The afternoon sessions of FDA’s Generic Drug Forum on April 28, 2021 were very information-intense and provided a significant amount of review information and suggestions for success in ANDA submission and approval.

Caliope Sarago, Senior Regulatory Health Project Manager, Office of Research and Standards, Office of Generic Drugs, gave a comprehensive review of the pre-ANDA meeting program and meetings for complex products.  The how, what, and when aspects of the program were outlined.  She also discussed the interplay of the product-specific guidance program as well as the controlled correspondence (CC) program in obtaining information regarding specific requirements, and also described when a CC may be more appropriate than a meeting request.  There were also a few dos and don’ts discussed relative to the pre-ANDA program and CC program.

Fang Yuan, Ph.D., Chemist, Office of Lifecycle Drug Products (OLDP) OPQ, provided further information on the pre-ANDA program.  Of particular interest were the GDUFA II, pre-ANDA metrics presented.  It was noted that, of the 44 pre-ANDA requests for non-complex products submitted, 9 or 20% were granted.  However, for complex products, of the 309 received, 233 or 75% were granted (non-granted requests were either denied or withdrawn).  The two most common reasons for denial were incomplete meeting packages or FDA’s instruction to submit as a controlled correspondence.  Examples in the form of case studies were provided to outline deny or grant decisions with many helpful tips provided.

Janice Brown, Chief, Division of Internal Policies and Programs Branch, gave a presentation of the CC program and provided a lot of good advice, as well as some statistics.  Of particular interest was the data presented on the top 10 CC question categories, which included questions in order of decreasing frequency – container closure, batch size, bracketing/matrixing, packaging, orientation, stability (amount), size/shape, dissolution, overage, and microbiology.  Based on the high number of questions on stability-related issues determined by the analysis of submitted CCs, OGD/OPQ will be revising the guidance ANDAs: Stability Testing of Drug Substances and Products, Questions and Answers.

A presentation from the Division of Filing Review provided tips on avoiding a refuse-to-receive (RTR) letter.  The presenters identified the top 10 reasons for major deficiencies that automatically result in an RTR action.

Common Major Deficiencies (FY 2020)

  • Stability-related issues
  • Not Q1/Q2 same to reference listed drug (RLD)
  • Inadequate dissolution
  • Inadequate justification of impurities
  • Incomplete/failed bioequivalence (BE) studies
  • Inadequate justification of excipients


Applicants have improved in meeting the filing acceptance criteria, as demonstrated by the decrease in RTR issued from 8.33% of all ANDA submissions FY 2018, to 5.09% in FY 2019 and 4.62% in FY 2020.

Other presentations focused on labeling deficiencies, addressing common challenges in bioequivalence studies due to Covid-19 issues, and learnings and insight from records requests under §704(a)(4) of the FD&C Act in lieu of pre-approval inspections.

Get all the slides by registering for the conference – there is still time!  Register here.