99-27640. Packaging and Handling of Infectious Substances and Select Agents  

  • [Federal Register Volume 64, Number 208 (Thursday, October 28, 1999)]
    [Proposed Rules]
    [Pages 58022-58031]
    From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
    [FR Doc No: 99-27640]
    
    
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    DEPARTMENT OF HEALTH AND HUMAN SERVICES
    
    Centers for Disease Control and Prevention
    
    42 CFR Part 72
    
    RIN 0920-AA02
    
    
    Packaging and Handling of Infectious Substances and Select Agents
    
    AGENCY: Centers for Disease Control and Prevention (CDC), HHS.
    
    ACTION: Notice of proposed rulemaking.
    
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    SUMMARY: The Centers for Disease Control and Prevention proposes to
    
    [[Page 58023]]
    
    amend the regulations concerning the interstate shipment of infectious 
    substances in order to clarify and expand the existing requirements for 
    proper packaging and handling of these agents. One purpose of the 
    proposed rule is to ensure that all biological materials that are known 
    or suspected of containing an infectious substance are packaged for 
    interstate shipment to minimize the potential for leakage of contents 
    that could contaminate the environment or come into direct physical 
    contact with persons handling such packages during transit. A second 
    purpose is to insure receipt of certain infectious substances. This new 
    regulation will harmonize CDC regulations with other Federal agencies' 
    regulations and with international regulations.
        It also updates the requirements for facilities transferring or 
    receiving select agents, incorporating by reference the 4th edition of 
    the CDC/NIH publication Biosafety in Microbiological and Biomedical 
    Laboratories.
    
    DATE: Written comments must be received on or before December 27, 1999. 
    Written comments on the proposed information collection requirements 
    should also be submitted on or before December 27, 1999.
    
    ADDRESSES: Mail written comments to the following address: Nashandra 
    Hayes, Office of Health and Safety, Centers for Disease Control and 
    Prevention, 1600 Clifton Road, Mail Stop--FO5, Atlanta, Georgia 30333.
        Mail written comments on the proposed information collection 
    requirements to: Wendy Taylor, Office of Information and Regulatory 
    Affairs, Office of Management and Budget, New Executive Office 
    Building, 725 17th Street, NW, rm. 10235, Washington, DC 20503, Att.: 
    Desk Officer for CDC.
    
    FOR FURTHER INFORMATION CONTACT: Dr. Jonathan Y. Richmond or Dr. 
    Richard Knudsen, Office of Health and Safety, Centers for Disease 
    Control and Prevention, 1600 Clifton Road, NE, Mail Stop F05, Atlanta, 
    Georgia 30333; telephone (404) 639-2453 or 639-3235, respectively.
    
    SUPPLEMENTARY INFORMATION:
    
    Revised Proposed Notice of Rulemaking
    
        Replaces NPRM at 55 FR 7678, March 2, 1990.
    
    I. Background
    
        Under 42 U.S.C. 264, the Department of Health and Human Services is 
    authorized to promulgate regulations to prevent the introduction, 
    transmission and spread of communicable diseases from foreign countries 
    and between the states. Authority was given to CDC in 1971 to regulate 
    the interstate shipment of infectious substances. The current 
    regulations are at 42 CFR part 72. The regulations provide requirements 
    for minimum packaging and labeling for biological products and 
    diagnostic specimens, and include a list of infectious agents for which 
    special tracking is required. These regulations were last updated in 
    1980.
        A Notice of Proposed Rulemaking (NPRM) was published in the Federal 
    Register on March 2, 1990 (55 FR 7678), to update the existing 
    packaging requirements for infectious substances. Impetus for that NPRM 
    came from postal workers and members of Congress who expressed concerns 
    about the potential risk of exposure to infectious agents for people 
    who handle improperly packaged or damaged packages of biomedical 
    material during transit. Persons shipping these materials also stated 
    that some definitions in the 1980 regulation were unclear. There had 
    also been changes in the list of infectious agents that required 
    notification of receipt.
        Comments on the 1990 NPRM focused on two major issues. Numerous 
    parties, including United States Postal Service workers, submitted 
    comments regarding the transport of clinical specimens for diagnostic 
    studies. Several parties encouraged CDC to harmonize the proposed 
    regulation with the international shipping regulations.
        Several government agencies and industry groups, in addition to 
    CDC, regulate the packaging, labeling and shipment of infectious 
    materials within the United States and internationally.
         The Department of Transportation (DOT) Hazardous Materials 
    regulations, at 49 CFR parts 171-180, regulate the interstate 
    transportation by surface or air of infectious substances, medical 
    waste, chemical and radioactive materials. That regulation does not 
    apply to the transport of clinical or diagnostic specimens, unless 
    specifically known to contain an infectious substance (49 CFR 173.134).
         The United States Postal Service (USPS) regulates the 
    shipment, by U.S. mail, of etiologic agents, infectious substances, 
    clinical specimens, biological products, and sharps (e.g., contaminated 
    needles and other sharp medical materials) and unsterilized containers 
    (39 CFR and Domestic Mail Manual C023, Etiologic Agent Preparations, 
    Clinical Specimens, and Biological Products; and International Mail 
    Manual 135 Mailable Dangerous Goods).
         The Department of Labor, Occupational Safety and Health 
    Administration (OSHA), at 29 CFR 1910.1030, Occupational Exposure to 
    Bloodborne Pathogens, regulates the worker safety aspects of the 
    handling, packaging and transport of human blood and body fluids, 
    unfixed tissues, organs and cell cultures, and other fluids from humans 
    and animals infected or possibly infected with bloodborne pathogens.
         The Department of Commerce (DOC) maintains a list of 
    controlled items, including certain microorganisms that cannot be 
    exported from the U.S. (15 CFR parts 768-799). The DOC recommends that 
    shippers follow the CDC regulation for packaging when a shipment is 
    allowed to a foreign country.
         The United Nations Committee of Experts on the Transport 
    of Dangerous Goods makes recommendations on the international transport 
    of infectious substances and clinical specimens. These recommendations 
    are included in the International Civil Aeronautics Organization (ICAO) 
    technical instructions, which have been adopted by the International 
    Air Transport Association (IATA).
    
