[Federal Register Volume 81, Number 86 (Wednesday, May 4, 2016)]
[Proposed Rules]
[Pages 26753-26759]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-10386]
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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; Companion to Direct Final Rule
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA or Agency or we) is
proposing to amend the general biological products standards relating
to dating periods and also to remove certain standards relating to
standard preparations and limits of potency. FDA is proposing this
action to update outdated requirements, and accommodate new and
evolving technology and testing capabilities, without diminishing
public health protections. This proposed action is part of FDA's
retrospective review of its regulations in response to an Executive
order.
DATES: Submit either electronic or written comments on this proposed
rule or its companion direct final rule by July 18, 2016. If FDA
receives any timely significant adverse comments on the direct final
rule with which this proposed rule is associated, the Agency will
publish a document withdrawing the direct final rule within 30 days
after the comment period ends. FDA will apply any significant adverse
comments received on the direct final rule to the proposed rule in
developing the final rule. FDA will then proceed to respond to comments
under this proposed rule using the usual notice and comment procedures.
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
[[Page 26754]]
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 the Proposed Rule
The proposed rule would revise and remove certain general
biological products standards, which would update outdated requirements
and accommodate new and evolving technology and testing capabilities
without diminishing public health protections. FDA is proposing 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 Proposed Rule
This proposed rule would remove the requirements contained in Sec.
610.20 (21 CFR 610.20) from the regulations. FDA is proposing 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 would no longer be necessary
to restrict the source of standard preparations to the Center for
Biologics Evaluation and Research (CBER), since appropriate standard
preparations can often be obtained from other sources. Furthermore, FDA
is proposing to remove Sec. 610.21 because these potency limits are
either obsolete or best described on a product specific basis in the
BLA. FDA is proposing to revise Sec. 610.50 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. FDA is
proposing to amend Sec. 610.53 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 proposing 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 proposed rule would 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. Companion Document to Direct Final Rulemaking
This proposed rule is a companion to the direct final rule
published in the rules section of this issue of the Federal Register.
This companion proposed rule provides the procedural framework to
finalize the rule in the event that the direct final rule receives any
significant adverse comment and is withdrawn. The comment period for
this companion proposed rule runs concurrently with the comment period
for the direct final rule. Any comments received in response to this
companion proposed rule will also be considered as comments regarding
the direct final rule. FDA is publishing the direct final rule because
we believe the rule contains noncontroversial changes and there is
little likelihood that there will be significant adverse comments
opposing the rule.
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 the 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 a part of the direct final 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 to the direct final rule are
received during the comment period, FDA will publish, within 30 days
after the comment period ends, a document withdrawing the direct final
rule. If we withdraw the direct final rule, any comments received will
be considered comments on the proposed rule and will be considered in
developing a final rule using the usual notice-and-comment procedures.
If no significant adverse comment is received in response to the
direct final rule, no further action will be taken related to this
proposed rule. Instead, we will publish a document confirming the
effective date within 30 days after the comment period ends. Additional
information about direct final
[[Page 26755]]
rulemaking procedures is set forth 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).
The guidance may be accessed at: http://www.fda.gov/RegulatoryInformation/Guidances/ucm125166.htm.
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 proposing to update outdated regulations as
specified in this proposed rule.
FDA's general biological products standards in part 610 (21 CFR
part 610) are intended to help ensure the safety, purity, and potency
of biological products administered to humans. The proposed 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 proposed
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, 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 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 proposes to remove 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 proposes to
remove Sec. 610.21. As a result of removing Sec. Sec. 610.20 and
610.21, we are proposing to remove and reserve part 610, subpart C.
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)). If the changes proposed in this proposed rule go
into effect, 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 proposing to amend 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 proposed removal of
Sec. Sec. 610.20 and 610.21 for reasons described in this document,
and as official potency tests no longer exist, FDA is proposing to
revise 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,
[[Page 26756]]
new methods of manufacture and testing often associated with new
biological products have been developed. The proposed revision to Sec.
