First Cycle ANDA Approvals – Fact, Fiction, or Aspiration?

At the Association for Accesible Medicines (AAM) CMC workshop last week, the issue of first cycle was on a lot of people’s minds.  Industry and FDA realize that the only real way to cut down on FDA workload is to get it right the first time.  Industry continues to say with the constantly changing requirements and FDA expectations, it makes this very difficult to achieve.  The Agency complains about the quality of ANDA submissions and wants Firms to up their game.

Well, as one FDA-er noted at the meeting, both the FDA and industry need to work better together to accomplish this goal.  With the likely submission of over 1000 (maybe closer to 1200) ANDAs this year, the need to work together is even more important to result in timely approvals and reduction of workload.  The communications cannot continually be in the form of Complete Response Letters and Easily Correctible Deficiencies communications.  More effort on communication, such as telephone conversations like the old telephone amendment, with appropriate documentation could bring an application to approval stage in a more efficient manner with a faster result.  While this might not be appropriate for all ANDAs, those that need simple clarifications or where minor issues may need to be addressed would benefit from such interactions that are, of course, properly documented.

One slide from Giuseppe Randazzo, Director, Office of Program and Regulatory Operations/OPQ/CDER outlined the requirements of such communications as follows:

Working together to increase 1st cycle approvals

  • OPQ to work on improving communications to industry
  • OPQ to work on frequency of communications and earlier communications in the review cycle
  • Industry to work on responses to FDA
    • Complete
    • Substantive
    • Timely
  • Industry to improve communications with their working partners (e.g., DMF and CMOs)

Looking at best practices from the PDUFA program and what FDA has learned under GDUFA, early communication prior to the issuance of certain formal written communications may well be the best and most efficient way to handle some of the review issues.  FDA has agreed to take a fresh look at applying such communication strategies to the review of ANDAs to increase first cycle approval rates (which now stand at about 8-9%).  This effort will be welcome by the industry, and serve to boost first cycle reviews.  The (unfortunate) dilemma is that, from the time the ANDA is submitted until it is picked up for review, there may be changes in expectations or requirements.  Bringing these issues to the attention of the sponsor very early in the review process will hopefully help both the FDA and industry achieve an improvement in the rate of first cycle approvals