    --ICAO publishes Technical Instructions for the Safe Transport of 
    Dangerous Goods by Air, based on the United Nations (UN) 
    recommendations for the domestic and international transport of 
    infectious substances and clinical (diagnostic) specimens.
    --IATA publishes the Dangerous Goods Regulations (DGR), which further 
    describe for IATA member airlines, the national and international 
    recommendations for air transport of infectious substances and clinical 
    (diagnostic) specimens. The IATA DGR are followed by the domestic and 
    international member airlines.
    
        CDC's regulation, currently at 42 CFR part 72, provides packaging 
    and labeling requirements for shipments of infectious materials. There 
    are several reasons why CDC regulates this area in addition to the 
    other agencies listed above. The focus of the CDC regulation is on 
    protection of the public health by minimizing the potential for (1) 
    Direct physical contact with package contents by persons handling such 
    packages during transit, (2) Contamination of the environment, and (3) 
    The spread of disease into the community. The CDC regulations serve by 
    filling the gaps where there is no governance, by complementing the 
    requirements of other agencies where there is overlapping authority, 
    and by providing CDC as a central reporting authority assures 
    availability of CDC's infectious
    
    [[Page 58024]]
    
    disease expertise to assist in the response when packages are damaged.
        Although there had been some review of the requirements of other 
    agencies when developing the 1990 NPRM, there had not been any 
    comprehensive attempt to harmonize the various requirements. When 
    comments to the 1990 NPRM were reviewed, it became clear that there was 
    confusion among shippers and handlers as to how all the various 
    requirements of other agencies related to the CDC regulations. Because 
    of substantive differences in the requirements and use of different 
    terminology, there was a clear need to harmonize the various 
    requirements.
        In response to the comments on the 1990 NPRM, and as part of the 
    regulatory reform/reinventing government initiative, CDC has 
    collaborated with the other agencies and groups to prepare revised 
    proposed CDC regulations that are in harmony with the other 
    requirements, thereby reducing the burden on shippers while still 
    maintaining, or even improving, packaging standards to protect the 
    public health. In some instances, one or more of the other agencies/
    groups will also be revising their requirements as part of our joint 
    effort to achieve complementary regulations. We invite specific comment 
    on any requirements contained in the proposed CDC regulations which are 
    thought to be inconsistent or unclear in relation to the requirements 
    of any other regulatory authority.
        CDC also serves as a Center for Applied Biosafety and Training for 
    the World Health Organization (WHO) and for the UN. In conjunction with 
    the National Institutes of Health, CDC has participated in developing 
    revised international guidelines for the shipment of infectious 
    materials and diagnostic specimens. This NPRM also reflects the 
    recommendations of the WHO biosafety advisory group, as published in 
    1997, in Guidelines for the Safe Transport of Infectious Substances and 
    Diagnostic Specimens.
        As a result of this extensive collaboration, significant changes 
    have been made to the 1990 NPRM, and a new NPRM is being published to 
    provide the opportunity for laboratories and other shippers of 
    infectious materials, persons who transport or handle packages, public 
    health officials and other affected parties to comment on these 
    proposed regulations to ensure that the final regulations are both 
    complementary to other packaging and shipping requirements and 
    protective of the public health.
        CDC believes these regulations will not be an additional burden to 
    shippers because shippers interested in ensuring the integrity of their 
    packages are already utilizing comparable packaging. These regulations 
    will help to ensure that all shippers are aware of and utilize 
    appropriate packaging when shipping infectious substances, thereby 
    protecting the public health.
    
    Comparison of CDC's Proposed Packaging and Labeling Requirements 
    With Other Agencies' and Groups' Packaging and Labeling 
    Requirements
    
        This NPRM proposes packaging and labeling requirements for: (1) 
    Clinical specimens because they may contain infectious agents, and (2) 
    materials known or suspected of containing infectious substances or 
    toxins.
        Table 1 shows which types of infectious materials are covered by 
    each regulating authority and the scope of that coverage. As noted in 
    the table, no single agency covers all aspects regarding the shipment 
    of infectious substances.
    
       Table 1.--Infectious Substances: Comparison of the CDC NPRM \1\ With OSHA,\2\ DOT,\3\ USPS,\4\ and IATA \5\
                                           Packaging and Labeling Requirements
    ----------------------------------------------------------------------------------------------------------------
                                                                                    Regulations
                   Requirements                 CDC NPRM \1\ -------------------------------------------------------
                                                                OSHA \2\       DOT \3\      USPS \4\      IATA \5\
    ----------------------------------------------------------------------------------------------------------------
    Infectious materials:
        Biological products...................            +             +          -\6\             +             +
        Clinical (diagnostic) specimens.......            +             +          -\6\             +             +
        Cultures and reference stocks.........            +             +             +             +             +
    Packaging materials:
        Watertight primary receptacle.........            +             +             +             +             +
        Absorbent material....................            +            na             +             +             +
        Watertight secondary packaging........            +            na             +             +             +
        List of contents......................            +            na             +          -\7\             +
        Outer packaging.......................            +            na             +             +             +
        Packaging performance standards.......            +            na             +             +             +
    Packaging labels:
        Infectious substance/biohazard symbol             +             +             +             +             +
         label................................
        Shipping label,\8\ outer packaging....            +            na          -\9\             +             +
        Shipping label, secondary packaging...            +            na            na             +            na
    Tracking special infectious substances....            +            na            na            na            na
    Terminology...............................            +             +             +             +             +
    Shipping modes covered....................          All           All           All     Mail only      Air only
    ----------------------------------------------------------------------------------------------------------------
    Legend: + = same or very similar to the CDC NPRM; - = significantly different from the CDC NPRM; na = not
      addressed in regulation.
     
    \1\ CDC: Centers for Disease Control and Prevention, 42 CFR Part 72 as proposed in this NPRM.
    \2\ OSHA: Occupational Safety and Health Administration, 29 CFR 1910.1030.
    \3\ DOT: Department of Transportation, 49 CFR Parts 171-180.
    \4\ USPS: United States Postal Service, Domestic Mail Manual CO23.
    \5\ IATA: International Air Transport Association, Dangerous Goods Regulations.
    \6\ Only those biological products and clinical specimens known to contain infectious substances are covered
      under 49 CFR 173.134.
    \7\ USPS requires a list of contents (manifest) for all sharps mailing containers, but only requires a list of
      contents for other items sent via air transportation
    \8\ Shipping label: Names, addresses, contact names and phone numbers of person shipping the package and
      intended recipient (addressee).
    \9\ DOT specifies that the shipper include an emergency response telephone number on the shipping documents (49
      CFR 172.604).
    
