Sponsor Responsibilities-Safety Reporting Requirements and Safety Assessment for Investigational New Drug Application and Bioavailability/Bioequivalence Studies; Guidance for Industry; Availability

<NOTICE> DEPARTMENT OF HEALTH AND HUMAN SERVICES <SUBAGY>Food and Drug Administration</SUBAGY> <DEPDOC>[Docket No. FDA-2020-D-2099]</DEPDOC> <SUBJECT>Sponsor Responsibilities—Safety Reporting Requirements and Safety Assessment for Investigational New Drug Application and Bioavailability/Bioequivalence Studies; Guidance for Industry; Availability</SUBJECT> <HD SOURCE="HED">AGENCY:</HD> Food and Drug Administration, HHS. <HD SOURCE="HED">ACTION:</HD> Notice of availability. <SUM> <HD SOURCE="HED">SUMMARY:</HD> The Food and Drug Administration (FDA or the Agency) is announcing the availability of a final guidance for industry entitled “Sponsor Responsibilities—Safety Reporting Requirements and Safety Assessment for Investigational New Drug Application and Bioavailability/Bioequivalence Studies.” The guidance provides recommendations for sponsors and sponsor-investigators to comply with the requirements of investigational new drug application (IND) safety reporting and safety reporting for bioavailability (BA) and bioequivalence (BE) studies. This guidance finalizes the draft guidance of the same title issued on June 28, 2021. </SUM> <DATES> <HD SOURCE="HED">DATES:</HD> The announcement of the guidance is published in the <E T="04">Federal Register</E> on December 16, 2025. </DATES> <HD SOURCE="HED">ADDRESSES:</HD> You may submit either electronic or written comments on Agency guidances at any time as follows: <HD SOURCE="HD2">Electronic Submissions</HD> Submit electronic comments in the following way: • <E T="03">Federal eRulemaking Portal: https://www.regulations.gov.</E> Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to <E T="03">https://www.regulations.gov</E> 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 <E T="03">https://www.regulations.gov.</E> • 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”). <HD SOURCE="HD2">Written/Paper Submissions</HD> Submit written/paper submissions as follows: • <E T="03">Mail/Hand Delivery/Courier (for written/paper submissions):</E> 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.” <E T="03">Instructions:</E> All submissions received must include the Docket No. FDA-2020-D-2099 for “Sponsor Responsibilities—Safety Reporting Requirements and Safety Assessment for Investigational New Drug Application and Bioavailability/Bioequivalence Studies.” Received comments will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at <E T="03">https://www.regulations.gov</E> 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 <E T="03">https://www.regulations.gov.</E> 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: <E T="03">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.</E> <E T="03">Docket:</E> For access to the docket to read background documents or the electronic and written/paper comments received, go to <E T="03">https://www.regulations.gov</E> 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 (CBER), Food and Drug Administration, 800-835-4709 or 240-402-8010, <E T="03">industry.biologics@fda.hs.gov.</E> Send one self-addressed adhesive label to assist that office in processing your requests. See the <E T="02">SUPPLEMENTARY INFORMATION</E> section for electronic access to the guidance document. <FURINF> <HD SOURCE="HED">FOR FURTHER INFORMATION CONTACT:</HD> Juanita Marner, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-2500, <E T="03">cderomp@fda.hhs.gov;</E> or Phillip Kurs, Center for Biologics Evaluation and Research, Food and Drug Administration, 240-402-7911. </FURINF> <SUPLINF> <HD SOURCE="HED">SUPPLEMENTARY INFORMATION:</HD> <HD SOURCE="HD1">I. Background</HD> FDA is announcing the availability of a guidance for industry entitled “Sponsor Responsibilities—Safety Reporting Requirements and Safety Assessment for Investigational New Drug Application and Bioavailability/Bioequivalence Studies.” The guidance provides recommendations to help sponsors and sponsor-investigators comply with the expedited safety reporting requirements for human drug and biological products that are being investigated (1) under an IND in accordance with § 312.32 (21 CFR 312.32) or (2) as part of a BA or BE study that is exempt from the IND requirements under § 320.31(d)(3) (21 CFR 320.31(d)(3)). In the <E T="04">Federal Register</E> of September 29, 2010 (75 FR 59935), FDA published a final rule amending the IND safety reporting requirements under § 312.32 and adding safety reporting requirements for persons conducting IND-exempt BA and BE studies under § 320.31. Compliance with these requirements increases the likelihood that submitted information will be interpretable and will meaningfully contribute to the developing safety profile of the investigational drug and improve the overall quality of safety reporting. An effective systematic approach by sponsors to safety surveillance, coupled with focusing on IND safety reports for suspected adverse reactions that are both serious and unexpected, allows sponsors, FDA, participating investigators, and institutional review boards to focus on important safety issues and take actions needed to minimize the risks of participation in a clinical trial. Following the publication of the final rule, FDA issued the guidance for industry and investigators entitled “Safety Reporting Requirements for Investigational New Drug Applications and Bioavailability/Bioequivalence Studies” (December 2012) (the 2012 final guidance) to help sponsors and investigators comply with safety reporting requirements for INDs and for BA/BE studies that meet the conditions for IND exemption under § 320.31(d)(3) (IND-exempt BA/BE studies). In 2015, FDA issued a draft guidance for industry entitled “Safety Assessment for Investigational New Drug Application Safety Reporting” (December 2015) (the 2015 draft guidance) that primarily focused on aggregate analysis of serious adverse events for reporting. In the <E T="04">Federal Register</E> of June 28, 2021 (86 FR 34020), FDA announced the draft guidance for industry entitled “Sponsor Responsibilities—Safety Reporting Requirements and Safety Assessment for Investigational New Drug Application and Bioavailability/Bioequivalence Studies” (the June 2021 draft guidance), which incorporated content from the 2012 final guidance and the 2015 draft guidance in terms of sponsors' responsibilities for safety reporting requirements for INDs and BA/BE studies. The 2015 draft guidance was withdrawn upon the publication of the June 2021 draft guidance. In September 2021, FDA issued the draft guidance for industry entitled “Investigator Responsibilities—Safety Reporting for Investigational Drugs and Devices” (the September 2021 draft guidance) to help clinical investigators comply with the safety reporting requirements of IND studies and investigational device exemption (IDE) studies. 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