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.

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 This guidance finalizes the draft guidance of the same title issued on May 31, 2018.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 1-800-835-4709 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 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.