    
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    II. Proposed Rule
    
        This proposed rule would amend the existing regulations at 42 CFR 
    part 72 concerning the interstate shipment of infectious substances to 
    clarify and expand the existing requirements for proper packaging and 
    handling of these agents. The purpose of this regulation is to ensure 
    that all biological materials that contain, or may contain, an 
    infectious substance are packaged for interstate shipment in a manner 
    that minimizes the potential for leakage and possible contamination of 
    the environment, or direct physical contact with the contents by 
    persons handling such packages during transit. This rule will also 
    require that infectious agents and toxins capable of causing serious 
    infection, illness or death be labeled and tracked during shipment.
        It also updates the requirements for facilities transferring or 
    receiving select agents, incorporating by reference the 4th edition of 
    the CDC/NIH publication Biosafety in Microbiological and Biomedical 
    Laboratories.
    
    A. Definitions
    
        Biological products--Biological product means a biological product 
    that is subject to preparation and manufacture in accordance with the 
    provisions of 9 CFR part 102 (Licensed Veterinary Biological Products), 
    9 CFR part 103 (Biological Products for Experimental Treatment of 
    Animals), 9 CFR part 104 (Imported Biological Products), 21 CFR part 
    312 (Investigational New Drug Application), or 21 CFR parts 600-680 
    (Biologics) and that, in accordance with such provisions, may be 
    shipped in interstate traffic. FDA-approved vaccines are exempt from 
    this regulation.
        Only biological products that are known or presumed to contain an 
    infectious substance are subject to this regulation.
        Clinical Specimens--A clinical specimen is any human or animal 
    material including, but not limited to excreta, secreta, blood and its 
    components, tissue and tissue fluids, that is collected for the purpose 
    of diagnosis, research, or other purposes. Formalin-fixed specimens are 
    excluded. Animal material clinical specimens are subject to the 
    regulation only if known or suspected of containing human pathogens.
        Under the concept of Universal Precautions all bodily fluids of 
    human origin must be handled as if they are infectious in order to 
    minimize the potential for exposure to bloodborne pathogens. Section 
    72.3 in this NPRM meets those requirements.
        Some clinical specimens are known or presumed to contain viable 
    infectious micro-organisms that could result in an infection if an 
    exposure occurred during a transport mishap. These specimens must be 
    packaged and labeled as infectious substances (see Sec. 72.4(a)). If 
    exposure could result in an extremely serious infection or illness in 
    an exposed worker or the public, such specimens are considered special 
    infectious substances and must be tracked during shipment.
        Infectious substance--CDC has replaced the term ``etiologic agent'' 
    with the DOT and international term ``infectious substance''. For 
    purposes of this regulation, an infectious substance is any substance, 
    clinical specimen or culture, isolate, or other derivative of a 
    clinical specimen that contains, or is suspected of containing a viable 
    infectious virus, prion, or a viable microorganism, such as a 
    bacterium, rickettsia, parasite or fungus, that is known or reasonably 
    believed to cause disease in humans. Toxins known to be pathogenic are 
    to be packaged and shipped either as infectious substances or as 
    special infectious substances (Sec. 72.5), as applicable.
        Examples of infectious substances include:
        1. All cultures containing or suspected of containing a 
    microorganism that causes or may cause disease in humans;
        2. All human or animal clinical specimens that are known or 
    suspected of containing an infectious microorganism or toxin;
        3. Environmental samples to the extent that they are suspected of 
    containing human pathogens at a level that presents risk of infection.
        4. Other specimens not included above and designated as infectious 
    by a qualified person (e.g., physician, scientist, veterinarian, 
    nurse).
        To maintain consistency with DOT regulations, a qualifying sentence 
    has been added to the definition of an infectious substance that states 
    that a microbial toxin that causes disease in humans will be packaged 
    and shipped as an infectious substance.
        Packaging--A change in this NPRM is the adoption of DOT and IATA 
    terminology to clarify that there is agreement among the various 
    organizations involved in regulating this area. The terms ``primary 
    container'', ``secondary container'', and ``outer container'' have been 
    replaced with the DOT terms and definitions of ``primary receptacle'', 
    ``secondary packaging'', and ``outer packaging'.
        Special infectious substance means any of the microbiological 
    agents or toxins listed in Sec. 72.5 or appendix A to part 72 (proposed 
    to be recodified as appendix to subpart B). These special infectious 
    substances include those agents listed in the CDC/NIH publication, 
    Biosafety in Microbiological and Biomedical Laboratories, as biosafety 
    level (BSL) 4 and most of the BSL3 agents. Special infectious 
    substances present a potentially high risk of infection and/or death to 
    persons exposed to them through either direct contact, aerosol or 
    ingestion. Therefore, shipments of special infectious substances are 
    tracked to assure their safe arrival.
    
    B. Transport of Clinical Specimens
    
        Clinical specimens are to be packaged in such a manner that they 
    will remain intact under conditions that normally occur during transit. 
    If the primary receptacle were to break or leak during transit, the 
    specimen would be contained by the absorbent material and by the 
    secondary packaging, so no material would leak to the outside surface 
    of the outer packaging.
        Packaging requirements for clinical specimens proposed in this NPRM 
    are similar to those for infectious substances, except that the 
    proposed performance standards are less rigorous. These packaging and 
    labeling requirements meet the specifications established by OSHA and 
    various international agencies.
    
    C. Transport of Infectious Substances
    
        Infectious substances are to be packaged in such a manner that they 
    would withstand conditions which would normally occur during transit 
    and would not leak even if the primary receptacle were to break. In 
    addition, the proposed packaging requirements have been enhanced by 
    adding a requirement that the packaging be capable of passing a drop 
    test. The completed package must be capable of passing the tests 
    specified in 49 CFR 178.609. The requirements established in this NPRM 
    meet those of DOT, OSHA, various international agencies and are 
    consistent with the 1999 IATA Dangerous Goods Regulations.
        In keeping with DOT and the international guidelines and 
    regulations, volume/weight limits have been changed to four liters or 
    four kilograms in a single package (excluding the packaging and coolant 
    weights). An itemized list of contents must be enclosed between the 
    secondary packaging and outer packaging. The proposed rule also details 
    provisions associated with substances shipped refrigerated or frozen 
    (prefrozen packs,
    
    [[Page 58026]]
    
    wet or dry ice), shipped in liquid nitrogen, or as lyophilized 
    materials.
        The proposed rule requires on the outer packaging a black and white 
    label bearing the words ``Infectious Substance'', CDC's telephone 
    number for reporting damaged packages, and the biohazard symbol. The 
    proposed rule also would require that the name, address, and telephone 
    number of both the shipper and recipient be affixed to the outer 
    package.
    
