[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remove unnecessary or outdated requirements.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

[[Page 45367]]

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

[[Page 45368]]

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

[[Page 45370]]

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