In a presentation to the Generic Pharmaceutical Association Fall Technical Workshop today, Dr. Janet Woodcock, Director, Center for Drug Evaluation and Research (CDER), told the audience that the new CDER quality initiatives under GDUFA are designed to have an Integrated team review to Chemistry Manufacturing and Controls, microbiology, dissolution and inspections through the new Office of Pharmaceutical Quality.  The inclusion of dissolution review appears to remove that assessment from the bioequivalence review within the Office of Generic Drugs’ (OGD) team.

One big time industry ask has been for real time communications to applicants in an effort to reduce the number of review cycles.  This will be implemented as the review process moves forward.  The improvement in efficiency according to Cook (Acting Director , OGD) is essential to getting ANDAs approved in a timely manner and will significantly improve the efficiency of the review process.  Dr. Lawrence Yu , Deputy Director, Office of Pharmaceutical Quality (OPQ), noted that only 1.4% of the quality reviews are found acceptable for generic applications in the first review cycle where the new drug model approached 90%.  This needs to be changed for generics to assure timely approval.  This will also help CDER to better meet GDUFA timelines and will allow an opportunity to resolve issues during the first review cycle.

Another new Office of Pharmaceutical Quality function that will be handled a bit differently from the way past post approval lifecycle management of ANDAs and will now involve a seamless hand-off from both original New Drugs (which is currently doing this) and Generics teams to post-approval to a Lifecycle team where new drugs and generic post approval changes will be managed within same unit.

Alignment of Field and Center regarding inspectional work and development of specialization of the inspectorate (pharmaceutical inspectors and drug compliance officers) will permit equivalent and timely inspection of all US and ex-US sites. The goal is to have consistent compliance policy across the entire Center so everyone is on the same page for inspectional requirements. This initiative will likely take several years to fully implement as new inspectors are currently being trained.  Historically, these type of changes are slow to smooth out because of the major organizational changes that are necessary.

Dr. Woodcock also noted that ORA and CDER are developing new inspection templates to assure consistency and to generate data to put into quality platform to help define quality metrics and outline the state and status of quality of the facilities inspected.

Cook noted that the generic program must be totally transformed and, during that transformation, still needs to perform.  During the last two years she noted that tensions are high and it is a stressful time for industry and FDA both as OGD is building a quality system to deal with the transformed review process.

Hiring and training has been a big effort.   OGD alone has hired >200 new FTEs and there is a need to “train, train, train and repeat, repeat and repeat” to bring new reviewers up to speed.  In addition, OGD needs to provide clear policy and procedures in place for both reviewers and industry.

Cook noted that their output has more than doubled when looking at Complete Response Letters, supplements and DMF reviews. She also indicated that, last fiscal year, there were >1500 compliance recommendations relative to ANDAs.   The need to coordinate those recommendations with the finalization of review has been challenging for both OGD and CDER.

Dr. Lawrence Yu talked about the new single quality concept for the entire center.  He also provided a look at the progress that OGD and OPQ have made in the backlog (pre-October 2012 submissions) and how the ANDA and supplemental reviews are progressing.    The Prior Approval Supplement (PAS) backlog bas gone from 847 in November 2013 down to 14 in October 2014.  That does not include the supplements that have come in since GDUFA; the chart below represents the totals of all supplements before OGD.

Pending Chemistry Supplements

Total pending chemistry ANDA numbers were provided by Dr. Yu in the following graph.  So even with the increased productivity, the submission rate of ANDAs appears to have blunted some of the increase in productivity, as the numbers in the entire backlog appears to be fairly constant over the last year.