    D. Transport of Special Infectious Substances; Failure to Receive
    
        This proposed rule would be unique in requiring that the most 
    dangerous human pathogens be shipped as ``special infectious 
    substances''. These agents include those identified for work at 
    biosafety level 3 and 4 as specified in the Biosafety in 
    Microbiological and Biomedical Laboratories publication.
        Special infectious substances must be shipped by the carrier and a 
    system that provides for tracking the shipment and notifying CDC if the 
    packages are not received. Information gathered by CDC from such 
    notifications will be useful in identifying problems and implementing 
    corrective actions.
    
    E. Select Agents
    
        Some of the microorganisms listed as special infectious substances 
    are also considered to be ``select agents'' and are regulated in 42 CFR 
    72.6 (Additional Requirements for Facilities Transferring or Receiving 
    Select Infectious Agents) (proposed here to be renumbered as Section 
    72.11). The only changes in this proposed rule to Sec. 72.6 are at 
    Sec. 72.6 (a)(5) (now Sec. 72.11 (a)(5)), and Sec. 72.6 (c)(1) (now 
    Sec. 72.11(c)(1)), which are revised to incorporate the 4th edition of 
    the CDC/NIH publication Biosafety in Microbiological and Biomedical 
    Laboratories.
    
    F. Variations
    
        To promote innovation and allow for new technologies, the proposed 
    rule would allow the Director, CDC, to approve variations from the 
    requirements of this subpart if, upon written application, it is found 
    that such variations provide protection at least equivalent to that 
    provided by the requirements in this subpart, as finalized, and such 
    findings are made a matter of official written record.
    
    G. Penalties
    
        Violations of the rule would be subject to criminal penalties as 
    prescribed in 42 U.S.C. 271 and 18 U.S.C. 3559, 3571. Specifically, 
    individuals in violation of the rule would be subject to a fine or 
    imprisonment of not more than one year, or both.
    
    III. Procurement of Labels
    
        Shippers will be able to order a supply of the two shipping labels 
    described in the regulations from private printers by furnishing them 
    the exact specifications provided in the final rule, or by purchasing 
    the labels from the Superintendent of Documents (U.S. Government 
    Printing Office, Mail Stop: SSOP, Washington, D.C. 20402-9328).
    
    IV. Analysis of Impacts
    
    A. Review Under Executive Order 12866, Sections 202 and 205 of the 
    Unfunded Mandate Reform Act of 1995 (P.L. 104-4), and by the Regulatory 
    Flexibility Act (5 U.S.C 603-605)
    
        The Department has examined the potential impact of this proposed 
    rule as directed by Executive Order 12866, by sections 202 and 205 of 
    the Unfunded Mandate Reform Act of 1995 (Pub. L. 104-4), and by the 
    Regulatory Flexibility Act (5 U.S.C. 603-605).
        Executive Order 12866 directs Federal agencies to assess the costs 
    and benefits of available regulatory alternatives, and, when regulation 
    is necessary, to select regulatory approaches that maximize net 
    benefits. This proposed rule is designed to ensure that all biological 
    materials that contain, or may contain, an infectious substance are 
    packaged in a manner for interstate shipment that minimizes the 
    potential for leakage and possible contamination of the environment or 
    direct physical contact with the contents by persons handling such 
    packages during transit. The proposed rule is designed to complement 
    other shipping requirements developed by the Departments of Commerce, 
    Agriculture, and Transportation, the USPS, OSHA, and the International 
    Air Transport Association and, thereby, to reduce the burden on 
    shippers while imposing minimal administrative costs, and to prevent 
    possible serious, harmful effects to public safety and health. (The 
    proposal has been reviewed by the Office of Management and Budget under 
    the terms of the Executive Order.)
        The Unfunded Mandates Reform Act of 1995, in sections 202 and 205, 
    requires Federal agencies to prepare several analytic statements before 
    proposing a rule that may result in expenditures of $100 million by 
    State, local and tribal governments, or by the private sector in any 
    one year. Because a final rule resulting from this proposal would not 
    result in expenditures of this magnitude, such statements are not 
    necessary.
        The Regulatory Flexibility Act requires Federal agencies to prepare 
    a regulatory flexibility analysis of the potential impact of the 
    proposed rule on small entities and permits agency heads to certify 
    that a proposed rule will not, if promulgated, have a significant 
    economic impact on a substantial number of small entities. CDC does not 
    know how many small entities will be impacted by this regulation, and 
    does not know what the economic impact on those small entities would 
    be. However, CDC believes that packaging requirements set forth in this 
    rule would not be an additional burden on shippers because this is an 
    amendment to existing PHS rules with which shippers must comply. In 
    addition, it will harmonize these rules with other existing regulations 
    that shippers must follow. CDC believes that this rule will lessen 
    confusion regarding proper packaging and shipping of infectious 
    materials and will bring HHS regulations into conformity with other 
    regulations. CDC is requesting information/comments on the number of 
    small entities that would be impacted by this NPRM, the economic burden 
    on those small entities and why the Secretary should not certify that 
    this rule will have no significant impact on small entities. CDC is 
    also requesting comments/recommendations on other possible less 
    burdensome approaches to ensuring that all infectious or potentially 
    infectious materials are packaged and shipped in a way that minimizes 
    risks to workers, the public and the environment.
        These regulations will help to ensure that all shippers are aware 
    of and utilize appropriate packaging when shipping infectious 
    substances, thereby protecting the public health.
    
