Let’s understand "Refuse to Receive" (RTR) with an Example:
Imagine a pharmaceutical company, PharmaX, is preparing an ANDA to get approval for their generic version of a widely used pain relief medication. They have completed their formulation, manufacturing process, and stability testing, and they're ready to submit their application to the regulatory agency, the U.S. Food and Drug Administration (FDA).
PharmaX compiles all the necessary documents, data, and forms as required by the FDA's submission guidelines. This includes information about the drug's composition, manufacturing process, bioequivalence studies, labeling, and stability data.
Upon submission, the FDA's review team begins assessing the application. During the initial screening, they identify some issues in PharmaX's submission:
1. Incomplete Stability Data: The FDA guidelines specify that stability data should be provided for a minimum of 180 days to demonstrate the product's shelf life. However, PharmaX's submission only includes stability data for 150 days.
2. Missing Bioequivalence Data: The submission lacks crucial bioequivalence studies that compare PharmaX's generic product to the reference (innovator) product. This is a fundamental requirement to establish that the generic is therapeutically equivalent.
3. Formatting Errors: Some sections of the submission are not organized according to the FDA's formatting guidelines, making it difficult for the reviewers to navigate the information.
Based on these issues, the FDA's review team determines that PharmaX's application is deficient and cannot be accepted for review in its current state. They issue a "Refuse to Receive" (RTR) designation to PharmaX, notifying them of the deficiencies and outlining the specific reasons for the refusal.
PharmaX receives the RTR notification and reviews the issues pointed out by the FDA. They recognize the need to address the stability data duration, provide the missing bioequivalence studies, and correct the formatting errors.
PharmaX revises their submission to include stability data for the required 180 days, conducts the necessary bioequivalence studies, and reorganizes their submission to adhere to the FDA's formatting guidelines.
After making the necessary corrections, PharmaX resubmits their revised ANDA to the FDA. This time, the application meets all the regulatory requirements, and the stability data covers the full 180-day period. The bioequivalence studies also demonstrate the therapeutic equivalence of their generic product to the reference product.
The FDA accepts PharmaX's resubmission, and the ANDA enters the review process. While the RTR caused a delay in the overall timeline, addressing the deficiencies ensured that PharmaX's application was now complete and eligible for review.
Realated:
- Filing Certifications for Generic Druig Approval
- Sameness Evaluation of a Generic Drug Product Formula
- Referencing Approved Drug Products in ANDA Submission
Resource Person: Amit Singh (Regulatory Affairs Specialist)
