[Federal Register Volume 86, Number 90 (Wednesday, May 12, 2021)]
[Notices]
[Pages 26043-26045]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-09963]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-1609]


Q12 Technical and Regulatory Considerations for Pharmaceutical 
Product Lifecycle Management; International Council for Harmonisation; 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a final guidance for industry entitled ``Q12 
Technical and Regulatory Considerations for Pharmaceutical Product 
Lifecycle Management.'' The guidance was prepared under the auspices of 
the International Council for Harmonisation (ICH), formerly the 
International Conference on Harmonisation. The guidance, which consists 
of a Guidance and Annexes, provides a framework to facilitate the 
management of postapproval chemistry, manufacturing, and controls 
changes for new and marketed pharmaceutical drug substances and drug 
products, including chemical and biotechnological/biological products. 
This guidance finalizes the draft guidance of the same title issued on 
May 31, 2018.

DATES: The announcement of the guidance is published in the Federal 
Register on May 12, 2021.

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-2018-D-1609 for ``Q12 Technical and Regulatory Considerations for 
Pharmaceutical Product Lifecycle Management.'' 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, 240-402-7500.
     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, 240-402-7500.
    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 
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, or the Office of 
Communication, Outreach and Development, Center for Biologics 
Evaluation and Research (CBER), Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send 
one self-addressed adhesive label to assist that office in processing 
your requests. The guidance may also be obtained by mail by calling 
CBER at 1-

[[Page 26044]]

800-835-4709 or 240-402-8010. See the SUPPLEMENTARY INFORMATION section 
for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Mahesh 
Ramanadham, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 
301-796-3272; or Stephen Ripley, 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.
    Regarding the ICH: Jill Adleberg, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 6364, Silver Spring, MD 20993-0002, 301-796-5259.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Q12 Technical and Regulatory Considerations for 
Pharmaceutical Product Lifecycle Management.'' The guidance was 
prepared under the auspices of ICH. ICH has the mission of achieving 
greater regulatory harmonization worldwide to ensure that safe, 
effective, high-quality medicines are developed, registered, and 
maintained in the most resource-efficient manner.
    By harmonizing the regulatory requirements in regions around the 
world, ICH guidelines have substantially reduced duplicative clinical 
studies, prevented unnecessary animal studies, standardized the 
reporting of important safety information, standardized marketing 
application submissions, and made many other improvements in the 
quality of global drug development and manufacturing and the products 
available to patients.
    The six Founding Members of the ICH are FDA; the Pharmaceutical 
Research and Manufacturers of America; the European Commission; the 
European Federation of Pharmaceutical Industries Associations; the 
Japanese Ministry of Health, Labour, and Welfare; and the Japanese 
Pharmaceutical Manufacturers Association. The Standing Members of the 
ICH Association include Health Canada and Swissmedic. Additionally, the 
Membership of ICH has expanded to include other regulatory authorities 
and industry associations from around the world (refer to https://www.ich.org/).
    ICH works by involving technical experts from both regulators and 
industry parties in detailed technical harmonization work and the 
application of a science-based approach to harmonization through a 
consensus-driven process that results in the development of ICH 
guidelines. The regulators around the world are committed to 
consistently adopting these consensus-based guidelines, realizing the 
benefits for patients and for industry.
    As a Founding Regulatory Member of ICH, FDA plays a major role in 
the development of each of the ICH guidelines, which FDA then adopts 
and issues as guidance for industry. FDA's guidance documents do not 
establish legally enforceable responsibilities. Instead, they describe 
the Agency's current thinking on a topic and should be viewed only as 
recommendations, unless specific regulatory or statutory requirements 
are cited.
    In the Federal Register of May 31, 2018 (83 FR 25018), FDA 
published a notice announcing the availability of a draft guidance 
entitled ``Q12 Technical and Regulatory Considerations for 
Pharmaceutical Product Lifecycle Management.'' The notice gave 
interested persons an opportunity to submit comments by December 15, 
2018.
    After consideration of the comments received and revisions to the 
guideline, a final draft of the guideline was submitted to the ICH 
Assembly and endorsed by the regulatory agencies in November 2019. 
Changes from the draft to the final guideline include: revision of the 
text regarding the compatibility of the guideline with regional legal 
frameworks, removal of the terms ``implicit'' and ``explicit'' as they 
referred to established conditions, removal of the term ``key process 
parameter,'' and revisions to the text to better explain the concept of 
critical process parameter and identification of established conditions 
for manufacturing processes. Other changes included revision of the 
description for identification of established conditions for analytical 
methods and development of an illustrative example, revisions to the 
recommended content of the product lifecycle management document and 
its location within the common technical document, and revisions to 
clarify the use of tools described in the guideline for master files. 
In addition, editorial changes were made to improve clarity.
    The guidance provides guidance on postapproval chemistry, 
manufacturing, and controls changes for new and marketed pharmaceutical 
drug substances and drug products. The guidance describes regulatory 
tools and enablers, along with associated guiding principles, that are 
intended to enhance the management of postapproval changes and 
transparency between industry and regulatory authorities, encouraging 
innovation and continual improvement. The guidance is intended to 
demonstrate how increased product and process knowledge can contribute 
to a more precise and accurate understanding of which postapproval 
changes require a regulatory submission as well as the definition of 
the level of reporting categories for such changes (i.e., a better 
understanding of risk to product quality). Increased knowledge and 
effective implementation of the tools and enablers described in this 
guidance should enhance industry's ability to manage many chemistry, 
manufacturing, and controls changes effectively under the company's 
Pharmaceutical Quality System (PQS) with less need for extensive 
regulatory oversight prior to implementation. This approach can 
incentivize continual improvement by providing an opportunity for 
greater flexibility in making postapproval changes. It could also 
result in fewer associated postapproval submissions to the Marketing 
Authorization Application and less associated regulatory burden. The 
extent of operational and regulatory flexibility and its adequate 
implementation is subject to the regulatory framework in place as well 
as product and process understanding (ICH Q8(R2) and Q11), application 
of risk management principles (ICH Q9), and an effective PQS (ICH Q10).
    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 ``Q12 Technical and Regulatory 
Considerations for Pharmaceutical Product Lifecycle Management.'' 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 contains no collection of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required.
    However, this guidance refers to previously approved FDA 
collections of information. These collections of information are 
subject to review by OMB under the PRA. The collections of information 
in 21 CFR part 314 have been approved under OMB control

[[Page 26045]]

number 0910-0001 and in part 601 under OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.regulations.gov, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, or https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.

    Dated: May 6, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-09963 Filed 5-11-21; 8:45 am]
BILLING CODE 4164-01-P