    B. Review Under the Paperwork Reduction Act of 1995
    
        The proposed rule contains information collection requirements that 
    are subject to review by the Office of Management and Budget (OMB) 
    under the Paperwork Reduction Act of 1995. The title, description and 
    respondent description of the information collection are shown below 
    with an estimate of the annual reporting burden. The estimate includes 
    the time for reviewing instructions, gathering and maintaining the 
    necessary data, and completing and reviewing the collection of 
    information. With respect to the following collection of information, 
    CDC invites comments on: (a) Whether the proposed collection of 
    information is necessary for the proper performance of CDC's public
    
    [[Page 58027]]
    
    health functions, including whether the information shall have 
    practical utility; (b) the accuracy of CDC's estimate of the burden of 
    the proposed collection of information including the validity of the 
    methodology and assumptions used; (c) ways to enhance the quality, 
    utility, and clarity of the information to be collected; and (d) ways 
    to minimize the burden of the collection of information on respondents, 
    including through the use of automatic collection techniques or other 
    forms of information technology.
        Title: Packaging and Handling of Infectious Substances and Select 
    Agents.
        Description: The CDC proposes to amend the regulations concerning 
    the interstate shipment of infectious substances in order to clarify 
    and expand requirements for proper packaging and handling of these 
    agents. The proposed rule would ensure that all biological materials 
    that may contain an infectious substance are packaged for interstate 
    shipment in a manner that minimizes the potential for leakage and 
    possible contamination of the environment or direct physical contact 
    with the contents by persons handling such packages during transport. 
    It also updates the requirements for facilities transferring or 
    receiving select agents, incorporating by reference the 4th edition of 
    the CDC/NIH publication Biosafety in Microbiological and Biomedical 
    Laboratories.
        Anyone handling damaged or leaking packages of infectious 
    substances during interstate shipment must isolate the package, notify 
    the shipper and intended recipient immediately and notify CDC as soon 
    as feasible (1-800-232-0124). When notifying CDC, the caller should 
    provide a description of the condition of the package, the name, 
    address and telephone number of the shipper, and any other pertinent 
    information, so that information and assistance can be provided, as 
    necessary, regarding appropriate decontamination and disposal 
    procedures.
        Persons who ship packages containing special infectious substances 
    must notify the addressee of the date of shipment, and the addressee 
    must confirm receipt by telephone or other electronic means. If the 
    shipper does not receive such confirmation within 3 days of anticipated 
    delivery, the shipper must then contact CDC within 24 hours to enable 
    the agency to determine whether a public health response is necessary. 
    Information gathered by CDC from such notifications will also be useful 
    in identifying problems and implementing corrective actions.
        Description of Respondents: Government agencies, universities, 
    research institutions, laboratories, private companies and others that 
    ship or receive infectious substances, and government or commercial 
    carriers of infectious substances.
    
                                            Estimated Annual Reporting Burden
    ----------------------------------------------------------------------------------------------------------------
                                                                   Frequency      Total
                      CFR section                     Number of        of         annual     Hours per   Total hours
                                                     respondents   reporting    responses     response
    ----------------------------------------------------------------------------------------------------------------
    72.4(b)........................................          500        1x/yr           50          0.1            5
    72.5(b)........................................          200        10/yr        2,000          0.1          200
    72.5(c)........................................          200        10/yr        2,000          0.1          200
    72.5(d)........................................           20         1/yr           20          0.2            4
                                                    ----------------------------------------------------------------
        Total                                                                                                   409
    ----------------------------------------------------------------------------------------------------------------
    
        Reporting or Disclosures: These estimates are an approximation of 
    the average time expected to be necessary for a collection of 
    information. They are based on past experiences of respondents 
    reporting such information to CDC. There are no capital costs or 
    operating and maintenance costs for the respondents associated with 
    this information collection.
        The agency has submitted a copy of this proposed rule to OMB for 
    its review of this information collection. Interested persons are 
    requested to submit written comments regarding this information 
    collection, including suggestions for reducing the burden, to the 
    Office of Information and Regulatory Affairs, OMB, New Executive Office 
    Building, 725 17th Street, NW, Rm. 10235, Washington, DC 20503, Att.: 
    Desk Officer for CDC.
    
    List of subjects in 42 CFR Part 72
    
        Biologics, packaging and containers, Transportation.
    
        Dated: March 12, 1999.
    Jeffrey Koplan,
    Director, Centers for Disease Control and Prevention.
    
        Dated: May 31, 1999.
    Donna E. Shalala,
    Secretary, Department of Health and Human Services.
    
        For the reasons stated in the preamble, it is proposed to amend 42 
    CFR Chapter I, part 72, as follows:
    
    PART 72--PACKAGING AND HANDLING OF INFECTIOUS SUBSTANCES AND SELECT 
    AGENTS
    
        1. The authority citation for Part 72 is revised to read as 
    follows:
    
        Authority: 42 U.S.C. 216, 264, 271; 31 U.S.C. 9701; 18 U.S.C. 
    3559, 3571; 42 U.S.C. 262 note.
    
        2. The heading of part 72 is revised to read as set forth above.
        3. Sections 72.1-72.5 are revised.
        4. 72.6 is redesignated as Sec. 72.11.
        5. A new Sec. 72.6 is added.
        6. A heading for subpart A is added and sections Secs. 72.1-72.6 
    are transferred to subpart A.
        7. A heading for subpart B is added and redesignated section 72.11 
    is transferred to subpart B and amended by revising paragraphs (a)(5) 
    and (c)(1).
        8. Section 72.7 is redesignated as section 72.21.
        9. A heading for subpart C is added and redesignated section 72.21 
    is transferred to subpart C.
        10. Appendix A to Part 72 is transferred to subpart B and the 
    heading is revised to read ``Appendix to Subpart B''.
        The additions and revisions to part 72 read as follows:
    
    Subpart A--Interstate Shipment of Biological Materials That Contain 
    or May Contain Infectious Substances
    
    
    Sec. 72.1  Purpose.
    
        The purpose of this regulation is to ensure that all materials that 
    contain or may contain an infectious substance are packaged for 
    interstate shipment in a manner that minimizes the potential for 
    leakage and possible contamination of the environment or direct 
    physical contact with the contents by persons handling such packages 
    during transit.
    
    [[Page 58028]]
    
    The rule also requires the tracking of shipments of special infectious 
    substances and requires registration of certain select agents. The 
    requirements of this subpart are in addition to and not in lieu of any 
    other packaging or other requirements for the transportation of 
    infectious substances in interstate traffic as prescribed by the US 
    Department of Transportation, the US Postal Service and other agencies 
    of the Federal Government.
    
