[Federal Register Volume 81, Number 86 (Wednesday, May 4, 2016)]
[Rules and Regulations]
[Pages 26687-26692]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-10385]
[[Page 26687]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 610
[Docket No. FDA-2016-N-1170]
Standard Preparations, Limits of Potency, and Dating Period
Limitations for Biological Products
AGENCY: Food and Drug Administration, HHS.
ACTION: Direct final rule.
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SUMMARY: The Food and Drug Administration (FDA or Agency or we) is
amending the general biological products standards relating to dating
periods and also removing certain standards relating to standard
preparations and limits of potency. FDA is taking this action to update
outdated requirements, and accommodate new and evolving technology and
testing capabilities, without diminishing public health protections.
This action is part of FDA's retrospective review of its regulations in
response to an Executive order. FDA is issuing these amendments
directly as a final rule because the Agency believes they are
noncontroversial and FDA anticipates no significant adverse comments.
DATES: This rule is effective September 16, 2016. Submit either
electronic or written comments on this direct final rule or its
companion proposed rule by July 18, 2016. If FDA receives no
significant adverse comments within the specified comment period, the
Agency intends to publish a document confirming the effective date of
the final rule in the Federal Register within 30 days after the comment
period on this direct final rule ends. If timely significant adverse
comments are received, the Agency will publish a document in the
Federal Register withdrawing this direct final rule within 30 days
after the comment period on this direct final rule ends.
ADDRESSES: You may submit comments as follows:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to http://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on http://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Division of
Dockets Management, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2016-N-1170 for ``Standard Preparations, Limits of Potency, and
Dating Period Limitations for Biological Products.'' Received comments
will be placed in the docket and, except for those submitted as
``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9
a.m. and 4 p.m., Monday through Friday.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on http://www.regulations.gov.
Submit both copies to the Division of Dockets Management. If you do not
wish your name and contact information to be made publicly available,
you can provide this information on the cover sheet and not in the body
of your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Tami Belouin, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.
SUPPLEMENTARY INFORMATION:
I. Executive Summary
A. Purpose of Direct Final Rule
FDA is issuing this direct final rule because revision and removal
of certain general biological products standards will update outdated
requirements and accommodate new and evolving technology and testing
capabilities without diminishing public health protections. FDA is
taking this action because the existing codified requirements are
duplicative of requirements that are also specified in biologics
license applications (BLAs) or are no longer necessary or appropriate
to help ensure the safety, purity, and potency of licensed biological
products.
B. Summary of the Major Provisions of the Direct Final Rule
This direct final rule removes the requirements contained in Sec.
610.20 (21 CFR 610.20) from the regulations. FDA is taking this action
because the standard preparations listed in the regulation are
obsolete, no longer available, or described on a product specific basis
in BLAs. In addition, FDA believes that it is no longer necessary to
restrict the source of standard preparations to the Center for
Biologics Evaluation and Research (CBER), since
[[Page 26688]]
appropriate standard preparations can often be obtained from other
sources. Section 610.21 is removed because these potency limits are
either obsolete or best described on a product specific basis in the
BLA. Section 610.50 is amended to remove references to Sec. Sec.
610.20 and 610.21 and official potency tests and to reflect FDA's
updated approach to establishing dates of manufacture. Section 610.53
is amended to remove products no longer manufactured and products for
which dating information is identified in the BLA of each individual
product, and to reflect updated practices for the remaining products.
C. Legal Authority
FDA is taking this action under the biological products provisions
of the Public Health Service Act (PHS Act), and the drugs and general
administrative provisions of the Federal Food, Drug, and Cosmetic Act
(the FD&C Act).
D. Costs and Benefits
Because this direct final rule does not impose any additional
regulatory burdens, this regulation is not anticipated to result in any
compliance costs and the economic impact is expected to be minimal.
