Document ID: FDA-2016-N-1170-0002
Agency: fda
Document Type: Proposed Rule
Title: Standard Preparations, Limits of Potency, and Dating Period Limitations for Biological Products; Companion to Direct Final Rule
Posted Date: 2016-05-04T04:00Z

[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]

=======================================================================
-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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action to update outdated requirements, and accommodate new and 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