    
    Sec. 72.2  Definitions.
    
        As used in this subpart:
        Absorbent material means material that is capable of absorbing 
    liquids. It may be either particulate or non-particulate, but if 
    particulate, it shall be contained so it does not leak out of the 
    package.
        Biological product means a biological product that is subject to 
    preparation and manufacture in accordance with the provisions of 9 CFR 
    part 102 (Licensed Veterinary Biological Products), 9 CFR part 103 
    (Biological Products for Experimental Treatment of Animals), 9 CFR part 
    104 (Imported Biological Products), 21 CFR part 312 (Investigational 
    New Drug Application), or 21 CFR parts 600-680 (Biologics) and that, in 
    accordance with such provisions, may be shipped in interstate traffic. 
    Only biological products that are known or presumed to contain an 
    infectious substance are subject to this regulation. FDA-approved 
    vaccines are exempt from this regulation.
        Clinical specimen (diagnostic specimen) is any human or animal 
    material including, but not limited to excreta, secreta, blood and its 
    components, tissue and tissue fluids, that is collected for the 
    purposes of diagnosis, research, or other purposes. Formalin-fixed 
    specimens are exempt from this regulation. Animal material clinical 
    specimens are subject to this regulation only if known or suspected of 
    containing human pathogens. All human clinical specimens are covered.
        Coolant material means material such as ice, dry ice, liquid 
    nitrogen, and gel packs, that is included in the package to cool the 
    contents.
        Infectious substance (etiologic agent) and infectious material are 
    considered synonymous. An infectious substance is defined as a 
    substance containing or suspected of containing an infectious virus, 
    prion, or a viable microorganism, such as a bacterium, rickettsia, 
    parasite or fungus, that is known or reasonably believed to cause 
    disease in humans. Toxins known to be pathogenic to humans are to be 
    packaged and shipped as infectious substances or special infectious 
    substances (Sec. 72.5). The term ``infectious substance'' excludes any 
    medical waste that is regulated under other federal regulations. For 
    purposes of this regulation, infectious substances include:
        (1) All cultures containing or suspected of containing a 
    microorganism that causes or may cause disease in humans;
        (2) All human or animal clinical specimens that are known or 
    suspected of containing an infectious microorganism or toxin;
        (3) Environmental samples if they are suspected of containing human 
    pathogens at a level that presents risk of infection.
        (4) Other specimens not included above and designated as infectious 
    by a qualified person (e.g., a physician, scientist, veterinarian, 
    nurse).
        Interstate traffic means the movement, including any portion 
    entirely within a State or possession, from a point of origin in any 
    State or possession or from outside the Untied States, to a point of 
    destination in any other State or possession; or form any State or 
    possession to another country; or between a point of origin and a point 
    of destination in the same State or possession but through any other 
    State, possession or contiguous foreign country.
        Outer packaging means the container in which a primary receptacle 
    and secondary package, together with any absorbent materials and 
    cushioning, is shipped.
        Primary receptacle means a tube, vial, bottle, ampule, or similar 
    item that contains the material being shipped.
        Secondary packaging means a container into which the primary 
    receptacle is placed.
        Special infectious substance means any of the microbiological 
    agents or toxins listed in Sec. 72.5 or appendix to subpart B of this 
    part, including any human or animal specimens known or suspected of 
    containing such a microbial agent, or any other microorganism that 
    could cause serious infection and/or death in persons exposed to them 
    through either direct contact, aerosol or ingestion. Additional changes 
    to this list may be made through publication of a notice in the Federal 
    Register.
    
    
    Sec. 72.3  Transportation of clinical specimens; minimum packaging 
    requirements.
    
        (a) General requirements. No person may knowingly transport or 
    cause to be transported in interstate traffic, directly or indirectly, 
    any clinical specimen unless such material is packaged, labeled, and 
    shipped in accordance with the requirements of this section. However, 
    any clinical specimens known or suspected to contain an infectious 
    substance shall be labeled and packaged as described under Sec. 72.4.
        (1) Clinical specimens shall be packaged to withstand conditions 
    incident to ordinary handling in transit, including shocks and pressure 
    changes, so that if leakage of the primary receptacle(s) occurs during 
    transit, the contents will be contained within the outer packaging. 
    Required packaging and components are as follows:
        (i) A watertight primary receptacle.
        (ii) Watertight secondary packaging.
        (iii) Absorbent material must be placed between the primary 
    receptacle(s) and the secondary packaging. If multiple primary 
    receptacles are placed in a secondary packaging, they msut be placed so 
    as to ensure that contact between them is prevented. The absorbent 
    material must be sufficient to absorb the entire contents of all 
    primary receptacles.
        (iv) Outer packaging must be of adequate strength for its capacity, 
    mass and intended use. Any package with liquid contents shall have 
    sturdy outer packaging constructed of corrugated cardboard, fiberboard, 
    wood, metal, or rigid plastic. Styrofoam, plastic bags and paper 
    envelopes are unacceptable outer packaging for such packages.
        (2) The size of the outer package must be at least 100 mm (3.9 
    inches) in the smallest overall external dimension.
        (3) The primary receptacle and the secondary packaging must be 
    capable of withstanding, without leakage, an internal pressure which 
    produces a pressure differential of not less than 95kPA (0.95 bar, 
    13.8lb/in2) in the temperature range of -40 deg. C to 
    +55 deg. C (-40 deg. F to 131 deg. F).
        (4) An itemized list of contents must be enclosed between the 
    secondary packaging and the outer packaging.
        (5) For substances shipped at ambient temperatures or higher, means 
    of ensuring a leak-proof seal of the primary receptacle, such as a heat 
    seal, skirted stopper or metal crimp seal must be provided. Screw caps 
    must be reinforced to ensure they do not leak. Evacuated specimen 
    collection tubes such as Vacutainer (Becton-Dickinson, 
    Franklin Lakes, NJ) tubes do not require additional sealing.
        (6) For substances shipped refrigerated or frozen (wet ice, 
    prefrozen packs, dry ice), ice or dry ice must be placed outside the 
    secondary packaging(s). Interior support must be provided to secure the 
    secondary packaging(s) in the original position as the ice or dry ice 
    melts or sublimates, respectively. If ice is used, the outer
    
