99-21292. Revisions to the Requirements Applicable to Blood, Blood Components, and Source Plasma  

  • [Federal Register Volume 64, Number 160 (Thursday, August 19, 1999)]
    [Rules and Regulations]
    [Pages 45366-45374]
    From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
    [FR Doc No: 99-21292]
    
    
    
    Federal Register / Vol. 64, No. 160 / Thursday, August 19, 1999 / 
    Rules and Regulations
    
    [[Page 45366]]
    
    
    
    DEPARTMENT OF HEALTH AND HUMAN SERVICES
    
    Food and Drug Administration
    
    21 CFR Parts 606 and 640
    
    [Docket No. 98N-0673]
    
    
    Revisions to the Requirements Applicable to Blood, Blood 
    Components, and Source Plasma
    
    AGENCY: Food and Drug Administration, HHS.
    
    ACTION: Direct final rule.
    
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    SUMMARY: The Food and Drug Administration (FDA) is amending the 
    biologics regulations by removing, revising, or updating specific 
    regulations applicable to blood, blood components, and Source Plasma to 
    be more consistent with current practices in the blood industry and to 
    remove unnecessary or outdated requirements. FDA is issuing these 
    amendments directly as a final rule because they are noncontroversial 
    and there is little likelihood that FDA will receive any significant 
    comments opposing the rule. Elsewhere in this issue of the Federal 
    Register, FDA is publishing a proposed rule under FDA's usual 
    procedures for notice and comment in the event the agency receives any 
    significant adverse comments. If FDA receives any significant adverse 
    comment sufficient to terminate the direct final rule, FDA will 
    consider such comments on the proposed rule in developing the final 
    rule. FDA is issuing this rule as part of the agency's ``Blood 
    Initiative'' in which FDA is reviewing and revising, when appropriate, 
    its regulations, policies, guidance, and procedures related to blood, 
    blood components, and Source Plasma.
    
    DATES: This rule is effective February 11, 2000. Submit written 
    comments on or before December 3, 1999. If no timely significant 
    comments are received, the agency will publish a document in the 
    Federal Register within 30 days after the comment period on this direct 
    final rule ends, confirming the effective date of the final rule. If 
    timely significant adverse comments are received, the agency will 
    publish a document in the Federal Register withdrawing the direct final 
    rule before its effective date.
    
    ADDRESSES: Submit written comments on the direct final rule to the 
    Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 
    Fishers Lane, rm. 1061, Rockville, MD 20852.
    
    FOR FURTHER INFORMATION CONTACT: Dano B. Murphy, Center for Biologics 
    Evaluation and Research (HFM-17), Food and Drug Administration, 1401 
    Rockville Pike, Rockville, MD 20852-1448, 301-827-6210.
    
    SUPPLEMENTARY INFORMATION:
    
    I. Blood Initiative
    
        For a variety of reasons, FDA has decided to comprehensively review 
    and, as necessary, revise its regulations, policies, guidance and 
    procedures related to the licensing and regulation of blood products. 
    In the Federal Register of June 3, 1994 (59 FR 28821 and 59 FR 28822, 
    respectively), FDA issued two documents entitled ``Review of General 
    Biologics and Licensing Regulations'' (Docket No. 94N-0066) and 
    ``Review of Regulations for Blood Establishments and Blood Products'' 
    (Docket No. 94N-0080). The documents announced the agency's intent to 
    review biologics regulations, 21 CFR parts 600, 601, 606, 607, 640, and 
    660 and requested written comments from the public. Interested persons 
    were given until August 17, 1994, to respond to the documents. In 
    response to requests for additional time, FDA twice extended the 
    comment period, as announced in the Federal Register of August 17, 1994 
    (59 FR 42193), and November 14, 1995 (59 FR 56448). In addition, FDA 
    responded to requests for a public meeting to allow for the 
    presentation of comments regarding the agency's intent to review the 
    biologics regulations. On January 26, 1995, FDA held a public meeting 
    to provide an opportunity for all interested individuals to present 
    their comments and to assist the agency in determining whether the 
    regulations should be revised, rescinded, or continued without change. 
    Since the time of the regulation review, FDA has implemented a number 
    of changes to its regulations and policies applicable to the general 
    biologics and licensing regulations, some of which applied to blood 
    products as well as other biological products. (See, e.g., the final 
    rules issued on May 14, 1996 (61 FR 24313); August 1, 1996 (61 FR 
    40153); November 6, 1996 (61 FR 57328); July 24, 1997 (62 FR 39890); 
    and October 15, 1997 (62 FR 53536).)
        Because of the importance of a safe national blood supply, the U.S. 
    House of Representatives Committee on Government Reform and Oversight, 
    Subcommittee on Human Resources and Intergovernmental Relations (the 
    Subcommittee) and other groups such as the General Accounting Office 
    (GAO), and the Institute of Medicine (IOM) have reviewed the agency's 
    polices, practices, and regulations. Reports issued following the 
    respective reviews contained a number of recommendations as to how FDA 
    might improve the biologics regulations, particularly as they apply to 
    the continued safety of blood products. The relevant reports are: (1) 
    ``Protecting the Nation's Blood Supply From Infectious Agents: The Need 
    for New Standards to Meet New Threats,'' by the Subcommittee (August 2, 
    1996); (2) ``Blood Supply: FDA Oversight and Remaining Issues of 
    Safety,'' by GAO (February 25, 1997); (3) ``Blood Supply: Transfusion-
    Associated Risks,'' by GAO (February 25, 1997); and (4) ``HIV and the 
    Blood Supply: An Analysis of Crisis Decisionmaking,'' by IOM (July 13, 
    1995). These reports are on file with the Dockets Management Branch 
    (address above) under the docket number found in brackets in the 
    heading of this document.
        FDA has reviewed these reports and agrees with the majority of the 
    recommendations contained within them. However, rather than to only 
    respond specifically to the recommendations from the Subcommittee, GAO, 
    IOM, and the public, FDA has convened a number of internal task forces 
    to review a variety of issues related to the regulation of blood and 
    blood products, including how to most appropriately update the existing 
    regulations applicable to blood and blood products. In the future, FDA 
    intends to issue a number of blood-related regulations that various FDA 
    task groups are preparing. FDA emphasizes that for many of the changes 
    discussed in section III of this document, additional issues related to 
    the regulations now being amended continue to be under consideration by 
    the agency. Further, more substantive changes may be proposed at a 
    later date. Accordingly, any comment recommending an additional change 
    to these regulations will not be considered to be an ``adverse 
    comment'' unless the comment demonstrates that the change being made in 
    the direct final rule represents a major departure from current 
    regulations or accepted industry standards, or cannot be implemented 
    without additional amendments to the regulations.
        FDA is not describing the specific recommendations it received and 
    the numerous objectives of the Blood Initiative in this document. 
    Future rulemaking and other notices will describe and discuss specific 
    recommendations and regulatory objectives as they apply to each 
    rulemaking.
    