610.50 would allow additional manufacturing activities other than those
currently listed to be used to determine the date of manufacture.
The proposed regulatory provision would require the date of
manufacture to 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 would specify how the date of manufacture
would be determined. A proposed paragraph, Sec. 610.50(c), would be
added, specifying how the date of manufacture for Whole Blood and blood
components would be determined. This provision would assist in
complying with the dating periods prescribed for Whole Blood and blood
components in the proposed 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. FDA is proposing to revise the current table in
Sec. 610.53(c) (which would be redesignated as Sec. 610.53(b)) 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 would be identified in the BLA. FDA is also proposing to
revise the current table in Sec. 610.53(c) to delete those products
that are no longer manufactured. We are proposing to retain 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 proposed list has been
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 proposing to remove 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 proposed rule would allow for changes
to the dating periods specified in proposed 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.
In conclusion, the proposed amendments to the regulations are
designed to be consistent with updated practices in the biological
product industry and to remove unnecessary or outdated requirements.
FDA is proposing 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. If finalized, FDA does not anticipate that
applicants for licensed biological products would need to revise
information in BLAs in order to conform to the proposed revised
regulations. Applicants must inform the Agency of any change to an
approved application in accordance with Sec. 601.12.
IV. Highlights of the Proposed Rule
FDA is proposing to revise the general biological products
standards relating to dating periods and proposing to remove certain
standard preparations and limits of potency. These proposed 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 proposing to remove 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
for the product and purpose (e.g., potency) in the BLA, and the
proposed standard preparations 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 proposing to remove 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 and purpose 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 proposing to revise 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, would be moved to Sec.
610.50(a) and edits will be made for better organization and
clarification. Section 610.50(b) would be revised and Sec. 610.50(c)
would be 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 proposing to amend the section heading of Sec. 610.53 to
reflect that it would only address dating periods for Whole Blood and
blood components. We are proposing to revise Sec. 610.53(a) since this
section would only apply to the dating periods for Whole Blood and
blood components. We are proposing to redesignate current Sec.
610.53(c) as Sec. 610.53(b) and revise the text to provide an
explanation on using the table and to correspond with 21 CFR
606.121(c)(7). We are proposing to revise the text and table to
eliminate those products for which storage periods, storage conditions,
and dating periods are better established by data
[[Page 26757]]
submitted in the BLA, and to delete those products which are no longer
manufactured. The dating period and storage conditions for these
products would be identified in the BLA. We are proposing to include 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 proposed
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 proposing to redesignate Sec. 610.53(c) as Sec.
610.53(b) and to remove all products regulated by FDA's Center for Drug
Evaluation and Research (CDER) from the table. Finally, we are
proposing to remove Sec. 610.53(d) because it is duplicative of Sec.
640.120.
V. Legal Authority
FDA is issuing this proposed 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 proposed 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 proposed 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 proposed rule would remove regulations and revise
regulations to be consistent with updated practice, we propose to
certify that the proposed 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 proposing ``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 proposed rule would
not result 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 proposed rule in accordance with the
principles set forth in Executive Order 13132. We have determined that
the proposed 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 proposed 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 proposed removal of Sec. 610.53(d) would
impact OMB control number 0910-0338. We would remove Sec. 610.53(d)
because it is duplicative of Sec. 640.120, which is also approved
under the same collection of information. While there would be no net
change in the burden estimate, the current approved collection of
information would be updated to reflect this removal. The actions that
we propose to take in this proposed rule would not create a substantive
or material modification to this approved collection of information.
Therefore, FDA tentatively concludes that OMB has already approved the
information collection proposed here and the proposed 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, it is proposed that 21 CFR part 610 be
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
[[Page 26758]]
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.
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 (e.g., ......do............ 24 hours after
deglycerolized, washed). entering bag.
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.
------------------------------------------------------------------------
[[Page 26759]]
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. 2016-10386 Filed 5-3-16; 8:45 am]
BILLING CODE 4164-01-P