II. Direct Final Rulemaking
In the document entitled ``Guidance for FDA and Industry: Direct
Final Rule Procedures,'' announced and provided in the Federal Register
of November 21, 1997 (62 FR 62466), FDA described its procedures on
when and how the Agency will employ direct final rulemaking. The
guidance may be accessed at: http://www.fda.gov/RegulatoryInformation/Guidances/ucm125166.htm. We have determined that this rule is
appropriate for direct final rulemaking because we believe that it
includes only noncontroversial amendments and we anticipate no
significant adverse comments. Consistent with our procedures on direct
final rulemaking, FDA is also publishing elsewhere in this issue of the
Federal Register a companion proposed rule proposing to amend the
general biological products standards relating to dating periods and to
remove those relating to standard preparations and limits of potency.
The companion proposed rule provides a procedural framework within
which the rule may be finalized in the event that the direct final rule
is withdrawn because of any significant adverse comments. The comment
period for the direct final rule runs concurrently with the companion
proposed rule. Any comments received in response to the companion
proposed rule will be considered as comments regarding the direct final
rule.
We are providing a comment period on the direct final rule of 75
days after the date of publication in the Federal Register. If we
receive any significant adverse comments, we intend to withdraw this
direct final rule before its effective date by publication of a notice
in the Federal Register. 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 an
adverse comment is significant and warrants terminating a direct final
rulemaking, we 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 regulation change in
addition to those in this direct final rule would not be considered a
significant adverse comment unless the comment states why the rule
would be ineffective without the additional change. In addition, if a
significant adverse comment applies to part of this rule and that part
can be severed from the remainder of the rule (e.g., where, as here, a
direct final rule deletes several unrelated regulations), we may adopt
as final those provisions of the rule that are not the subject of the
significant adverse comment.
If any significant adverse comments are received during the comment
period, FDA will publish, before the effective date of this direct
final rule, a document withdrawing the direct final rule. If we
withdraw 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 notice-and-comment procedures.
If FDA receives no significant adverse comments during the
specified comment period, FDA intends to publish a document confirming
the effective date within 30 days after the comment period ends.
III. Background
On January 18, 2011, President Barack Obama issued Executive Order
13563, ``Improving Regulation and Regulatory Review'' (76 FR 3821,
January 21, 2011). One of the provisions in the Executive Order
requires Agencies to consider how best to promote the retrospective
analysis of rules that may be outmoded, ineffective, insufficient, or
excessively burdensome, and to modify, streamline, expand, or repeal
them in accordance with what has been learned (76 FR 3821 at 3822). As
one step in implementing the Executive Order, FDA published a notice in
the Federal Register of April 27, 2011 (76 FR 23520) entitled
``Periodic Review of Existing Regulations; Retrospective Review Under
E.O. 13563.'' In that notice, FDA announced that it was conducting a
review of existing regulations to determine, in part, whether they can
be made more effective in light of current public health needs and to
take advantage of, and support, advances in innovation that have
occurred since those regulations took effect. As part of this
initiative, FDA is updating outdated regulations as specified in this
rule.
FDA's general biological products standards in part 610 are
intended to help ensure the safety, purity, and potency of biological
products administered to humans. The revision and removal of certain
general biological products standards are designed to update outdated
requirements and accommodate new and evolving manufacturing and control
testing technology. The rule provides manufacturers of biological
products with flexibility, as appropriate, to employ advances in
science and technology as they become available, without diminishing
public health protections.
A. Sections 610.20 and 610.21
Standard preparations are generally used to perform lot release
testing or other specific product characterization assays. Under the
current standard preparations, Sec. 610.20, FDA requires specific
standard preparations to be used for a small number of the biological
products FDA regulates unless a modification is permitted under Sec.