    [[Page 58029]]
    
    packaging must be leak-proof. If dry ice is used, the outer packaging 
    must permit the release of carbon dioxide gas. The primary receptacle 
    must maintain its containment integrity at the temperature of the 
    refrigerant as well as the temperatures and pressure of air transport 
    to which the receptacle could be subjected if refrigeration were to be 
    lost.
        (7) For substances shipped in liquid nitrogen, a watertight 
    material, capable of withstanding cryogenic temperatures must be used 
    as the primary receptacles. Secondary packaging must also withstand 
    very low temperatures. All requirements for shipment of liquid nitrogen 
    must also be observed. The primary receptacle must maintain its 
    containment integrity at the temperature of the refrigerant as well as 
    at the temperatures and pressure of air transport to which the 
    receptacle could be subjected if refrigeration were to be lost.
        (8) For lyophilized substances, primary receptacles capable of 
    containing lyophilized substances must be used (including, but not 
    limited to, flame-sealed glass ampules or rubber-stoppered glass vials 
    with metal seals).
        (9) The completed package must be capable of withstanding at least 
    a 1.2 meter drop on a hard unyielding surface without release of its 
    contents.
        (10)(i) Biohazard Labeling is required for the primary receptacle 
    and outer packaging as described in 29 CFR 1910.1030, Occupational 
    Exposure to Bloodborne Pathogens.
        (ii) The outer packaging shall bear a label as illustrated and 
    described below:
    [GRAPHIC] [TIFF OMITTED] TP28OC99.052
    
        (A) The color of material on which the label is printed shall be 
    bright orange; the printing shall be black. The color of the biohazard 
    symbol shall be black.
        (B) The label shall be a rectangle measuring 51 mm (2 inches) high 
    by 102.5 mm (4 inches) long.
        (C) The biohazard symbol, measuring 40 mm (1.56 inches) in 
    diameter, shall be centered on a square measuring 51 mm (2 inches) on 
    each side.
        (D) Size of the letters (Helvetica) on the label shall be as 
    follows:
    
    Biohazard--16 pt.
    Clinical specimens--14 pt.
    Packaged in compliance with 42 CFR part 72--6 pt.
    In case of damage or leakage, notify--10 pt.
    Shipper and Receiver--10 pt.
    
        (iii) The outer packaging shall also bear a shipping label with the 
    names, addresses, and contact names and telephone numbers of the 
    individual/institution sending the package and the intended recipient 
    (addressee).
        (b) Leaking packages. The carrier, the receiver, or anyone handling 
    a package described in paragraph (a) of this section that is leaking, 
    shall upon discovery of leakage, isolate the package, and immediately, 
    or as soon as feasible, notify the shipper and intended recipient to 
    receive instructions on clean-up and disposition of the package.
    
    
    Sec. 72.4  Transportation of infectious substances; minimum packaging 
    requirements.
    
        (a) General requirements. No person may knowingly transport or 
    cause to be transported in interstate traffic, directly or indirectly, 
    any infectious substance, including clinical specimens or biological 
    products that are known or presumed to contain infectious substances, 
    unless such material is packaged, labeled, and shipped in accordance 
    with the requirements of this section.
        (1) Infectious substances shall be packaged to meet the 
    requirements of Sec. 72.3(a) (1)-(8).
        (2) The maximum amount of infectious substances that may be placed 
    in a single outer shipping package shall not exceed four liters or four 
    kilograms, excluding the packaging and coolant weights.
        (3) In addition, each complete package must be capable of passing 
    the tests specified in 49 CFR 178.609.
        (4)(i) Biohazard Labeling is required for the primary receptacle 
    and outer package as described in 29 CFR 1910.1030, Occupational 
    Exposure to Bloodborne Pathogens.
        (ii) The outer packaging shall bear a label as illustrated and 
    described below:
    
    [[Page 58030]]
    
    [GRAPHIC] [TIFF OMITTED] TP28OC99.053
    
    
        (A) The color of material on which the label is printed shall be 
    white and the printing shall be in black; the biohazard symbol shall be 
    in black.
        (B) The label shall be a diamond-on-point measuring, at a minimum, 
    51 mm (4 inches) on each side.
        (C) The black biohazard symbol, measuring 21 mm (.81 inches) in 
    diameter, shall be centered on a square measuring 51 mm (2 inches) on 
    each side.
        (D) Size of the letters (Helvetica) on the label shall be as 
    follows:
    
    Infectious Substance--16 pt.
    Packaged in compliance with 42 CFR Part 72--5 pt.
    In case of damage or leakage--7 pt.
    Immediately notify--7 pt.
    Public Health Authority--7 pt.
    In U.S.A.--5 pt
    Centers for Disease Control and Prevention--5 pt.
    Atlanta, GA--5 pt
    1-800-232-0124--5 pt.
    6--24 pt.
    
        (E) The number 6 (mandated by the DOT) shall be centered at the 
    bottom of the label.
        (iii) The outer packaging and the secondary packaging shall also 
    bear labels with the names, addresses, and contact names and telephone 
    numbers of the individual/institution sending the package and of the 
    intended recipient (addressee).
        (b) Damaged or leaking packages. The carrier, the receiver, or 
    anyone handling a package described in paragraph (a) of this section 
    that is damaged or leaking, shall upon discovery of damage or leakage, 
    isolate the package and immediately, or as soon as feasible, in order 
    to receive instructions on appropriate decontamination and disposal, 
    notify the shipper, receiver, and the Centers for Disease Control and 
    Prevention by telephone at 1-800-232-0124. The caller shall provide a 
    description of the condition of the package; the name, address and 
    telephone number of the shipper; and other pertinent information.
    
    (This information collection has been approved by OMB (0920-0199)).
    
    
    Sec. 72.5  Packaging and method of shipment of special infectious 
    substances; failure to receive.
    
        (a) List of special infectious substances. (1) The following 
    microorganisms and toxins are considered special infectious substances 
    because they present a potentially high risk of infection and/or death 
    to persons exposed to them through either direct contact, aerosol or 
    ingestion. Shipments of special infectious substances must be tracked 
    to assure their safe arrival.
    