    II. Legal Authority
    
         FDA is issuing this new rule under the biologics products and
    
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    communicable disease provisions of the Public Health Service Act (the 
    PHS Act) (42 U.S.C. 262-264) and the drug, device, and general 
    administrative provisions of the Federal Food, Drug, and Cosmetic Act 
    (the act) (21 U.S.C. 321, 331, 351-353, 355, 360, 360j, 371, and 374). 
    Under these provisions of the PHS Act and the act, FDA has the 
    authority to issue and enforce regulations designed to ensure that 
    biological products are safe, pure, potent, and properly labeled and to 
    prevent the introduction, transmission, and spread of communicable 
    disease.
    
     III. Highlights of the Direct Final Rule
    
        FDA is amending the biologics regulations by removing, revising, or 
    updating specific regulations applicable to blood, blood components, 
    and Source Plasma to be more consistent with current practices and to 
    remove unnecessary or outdated requirements. FDA is issuing these 
    amendments as a direct final rule because the agency has concluded they 
    are noncontroversial and that there is little likelihood that there 
    will be comments opposing the rule. FDA emphasizes that for many of the 
    following changes, additional issues related to the regulations now 
    being amended continue to be under consideration by the agency. 
    Further, more substantive changes may be proposed at a later date. 
    Accordingly, any comment recommending additional changes to these 
    regulations will not be considered to be an ``adverse comment'' unless 
    the comment demonstrates that the change being made in the direct final 
    rule represents a major departure from current regulations or accepted 
    industry standards, or cannot be implemented without additional 
    amendments to the regulation. In the following paragraphs, FDA 
    discusses each of the rule changes in the direct final rule.
        Part 606 (21 CFR part 606) is amended as follows:
        Section 606.3, Definitions, is amended so that the definitions 
    provided in the section are consistent with current meanings and 
    usages.
        The definition of ``Component'' in Sec. 606.3(c) is amended to 
    apply to blood obtained from a single donor and no longer includes the 
    wording ``single-donor unit.'' This change is to clarify that blood 
    components may be collected by means other than separation from a unit 
    of whole blood, such as by automated plasmapheresis.
        The definition of ``Plasmapheresis'' in Sec. 606.3(e) is amended by 
    removing the restriction that plasmapheresis may be ``immediately 
    repeated, once'' because current automated plasmapheresis collection 
    practices often use more than two cycles for collection.
        The definition of ``Plateletpheresis'' in Sec. 606.3(f ) is amended 
    to provide for the common practice of collecting plasma as a by-product 
    of a plateletpheresis procedure in lieu of returning all of the 
    residual plasma to the donor.
        The definition of ``Compatibility testing'' in Sec. 606.3(j) is 
    amended by removing the reference to serological tests and making the 
    definition more general to apply to all tests performed to establish 
    the matching of a donor's blood or blood components with that of a 
    potential recipient. This change will provide for current practices 
    used in compatibility testing, such as the electronic crossmatch and 
    the immediate spin crossmatch.
        Section 606.100(b) and (d) are amended to reflect changes in 
    terminology, requirements for testing, and availability of standard 
    operating procedures (SOP's) to be consistent with current practices. 
    Section 606.100(b) is also amended by removing the references to 
    homologous and autologous transfusion because subpart F of part 606, 
    applies to all blood products intended for transfusion. In addition, 
    the phrase ``unless this is impractical'' is removed because it is 
    current good manufacturing practice (CGMP) to make the applicable SOP's 
    available in all areas where procedures are performed. Section 
    606.100(b)(7) is amended by removing ``including testing for hepatitis 
    B surface antigen as prescribed in Sec. 610.40 of this chapter'' 
    because other tests, in addition to tests for hepatitis B surface 
    antigen, are now required and specific reference to this test is 
    unnecessary. Section 606.100(b)(18) is amended by removing the 
    bracketed term ``salvaged'' because its use in Sec. 606.100 is 
    inconsistent with the use of ``salvaged plasma'' in Sec. 640.76. 
    Section 606.100(d) is amended by removing references to specific 
    organizations because any SOP's meeting FDA requirements would be 
    acceptable, regardless of their source, and because FDA cannot assure 
    that SOP's adopted by particular organizations remain in compliance 
    with FDA's regulatory requirements.
        Section 606.121(a) is amended by removing the reference that the 
    ``Guideline for the Uniform Labeling of Blood and Blood Components'' is 
    available from Dockets Management Branch as this is no longer the 
    appropriate office from which to request this document and by removing 
    the reference to the American Blood Commission because the organization 
    no longer exists.
        Section 606.121(d)(2) specifies the color requirements for printing 
    the container label and is amended by adding ``or in solid black'' 
    because some blood centers use on-demand printers for printing labels, 
    that do not have the capability to print in multiple colors.
        Section 606.121(e)(1)(ii) prescribes the specific anticoagulants 
    that shall be identified on the container label. Section 
    606.121(e)(1)(ii) is amended by deleting the references to the names of 
    specific anticoagulants. This change will allow for more flexibility 
    for the acceptance and use of new anticoagulants or changes in 
    nomenclature of existing anticoagulants without requiring amendments to 
    the regulations.
        Section 606.122(f) specifies the warning statement required in the 
    instruction circular and is amended by removing the reference to 
    ``hepatitis'' and adding ``infectious agents'' to include a reference 
    to the additional infectious disease marker tests routinely performed 
    on blood and blood components because the product intended for 
    transfusion carries the risk of transmitting other infectious agents.
        Section 606.122(n)(4) specifies that the instruction circular for 
    cryoprecipitated AHF shall contain instructions to thaw the product at 
    a temperature of 37  deg.C and is amended to allow instructions for 
    thawing between 30 and 37  deg.C, permitting more flexibility in the 
    preparation of the component.
        Section 606.151(b) is amended, consistent with current accepted 
    practices, to permit SOP's to include use of recipient serum samples 
    less than 3-days old for compatibility testing if the recipient has 
    been pregnant or transfused within the preceding 3 months.
        Section 606.151(c) describes compatibility testing and is amended 
    by changing ``the testing of the donor's cells with the recipient's 
    serum'' to ``the testing of the donor's cell type with the recipient's 
    serum type'' and by replacing ``agglutinating, coating, and hemolytic 
    antibodies, which shall include the antiglobulin method'' with 
    ``incompatibility.'' This change is intended to accommodate the use of 
    such procedures as an immediate spin crossmatch and an electronic 
    crossmatch.
        Section 606.151(e) is amended by changing ``by the physician 
    requesting the procedure.'' to ``by a physician.'' to take into account 
    that a patient may have more than one physician in attendance at any 
    time.
        Section 606.160(b)(2)(v) is amended by changing ``person(s) 
    responsible'' to ``the person(s) performing the
    
