The Office of Generic Drug has published the newly revised Manual of Policy and Procedures (MaPP) 5016.8 titled Using Four-Part Harmony in Quality-Related Assessment Communications (here). The-Four Part Harmony assessment is used in several of the Agency’s Centers and its goal is to promote communication clarity between reviewers and applicants. It also answers the questions of when, what, and why. The “why” is particularly important as the FDA (especially the OGD) has had a penchant for creating the age-old problem of asking what is “nice to know” versus “what is needed to know.” In fact, this specific statement was made at the recent AAM GRx+Biosims meeting by a presenter who complained about some of the questions asked by the OGD. This problem has been felt by industry since the beginning of Hatch-Waxman as the data requirements have increased over time and the questions some reviewers ask often seem to be part of a quest for knowledge without an obvious benefit to increasing the safety of the product or quality of the data already provided.
Anyway, the revised guidance provides a road map (no pun intended) for communicating in a clear and concise manner with sponsors in complete response letters, information requests, and discipline review letters as well as other correspondence. As stated by the MaPP, the four parts of the harmony are to ask:
(1) What was provided? Acknowledge the information submitted by the applicant and provide a reference to relevant modules, sections, page numbers, or tables unless the part of the application being referenced is obvious from the description (e.g., “your proposed drug product specification”).
(2) What is the issue? Identify missing information or information that the FDA considers inadequate.
(3) What is needed? Request additional information or recommend an alternative approach to address the issue.
(4) Why is it needed? State the basis for the information request or deficiency, and include:
a. The impact of the issue on the overall regulatory decision.
b. References to all or part of applicable regulations, statutes, guidances, and/or FDA-recognized consensus standards, as appropriate.
This approach, if followed, will provide a better understanding of what the OGD is asking, what the issue is, what is needed, and why the Agency is asking for additional information. This process (in theory) should guide reviewers to be more circumspect in their requests and provide the basis for the needed information. This should also make it easier for sponsors to understand and reply more fully and accurately to the FDA’s questions. Let’s see whether the process works as it is adopted by the OGD; perhaps at next year’s GRx+Biosims meeting we’ll get a reading from industry of whether Four-Part Harmony sings to sponsors and whether the tune is a good one.
