed adult sheep- and goat-
specified offal in ruminant feed is not in effect. Therefore, it is
FDA's preliminary conclusion that any ruminant feed that contains such
an ingredient is adulterated. Accordingly, FDA is proposing to list
specified offal from sheep or goat over 12 months of age in 21 CFR Part
589--Substances Prohibited From Use in Animal Food or Feed.
III. Description of the Proposed Rule
The proposed rule would prohibit use of any feed ingredient
containing specified offal from sheep and goats over 12 months of age
in ruminant feed. Specified offal is defined as any tissue from the
brain, spinal cord, spleen, thymus, tonsil, lymph nodes, or intestines
(duodenum to anus, inclusive) of sheep or goats, or any processed
product that is reasonably expected to contain specified offal.
A. Exclusion of Sheep and Goats Under 12 Months
The exclusion of animal tissues from young animals is based on the
observation that sheep less than 12 months old rarely exhibit clinical
symptoms of scrapie, although a few cases have been reported in sheep
as young as 7 months (Ref. 49). Historically, APHIS scrapie regulations
and indemnity programs have used a 12-month cutoff for eligible adult
sheep. The NRA and APPI voluntary ban on rendering sheep for cattle
feed also used a 12-month cutoff for high-risk sheep. The median age of
onset of clinical scrapie is 3 1/2 years, and 82 percent of sheep died
of scrapie between the ages of 2 and 5 years (Ref. 14). Based on all of
the available data, the agency has tentatively concluded that any
ruminant feed ingredients derived from sheep and goats under 12 months
of age represent a minimal risk of exposure to the scrapie agent. The
agency invites comment on the exclusion of sheep and goats less than 12
months old from the proposed ban.
B. Inclusion of Goats
Scrapie is a disease which may affect both sheep and goats.
However, in the United States only four cases have been diagnosed in
goats (Ref. 18). All four goats were raised with sheep flocks in which
sheep scrapie was present. Even though the number of reported cases in
goats is low, there may be a substantial number of cases undiagnosed
and unreported. Because of the possibility of unreported scrapies in
goats, FDA is proposing to include adult goats in this regulation. The
agency invites comment on the inclusion of adult goats in the proposed
rule.
C. Exemption of APHIS-Certified Flocks
FDA has considered exempting adult sheep and goats from one or more
categories of APHIS-certified flocks from this prohibition. This would
provide added incentive for producers to enroll in the certification
program. On the other hand, such exclusion could cause enforcement
difficulties, because of the need for separate identification of sheep
and goats from certified flocks. The agency has tentatively decided not
to exempt specified offal from certified flocks. However, the agency
invites comment on this issue, and will consider adding the exclusion
to the final rule.
D. Summary of the Basis for FDA Regulation
Epidemiological studies in the United Kingdom indicate that feeding
calves products containing feed ingredients processed from sheep
infected with scrapie initiated BSE in cattle. Scrapie-infected sheep
flocks are present in the United States, and the scrapie agent is known
to survive the rendering procedures currently in use. A 1992 FDA survey
showed that renderers have not complied fully with their voluntary ban
on selling rendered adult sheep products for use in cattle feed. Thus,
to help prevent a BSE outbreak in the United States, regulation and
enforcement are needed to ensure that feed ingredients made from
specified offal derived from processed slaughter inedibles and
carcasses of adult sheep and goats are not used in ruminant feed.
The agency has considered whether to impose a broader ruminant-to-
ruminant ban, i.e., a restriction on feeding to cattle and other
ruminants the specified offal from all ruminants rather than just from
sheep and goats. The purpose of a ruminant-to-ruminant ban would be to
prevent the spread of BSE between cows. Since no case of BSE has been
documented in the United States under the extensive monitoring
described in section I.D.2. of this document, the agency has determined
that a broader ruminant-to-ruminant ban is not warranted at this time.