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    procedure'' to clarify that the person(s) performing the labeling 
    procedure is responsible for documenting the performance of that 
    procedure.
        Section 606.170(b) is amended by deleting ``telegraph'' and adding 
    ``facsimile, express mail, or electronically transmitted mail'' to the 
    possible methods by which the Director, Office of Compliance and 
    Biologics Quality, Center for Biologics Evaluation and Research, shall 
    be notified of a complication of blood collection or transfusion 
    resulting in a fatality.
        Part 640 (21 CFR part 640) is amended as follows:
        Section 640.2(b) is removed because Whole Blood collection in open 
    systems is no longer acceptable nor has it been performed for many 
    years. Section 640.2(d) is revised. In Sec. 640.2 paragraphs (c), (e), 
    and (f) are redesignated as paragraphs (b), (c), and (d), respectively. 
    Redesignated Sec. 640.2(b) and (c)(2) are revised by removing 
    references to the original blood container because, consistent with 
    current accepted practices such as washing, freezing, 
    deglycerolization, and division of units using sterile connecting 
    devices, the original blood container may, in many cases, no longer be 
    the final container.
        Section 640.3(b) is amended by adding a reference to autologous 
    donations to permit the collection of autologous Whole Blood at 
    intervals of less than 8 weeks, consistent with the current practice of 
    shorter time intervals between collections of blood and blood 
    components from donors participating in autologous collection programs. 
    Section 640.3(b)(3) is amended to provide hematocrit and hemoglobin 
    values to be used when determining whether a potential donor can donate 
    Whole Blood, by adding to the end of the current paragraph ``or a 
    hematocrit value of 38 percent, and for autologous donations, a blood 
    hemoglobin level which shall be demonstrated to be no less than 11.0 g 
    of hemoglobin per 100 mL of blood or a hematocrit value of 33 
    percent.'' The acceptable hemoglobin and hematocrit values for 
    autologous donors are consistent with current industry practice and the 
    American Association of Blood Banks technical manual, 12th edition.
        Sections 640.3(c)(1) and 640.63(c)(11) are amended by inserting 
    ``after the age of eleven'' after the term ``hepatitis'' because 
    establishments may collect Whole Blood from donors who have a history 
    of hepatitis prior to age eleven to be consistent with recommendations 
    in the FDA memorandum dated April 23, 1992, entitled ``Exemptions to 
    Permit Persons with a History of Viral Hepatitis Before the Age of 
    Eleven to serve as Donors of Whole Blood and Plasma: Alternative 
    Procedure''(21 CFR 640.120). Additional issues concerning donors who 
    have a history of viral hepatitis continued to be reviewed by the 
    agency and may be addressed in future rulemaking objectives.
        Sections 640.3(c)(2) and 640.63(c)(12) are amended by changing the 
    deferral period for donors of Whole Blood who have had close contact 
    with an individual having viral hepatitis from ``six months'' to ``12 
    months.'' Similarly, Secs. 640.3(c)(3) and 640.63(c)(13) are amended by 
    changing the deferral period from ``six months'' to ``12 months'' for 
    donors of Whole Blood who received human blood, or any derivative of 
    human blood which FDA has identified as a possible source of viral 
    hepatitis. These changes are consistent with recommendations made in 
    the FDA memoranda dated April 23, 1992, entitled ``Revised 
    Recommendations for the Prevention of Human Immunodeficiency Virus 
    Transmission by Blood and Blood Products and Revised Recommendations 
    for Testing Whole Blood, Blood Components, Source Plasma and Source 
    Leukocytes for Antibody to Hepatitis C Virus Encoded Antigen (Anti-
    HCV).'' In addition, Secs. 640.3(c)(3) and 640.63(c)(13) have been 
    amended by changing the reference from a ``licensed establishment'' to 
    a ``blood establishment'' to clarify that the regulation applies to all 
    establishments engaged in the collection of blood and blood products.
        Sections 640.3(e), 640.31(c), and 640.51(c) are removed because FDA 
    has concluded that it is no longer necessary to defer donors 
    participating in red blood cell immunization programs. Previously, 
    donors participating in red blood cell immunization programs were 
    deferred for 12 months because fresh red blood cells were used to 
    immunize donors. Red blood cells now used in immunization programs are 
    carefully screened and quarantined thereby minimizing the risk of 
    transmitting infectious agents. See FDA memorandum dated March 14, 
    1995, entitled ``Revised Recommendations for Red Blood Cell 
    Immunization Programs for Source Plasma Donors'' for additional 
    information about current red blood cell immunization practices.
        Section 640.4(b) is amended by removing the word ``clinic'' and 
    replacing it with the word ``center'' to reflect current terminology 
    and by changing the word ``licensed'' to ``blood'' to clarify that the 
    regulation applies to all blood establishments engaged in the 
    collection of blood and blood products. Section 640.4(d) is amended by 
    removing the reference to the specific anticoagulant formulae. Section 
    640.4(d)(1) through (d)(4) is removed because FDA has determined it is 
    unnecessary to provide specific formulae for anticoagulant solutions in 
    the regulations and that manufacturers should be able to use any 
    anticoagulant approved by FDA for such use. Sections 640.13(a), 
    640.22(a), 640.32(a), and 640.52(a) are amended to remove references to 
    Sec. 640.4(d)(2) and (h), which are being removed.
        Section 640.4(g)(5) has been changed to include the use of 
    different anticoagulants in segments for compatibility testing to be 
    consistent with the use of different approved anticoagulants in the 
    manufacture of blood and blood products. Section 640.4(h) is removed 
    because heparin anticoagulant solutions are no longer used for the 
    routine collection of blood.
        Section 640.5(c) is amended to be consistent with current Rh factor 
    testing practices by removing ``and for other Rh-Hr factors,'' because 
    these tests are not routinely performed. The section is also changed to 
    specify that blood testing negative using Anti-D Blood Grouping 
    Reagents may only be labeled ``Rh Negative'' if the confirmatory 
    testing includes tests for weak expressions of D. These changes have 
    been made to be consistent with current accepted practices which 
    designate that tests for weak expressions of D be performed and the 
    product labeled consistent with the results of those tests.
        Sections 640.6(c) and 640.15(c) are removed because the use of more 
    modern methods of manufacturing and equipment have eliminated the use 
    of pilot tubes attached to blood units. In Sec. 640.15 paragraph (d) is 
    redesignated as paragraph (c).
        Section 640.16(a) is amended by inserting ``or additive solution'' 
    after ``cryoprotective substance'' to reflect an additional procedure 
    for prolonging shelf life now in use in which all the plasma is removed 
    from a unit of blood.
        Section 640.16(b) is amended by removing all but the first 
    sentence. The removed text describes blood collection procedures to be 
    followed when using open vented systems. Use of open vented systems is 
    no longer consistent with CGMP and has not been used for many years.
        All references to ``pilot tubes'' and ``pilot samples'' have been 
    replaced with the words ``sample(s)'' or ``segment(s)'' to reflect 
    current terminology for various testing specimens. The following 
    sections are amended by replacing ``pilot tubes,''
    
