Document ID: FDA-2016-N-1170-0001
Agency: fda
Document Type: Rule
Title: Standard Preparations, Limits of Potency, and Dating Period Limitations for Biological Products
Posted Date: 2016-05-04T04:00Z

[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outdated requirements, and accommodate new and evolving technology and 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