Document Headings

                    Document headings vary by document type but may contain                    the following:                  
                -                       the agency or agencies that issued and signed a document                    
                -                       the number of the CFR title and the number of each part                      the document amends, proposes to amend, or is directly                      related to                    
                -                       the agency docket number / agency internal file number                    
                -                       the RIN which identifies each regulatory action listed in                      the Unified Agenda of Federal Regulatory and Deregulatory                      Actions                    

                    See the                                          Document Drafting Handbook                                        for more details.                  

###### Department of Health and Human Services

###### Food and Drug Administration

          - [Docket No. FDA-2020-D-2316]

# 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 “Benefit-Risk Assessment for Human Drug and Biological Products.” FDA has developed this guidance document in accordance with goals associated with the sixth authorization of the Prescription Drug User Fee Act (PDUFA VI) under Title I of the FDA Reauthorization Act of 2017 and requirements under the 21st Century Cures Act. The intent of this guidance is to provide drug sponsors and other stakeholders with better clarity on how considerations about a drug's benefits, risks, and risk management options factor into FDA's pre- and postmarket regulatory decisions about new drug applications (NDAs) or biologics license applications (BLAs). This guidance finalizes the draft guidance of the same title issued in September 2021.

# DATES:

                        The announcement of the guidance is published in the                         **Federal Register**                         on October 20, 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-2020-D-2316 for “Benefit-Risk Assessment for New Drug and Biological Products.” 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       ( print page 72492)       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 (CDER), 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 (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. See the                     **SUPPLEMENTARY INFORMATION**                     section for electronic access to the guidance document.                

# FOR FURTHER INFORMATION CONTACT:

                        Graham Thompson, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-5003,                         *Graham.Thompson@fda.hhs.gov;*                         or Anne Taylor, 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 final guidance for industry entitled “Benefit-Risk Assessment for Human Drug and Biological Products.” This guidance articulates the key considerations that factor into CDER's and CBER's benefit-risk assessments, including how patient experience data may be used to inform benefit-risk assessment. It discusses how sponsors, through their decisions and activities throughout the drug lifecycle, can inform FDA's benefit-risk assessment, as well as opportunities for interaction between FDA and sponsors to discuss benefit-risk considerations. It also discusses unique considerations for benefit-risk assessments that inform regulatory decision-making that occurs in the postmarket setting.

Industry stakeholders have indicated having a clearer understanding of FDA's decision-making context and benefit-risk considerations can help inform sponsors' decisions about their drug development programs and the evidence they generate in support of their NDA or BLA. Patients and other stakeholders may gain further insight into the key issues that inform FDA's assessment of benefit and risk, and a clearer understanding of how these issues fit into the regulatory framework of drug development and evaluation.

This guidance finalizes the draft guidance entitled “Benefit-Risk Assessment for New Drug and Biological Products” issued on September 30, 2021 (86 FR 54211). FDA considered comments received on the draft guidance in developing the final guidance. Changes from the draft to the final guidance include clarifying language on FDA's approach to benefit-risk assessment of new drugs and biologics, clarifying language on important considerations for FDA's premarket benefit-risk assessment of drugs and biologics, clarifying language on activities that occur in premarket development that inform benefit-risk assessment, and other editorial changes.

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 “Benefit-Risk Assessment for New Drug and Biological Products.” 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

While this guidance contains no collection of information, it does refer to previously approved FDA collections of information. The previously approved collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521). The collections of information in 21 CFR part 314 have been approved under OMB control number 0910-0001 as follows: (1) the content and format of investigational new drugs applications, (2) expanded access uses and treatment of patients with immediately life-threatening conditions or serious diseases or conditions, (3) regulatory requirements pertaining to postmarketing study commitments, and (4) risk evaluation and mitigation strategies pertaining to benefit-risk assessments. The collections of information in 21 CFR part 312 have been approved under OMB control number 0910-0014 as follows: (1) the content and format of NDAs, (2) the submission of the patient population, (3) the submission of clinical trial data, and (4) benefit-risk planning, including early consultations with FDA meetings in end-of-phase 2 and pre-NDA meetings. The collections of information for good laboratory practices for nonclinical laboratory studies have been approved under OMB control number 0910-0119. The collections of information for the submission of postmarketing adverse drug experience reporting have been approved under OMB control number 0910-0230. The collections of information in 21 CFR 201.56 and 201.57 for the content and format requirements for labeling of drugs and biologics have been approved under OMB control number 0910-0572. The collections of information in the guidance for industry entitled “Expedited Programs for Serious Conditions—Drugs and Biologics” have been approved under OMB control number 0910-0765. The collections of information in the guidance for industry entitled “Providing Postmarket Periodic Safety Reports in the International Conference on Harmonisation E2C(R2) Format (Periodic Benefit-Risk Evaluation Report)” have been approved under OMB control number 0910-0230.

## III. Electronic Access

                    Persons with access to the internet may obtain the guidance at                     *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, https://www.fda.gov/​regulatory-information/​search-fda-guidance-documents,*                     or                     *https://www.regulations.gov.*

      ( print page 72493)    
Dated: October 17, 2023.

Lauren K. Roth,

Associate Commissioner for Policy.

[FR Doc. 2023-23161 Filed 10-19-23; 8:45 am]

BILLING CODE 4164-01-P