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    ``pilot samples,'' or ``pilot sample tubes'' with ``segments'' or 
    ``samples'' as appropriate: Secs. 640.2(e)(2), 640.4(g) introductory 
    text, and paragraphs (g)(1), (g)(2), (g)(4), and (g)(5), 640.5, 
    640.15(a) through (c), and 640.69(d) introductory text, and paragraphs 
    (d)(1) through (d)(4).
        Section 640.23(a) is amended to include the preparation of 
    Platelets prepared by automated collection procedures and to allow the 
    group and typing tests performed on Platelets prepared by apheresis to 
    be valid for a period not to exceed 3 months, thereby, eliminating the 
    necessity of repeat testing of blood samples from donors participating 
    in frequent plateletpheresis collection procedures.
        Section 640.24(b) is amended by changing the time period for 
    separation of the platelet concentrate from ``4 hours'' to ``within the 
    time period specified in the directions for use for the specific 
    device.'' Similar changes are made to the timeframe for the storage of 
    plasma that is set forth in Sec. 640.34(a) through (d) and (e)(1) and 
    the freezing of plasma set forth in Sec. 640.54(a)(2). These changes, 
    consistent with current accepted practices, permit more flexibility by 
    permitting different timeframes depending on the particular blood 
    collection device being used.
        Sections 640.25(b) and 640.56(a) are amended to require testing 
    only in those months in which blood products are prepared for use. This 
    eliminates the need for performing quality control procedures during 
    those months when product is not being manufactured.
        Sections 640.25(c), 640.56(c), and 640.71(a) are amended to update 
    references to cite the ``Clinical Laboratories Improvement Amendments 
    of 1988 (CLIA)'' consistent with nomenclature in the regulations 
    implementing CLIA in 42 CFR part 493.
        Section 640.34(d) is amended by deleting the reference to storing 
    platelet rich plasma at temperatures between 1 and 6  deg.C because 
    storage at such temperatures adversely affects platelet function.
        Section 640.34(e)(2) and (e)(3) are amended to include the proper 
    name of the product ``Plasma, Cryoprecipitate Reduced'' as per 
    recommendations of the Blood Products Advisory Committee at its 
    September 18 and 19, 1997 meeting. Section 640.34(g)(2) is amended to 
    permit proof of continuous monitoring of the temperature to be within 
    acceptable ranges for the product as an alternative to requiring the 
    storing of the product in a manner to show evidence of thawing. FDA 
    believes that, with current technology, monitoring systems of freezers 
    used for storage are adequately sensitive and reliable to detect any 
    significant rise in storage temperature.
        Section 640.62 requiring that a qualified licensed physician be on 
    the premises when donor suitability is being determined is amended to 
    require a qualified licensed physician to be physically available on 
    the premises, or be available to attend to the donor within 15 minutes, 
    when a pheresis procedure is being performed, for consultation and 
    management of donor adverse reactions, except that the qualified 
    licensed physician shall be physically available on the premises when 
    red blood cell immunizations are being performed. FDA has determined 
    that a qualified licensed physician must always be readily available, 
    if needed, and shall be on the premises for red blood cell 
    immunizations.
        Section 640.63(c)(3) is amended by adding at the end of the 
    sentence ``or a hematocrit level of 38 percent,'' which is equivalent 
    to a hemoglobin level of 12.5 g per 100 mL of blood, to be consistent 
    with current accepted practices.
        Section 640.63(c)(5) is amended by adding ``or total plasma'' after 
    ``A total serum'' to be consistent with current accepted practice of 
    using a capillary tube coated with anticoagulant for fingerstick sample 
    collection.
        Section 640.65(b)(4) is amended by changing ``in any 48-hour 
    period'' to ``2-day'' to permit more flexibility in scheduling donor 
    appointments and by adding the word ``manual'' to the phrases ``during 
    a plasmapheresis procedure'' to clarify that the regulation applies to 
    a manual plasmapheresis collection procedure, but does not apply to 
    automated apheresis.
        Section 640.65(b)(5) is amended by adding ``during a manual 
    plasmapheresis procedure'' after the phrases ``removed from the donor'' 
    to clarify that the regulation applies to a manual plasmapheresis 
    collection procedure, but does not apply to automated apheresis..
        Section 640.65(b)(8) is added to address the collection of Source 
    Plasma using automated collection devices. The regulation delineates 
    the frequency of collection consistent with Sec. 640.65(b)(4) and 
    (b)(5) and the volume of plasma to be collected during such procedures 
    consistent with the plasma collection volumes approved for each device 
    and with recommendations included in the FDA memorandum to all plasma 
    establishments dated November 4, 1992, entitled ``Volume Limits for 
    Automated Collection of Source Plasma.''
        Section 640.72(a)(1) is amended by replacing ``compiled every 3 
    months'' with ``shall be available'' to eliminate the necessity of 
    compiling documents at specified time intervals.
    
     IV. Rulemaking Action
    
        In the Federal Register of November 21, 1997 (62 FR 62466), FDA 
    described its procedures on when and how FDA will employ direct final 
    rulemaking. FDA has determined that this rule is appropriate for direct 
    final rulemaking because FDA views this rule as including only 
    noncontroversial amendments and anticipates no significant adverse 
    comments. Consistent with FDA's procedures on direct final rulemaking, 
    FDA is publishing elsewhere in this issue of the Federal Register, a 
    companion proposed rule to amend the biologics regulations by removing, 
    revising, and updating existing regulations to be more consistent with 
    current accepted practices. The companion proposed rule provides a 
    procedural framework within which the rule may be finalized in the 
    event the direct final rule is withdrawn because of any significant 
    adverse comment. The comment period for the direct final rule runs 
    concurrently with the companion proposed rule. Any comment received 
    under the companion proposed rule will be considered as comments 
    regarding the direct final rule.
        FDA has provided a comment period on the direct final rule of 75 
    days after August 19, 1999. If the agency receives any significant 
    adverse comment, FDA intends to withdraw this direct final rule action 
    by publication of a document in the Federal Register within 30 days 
    after the comment period ends. A significant adverse comment is defined 
    as a comment that explains why the rule would be inappropriate, 
    including challenges to the rule's underlying premise or approach, or 
    would be ineffective or unacceptable without a change. In determining 
    whether a significant adverse comment is sufficient to terminate a 
    direct final rulemaking, FDA will consider whether the comment raises 
    an issue serious enough to warrant a substantive response in a notice-
    and-comment process. Comments that are frivolous, insubstantial, or 
    outside the scope of the rule will not be considered significant or 
    adverse under this procedure. A comment recommending a rule change in 
    addition to the rule would not be considered a significant adverse 
    comment, unless the comment states why the rule would be ineffective 
    without additional change. In addition, if a significant adverse 
    comment applies to an amendment, paragraph, or section of this rule and
    
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    that provision can be severed from the remainder of the rule, FDA may 
    adopt as final those provisions of the rule that are not subjects of a 
    significant adverse comment.
        If any significant adverse comment is received during the comment 
    period, FDA will publish, within 30 days after the comment period ends, 
    a document withdrawing the direct final rule. If FDA withdraws the 
    direct final rule, any comments received will be applied to the 
    proposed rule and will be considered in developing a final rule using 
    the usual Administrative Procedure Act notice-and-comment procedures.
        If FDA receives no significant adverse comments during the 
    specified comment period, FDA intends to publish a confirmation 
    document within 30 days after the comment period ends confirming the 
    effective date.
    
