At the Association for Accessible Medicines GRx-Biosims conference currently ongoing in Bethesda, members of the FDA and industry came together to present opinions and discuss the Controlled Correspondence process.  Controlled Correspondence (CC) between the FDA and industry is very much like an important pen pal relationship (where you only write to each other regularly, but never meet).  From both sides, some things are going well, and there also some problems.  But, like any relationship, communication is vital to this process, and here it seems that the quality of communication might be lacking a bit.

The amount of Control Correspondences has tripled from 2013 to 2019.  Industry generally reports that the FDA portal is working, is easy to use, and provides some form of archival.  The FDA responses to CCs are, for the most part, being issued within GDUFA II commitment timelines (sixty days), and industry has the benefit of FDA acknowledgement of receipt.  There are some things that the industry would like to see, including, but not limited to: the ability to share Next-Gen portal accounts, not being told to “read the guidance” as a response to a question asking for guidance clarification, changes in Q1/Q2 determination process, reducing the risk of multiple submissions due to rejections, and inconsistencies in feedback from the FDA.

For the FDA’s part, they seem to be struggling with the same lack of clarity and conciseness of language submitted in the CCs they receive.  The FDA is looking at guidance and policy for gaps and where they may be able to issue updates or revisions to cover repeat or common questions.  But, in looking closer at an issue like the example of batch size, they felt the current guidance was clear and that further guidance would not help.

It was apparent in the information presented, that the Industry takes the FDA’s CC responses very seriously and are actively planning for an expenditure of resources and cost upon receipt.  In many cases, before a CC is submitted, there has been a significant amount of work done by the industry on a product targeted as a candidate for submission.  During the early development stage where deformulation and associated activities are occurring, Controlled Correspondence with the FDA is an important step to confirm acceptability before completing product development and other studies needed to support ANDA submission.  Certainly, the industry appreciates that the FDA is holding to expected timelines (as speed is of the essence in generic drug development), clarity of response is also an expectation so that they can confidently move forward with their product.

It would be nice to know that there are clear initiatives on improvements on the FDA’s part; unfortunately, this does not seem to be the case for CCs.  There were some suggestions presented by industry for the FDA’s consideration, such as issuance of additional Q&A guidance, and an FDA resource that could be contacted directly by telephone to address unclear responses from the FDA.  It seems reasonable that Q&A guidance on the highest trending questions may help alleviate the increasing numbers of CCs submitted and might be a good first step for the FDA to consider.  However, the key issue seems to be that both sides are struggling to fully understand each other.  A mechanism is needed that would allow for clarification requests for both Industry and the FDA.  This may be a good option to overcome the apparent confusion in communication, and adding a little more flexibility to the communication process may be a big help to both sides.