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505(b)(2) – Part 2: The Assessment: Efficacy Review

One of the key attractions to the 505(b)(2) route is the potential of gaining approval with only one Phase 3 study.  Moreover, this Phase 3 study is often small, at least compared to the thousands of patients in 505(b)(1) submissions.  There are exceptions, to be sure.  For example, 2 or more trials may be needed if your goal is to add a new indication;  most 505(b)(2) clinical plans are designed to confirm that the drug product alterations maintain the same efficacy (non-inferiority).

One of the most important questions CEO’s ask is what is the Phase 3 study going to cost?  And what is the duration of the study?  There are two NDA goals to be met in the study – efficacy and safety.  For the answer to study duration, safety is often the predominate driver.  For cost, efficacy measurements are the likely driver.

The Efficacy Review provides a comprehensive review of all available information pertaining to the efficacy of the proposed product.  Individual studies are examined and summarized on the basis of dose, patient population, indication, duration, primary and secondary endpoints, and safety findings.   Additionally, all relevant studies are integrated into overall efficacy summary and exposure tables.

Potential sources from which this information is obtained include: (1) randomized placebo-controlled trials [PubMed]; (2) approved product labeling [PDR]; (3) the FDA Center for Drug Evaluation and Research (CDER) Web site, which provides an extensive database of information for individual drugs []; and (4) Freedom of Information (FOI) requests, which provide the SBA documents for approved NDA products.  Relevant information obtained from SBA documents is summarized and presented as support for the proposed clinical development plan.  For products selected to follow the 505(b)(2) pathway, this information is used to provide support for this regulatory route.