    V. Analysis of Impacts
    
    A. Review Under Executive Order 12866 and the Regulatory Flexibility 
    Act and Unfunded Mandates Reform Act of 1995
    
        FDA has examined the impact of the direct final rule under 
    Executive Order 12866, the Regulatory Flexibility Act (5 U. S. C. 601-
    612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4). 
    Executive Order 12866 directs agencies to assess all costs and benefits 
    of available regulatory alternatives and, when regulation is necessary, 
    to select regulatory approaches that maximize net benefits (including 
    potential economic, environmental, public health and safety, and other 
    advantages; distributive impact; and equity). The agency believes that 
    this direct final rule is consistent with the regulatory philosophy and 
    principles identified in the Executive Order. This direct final rule is 
    not a significant regulatory action as defined by the Executive Order 
    and therefore is not subject to review under the Executive Order.
        The Regulatory Flexibility Act requires agencies to analyze 
    regulatory options to minimize any significant impact of a rule on 
    small business entities. Because the direct final rule amendments have 
    no compliance costs and do not result in any new requirements, the 
    agency certifies that the direct final rule will not have a significant 
    negative economic impact on a substantial number of small entities. 
    Therefore, under the Regulatory Flexibility Act, no further analysis is 
    required. This direct final rule also does not trigger the requirement 
    for a written statement under section 202(a) of the Unfunded Mandates 
    Reform Act because it does not impose a mandate that results in an 
    expenditure of $100 million or more by State, local, and tribal 
    governments in the aggregate, or by the private sector in any 1 year.
    
    B. Environmental Impact
    
        The agency has determined under 21 CFR 25.31(j) that this action is 
    of a type that does not individually or cumulatively have a significant 
    effect on the human environment. Therefore, neither an environmental 
    assessment nor an environmental impact statement is required.
    
    VI. The Paperwork Reduction Act of 1995
    
        This direct final rule contains no collection of information. 
    Therefore, clearance by the Office of Management and Budget under the 
    Paperwork Reduction Act of 1995 is not required.
    
    VII. Request for Comments
    
        Interested persons may, on or before December 3, 1999, submit to 
    the Docket Management Branch (address above) written comments regarding 
    this final rule. 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
    
    21 CFR Part 606
    
         Blood, Labeling, Laboratories, Reporting and recordkeeping 
    requirements.
    
    21 CFR Part 640
    
         Blood, Labeling, Reporting and recordkeeping requirements.
        Therefore under the Federal Food, Drug, and Cosmetic Act, the 
    Public Health Service Act, and authority delegated by the Commissioner 
    of Food and Drugs, 21 CFR parts 606 and 640 are amended as follows:
    
     PART 606--CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD 
    COMPONENTS
    
        1. The authority citation for 21 CFR part 606 continues to read as 
    follows:
    
         Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 360j, 371, 
    374; 42 U.S.C. 216, 262, 263a, 264.
    
        2. Section 606.3 is amended by revising paragraphs (c), (e), (f), 
    and (j) to read as follows:
    
    Sec. 606.3   Definitions.
    
    * * * * *
         (c) Component means that part of a single-donor's blood separated 
    by physical or mechanical means.
    * * * * *
         (e) Plasmapheresis means the procedure in which blood is removed 
    from the donor, the plasma is separated from the formed elements and at 
    least the red blood cells are returned to the donor.
         (f) Plateletpheresis means the procedure in which blood is removed 
    from a donor, a platelet concentrate is separated, and the remaining 
    formed elements are returned to the donor along with a portion of the 
    residual plasma.
    * * * * *
         (j) Compatibility testing means the tests performed to establish 
    the matching of a donor's blood or blood components with that of a 
    potential recipient.
        3. Section 606.100 is amended by revising the introductory text of 
    paragraphs (b) and (d), and by revising paragraphs (b)(7) and (b)(18) 
    to read as follows:
    
    
    Sec. 606.100   Standard operating procedures.
    
    * * * * *
         (b) Written standard operating procedures shall be maintained and 
    shall include all steps to be followed in the collection, processing, 
    compatibility testing, storage, and distribution of blood and blood 
    components for transfusion and further manufacturing purposes. Such 
    procedures shall be available to the personnel for use in the areas 
    where the procedures are performed. The written standard operating 
    procedures shall include, but are not limited to, descriptions of the 
    following, when applicable:
    * * * * *
         (7) All tests and repeat tests performed on blood and blood 
    components during manufacturing.
    * * * * *
         (18) Procedures for preparing recovered plasma, if performed, 
    including details of separation, pooling, labeling, storage, and 
    distribution.
    * * * * *
         (d) In addition to the requirements of this subpart and in 
    conformity with this section, any facility may utilize current standard 
    operating procedures such as the manuals of the organizations, as long 
    as such specific procedures are consistent with, and at least as 
    stringent as, the requirements contained in this part.
    * * * * *
        4. Section 606.121 is amended by revising paragraphs (a), (d)(2), 
    and (e)(1)(ii) to read as follows:
    
    
    [[Page 45371]]
    
    
    
    
    Sec. 606.121   Container label.
    
        (a) The container label requirements are designed to facilitate the 
    use of a uniform container label for blood and blood components (except 
    Source Plasma) by all blood establishments.
    * * * * *
         (d) * * *
        (2) The proper name of the product, any appropriate modifier(s), 
    the donor classification statement, and the statement ``properly 
    identify intended recipient'' shall be printed in solid red or in solid 
    black.
    * * * * *
        (e) * * *
        (1) * * *
        (ii) The name of the applicable anticoagulant immediately preceding 
    and of no less prominence than the proper name approved for use by the 
    Director, Center for Biologics Evaluation and Research.
    * * * * *
        5. Section 606.122 is amended by revising paragraphs (f) and (n)(4) 
    to read as follows:
    
    Sec. 606.122   Instruction circular.
    
    * * * * *
         (f) The statements: ``Warning. The risk of transmitting infectious 
    agents is present. Careful donor selection and available laboratory 
    tests do not eliminate the hazard.''
    * * * * *
        (n) * * *
        (4) Instructions to thaw the product for no more than 15 minutes at 
    a temperature between 30 and 37  deg.C.
    * * * * *
        6. Section 606.151 is amended by revising paragraphs (b), (c), and 
    (e) to read as follows:
    
    Sec. 606.151   Compatibility testing.
    