If, and when, BSE is documented in the United States, the agency will
reevaluate this determination.
While controlled scientific studies have not established a
definitive association between scrapie and BSE, epidemiologic studies
have linked the feeding of scrapie infected feedstuffs to cattle with
the occurrence of BSE. Therefore, the agency believes the action set
forth in this proposal is warranted to minimize the potential risk that
scrapie from sheep and goats may result in the introduction of BSE to
cattle in the United States in light of the impact that BSE may have on
animal and human health. The agency's proposal is consistent with
action taken by APHIS, USDA to reduce the risk that BSE will occur in
the United States by eliminating scrapie from U.S. sheep.
IV. Environmental Impact
FDA has carefully considered the potential environmental effects of
this proposed rule and 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.
V. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354).
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; distributive impacts; and equity). The agency believes that
this proposed rule is consistent with the regulatory philosophy and
principles identified in the Executive Order. In addition, the proposed
rule is not a significant regulatory action as defined by the Executive
Order and so is not subject to review under the Executive Order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Based on a study conducted for the agency by the
Eastern Research Group (ERG), a private consulting firm, FDA has
determined the annual costs of the proposed regulation to the affected
industries. FDA estimated the annual loss of revenues to the sheep
ranching and goat ranching industries to be $2,400,000 and $1,500,000,
respectively. FDA further estimated the decrease in profits to the
slaughtering and rendering industries due to the decline in
slaughtering and rendering activities to be $356,000 per year.
Additional disposal costs to slaughterers are estimated to range from
$111,000 to $166,000 per year. The effects of the proposed regulation
on feed manufacturers are believed to be negligible. Therefore, the
agency certifies that the proposed rule will not have a significant
economic impact on a substantial number of small entities, and, under
the Regulatory Flexibility Act, no further analysis is required.
A copy of the ERG report supporting these determinations is on file
with the Dockets Management Branch (address above).
VI. 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. AAFCO, ``Official Publication 1993 Association of American
Feed Control Officials,'' pp. 128-137, 1993.
2. John, R. E., ``National Renderers Association Feed Safety
Assurance Efforts,'' in a symposium, ``Feed Quality Assurance, A
System-Wide Approach,'' p. 67, 1990.
3. FDA, Compliance Policy Guide 7126.24, ``Rendered Animal Feed
Ingredients,'' 1980.
4. Hope, J. et al., ``Fibrils From Brains of Cows With New
Cattle Disease Contain Scrapie-Associated Protein,'' Nature,
336:390, 1988.
5. Kimberlin, R. H., ``Transmissible Encephalopathies in
Animals,'' Canadian Journal of Veterinary Research, 54:30-37, 1990.
6. Taylor, D. M., ``Inactivation of BSE Agent,'' in ``Symposium
on Virological Aspects of the Safety of Biological Products,'' 1990.
7. USDA, ``Bovine Spongiform Encephalopathy Surveillance in the
United States,'' 1993.
8. McCaskey, P. C., ``Spongiform Encephalopathy in Other
Species,'' Toxicology Forum, 185-195, 1991.
9. Brown, P., P. P. Liberski, A. Wolff, and D. C. Gajdusek,
``Resistance of Scrapie Infectivity to Steam Autoclaving After
Formaldehyde Fixation and Limited Survival After Ashing at 360
deg.C: Practical and Theoretical Implications,'' Journal of
Infectious Diseases, 161:467-472, 1989.
10. Prusiner, S. B. et al., ``Immunologic and Molecular Biologic
Studies of Prion Proteins in Bovine Spongiform Encephalopathy,''
Journal of Infections Diseases, 167:602-613, 1993.
11. Stahl, N. and S. B. Prusiner, ``Prions and Prion Proteins,''
FASEB Journal, 5:2799-2807, 1991.
12. Hsiao, K., ``Mutation of the Prion Protein in Libyan Jews
With Creutzfeldt-Jakob Disease,'' New England Journal of Medicine,
324:1091-1097, 1991.
