[Federal Register Volume 85, Number 161 (Wednesday, August 19, 2020)]
[Notices]
[Pages 51036-51037]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-17798]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-D-0276]


Compliance Policy for the Quantity of Bioavailability and 
Bioequivalence Samples Retained Under 21 CFR 320.38(c); Guidance for 
Industry; Availability

AGENCY: Food and Drug Administration, Health and Human Services (HHS).

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a final guidance for industry entitled ``Compliance 
Policy for the Quantity of Bioavailability and Bioequivalence Samples 
Retained Under 21 CFR 320.38(c).'' This guidance describes FDA's policy 
concerning the conditions under which the Agency generally does not 
intend to take regulatory action against an applicant or a contract 
research organization (CRO) that retains less than the quantity of 
reserve samples (that is, samples of the test article and reference 
standard that were used in bioavailability (BA) or bioequivalence (BE) 
testing) required in our regulations. FDA developed this guidance in 
light of technological advances in FDA's ability to test retention 
samples and in response to communications from applicants and CROs 
requesting to retain a lower quantity of these reserve samples.

DATES: The announcement of the guidance is published in the Federal 
Register on August 19, 2020.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://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 https://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): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, 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-2020-D-0276 for ``Compliance Policy for the Quantity of 
Bioavailability and Bioequivalence Samples Retained Under 21 CFR 
320.38(c).'' Received comments will be placed in the docket and, except 
for those submitted as ``Confidential Submissions,'' publicly viewable 
at https://www.regulations.gov or at the Dockets Management Staff 
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 https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. 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: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of this guidance to the 
Office of Communications, Division of Drug Information, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10001 New 
Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 
20993-0002. Send two self-addressed adhesive labels to assist that 
office in processing your requests. See the SUPPLEMENTARY INFORMATION 
section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Melissa Mannion, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Silver Spring, MD 20993, 301-796-2747, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Compliance Policy for the Quantity of Bioavailability and 
Bioequivalence Samples Retained Under 21 CFR 320.38(c).'' The Agency is 
issuing this guidance consistent with good guidance practices (GGP) 
regulations (21 CFR 10.115) and is implementing this guidance without 
prior public comment because FDA has determined that prior public 
participation is not feasible or appropriate as public comment would 
not affect the specifications of FDA's testing of retention samples 
(Sec.  10.115(g)(2)). FDA has made this determination under Sec.  
10.115(g)(2) because, with technological advances, the reduced quantity 
of reserve samples is now sufficient for FDA testing; this reduced 
quantity will provide a less burdensome approach for applicants and 
CROs but remains consistent with the Agency's mission to ensure public 
health. Although this guidance

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document is immediately in effect, it remains subject to comment in 
accordance with FDA's GGP regulation and FDA will consider all comments 
received and revise the guidance document as appropriate (Sec.  
10.115(g)(3)).
    On November 8, 1990, we issued an interim rule that amended, in 
relevant part, part 320 (21 CFR 320) by adding a requirement to retain 
reserve samples of drug products (that is, samples of the drug products 
that were used to conduct BA or BE studies) for a specified period and, 
when specifically requested, to release the reserve samples to us. The 
interim rule was intended to help ensure BE between generic drugs and 
their reference listed drugs and to help us investigate possible fraud 
in BA and BE testing. After consideration of public comments, we 
published a final rule in the Federal Register on April 28, 1993 (58 FR 
25918).
    In the final rule, 21 CFR 320.38 and 320.63 require a new drug 
application or abbreviated new drug application applicant (or its CRO) 
to retain reserve samples of the test article and reference standard 
that were used in conducting any in vivo BA and in vivo or in vitro BE 
study that supports the approval of an application or supplemental 
application. Specifically, Sec.  320.38(c) requires these applicants 
(or their CROs) to retain a quantity of the test article and reference 
standard that were used in BA or BE testing that is at least five times 
the amount of product required for release testing.
    Section 320.38(c) requires that reserve samples of the test article 
and reference standard used in a BA or BE study are of a sufficient 
quantity to perform five times all of the release tests required in the 
application or supplemental application. Since the final rule was 
issued in 1993, technological advances in our ability to test these 
products have led to test methods that are less destructive and more 
sensitive, allowing us to detect the identity and composition of the 
test article and reference standard with smaller volumes of samples. 
Consistent with these developments, FDA has received communications 
from applicants and CROs requesting to retain a lower quantity of the 
reserve samples.
    In light of these technological advances, this guidance discusses 
the conditions under which we do not generally intend to take 
regulatory action against an applicant or CRO that retains an 
appropriate reduced quantity of reserve samples of the test article and 
reference standard that were used in its BA or BE testing.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``Compliance Policy for the Quantity of 
Bioavailability and Bioequivalence Samples Retained Under 21 CFR 
320.38(c).'' It does not establish any rights for any person and is not 
binding on FDA or the public. You can use an alternative approach if it 
satisfies the requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). The 
collections of information in 21 CFR parts 312 and 314 have been 
approved under OMB control numbers 0910-0014 and 0910-0001, 
respectively. The collections of information in part 320 for 
``Investigational New Drug Safety Reporting Requirements for Human Drug 
and Biological Products and Safety Reporting Requirements for 
Bioavailability and Bioequivalence Studies in Humans'' have been 
approved under OMB control number 0910-0672. The recordkeeping 
requirement for CGMP sample retention in 21 CFR 211.170 has been 
approved under OMB control number 0910-0139.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs or https://www.regulations.gov. Use the FDA 
website listed in the previous sentence to find the most current 
version of the guidance.

    Dated: August 10, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-17798 Filed 8-18-20; 8:45 am]
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