610.9. Specifically, according to current Sec. 610.20 Standard
preparations, standard preparations, made available by CBER, are
required to be used in the testing of potency or opacity of certain
biological products, mostly biological products that were initially
licensed several decades ago. Most of these standard preparations
requirements are now obsolete, because either CBER no longer provides
the listed standard preparations, or the specific biological products
are no longer manufactured, or both. In addition, standard preparations
to help ensure the safety, purity, and potency of particular biological
products can often be obtained from sources other than CBER now,
including international sources, or can be
[[Page 26689]]
developed internally by the applicant. Thus, FDA believes it is no
longer necessary to specify CBER as the source of standard preparations
in Sec. 610.20. For these reasons, FDA is removing Sec. 610.20.
Consistent with current practice and BLAs, CBER will continue to make
and supply standard preparations when appropriate, as well as continue
to collaborate with external organizations in the development and
assessment of physical standard preparations for biological products.
Under the current Sec. 610.21 Limits of potency, FDA specifies
minimal potency limits to be met for the antibodies and antigens
listed. However, most of the biological products subject to the
specified potency limits are no longer manufactured. In addition, for
those that are still manufactured, or for anyone wanting to manufacture
the listed products, FDA's updated practice is to have the potency
limit also be specified in the BLA. For this reason, FDA is removing
Sec. 610.21. As a result of removing Sec. Sec. 610.20 and 610.21,
part 610, subpart C is removed and reserved.
In addition to sometimes being duplicative of information provided
in the BLA and unnecessarily restrictive regarding the source of
standard preparations, the codification by regulation of many of the
standard preparations and limits of potency for certain biological
products sometimes does not keep abreast of technological advances in
science related to manufacturing and testing. For many years, because
of the potential for impeding scientific progress, FDA has not codified
additional specific standard preparations and limits of potency for
licensed biological products, but instead the standards are established
in the BLA. Failure to conform to applicable standards established in
the license is grounds for revocation under Sec. 601.5(b)(1)(iv) (21
CFR 601.5(b)(1)(iv)). Notwithstanding the changes in this rule, FDA
will continue to require that each biological product meet standards to
assure that the product is safe, pure, and potent, and will continue to
require that each lot demonstrate conformance with the standards
applicable to that product (see Sec. 610.1) through appropriate
testing. Therefore, we expect that standard preparations and potency
limits will be established in the BLA and may be changed only in
accordance with regulations for reporting post-approval changes (see
Sec. 601.12). Furthermore, no lot of any licensed product may be
released by the manufacturer prior to the completion of tests for
conformity with standards applicable to such product (see Sec. 610.1).
FDA is therefore amending its regulations to remove Sec. Sec.
610.20 and 610.21 because appropriate standard preparations and potency
limits for any listed product are specified during the licensing
process on a product specific basis. The removal of Sec. Sec. 610.20
and 610.21 will also increase regulatory flexibility by allowing
industry and FDA to more readily use and incorporate current scientific
technology and other appropriate reference materials in the manufacture
and regulation of licensed biological products.
B. Sections 610.50 and 610.53
A biological product is expected to remain stable and retain its
identity, strength, quality, and purity for a period of time after
manufacture when it is properly stored. The dating period limitations
regulations provided at Sec. Sec. 610.50 and 610.53 specify how the
date of manufacture for biological products will be determined, when
the dating begins, and dating periods for certain biological products.
The existing Sec. 610.50 prescribes how the date of manufacture is
determined for biological products and relies in part upon Sec. Sec.
610.20 and 610.21 or official standards of potency (i.e., a specific
test method described in regulation). With the removal of Sec. Sec.
610.20 and 610.21 for reasons described in this document, FDA is
revising Sec. 610.50 to reflect FDA's updated approach to establishing
dates of manufacture.
In addition, current Sec. 610.50(b) does not provide FDA or
applicants with flexibility to consider the variety of manufacturing
situations and technologies that exist today and which may occur in the
future. Since 1977, when the regulation was last amended, new methods
of manufacture and testing often associated with new biological
products have been developed. The revisions to Sec. 610.50 provided in
this direct final rule therefore allow additional manufacturing
activities other than those currently listed to be used to determine
the date of manufacture.
