Compliance Policy for Combination Product Postmarketing Safety Reporting Requirements
This guidance outlines FDA's compliance policy for the Combination Product Postmarketing Safety Reporting (PMSR) Final Rule, specifically addressing enforcement delays for certain requirements to allow manufacturers sufficient time to update their reporting and recordkeeping systems.
What You Need to Know? 👇
What is the FDA’s compliance policy for combination product postmarketing safety reporting?
FDA is delaying enforcement of certain provisions (21 CFR 4.102(c)(d), 4.104(b)(1)(2), and 4.105(b)) until July 2020 for FAERS/eMDR users and January 2021 for VAERS users, allowing time for system updates and guidance development.
Which entities are subject to the combination product PMSR final rule?
The rule applies to Combination Product Applicants (holding all applications for a combination product) and Constituent Part Applicants (holding applications for individual constituent parts when different applicants market the parts separately).
What are the two main types of PMSR requirements for combination products?
Combination Product Applicants must comply with application type-based PMSR requirements (based on marketing authorization type) and constituent part-based PMSR requirements (based on the types of constituent parts in the product).
When did the combination product PMSR final rule become effective?
The final rule became effective January 19, 2017. Application type-based requirements had immediate compliance, while constituent part-based requirements originally had a compliance date of July 19, 2018, now delayed per FDA’s compliance policy.
What reporting systems are mentioned for combination product safety reporting?
The guidance references three FDA reporting systems: FAERS (FDA Adverse Event Reporting System), eMDR (Electronic Medical Device Reporting System), and VAERS (Vaccine Adverse Event Reporting System) for submitting Individual Case Safety Reports.
Why is FDA delaying enforcement of certain combination product PMSR requirements?
FDA recognizes that Combination Product Applicants need sufficient time to update reporting and recordkeeping systems, including IT infrastructure, and to consider forthcoming FDA guidance with technical specifications for compliance implementation.
What You Need to Do 👇
Recommended Actions
- Review and identify which reporting system(s) apply to your combination product (FAERS, eMDR, or VAERS)
- Develop a timeline for updating systems and procedures based on the applicable enforcement deadline
- Update IT systems and procedures to comply with:
- Constituent part-based PMSR requirements
- Submission processes for ICSRs
- Recordkeeping requirements
- Implement training programs for staff on new reporting and recordkeeping requirements
- Monitor FDA communications for additional guidance and technical specifications
- Ensure compliance with non-delayed requirements under 21 CFR Part 4, Subpart B
- Establish a process to verify compliance with all requirements before the end of the enforcement delay period
Key Considerations
Software
- Systems and procedures, including IT systems, must be updated to comply with reporting requirements
- Different reporting systems (FAERS, eMDR, VAERS) have different compliance deadlines
Safety
- Combination Product Applicants must comply with application type-based PMSR requirements
- Constituent part-based PMSR requirements must be followed
- Individual Case Safety Reports (ICSRs) must be submitted through appropriate systems
Other considerations
- Delayed enforcement periods:
- Until July 31, 2020, for FAERS and eMDR reporting systems
- Until January 31, 2021, for VAERS reporting system
- Requirements apply to combination products subject to premarket review
- Recordkeeping requirements must be implemented according to 21 CFR 4.105(b)
Relevant Guidances 🔗
- Postmarketing Safety Reporting Requirements for Combination Products
- Current Good Manufacturing Practice Requirements for Combination Products
- Premarket Review Pathways for Combination Products
- User Fees for Combination Products and Associated Waivers
- Obtaining FDA Feedback for Combination Products: Best Practices and Meeting Procedures
- Early Development Considerations for Combination Products
- Human Factors Studies and Related Analyses for Combination Products
- Postapproval Changes to Combination Products: Marketing Submission Requirements (Draft)
Related references and norms 📂
- 21 CFR Part 4, Subpart B: Postmarketing Safety Reporting for Combination Products
- 21 CFR 3.2(e): Combination Product Definition
- 21 CFR 803: Medical Device Reporting