13. Kimberlin, R. H., ``Bovine Spongiform Encephalopathy,''
Scientific and Technical Review, 11(2):347-390, 1992.
14. Detweiler, L. A., ``Scrapie,'' Revue Scientifique et
Technique, Office Internationale Epizootics, 11(2):491-537, 1992.
15. Hadlow, W. J., R. C. Kennedy, and R. E. Race, ``Natural
Infection of Suffolk Sheep With Scrapie Virus,'' Journal of
Infectious Diseases, 146:657, 1982.
16. Foster, J. D. et al., ``Studies on Maternal Transmission of
Scrapie in Sheep,'' Veterinary Record, 130:341-343, 1992.
17. Kimberling, C. V., ``Jensen and Swift's Diseases of Sheep,''
Lea and Febiger, pp. 336-340, Philadelphia, 1988.
18. USDA, APHIS, Veterinary Services, ``Fact Sheet: Scrapie,''
June 1993.
19. Lang, J., ``Scrapie Progress Report,'' 1(1):1-4, March 15,
1993.
20. Wells, G. A. H., A. C. Scott, and C. T. Johnson, et al., ``A
Novel Progressive Spongiform Encephalopathy in Cattle,'' Veterinary
Record, 121:419-420, 1987.
21. Bradley, R., ``Editorial: Bovine Spongiform Encephalopathy:
The Need for Knowledge, Balance, Patience, and Action,'' Journal of
Pathology, 160:283-285, 1990.
22. Denny, O, A. Doherty, B. Hornlimann, and J. Wilesmith,
``Bovine Spongiform Encephalopathy,'' in ``DxMonitor,'' Summer 1993.
23. Hueston, W., ``Clinical Signs of BSE,'' in ``Animal Health
Insight,'' Summer:4, 1991.
24. Wilesmith, J. W., G. A. H. Wells, M. P. Cranwell, and J. B.
M. Ryan, ``Bovine Spongiform Encephalopathy: Epidemiological
Studies,'' Veterinary Record, 123:638-644, 1988.
25. Wells, G. A. H. et al., ``Bovine Spongiform Encephalopathy:
Diagnostic Significance of Vacuolar Changes in Selected Nuclei of
the Medulla Oblongata,'' Veterinary Record, 125:521-524, 1989.
26. Davis, A. J., A. L. Jenny, and L. D. Miller, ``Diagnostic
Characteristics of Bovine Spongiform Encephalopathy,'' Journal of
Veterinary Diagnostic Investigations, 3:266-271, 1991.
27. Marsh, R. F. and R. A. Bessen, ``Epidemiologic and
Experimental Studies on Transmissible Mink Encephalopathy,'' in
``Transmissible Spongiform Encephalopathy--Impact on Animal and
Human Health,'' 80:105-112, 1993.
28. Bridges, V., A. Bleem, and K. Walker, ``Risk of
Transmissible Mink Encephalopathy in the United States,'' in
``Animal Health Insight,'' pp. 7-14, USDA Veterinary Services, Fall
1991.
29. Williams, E. S. and S. Young, ``Neuropathology of Chronic
Wasting Disease of Mule Deer and Elk,'' Veterinary Pathology, 30:36-
45, 1993.
30. Williams, E. S. and S. Young, ``Chronic Wasting Disease of
Captive Mule Deer: A Spongiform Encephalopathy,'' Journal of
Wildlife Diseases, 16-1:89-98, 1980.
31. Fleetwood, A. J. and C. W. Furley, ``Spongiform
Encephalopathy in an Eland,'' Veterinary Record, April 21, 1990.
32. Jeffrey, M. and G. A. H. Wells, ``Spongiform Encephalopathy
in a Nyala,'' Veterinary Pathology, 25:398-399, 1988.
