2022-28602. Format and Content of a Risk Evaluation and Mitigation Strategy Document; 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 “Format and Content of a REMS Document.” This final guidance describes the format for a proposed risk evaluation and mitigation strategy (REMS) document. This format was created based on extensive stakeholder feedback. This guidance finalizes the revised draft guidance of the same title issued on October 12, 2017, and announces the availability of the technical specifications document entitled “REMS Document Technical Conformance Guide.”

DATES:

The announcement of the guidance is published in the Federal Register on January 5, 2023.

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-2009-D-0461 for “Format and Content of a REMS Document.” 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 to the Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research, 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. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT:

Suzanne Robottom, Center for Drug Evaluation and Research, Food and Drug Administration,10903 New Hampshire Ave, Bldg. 22, Rm. 4475, Silver Spring, MD 20993-0002, 301-796-3554, 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.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry entitled “Format and Content of a REMS Document.” Section 505-1 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355-1) authorizes FDA to require a REMS for certain drugs if FDA determines that a REMS is necessary to ensure that the benefits of the drug outweigh its risks (see section 505-1(a) of the FD&C Act). A REMS is a required risk management strategy that can include one or more elements to ensure that the benefits of a drug outweigh its risks (see section 505-1(e) of the FD&C Act). The REMS document should include concise information that describes the goals and requirements of a REMS as they relate to the elements described under the FD&C Act.

In the Federal Register of October 12, 2017 (82 FR 47529), FDA announced the availability of a revised draft guidance for industry entitled “Format and Content of a REMS Document.” This draft guidance communicated changes to the format of the REMS document based on stakeholder feedback that REMS requirements are not communicated to stakeholders in a clear and consistent manner. (For more general information on REMS as well as a more comprehensive discussion of the issues summarized in this paragraph, please refer to the Background Materials http://www.fda.gov/​downloads/​ForIndustry/​UserFees/​PrescriptionDrugUserFee/​UCM362078.pdf for the July 2013 REMS Standardization and Evaluation Public Meeting.)

This guidance finalizes the revised draft guidance entitled “Format and Content of a REMS Document” issued on October 12, 2017. FDA considered comments received on the revised draft guidance as the guidance was finalized. Changes from the revised draft guidance to the final guidance include: revising the REMS document to add and clarify requirements participants, including the applicants, must complete to comply with the REMS, adding a reference to a new authority to require certain packaging and safe disposal technologies for drugs that pose a serious risk of abuse or overdose, adding a new section to list the statutory elements of the REMS, adding a prompt to identify the risk addressed by the REMS, and relocating the information contained in the appendix of the guidance ( i.e., REMS document template) to a technical specifications document entitled “REMS Document Technical Conformance Guide” available on FDA's website ( https://www.fda.gov/​drugs/​risk-evaluation-and-mitigation-strategies-rems/​roles-different-participants-rems). In addition, editorial changes were made to improve clarity and consistency between the guidance and the standardized text in the REMS document template.

The guidance, along with the new technical specifications document, can be used for drafting a REMS document for a single product and shared system REMS and includes recommendations for drafting a Bifurcated REMS document.^[1]

The recommendations in this guidance and the associated technical specifications document are intended to help ensure that REMS documents are clear; understandable to stakeholders; and to the extent possible, consistent in content and format, as well as support submission of a REMS document in Structured Product Labeling format, which is required starting December 28, 2022.^[2]

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 the format and content of a REMS document. 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. The Paperwork Reduction Act of 1995

While this guidance contains no collection of information, it does refer to previously approved FDA collections 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 for this guidance. The previously approved collections of information are subject to review by OMB under the PRA. The collections of information in 21 CFR part 314 pertaining to the submission of new drug applications (NDAs), abbreviated new drug applications (ANDAs), and supplements to NDAs and ANDAs have been approved under 0910-0001. The collections of information in 21 CFR part 601 pertaining to biologics license applications (BLAs) and supplements to BLAs have been approved under OMB control number 0910-0338. The collections of information pertaining to Medication Guides for prescription drug products have been approved under OMB control number 0910-0393.

III. Electronic Access

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

Dated: December 29, 2022.

Lauren K. Roth,

Associate Commissioner for Policy.

Footnotes

1.  A Bifurcated REMS Document is used when the approval of a shared system REMS may coincide with tentative approval of an abbreviated new drug application or section 505(b)(2) application (described in section 505(b)(2) of the FD&C Act (21 U.S.C. 355(b)(2)). For more information, refer to the guidance for industry, “Development of a Shared System REMS” (June 2018), available at https://www.fda.gov/​media/​113869/​download.

2.  See guidance for industry entitled “Providing Regulatory Submissions in Electronic Format—Content of the Risk Evaluation and Mitigation Strategies Document Using Structured Product Labeling Format” (December 2020).