Under the revised regulation, the date of manufacture must be
identified in the approved BLA. FDA recommends that applicants discuss
a suitable date of manufacture with FDA during late clinical
development and propose a date of manufacture in the BLA. We consider
the underlying science and manufacturing process testing methods in
determining the date of manufacture for each specific product. The
approved BLA will specify how the date of manufacture is determined. A
paragraph is being added, Sec. 610.50(c), specifying how the date of
manufacture for Whole Blood and blood components is determined. This
will assist in complying with the dating periods prescribed for Whole
Blood and blood components in the revised table in redesignated Sec.
610.53(b).
The current table at Sec. 610.53(c) lists dating periods,
manufacturer's storage periods, and storage conditions for many
biological products. The table in Sec. 610.53(c) (which is
redesignated as Sec. 610.53(b)) is revised to remove products where
storage conditions and dating periods are established to help ensure
the continued safety, potency, and purity of each individual product,
based upon information submitted in the relevant BLA. The dating period
and storage conditions for these products will be identified in the
BLA. The table in Sec. 610.53(c) is also revised to delete those
products that are no longer manufactured. We are retaining those
products, specifically Whole Blood and blood components, whose dating
periods are based upon data relating to the anticoagulant or
preservative solution in the product, usage, clinical experience,
laboratory testing, or further processing. The list is updated to
include currently licensed Whole Blood and blood component products
with their applicable storage temperatures and dating periods.
In listing the dating periods for Whole Blood and blood component
products, we took into account existing regulations, guidance
documents, package inserts for solutions used for manufacture or
storage of Whole Blood and blood components, and operator instruction
manuals for devices used in the manufacture of Whole Blood and blood
component products. Because we understand from these materials that
these dating periods are in current use, and because blood
establishments can request an exception under Sec. 640.120 (21 CFR
640.120), we do not anticipate significant objections to codifying this
information. Similarly, we are removing Sec. 610.53(d) because it is
duplicative of Sec. 640.120. In addition, we recognize that future
scientific understanding and new technology, such as the implementation
of pathogen reduction technology or the approval of extended storage
systems, could affect what dating periods would be necessary, as a
scientific matter, for Whole Blood and blood components. For this
reason, the rule allows for changes to the dating periods specified in
Sec. 610.53(b) when the dating period is otherwise specified in the
instructions for use by the blood collection, processing, and storage
system approved or cleared for such use by FDA.
[[Page 26690]]
In conclusion, the amendments to the regulations provided by this
rule are designed to be consistent with updated practices in the
biological product industry and to remove unnecessary or outdated
requirements. FDA is taking this action as part of our continuing
effort to reduce the burden of unnecessary regulations on industry and
to revise outdated regulations to provide flexibility without
diminishing public health protection. Given the additional flexibility
provided by these revised regulations, FDA does not anticipate that
applicants for licensed biological products will need to revise
information in BLAs in order to conform to the revised regulations.
IV. Highlights of the Direct Final Rule
FDA is revising the general biological products standards relating
to dating periods and removing certain standard preparations and limits
of potency. These changes are designed to remove unnecessary or
outdated requirements, and accommodate new and evolving technology and
testing capabilities without diminishing public health protections. FDA
is issuing these revisions directly as a final rule because the Agency
believes they include only noncontroversial amendments and FDA
anticipates no significant adverse comments.
FDA is removing Sec. 610.20 because the standard preparations
listed are obsolete or no longer available; standard preparations to
ensure the safety, purity, and potency of a product can best be
determined on a product specific basis; and standard preparations may
be obtained from other sources. Applicants for biological product
licenses currently identify standard preparations in the BLA, and the
proposed standard preparations and their purpose are reviewed by FDA
during the regulatory process. The standard preparations may include
standard preparations developed by the applicant as well as appropriate
standard preparations that can be obtained from other sources.