    Bacterial Agents
    
    Bacillus anthracis
    Bartonella bacilliformis
    Brucella, all species
    Burkholderia (Pseudomonas) mallei
    Burkholderia (Pseudomonas) pseudomallei
    Clostridium botulinum
    Francisella tularensis
    Mycobacterium tuberculosis (drug-resistant strains)
    Yersinia pestis
    
    Viral and Rickettsial Agents
    
        Arboviruses assigned to Biosafety level 3 or 4 in the CDC/NIH 
    publication Biosafety in Microbiological and Biomedical 
    Laboratories, which may be purchased from the Superintendent of 
    Documents, U.S. Government Printing Office, Washington, D.C. 20402.
    
    Other Viral Agents
    
    Crimean-Congo hemorrhagic fever virus
    Eastern Equine Encephalitis virus
    Ebola virus
    Hantaan virus (Korean hemorrhagic fever virus)
    Hantavirus (all viruses of genus)
    Herpesvirus simiae (B virus)
    Lassa fever virus
    Lymphocytic choriomeningitis virus
    Marburg virus
    Pox viruses pathogenic for humans (e.g., smallpox, monkeypox)
    South American Hemorrhagic fever viruses (Junin, Machupo, Sabia, 
    Flexal, Guanarito)
    Tick-borne Encephalitis complex viruses
    Venezuelan Equine Encephalitis virus
    Yellow fever virus
    
    Rickettsial Agents:
    
    Rickettsia rickettsiae
    Rickettsia prowazekii
    Coxiella burnetti
    
    Fungal Agents
    
    Coccidioides immitis
    Histoplasma capsulatum
    Histoplasma duboisii
    
    Toxins
    
        Toxins listed in appendix to Subpart B of this part are to be 
    shipped as special infectious substances. Other microbial toxins 
    known to be pathogenic shall be shipped as infectious substances, as 
    provided under Sec. 72.4.
    
        (2) This list may be supplemented through publication of a notice 
    in the Federal Register. Call 1-888-232-3299 (the FAX Information 
    system in CDC's Office of Health and Safety) for a copy of the current 
    list, or check the CDC website at http://www.cdc.gov/od/ohs.
        (b) Packaging and method of shipment. All materials that contain or 
    are reasonably believed to contain a special infectious substance shall 
    be packaged and labeled for interstate shipment according to the 
    requirements of Sec. 72.4. In addition, the shipper shall: Use a 
    shipping system that provides for tracking during transport (e.g., 
    registered mail or those of certain
    
    [[Page 58031]]
    
    private carriers); Provide 24 hours-per-day telephonic response to 
    emergency calls from carriers in case of a spill or incident involving 
    a package containing a special infectious agent; and, Notify the 
    addressee by telephone or other electronic means of the date of 
    shipment on the date of shipment, or provide a written schedule of 
    shipment in advance, and request confirmation of receipt of each 
    shipment. Records of such notifications shall be retained by the 
    shipper until notified of receipt.
        (c) Confirmation of receipt. Upon receipt, the addressee shall 
    provide confirmation to the shipper by telephone or other electronic 
    means.
        (d) Failure to receive. When confirmation of receipt of material 
    designated in paragraph (a) of this section is not received by the 
    shipper within 3 days following anticipated delivery of the package, 
    the shipper shall notify the carrier which shall immediately seek to 
    ascertain the disposition of the package. In addition, the shipper 
    shall notify the Centers for Disease Control and Prevention within 24 
    hours by telephone at 1-800-232-0214 to enable the agency to determine 
    whether a public health response is necessary.
    
    
    Sec. 72.6  Requirements; variations.
    
        The Director, Centers for Disease Control and Prevention, may 
    approve variations from the requirements of this subpart if, upon 
    written application, review and evaluation, it is found that such 
    variations provide protection at least equivalent to that provided by 
    compliance with the requirements specified in this subpart, and such 
    findings are made a matter of official written record.
    
    
    Sec. 72.7  [Redesignated as Sec. 72.21]
    
    Subpart B--Handling of Select Agents
    
    
    Sec. 72.11  Additional requirements for facilities transferring or 
    receiving select agents.
    
        (a) * * *
        (5) The requirements for BSL-2, 3, and 4 operations pertaining to 
    this section are contained in the CDC/NIH publication, ``Biosafety in 
    Microbiological and Biomedical Laboratories,'' Fourth Edition, May 1999 
    which is hereby incorporated by reference. The Director of the Federal 
    Register has approved under 5 U.S.C. 552(a) and 1 CFR part 51 the 
    incorporation by reference of the above publication. Copies may be 
    obtained from the Superintendent of Documents, U.S. Government Printing 
    Office, Washington, DC 20402. Copies may be inspected at the Centers 
    for Disease Control and Prevention, 1600 Clifton Road, Atlanta, 
    Georgia, or at the Office of the Federal Register, 800 North Capitol 
    Street NW, Suite 700, Washington, DC. The manual is also available on 
    the CDC web site at www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4toc.htm.
    * * * * *
        (c) * * *. (1) The Secretary may authorize a state agency or 
    private entity to register facilities under paragraph (a) of this 
    section, if the Secretary determines that the registering entity's 
    criteria for determining the biosafety standards for facilities 
    handling select agents are consistent with the requirements contained 
    in the CDC/NIH publication ``Biosafety in Microbiological and 
    Biomedical Laboratories,'' Fourth Edition.
    * * * * *
    
    Subpart C--Penalties
    
    
    Sec. 72.21  [Redesignated from Sec. 72.7]
    
    Appendix A to Part 72 [Transferred to Subpart B and heading 
    revised]
    
    Appendix to Subpart B
    
    * * * * *
    [FR Doc. 99-27640 Filed 10-27-99; 8:45 am]
    BILLING CODE 4163-18-P
    
    
    

Document Information

Published:
10/28/1999
Department:
Centers for Disease Control and Prevention
Entry Type:
Proposed Rule
Action:
Notice of proposed rulemaking.
Document Number:
99-27640
Dates:
Written comments must be received on or before December 27, 1999. Written comments on the proposed information collection requirements should also be submitted on or before December 27, 1999.
Pages:
58022-58031 (10 pages)
RINs:
0920-AA02: Packaging and Handling of Infectious Substances and Select Agents
RIN Links:
https://www.federalregister.gov/regulations/0920-AA02/packaging-and-handling-of-infectious-substances-and-select-agents
PDF File:
99-27640.pdf
CFR: (11)
9 CFR 72.11(c)(1))
9 CFR 72.6
42 CFR 72.1
42 CFR 72.2
42 CFR 72.3
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