This page provides resources regarding the final rule on postmarketing safety reporting (PMSR) requirements for combination products that FDA issued on December 20, 2016 (81 FR 92603). The rule, as codified in 21 CFR 4, Subpart B, describes how to comply with PMSR requirements for combination products that have received FDA marketing authorization. Stakeholders with questions on PMSR requirements for combination products are encouraged to review these resources and, if you have questions, contact the Office of Combination Products at email@example.com.
Regulations and Guidance
21 CFR 4, Subpart B. Postmarketing Safety Reporting for Combination Products
Postmarketing Safety Reporting for Combination Products Guidance for Industry and FDA Staff
Combination Product Applicants should submit PMSRs according to the application-based PMSR requirements (21 CFR 4.102(c) and (d), 21 CFR 4.104(b)(1) and (b)(2)) and recordkeeping requirements (21 CFR 4.105(b)). Enforcement of these requirements went into effect on July 31, 2020 for Combination Product Applicants using the FDA Adverse Event Reporting System (FAERS) and Electronic Medical Device Reporting System (eMDR) to report ICSRs and on January 31, 2021 for Combination Product Applicants using the Vaccine Adverse Event Reporting System (VAERS) to report ICSRs.
Compliance Policy for Combination Product Postmarketing Safety Reporting Immediately in Effect Guidance for Industry and FDA Staff
Adverse Event Electronic Reporting Systems
The adverse event electronic reporting systems, FDA Adverse Event Reporting System (FAERS), Electronic Medical Device Reporting System (eMDR), and Vaccine Adverse Event Reporting System (VAERS) have been updated to address combination product reporting considerations, including allowing Combination Product Applicants to satisfy multiple reporting requirements in a single report. For additional information, see the associated Technical Specifications:
FDA welcomes comments from combination product reporters. Comments may be submitted to the Office of Combination Products, firstname.lastname@example.org.
Combination Product PMSR Examples and Other Resources
The content included here is intended to assist combination product applicants in presenting certain combination product information in the data fields of postmarketing safety reporting systems (e.g., FAERS and eMDR)1. FDA issued Federal Register notices describing a voluntary program for summary reporting of malfunctions available for certain device-led combination products.
Refer to Postmarketing Safety Reporting for Combination Products Guidance for Industry and FDA Staff (“PMSR Guidance”) for additional information. Reporters should refer to current technical specifications and other documents for detailed instructions for how to complete and submit ICSRs and other postmarketing safety reports.
- Example Scenarios. Scenarios to illustrate how to report combination product information identified in sections V.B.2 and V.B.5 of the PMSR Guidance in the electronic reporting systems.
- NDA-approved prefilled on-body infusor (FAERS)
- BLA-approved product consisting of one vial of biological product along with three device constituent parts (FAERS)
- PMA-approved steroid-eluting lead (eMDR)
- Reporting for same or similar device constituent parts (FAERS)
- Field Alert Report for PMA-approved combination product (Form 3331a)
- Reporting Elements. Identifies the data fields for the combination product information described in Section V.B.2 of the PMSR Guidance.
- Device Product Codes (procodes). Includes common procodes for device constituent parts of ANDA/NDA/BLA combination products.
- Including Multiple Entities and/or Multiple Lot Numbers. Illustrates how to submit information on more than one entity involved in the manufacture of the combination product and/or the specific lots of the constituent parts that comprise a combination product.
Training and Outreach
- 1. FDA has issued Federal Register (FR) notices describing a voluntary program for summary reporting of malfunctions, available for certain device-led combination products see https://www.fda.gov/medical-devices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems#malfunction.