Description
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 provides interpretations of terms used for safety reporting, makes recommendations on when and how to submit a safety report, and provides information on other safety reporting issues raised by sponsors. To facilitate appropriate IND safety reporting practices, this guidance also provides recommendations related to the two IND safety reporting provisions that require assessment of aggregate data.
Scope & Applicability
Product Classes
1Products that modify or manipulate the expression of a gene; Products involving genetic modification; A research scientist in a university laboratory has developed a gene therapy.
Stakeholders
9Entity responsible for submitting applications under section 524B
Data monitoring committee; Oversight body that may request interim analysis
Entity to which obligations may be transferred
Group responsible for identifying events that should not be individually reported
Safety oversight body for interpreting adverse events; Safety oversight body for study design
Veterinarian responsible for selecting anesthetic regimens and conducting field studies
Governs top dose in clinical studies
facilitate discussions between a prospective subject and an investigator; Responsible for conducting research and providing informed consent
individual who both initiates and conducts a clinical investigation
Regulatory Context
Attributes
6Causality standard for suspected adverse reactions; standard for determining a suspected adverse reaction; The threshold for determining if a drug caused an adverse event.
Predicted rate used to determine if unblinding is necessary
The day the sponsor initially receives information or determines qualification for expedited reporting
comparative interim results used for safety or adaptation decisions
Estimated rate of an event in the study population
event not listed in the investigator's brochure
Related CFR Sections (15)
- 21CFR312.32§ 312.32 IND safety reporting.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR310.305§ 310.305 Records and reports concerning adverse drug experiences on marketed prescription drugs for human use without approved new drug applications.
(a) Scope. FDA is requiring manufacturers, packers, and distributors of marketed prescription drug products that are not the subject of an approved new drug or abbreviated new drug application to establish and maintain records and make reports to FDA of all serious, unexpected adverse drug experiencRead full regulation →
- 21CFR314.97§ 314.97 Supplements and other changes to an approved ANDA.
(a) General requirements. The applicant must comply with the requirements of §§ 314.70 and 314.71 regarding the submission of supplemental ANDAs and other changes to an approved ANDA.Read full regulation →
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead full regulation →
- 21CFR320.31§ 320.31 Applicability of requirements regarding an “Investigational New Drug Application.”
(a) Any person planning to conduct an in vivo bioavailability or bioequivalence study in humans shall submit an “Investigational New Drug Application” (IND) if:Read full regulation →
- 21CFR312.56§ 312.56 Review of ongoing investigations.
(a) The sponsor shall monitor the progress of all clinical investigations being conducted under its IND.Read full regulation →
- 21CFR312.52§ 312.52 Transfer of obligations to a contract research organization.
(a) A sponsor may transfer responsibility for any or all of the obligations set forth in this part to a contract research organization. Any such transfer shall be described in writing. If not all obligations are transferred, the writing is required to describe each of the obligations being assumed bRead full regulation →
- 21CFR312.58§ 312.58 Inspection of sponsor's records and reports.
(a) FDA inspection. A sponsor shall upon request from any properly authorized officer or employee of the Food and Drug Administration, at reasonable times, permit such officer or employee to have access to and copy and verify any records and reports relating to a clinical investigation conducted undRead full regulation →
- 21CFR312.30§ 312.30 Protocol amendments.
Once an IND is in effect, a sponsor shall amend it as needed to ensure that the clinical investigations are conducted according to protocols included in the application. This section sets forth the provisions under which new protocols may be submitted and changes in previously submitted protocols maRead full regulation →
- 21CFR312.64§ 312.64 Investigator reports.
(a) Progress reports. The investigator shall furnish all reports to the sponsor of the drug who is responsible for collecting and evaluating the results obtained. The sponsor is required under § 312.33 to submit annual reports to FDA on the progress of the clinical investigations.Read full regulation →
- 21CFR314.80§ 314.80 Postmarketing reporting of adverse drug experiences.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR600.80§ 600.80 Postmarketing reporting of adverse experiences.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR606.170§ 606.170 Adverse reaction file.
(a) Records shall be maintained of any reports of complaints of adverse reactions regarding each unit of blood or blood product arising as a result of blood collection or transfusion. A thorough investigation of each reported adverse reaction shall be made. A written report of the investigation of aRead full regulation →
- 21CFR312.3§ 312.3 Definitions and interpretations.
(a) The definitions and interpretations of terms contained in section 201 of the Act apply to those terms when used in this part:Read full regulation →
- 21CFR312.33§ 312.33 Annual reports.
A sponsor shall within 60 days of the anniversary date that the IND went into effect, submit a brief report of the progress of the investigation that includes:Read full regulation →
Related Warning Letters (10)
- 2025-12-23
In Vivo Bioavailability-Bioequivalence Studies – Clinical
Maria A. Carballosa, M.D.
- 2025-12-09
Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)
Celularity, Inc
- 2025-11-25
Compounding Pharmacy/Adulterated Drug Products
Wells Pharma of Houston, LLC
- 2025-11-18
Sponsor/Investigator
Verdure Sciences, Inc.
- 2025-09-30
Clinical Investigator (Sponsor)
Pamela K. Den Besten, DDS, MS
- 2025-09-23
Clinical Investigator/Sponsor
Ralph A. DeFronzo, M.D.
- 2025-09-09
Clinical Investigator
Shirish M. Gadgeel, M.D.
- 2025-07-15
Clinical Investigator
Mark J. Savant, M.D
- 2025-07-01
Clinical Investigator
Peter Michael, M.D.
- 2025-06-10
Clinical Investigator (Sponsor)
American Behavioral Research Institute, LLC
See Also (8)
- Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers (Status: Final)
- Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-derived Products: Guidance for Industry (Status: Final)
- PHS Guideline on Infectious Disease Issues in Xenotransplantation: PHS Guideline (Status: Final)
- Postmarketing Safety Reporting for Human Drug and Biological Products Including Vaccines: Draft Guidance for Industry (Status: Draft)
- Guidance for Industry: Providing Regulatory Submissions to CBER in Electronic Format -- Investigational New Drug Applications (INDs) (PDF) (Status: Final)
- Gingivitis: Development and Evaluation of Drugs for Treatment or Prevention (Status: Draft)
- How to Comply with the Pediatric Research Equity Act (Status: Draft)
- Establishment and Operation of Clinical Trial Data Monitoring Committees: Guidance for Clinical Trial Sponsors (Status: Final)