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 firstname.lastname@example.org.
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
At this time, Combination Product Applicants should submit PMSRs consistent with the requirements of the application type for the combination product (application-based PMSR requirements). FDA does not intend to enforce the additional constituent part-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)) until:
- 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.
- January 31, 2021, for Combination Product Applicants using the Vaccine Adverse Event Reporting System (VAERS) to report ICSRs.
FDA is delaying enforcement of these provisions to ensure that Combination Product Applicants have sufficient time to update reporting and recordkeeping systems and procedures, including their information technology systems, to comply with the combination product PMSR requirements. See:
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) and Electronic Medical Device Reporting System (eMDR) 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 has proposed similar updates to address combination products for vaccine combination product manufacturers that submit ICSRs via the Vaccine Adverse Event Reporting System (VAERS). See CBER Vaccine ICSR Proposed Updates.
FDA welcomes comments from combination product reporters. Comments may be submitted to the Office of Combination Products, email@example.com.
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 the drug and device reporting systems (FAERS and eMDR, respectively)1. 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 electronic ICSRs.
- Example Scenarios. Scenarios to illustrate how to report combination product information identified in section V.B.2 of the PMSR Guidance in the electronic reporting systems.
- 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
 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.