    * * * * *
        (b) The use of fresh recipient serum samples less than 3-days old 
    for all pretransfusion testing if the recipient has been pregnant or 
    transfused within the previous 3 months.
        (c) The testing of the donor's cell type with the recipient's serum 
    type by a method that will demonstrate incompatibility.
     * * * * *
         (e) Procedures to expedite transfusion in life-threatening 
    emergencies. Records of all such incidents shall be maintained, 
    including complete documentation justifying the emergency action, which 
    shall be signed by a physician.
        7. Section 606.160 is amended by revising paragraph (b)(2)(v) to 
    read as follows:
    
    Sec. 606.160   Records.
    
    * * * * *
        (b) * * *
        (2) * * *
        (v) Labeling, including initials of the person(s) performing the 
    procedure.
    * * * * *
        8. Section 606.170 is amended by revising paragraph (b) to read as 
    follows:
    
    Sec. 606.170   Adverse reaction file.
    
    * * * * *
         (b) When a complication of blood collection or transfusion is 
    confirmed to be fatal, the Director, Office of Compliance and Biologics 
    Quality, Center for Biologics Evaluation and Research, shall be 
    notified by telephone, facsimile, express mail, or electronically 
    transmitted mail as soon as possible; a written report of the 
    investigation shall be submitted to the Director, Office of Compliance 
    and Biologics Quality, Center for Biologics Evaluation and Research, 
    within 7 days after the fatality by the collecting facility in the 
    event of a donor reaction, or by the facility that performed the 
    compatibility tests in the event of a transfusion reaction.
         (Information collection requirements approved by the Office of 
    Management and Budget under control number 0910-0116)
    
    PART 640--ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS
    
        9. The authority citation for 21 CFR part 640 continues to read as 
    follows:
    
        Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371; 42 
    U.S.C. 216, 262, 263, 263a, 264.
    
        10. Section 640.2 is amended by removing paragraphs (b) and (d), by 
    redesignating paragraphs (c), (e), and (f) as paragraphs (b), (c), and 
    (d), respectively, and by revising newly redesignated paragraphs (b) 
    and (c)(2) to read as follows:
    
    Sec. 640.2   General requirements.
    
    * * * * *
         (b) Blood container. The blood container shall not be entered 
    prior to issue for any purpose except for blood collection. Such 
    container shall be uncolored and transparent to permit visual 
    inspection of the contents and any closure shall be such as will 
    maintain an hermetic seal and prevent contamination of the contents. 
    The container material shall not interact with the contents under the 
    customary conditions of storage and use, in such a manner as to have an 
    adverse effect upon the safety, purity, or potency of the blood.
        (c) * * *
        (2) A segment is properly attached and has not been removed, except 
    that blood lacking a properly attached segment may be reissued in an 
    emergency provided it is accompanied by instructions for sampling and 
    for use within 6 hours after entering the container for sampling;
    * * * * *
        11. Section 640.3 is amended by revising the introductory text of 
    paragraph (b), by revising paragraphs (b)(3), (c)(1), (c)(2), and 
    (c)(3) and by removing and reserving paragraph (e) to read as follows:
    
    Sec. 640.3   Suitability of donor.
    
    * * * * *
        (b) Qualifications of donor; general. Except as provided in 
    paragraph (f) of this section and for autologous donations, a person 
    may not serve as a source of Whole Blood more than once in 8 weeks. In 
    addition, donors shall be in good health, as indicated in part by:
    * * * * *
         (3) For allogeneic donors, a blood hemoglobin level which shall be 
    demonstrated to be no less than 12.5 grams (g) of hemoglobin per 100 
    milliliters (mL) of blood; or a hematocrit value of 38 percent, and for 
    autologous donors, a blood hemoglobin level which shall be demonstrated 
    to be no less than 11.0 g of hemoglobin per 100 mL of blood or a 
    hematocrit value of 33 percent.
    * * * * *
        (c) * * *
        (1) A history of viral hepatitis after the age of eleven;
        (2) A history of close contact within 12 months of donation with an 
    individual having viral hepatitis;
         (3) A history of having received within 12 months of donation, 
    human blood or any derivative of human blood which the Food and Drug 
    Administration has advised the blood establishment is a possible source 
    of viral hepatitis.
    * * * * *
        12. Section 640.4 is amended by removing paragraphs (d)(1) through 
    (d)(4) and (h), by redesignating paragraph (i) as paragraph (h), and 
    revising paragraphs (b) and (d), the introductory text of paragraph 
    (g), and paragraphs (g)(1), (g)(2), (g)(4), and (g)(5) to read as 
    follows:
    
    Sec. 640.4   Collection of the blood.
    
    * * * * *
         (b) The donor center. The pertinent requirements of Secs. 600.10 
    and 600.11 of this chapter shall apply at both the
    
    [[Page 45372]]
    
    blood establishment and at any other place where the bleeding is 
    performed.
    * * * * *
         (d) The anticoagulant solution. The anticoagulant solution shall 
    be sterile and pyrogen-free. Anticoagulant solutions shall be 
    compounded and used according to a formula approved by the Director, 
    Center for Biologics Evaluation and Research.
    * * * * *
         (g) Samples for laboratory tests. Samples for laboratory tests 
    shall meet the following standards:
         (1) One or more segments shall be provided with each unit of blood 
    when issued or reissued except as provided in Sec. 640.2(e)(2) and all 
    segments shall be from the donor who is the source of the unit of 
    blood.
         (2) All samples for laboratory tests performed by the manufacturer 
    and all segments accompanying a unit of blood shall be collected at the 
    time of filling the original blood container.
     * * * * *
        (4) All segments accompanying a unit of blood shall be attached to 
    the whole blood container before blood collection, in a tamper proof 
    manner that will conspicuously indicate removal and reattachment.
        (5) Segments for compatibility testing shall contain blood mixed 
    with the appropriate anticoagulant.
    * * * * *
        13. Section 640.5 is amended by revising the introductory text and 
    paragraph (c) to read as follows:
    
    Sec. 640.5   Testing the blood.
    
        All laboratory tests shall be made on a specimen of blood taken 
    from the donor at the time of collecting the unit of blood, and these 
    tests shall include the following:
    * * * * *
        (c) Determination of the Rh factors. Each container of Whole Blood 
    shall be classified as to Rh type on the basis of tests done on the 
    sample. The label shall indicate the extent of typing and the results 
    of all tests performed. If the test, using Anti-D Blood Grouping 
    Reagent, is positive, the container may be labeled ``Rh Positive''. If 
    this test is negative, the results shall be confirmed by further 
    testing which shall include tests for the Rho variant 
    (Du). Blood may be labeled ``Rh Negative'' if further 
    testing is negative. Units testing positive after additional more 
    specific testing shall be labeled as ``Rh Positive.'' Only Anti-Rh 
    Blood Grouping Reagents licensed under, or that otherwise meet the 
    requirements of, the regulations of this subchapter shall be used, and 
    the technique used shall be that for which the reagent is specifically 
    designed to be effective.
    * * * * *
    
    
    Sec. 640.6  [Amended]
    
        14. Section 640.6 Modifications of Whole Blood is amended by 
    removing paragraph (c).
        15. Section 640.13 is amended by revising paragraph (a) to read as 
    follows:
    
    Sec. 640.13   Collection of the blood.
    