Consistent with current practice, CBER will continue to make and supply
standard preparations when appropriate, as well as continue to
collaborate with external organizations in the development and
assessment of physical standard preparations for licensed biological
products.
We are removing Sec. 610.21 because these potency limits are best
described in the BLAs on a product specific basis. Applicants for
biological product licenses already identify standards for potency to
help ensure the safety, purity, and potency of the product within their
BLA, and the proposed standards are reviewed by FDA during the
regulatory process. The use of a potency limit is suitably described in
the specific product's BLA and allows for its continued and appropriate
use in the absence of Sec. 610.21.
We are revising Sec. 610.50 by making a minor amendment to the
section heading, removing the current language, redesignating Sec.
610.53(b) as Sec. 610.50(a) with edits, revising Sec. 610.50(b), and
adding new Sec. 610.50(c). Current Sec. 610.53(b), which applies to
all biological products, has been moved to Sec. 610.50(a) and edits
have been made for better organization and clarification. Section
610.50(b) is being revised and Sec. 610.50(c) is being added to
clarify how the date of manufacture is set for purposes of determining
the dating period for general biological products and for Whole Blood
and blood components, respectively.
We are amending the section heading of Sec. 610.53 to reflect that
it only addresses dating periods for Whole Blood and blood components.
We are revising Sec. 610.53(a) since this section only applies to the
dating periods for Whole Blood and blood components. We are
redesignating Sec. 610.53(c) as Sec. 610.53(b) and revising the text
to provide an explanation on using the table and to correspond with 21
CFR 606.121(c)(7). We are revising the text and table to eliminate
those products for which storage periods, storage conditions, and
dating periods are better established by data submitted in the BLA, and
to delete those products which are no longer manufactured. The dating
period and storage conditions for these products are identified in the
BLA. We are including an updated list of Whole Blood and blood
component products with their applicable storage temperatures and
dating periods, which are based upon available information, including
data relating to the anticoagulant or preservative solution in the
product, usage, clinical experience, laboratory testing, or further
processing. The table contains a list of storage temperatures and
dating periods for Whole Blood and blood components that FDA has
reviewed and determined to be necessary to help ensure the safety,
potency, and purity of these products. In listing the dating periods
for the Whole Blood and blood component products, we took into account
existing guidance documents, package inserts for solutions used for
manufacture or storage of Whole Blood and blood components, and
operator instruction manuals for devices used in the manufacture of
Whole Blood and blood component products. We are redesignating Sec.
610.53(c) as Sec. 610.53(b) and removing all products regulated by
FDA's Center for Drug Evaluation and Research (CDER) from the table.
Finally, we are removing Sec. 610.53(d) because it is duplicative of
Sec. 640.120.
V. Legal Authority
FDA is issuing this rule under the biological products provisions
of the PHS Act (42 U.S.C. 216, 262, 263, 263a and 264) and the drugs
and general administrative provisions of the FD&C Act (21 U.S.C. 321,
331, 351, 352, 353, 355, 360, 360c, 360d, 360h, 360i, 371, 372, 374,
and 381). Under these provisions of the PHS Act and the FD&C Act, we
have the authority to issue and enforce regulations designed to ensure
that biological products are safe, pure, and potent, and prevent the
introduction, transmission, and spread of communicable disease.
VI. Economic Analysis of Impacts
We have examined the impacts of the direct final rule under
Executive Order 12866, Executive Order 13563, and the Regulatory
Flexibility Act (5 U.S.C. 601-612), and the Unfunded Mandates Reform
Act of 1995 (Pub. L. 104-4). Executive Orders 12866 and 13563 direct us
to assess all costs and benefits of available regulatory alternatives
and, when regulation is necessary, to select regulatory approaches that
maximize net benefits (including potential economic, environmental,
public health and safety, and other advantages; distributive impacts;
and equity). We believe that this direct final rule is not a
significant regulatory action as defined by Executive Order 12866.