33. Kirkwood, J. K. et al, ``Spongiform Encephalopathy in an
Arabian Oryx and a Greater Kudu,'' Veterinary Record, 127,17:418-
420, 1990.
34. Wyatt, J. M. et al., ``Naturally Occurring Scrapie-like
Spongiform Encephalopathy in Five Domestic Cats,'' Veterinary
Record, 129:233-236, 1991.
35. Leggett, M. M., J. Dukes, and H. M. Pirie, ``A Spongiform
Encephalopathy in a Cat,'' Veterinary Record, 1990.
36. Collee, J. G., ``Food Borne Illness--Bovine Spongiform
Encephalopathy,'' Lancet, 336:1300-1303, 1990.
37. Fraser, H. et al., ``Transmission of Bovine Spongiform
Encephalopathy and Scrapie to Mice,'' Journal of General Virology,
73:1891-1897, 1992.
38. Robinson, M. M., ``Bovine Spongiform Encephalopathy,''
Foreign Animal Disease, pp. 134-138, 1992.
39. USDA, APHIS, ``Qualitative Analysis of BSE Risk Factors in
the United States,'' 1991.
40. USDA, APHIS, ``Quantitative Risk Assessment of BSE in United
States,'' 1991.
41. Walker, K. D. et al, ``Comparison of Bovine Spongiform
Encephalopathy Risk Factors in the United States and Great
Britain,'' Journal of the American Veterinary Medical Association,
199:11, 1554-1561, 1991.
42. USDA, ``A Review of Bovine Spongiform Encephalopathy in
Great Britain and an Update on Risk Factors for BSE in the United
States,'' 1993.
43. Wilesmith, J. W., ``The Epidemiology of Bovine Spongiform
Encephalopathy,'' Seminars in Virology, 2:239-245, 1991.
44. Office Internationale Epizootics, International Animal
Health Code, chapter 3.2.13 on BSE, pp. 231-235, July 1993.
45. 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.
46. Fancy, B., W. Hueston, A. Davis, A. Jenny, and L. Miller,
``Retrospective Surveillance for Bovine Spongiform Encephalopathy
(BSE) in the United States,'' in ``Animal Health Insight,'' pp. 11-
16, Winter 1991.
47. Bisplinghoff, F. D., National Renderers Association letter
to Animal Protein Producers, 1989.
48. FDA, ``Report of Findings of Directed Inspections of Sheep
Rendering Facilities,'' January 1993.
49. 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.
VII. Comments
Interested persons may, on or before November 14, 1994, submit
comments 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 Specified offal from sheep and goats over 12 months old.
(a) The Food and Drug Administration has determined that specified
offal from sheep and goats over 12 months old is not generally
recognized as safe for use in ruminant feed and is a food additive
subject to section 409 of the Federal Food, Drug, and Cosmetic Act (the
act). The Food and Drug Administration has determined that specified
offal from sheep and goats over 12 months old is not prior sanctioned
for use in ruminant feed. In the absence of a regulation providing for
its safe use as a food additive under section 409 of the act, the use
in ruminant feed of ingredients containing specified offal from sheep
and goats over 12 months old causes the feed to be adulterated and in
violation of the act, unless it is subject to an effective notice of
claimed exemption for a food additive under Sec. 570.17 of this
chapter.
(b) For purposes of this part, the term ``specified offal'' means
any tissue from the brain, spinal cord, spleen, thymus, tonsil, lymph
nodes, or intestines (duodenum to anus, inclusive) of sheep or goats or
any processed product that is reasonably expected to contain specified
offal. Processed products that may contain specified offal include, but
are not limited to, meat meal, meat and bone meal, animal byproduct
meal, meat byproducts, glandular meal, and cooked bone meal.
Dated: August 16, 1994.
Linda A. Suydam,
Interim Deputy Commissioner for Operations.
[FR Doc. 94-21278 Filed 8-26-94; 8:45 am]
BILLING CODE 4160-01-F