        (a) The source blood shall be collected as prescribed in 
    Sec. 640.4.
    * * * * *
        16. Section 640.15 is revised to read as follows:
    
    
    Sec. 640.15   Samples for testing.
    
        Samples collected in integral tubing shall meet the following 
    standards:
        (a) One or more segments of either the original blood or of the Red 
    Blood Cells being processed shall be provided with each unit of Red 
    Blood Cells when issued or reissued.
        (b) Before they are filled, all segments shall be marked or 
    identified so as to relate them to the donor of that unit of red cells.
        (c) All segments accompanying a unit of Red Blood Cells shall be 
    filled at the time the blood is collected or at the time the final 
    product is prepared.
        17. Section 640.16 is amended by revising paragraphs (a) and (b) to 
    read as follows:
    
    Sec. 640.16   Processing.
    
        (a) Separation. Within the timeframe specified in the directions 
    for the use of the specific devices, Red Blood Cells may be prepared 
    either by centrifugation, done in a manner that will not tend to 
    increase the temperature of the blood, or by normal undisturbed 
    sedimentation. A portion of the plasma sufficient to insure optimal 
    cell preservation shall be left with the red cells except when a 
    cryoprotective substance or additive solution is added for prolonged 
    storage.
        (b) Sterile system. All surfaces that come in contact with the red 
    cells shall be sterile and pyrogen-free.
    * * * * *
        18. Section 640.22 is amended by revising paragraph (a) to read as 
    follows:
    
    Sec. 640.22   Collection of source material.
    
        (a) Whole blood used as the source of Platelets shall be collected 
    as prescribed in Sec. 640.4.
    * * * * *
        19. Section 640.23 is amended by revising paragraph (a) to read as 
    follows:
    
    Sec. 640.23   Testing the blood.
    
         (a) Blood from which plasma is separated for the preparation of 
    Platelets or Platelets, Pheresis shall be tested as prescribed in 
    Secs. 610.40 and 610.45 of this chapter and Sec. 640.5(a), (b), and 
    (c). Results of tests performed in accordance with Sec. 640.5(b) and 
    (c) for Platelets, Pheresis products shall be valid for a period not to 
    exceed 3 months.
    * * * * *
        20. Section 640.24 is amended by revising paragraph (b) to read as 
    follows:
    
    Sec. 640.24   Processing.
    
    * * * * *
        (b) Immediately after collection, the whole blood or plasma shall 
    be held in storage between 20 and 24  deg.C, unless it must be 
    transported from the collection center to the processing laboratory. 
    During such transport, all reasonable methods shall be used to maintain 
    the temperature as close as possible to a range between 20 and 24 
    deg.C until it arrives at the processing laboratory where it shall be 
    held between 20 and 24  deg.C until the platelets are separated. The 
    platelet concentrate shall be separated within the timeframe specified 
    in the directions for use for the specific device used for the 
    collection of the unit of whole blood or plasma.
    * * * * *
    
    
    Sec. 640.31  [Amended]
    
        21. Section 640.31 Suitability of donors is amended by removing 
    paragraph (c).
    
        22. Section 640.32 is amended by revising the first sentence of 
    paragraph (a) to read as follows:
    
    Sec. 640.32   Collection of source material.
    
        (a) Whole blood shall be collected, transported, and stored as 
    prescribed in Sec. 640.4. * * *
    * * * * *
        23. Section 640.34 is amended by revising paragraphs (a) through 
    (d), (e)(1) through (e)(3), and (g)(2) to read as follows:
    
    Sec. 640.34   Processing.
    
        (a) Plasma. Plasma shall be separated from the red blood cells and 
    shall be stored at -18  deg.C or colder within the timeframe specified 
    in the directions for use for the specific device after transfer to the 
    final container, unless the product is to be stored as Liquid Plasma.
        (b) Fresh Frozen Plasma. Fresh Frozen Plasma shall be prepared from 
    blood collected by a single uninterrupted venipuncture with minimal 
    damage to and minimal manipulation of the donor's tissue. The plasma 
    shall be
    
    [[Page 45373]]
    
    separated from the red blood cells, frozen solid within the timeframe 
    specified in the directions for use for the specific device, and stored 
    at -18  deg.C or colder.
        (c) Liquid Plasma. Liquid Plasma shall be separated from the red 
    blood cells and shall be stored at a temperature of 1 to 6  deg.C 
    within the timeframe specified in the directions for use for the 
    specific device after filling the final container.
        (d) Platelet Rich Plasma. Platelet Rich Plasma shall be prepared 
    from blood collected by a single uninterrupted venipuncture with 
    minimal damage to and manipulation of the donor's tissue. The plasma 
    shall be separated from the red blood cells by centrifugation within 
    the timeframe specified in the directions for use for the specific 
    device after completion of the phlebotomy. The time and speed of 
    centrifugation shall have been shown to produce a product with at least 
    250,000 platelets per microliter. The plasma shall be stored at a 
    temperature between 20 and 24  deg.C, immediately after filling the 
    final container. A gentle and continuous agitation of the product shall 
    be maintained throughout the storage period, if stored at a temperature 
    of 20 to 24  deg.C.
        (e) * * *
        (1) Platelets shall be separated as prescribed in subpart C of part 
    640, prior to freezing the plasma. The remaining plasma may be labeled 
    as ``Fresh Frozen Plasma,'' if frozen within the timeframe specified in 
    the directions for use for the specific device after filling the final 
    container.
        (2) Cryoprecipitated AHF shall be removed as prescribed in subpart 
    F of part 640. The remaining plasma shall be labeled ``Plasma, 
    Cryoprecipitate Reduced.''
        (3) Plasma remaining after both Platelets and Cryoprecipitated AHF 
    have been removed may be labeled ``Plasma, Cryoprecipitate Reduced.''
    * * * * *
        (g) *  *  *
        (2) With the exception of Platelet Rich Plasma and Liquid Plasma 
    the final product shall be inspected for evidence of thawing or 
    breakage at the time of issuance, however, the containers need not be 
    stored in a manner that shows evidence of thawing if records of 
    continuous monitoring of the storage temperature establish that the 
    temperature remained at -18  deg.C or colder. If continuous monitoring 
    of the product is not available, the final product shall be stored in a 
    manner that will show evidence of thawing and shall not be issued if 
    there is any evidence of thawing.
    * * * * *
    
    
    Sec. 640.51  [Amended]
    
        24. Section 640.51 Suitability of donors is amended by removing 
    paragraph (c).
    
        25. Section 640.52 is amended by revising paragraph (a) to read as 
    follows:
    
    Sec. 640.52   Collection of source material.
    
        (a) Whole blood used as a source of Cryoprecipitated AHF shall be 
    collected as prescribed in Sec. 640.4. Whole blood from which both 
    Platelets and Cryoprecipitated AHF is derived shall be maintained as 
    required under Sec. 640.24 until the platelets are removed.
    * * * * *
        26. Section 640.54 is amended by revising paragraph (a)(2) to read 
    as follows:
    
    Sec. 640.54   Processing.
    
