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Combination product submissions require a tailored regulatory strategy that blends device, drug, and biologic requirements. The complexity increases when multiple FDA centers could be involved.
The journey begins with identifying the product’s primary mode of action (PMOA). This determines which FDA center will lead the review:
- CDER: Center for Drug Evaluation and Research
- CBER: Center for Biologics Evaluation and Research
- CDRH: Center for Devices and Radiological Health
If the PMOA is unclear, companies can submit a Request for Designation (RFD) to the Office of Combination Products.
Once the lead center is determined, companies must ensure their submission addresses the regulatory requirements of both drug/biologic and device frameworks. This includes integrating device GMPs (21 CFR Part 820) with existing pharma QMS (21 CFR Part 210/211).
Key requirements typically include:
- Quality system alignment with 21 CFR Part 4
- Documentation of design controls, CAPA, and purchasing controls
- Evidence of human factors testing for design validation
- Management responsibility and risk management processes
Recent FDA draft guidance (e.g., on essential performance outputs) further clarifies what must be demonstrated in combination product submissions. The focus is shifting toward system-level outputs that directly impact drug delivery and therapeutic performance.
For companies planning international expansion, the regulatory roadmap extends beyond the U.S. CE marking under the EU MDR often requires a Notified Body Opinion confirming that the device component is adequately controlled.
Success starts with early planning and cross-functional alignment. Regulatory, quality, and product development teams must work together to:
- Identify regulatory gaps
- Align SOPs and systems
- Develop submission-ready documentation
- Engage proactively with regulatory bodies
Navigating the regulatory maze of combination product submissions is complex but manageable—with the right roadmap, tools, and expertise in place.
Work with RCA to Streamline Your Submission Process Regulatory Compliance Associates helps companies navigate the complexities of combination product submissions in both U.S. and global markets. From regulatory strategy to documentation support, RCA is your trusted partner. Reach out today to get started.
