Category: Manufacturing and Bioprocessing
Purpose: It is essential to meet the quality standards established by the Food and Drug Administration (FDA) for a new or generic drug product application to be approved for U.S. market. High shear wet granulation (HSWG) is one of the pharmaceutical manufacturing processes widely used to produce solid oral dosage forms. To demonstrate the adequacy of a HSWG process, the control of critical process parameters should be well established based on sufficient development data and scientific rationales. Deficiencies related to HSWG critical process parameters may delay the application review and approval process. Commonly observed HSWG deficiencies are discussed as a reference to the future drug application submissions.
Methods: We have surveyed the new and abbreviated drug applications (NDAs and ANDAs) submitted since 2015 to identify the most commonly occurred deficiencies in HSWG process.
Results: Recurring deficiencies are found in the NDAs and ANDAs reviewed by the FDA’s Office of Process and Facility. The most common deficiencies were related to the granulation end point selection (~56% occurring rate), granulation fluid level (~43% occurring rate), granulation fluid addition rate (~56 % occurring rate), granulation total time (~37.5% occurring rate), and scale up (~12% occurring rate).
Conclusion: Common deficiencies observed for HSWG of ANDAs and NDAs recently submitted are mostly related to lack of controls of granulation end point, granulation fluid level, granulation fluid addition rate, and scale up strategy. The process reviews and approval of new or generic drugs manufactured using HSWG process could be accelerated if these common deficiencies are avoided.
Hang Guo– Silver Spring, Maryland
Feiyan Jin– Silver Spring, Maryland
Haitao Li– Silver Spring, Maryland
Daniel Obrzut– Silver Spring, Maryland
Steve Rhieu– Program Management Officer, U.S. Food and Drug Administration, Silver Spring, Maryland