        (a) * * *
        (2) The plasma shall be frozen solid after blood collection within 
    the timeframe specified in the directions for use for the specific 
    device. A combination of dry ice and organic solvent may be used for 
    freezing: Provided, That the procedure has been shown not to cause the 
    solvent to penetrate the container or leach plasticizer from the 
    container into the plasma.
    * * * * *
        27. Section 640.56 is amended by revising the introductory text of 
    paragraph (c) to read as follows:
    
    Sec. 640.56   Quality control test for potency.
    
    * * * * *
        (c) The quality control test for potency may be performed by a 
    clinical laboratory which meets the standards of the Clinical 
    Laboratories Improvement Act of 1988 (CLIA) (42 U.S.C. 263a) and is 
    qualified to perform potency tests for antihemophilic factor. Such 
    arrangements must be approved by the Director, Center for Biologics 
    Evaluation and Research, Food and Drug Administration. Such testing 
    shall not be considered as divided manufacturing, as described in 
    Sec. 610.63 of this chapter, provided the following conditions are met:
    * * * * *
        28. Section 640.62 is revised to read as follows:
    
    Sec. 640.62   Medical supervision.
    
        A qualified licensed physician shall be available to attend to the 
    donor within 15 minutes when donor suitability is being determined, 
    immunizations are being made, whole blood is being collected, and red 
    blood cells are being returned to the donor, except that during the 
    administration of immunization red blood cells a qualified licensed 
    physician shall be on the premises.
        29. Section 640.63 is amended by revising paragraphs (c)(3), 
    (c)(5), (c)(11), (c)(12), and (c)(13) to read as follows:
    
    Sec. 640.63   Suitability of donor.
    
    * * * * *
        (c) * * *
        (3) A blood hemoglobin level of no less than 12.5 grams of 
    hemoglobin per 100 milliliters of blood or a hematocrit level of 38 
    percent;
    * * * * *
        (5) A total serum or total plasma protein of no less than 6.0 grams 
    per 100 milliliters of blood;
    * * * * *
        (11) A history of viral hepatitis after the age of eleven;
        (12) Freedom from a history of close contact within 12 months of 
    donation with an individual having viral hepatitis;
        (13) Freedom from a history of having received, within 12 months, 
    human blood or any derivative of human blood which the Food and Drug 
    Administration has advised the blood establishment is a possible source 
    of viral hepatitis, except for specific immunization performed in 
    accordance with Sec. 640.66.
    * * * * *
        30. Section 640.65 is amended by revising paragraphs (b)(4) and 
    (b)(5) and by adding paragraph (b)(8) to read as follows:
    
    Sec. 640.65   Plasmapheresis.
    
    * * * * *
        (b) *  *  *
        (4) The amount of whole blood, not including anticoagulant, removed 
    from a donor during a manual plasmapheresis procedure or in any 2-day 
    period shall not exceed 1,000 milliliters unless the donor's weight is 
    175 pounds or greater, in which case the amount of whole blood, not 
    including anticoagulant, removed from the donor during a manual 
    plasmapheresis procedure or in any 2-day period shall not exceed 1,200 
    milliliters.
        (5) The amount of whole blood, not including anticoagulant, removed 
    from a donor during a manual plasmapheresis procedure within a 7-day 
    period shall not exceed 2,000 milliliters unless the donor's weight is 
    175 pounds or greater, in which case the amount of whole blood, not 
    including
    
    [[Page 45374]]
    
    anticoagulant, removed from a donor during a manual plasmapheresis 
    procedure within a 7-day period shall not exceed 2,400 milliliters.
    * * * * *
        (8) The volume of plasma collected during an automated 
    plasmapheresis collection procedure shall be consistent with the 
    volumes specifically approved by the Director, Center for Biologics 
    Evaluation and Research, and collection shall not occur less than 2 
    days apart or more frequently than twice in a 7-day period.
        31. Section 640.69 is amended by revising paragraph (d) to read as 
    follows:
    
    Sec. 640.69   General requirements.
    
    * * * * *
        (d) Samples. If samples are provided, they shall meet the following 
    standards:
        (1) Prior to filling, all samples shall be marked or identified so 
    as to relate them directly to the donor of that unit of plasma.
        (2) All samples shall be filled at the time the final product is 
    prepared by the person who prepares the final product.
        (3) All samples shall be representative of the contents of the 
    final product or be collected from the donor at the time of filling the 
    collection container.
        (4) All samples shall be collected in a manner that does not 
    contaminate the contents of the final container.
        32. Section 640.71 is amended by revising the introductory text of 
    paragraph (a) to read as follows:
    
    Sec. 640.71   Manufacturing responsibility.
    
        (a) All steps in the manufacturing of Source Plasma, including 
    donor examination, blood collection, plasmapheresis, laboratory 
    testing, labeling, storage, and issuing shall be performed by personnel 
    of the establishment licensed to manufacture Source Plasma, except that 
    the following tests may be performed by personnel of an establishment 
    licensed for blood and blood derivatives under section 351(a) of the 
    Public Health Service Act, or by a clinical laboratory that meets the 
    standards of the Clinical Laboratories Improvement Act of 1988 (CLIA) 
    (42 U.S.C. 263a): Provided, The establishment or clinical laboratory is 
    qualified to perform the assigned test(s).
    * * * * *
        33. Section 640.72 is amended by revising paragraph (a)(1) to read 
    as follows:
    
    Sec. 640.72   Records.
    
        (a) * * *
        (1) Documentation shall be available to ensure that the shipping 
    temperature requirements of Sec. 600.15 of this title and of 
    Sec. 640.74(b)(2) are being met for Source Plasma intended for 
    manufacture into injectable products.
    * * * * *
    
        Dated: April 20, 1999.
    Jane E. Henney,
    Commissioner of Food and Drugs.
    Donna E. Shalala,
    Secretary of Health and Human Services.
    [FR Doc. 99-21292 Filed 8-18-99; 8:45 am]
    BILLING CODE 4160-01-F
    
    
    

Document Information

Effective Date:
2/11/2000
Published:
08/19/1999
Department:
Food and Drug Administration
Entry Type:
Rule
Action:
Direct final rule.
Document Number:
99-21292
Dates:
This rule is effective February 11, 2000. Submit written comments on or before December 3, 1999. If no timely significant comments are received, the agency will publish a document in the Federal Register within 30 days after the comment period on this direct final rule ends, confirming the effective date of the final rule. If timely significant adverse comments are received, the agency will publish a document in the Federal Register withdrawing the direct final rule before its effective date.
Pages:
45366-45374 (9 pages)
Docket Numbers:
Docket No. 98N-0673
PDF File:
99-21292.pdf
CFR: (34)
21 CFR 640.74(b)(2)
21 CFR 640.4(d)(2)
21 CFR 606.3
21 CFR 606.100
21 CFR 606.121
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