The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because the direct final rule is removing regulations and
revising regulations to be consistent with updated practice, we certify
that this direct final rule will not have a significant economic impact
on a substantial number of small entities.
The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires
us to prepare a written statement, which includes an assessment of
anticipated costs and benefits, before issuing ``any rule that includes
any Federal mandate that may result in the expenditure by State, local,
and tribal governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted annually for inflation) in any one
year.'' The current threshold after adjustment for inflation is $144
million, using the most current (2014) Implicit Price Deflator for the
Gross Domestic Product. This direct final rule would not result
[[Page 26691]]
in an expenditure in any year that meets or exceeds this amount.
VII. Analysis of Environmental Impact
We have determined under 21 CFR 25.31(h) 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.
VIII. Federalism
We have analyzed this direct final rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the rule does not contain policies that have substantial direct effects
on the States, on the relationship between the National Government and
the States, or on the distribution of power and responsibilities among
the various levels of government. Accordingly, we conclude that the
rule does not contain policies that have federalism implications as
defined in the Executive order and, consequently, a federalism summary
impact statement is not required.
IX. Paperwork Reduction Act of 1995
This direct final rule contains collections of information that are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3520). The
collections of information in part 610 have been approved under OMB
control number 0910-0338. The removal of Sec. 610.53(d) impacts OMB
control number 0910-0338. We are removing Sec. 610.53(d) because it is
duplicative of Sec. 640.120, which is also approved under the same
collection of information. While there is no net change in the burden
estimate, the current approved collection of information will be
updated to reflect this removal. The actions taken by this direct final
rule do not create a substantive or material modification to this
approved collection of information. Therefore, FDA concludes that OMB
has already approved this information collection and the requirements
in this document are not subject to additional review by OMB.
List of Subjects in 21 CFR Part 610
Biologics, Labeling, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, 21 CFR part 610 is amended as follows:
PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS
0
1. The authority citation for part 610 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c,
360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a,
264.
Subpart C [Removed and Reserved]
0
2. Remove and reserve subpart C, consisting of Sec. Sec. 610.20 and
610.21.
0
3. Revise Sec. 610.50 to read as follows:
Sec. 610.50 Date of manufacture for biological products.
(a) When the dating period begins. The dating period for a product
must begin on the date of manufacture as described in paragraphs (b)
and (c) of this section. The dating period for a combination of two or
more products must be no longer than the dating period of the component
with the shortest dating period.
(b) Determining the date of manufacture for biological products
other than Whole Blood and blood components. The date of manufacture
for biological products, other than Whole Blood and blood components,
must be identified in the approved biologics license application as one
of the following, whichever is applicable: The date of:
(1) Potency test or other specific test as described in a biologics
license application or supplement to the application;
(2) Removal from animals or humans;
(3) Extraction;
(4) Solution;
(5) Cessation of growth;
(6) Final sterile filtration of a bulk solution;
(7) Manufacture as described in part 660 of this chapter; or
(8) Other specific manufacturing activity described in a biologics
license application or supplement to the biologics license application.
(c) Determining the date of manufacture for Whole Blood and blood
components. (1) The date of manufacture for Whole Blood and blood
components must be one of the following, whichever is applicable:
(i) Collection date and/or time;
(ii) Irradiation date;
(iii) The time the red blood cell product was removed from frozen
storage for deglycerolization;
(iv) The time the additive or rejuvenation solution was added;
(v) The time the product was entered for washing or removing plasma
(if prepared in an open system);
(vi) As specified in the instructions for use by the blood
collection, processing, and storage system approved or cleared for such
use by FDA; or
(vii) As approved by the Director, Center for Biologics Evaluation
and Research, in a biologics license application or supplement to the
application.
(2) For licensed Whole Blood and blood components, the date of
manufacture must be identified in the approved biologics license
application or supplement to the application.
