Regulations of combination products often present unique situations in the review process. The FDA is attempting to modernize and improve regulations around combo products in conjunction with requirements in the recently enacted 21st Century Cures Act to provide clear rationales for combination product designations.
In 2016, the FDA established a Combination Product Policy Council and launched a new pilot project on inter-center consults among the FDA for combo products. In January 2017, the FDA released final guidance describing and explaining the current good manufacturing practice (CGMP) requirements for combo products and draft guidance on human factors studies for generic combination products.
The final CGMP guidance for combination products describes and explains the final rule on 21 CCFR part 4. Up until the issuance of the final rule, only individual products had established CGMP requirements. The guidance is intended to clarify and explain the application of the individual CGMP requirements to combination products and specify how compliance may be demonstrated.
The draft guidance on Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA recommends sponsors focus on three main areas:
- Side-by-side, line-by-line comparison of the generic combination product and reference listed drug (RLD).
- Comparative task analysis: analysis of the differences between the use process for each product with the goal to characterize the potential for use error.
- Physical comparison of the delivery device constituent part: physical comparison of RLD to the physical features of the proposed generic combination product.
Moving forward, the FDA is aiming to advance an evidence-based approach to developing, evaluating, and approving combination products and increase operational efficiencies within the FDA.