0
4. Revise Sec. 610.53 to read as follows:
Sec. 610.53 Dating periods for Whole Blood and blood components.
(a) General. Dating periods for Whole Blood and blood components
are specified in the table in paragraph (b) of this section.
(b) Table of dating periods. In using the table in this paragraph,
when a product in column A is stored at the storage temperature
prescribed in column B, storage of a product must not exceed the dating
period specified in column C, unless a different dating period is
specified in the instructions for use by the blood collection,
processing and storage system approved or cleared for such use by FDA.
Container labels for each product must include the recommended storage
temperatures.
Whole Blood and Blood Components Storage Temperatures and Dating Periods
------------------------------------------------------------------------
A B C
------------------------------------------------------------------------
Product Storage temperature Dating period
------------------------------------------------------------------------
Whole Blood
------------------------------------------------------------------------
ACD, CPD, CP2D.............. Between 1 and 6 21 days from date of
[deg]C. collection.
[[Page 26692]]
CPDA-1...................... do \1\.............. 35 days from date of
collection.
------------------------------------------------------------------------
Red Blood Cells
------------------------------------------------------------------------
ACD, CPD, CP2D.............. Between 1 and 6 21 days from date of
[deg]C. collection.
CPDA-1...................... do.................. 35 days from date of
collection.
Additive solutions.......... do.................. 42 days from date of
collection.
Open system................. do.................. 24 hours after
(e.g., deglycerolized, entering bag.
washed).
Deglycerolized in closed do.................. 14 days after
system with additive entering bag.
solution added.
Irradiated.................. do.................. 28 days from date of
irradiation or
original dating,
whichever is
shorter.
Frozen...................... -65 [deg]C or colder 10 years from date
of collection.
------------------------------------------------------------------------
Platelets
------------------------------------------------------------------------
Platelets................... Between 20 and 24 5 days from date of
[deg]C. collection.
Platelets................... Other temperatures As specified in the
according to instructions for
storage bag use by the blood
instructions. collection,
processing and
storage system
approved or cleared
for such use by
FDA.
------------------------------------------------------------------------
Plasma
------------------------------------------------------------------------
Fresh Frozen Plasma......... -18 [deg]C or colder 1 year from date of
collection.
Plasma Frozen Within 24 do.................. 1 year from date of
Hours After Phlebotomy. collection.
Plasma Frozen Within 24 do.................. 1 year from date of
Hours After Phlebotomy Held collection.
at Room Temperature Up To
24 Hours After Phlebotomy.
Plasma Cryoprecipitate do.................. 1 year from date of
Reduced. collection.
Plasma...................... do.................. 5 years from date of
collection.
Liquid Plasma............... Between 1 and 6 5 days from end of
[deg]C. Whole Blood dating
period.
Source Plasma (frozen -20 [deg]C or colder 10 years from date
injectable). of collection.
Source Plasma Liquid 10 [deg]C or colder. According to
(injectable). approved biologics
license
application.
Source Plasma Temperature 10 years from date
(noninjectable). appropriate for of collection.
final product.
Therapeutic Exchange Plasma. -20 [deg]C or colder 10 years from date
of collection.
------------------------------------------------------------------------
Cryoprecipitated AHF
------------------------------------------------------------------------
Cryoprecipitated AHF........ -18 [deg]C or colder 1 year from date of
collection of
source blood or
from date of
collection of
oldest source blood
in pre-storage
pool.
------------------------------------------------------------------------
Source Leukocytes
------------------------------------------------------------------------
Source Leukocytes........... Temperature In lieu of
appropriate for expiration date,
final product. the collection date
must appear on the
label.
------------------------------------------------------------------------
\1\ The abbreviation ``do.'' for ditto is used in the table to indicate
that the previous line is being repeated.
Dated: April 27, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-10385 Filed 5-3-16; 8:45 am]
BILLING CODE 4164-01-P