Culture Change in Industry Necessary for Success Under GDUFA

It may be almost too late to assure that the culture of generic companies can change to meet the new more demanding standards and requirements that the Generic Drug User Fee Act (GDUFA) indirectly imposes.  But if now is almost too late, tomorrow is for sure!

If, over the first year of GDUFA implementation, generic firms have not figured out that they must push their development programs back a bit to permit applying the principles of Quality by Design (QbD) and ifthey have not figured out that the drug product, manufacturing process, site(s), API suppliers, testing labs, etc., that are the subject of the application they submit do not accurately represent how and where they want their commercial product to be made, then they will already find themselves behind the proverbial 8 ball.

The tightening of the Refuse-to-Receive (RTR) requirements (see previous post here) as well as the GDUFA “penalty box” provisions (see previous post here) can have both an immediate and long term financial penalty. Remember, if your application receives an RTR letter, you will lose 25% of your filing fee and even worse, if that application represents a first–to-file opportunity, you may lose cashing in on that chance.  Developing your product on the review clock will require firms to submit amendments to their applications.  Each amendment can have significant time penalties associated with your GDUFA goal dates and where your application ultimately is positioned in the review queue.  Too many amendments or one major amendment after ANDA receipt and your application will no longer be subject to a GDUFA goal date!  So the quality of your initial submission will be paramount to success.

What can firms do to assure improved submission quality and minimize the risk that you will be facing a penalty? Start early in development.  Map out what your marketing and commercial folks really want to sell.  Look for the proper API suppliers and assure they have Drug Master Files (DMFs) on the FDA’s Acceptable for Reference List or be certain they submit their new DMFs submitted at least 6 months prior to the proposed submission date of your application.  Don’t rush your application to submission, and if there is a NCE-1 date or a first-to-file opportunity, start the entire process earlier than you would if the application would not be impacted by failing to meet a such a definitive deadline.

It also pays to have another set of eyes review your submission, for example, a third party consultant or even a reviewer from another internal department.   Don’t get fooled into thinking that even that will be enough avoid a penalty because the RTR review, no matter how good the OGD’s ANDA checklist might be, will be somewhat subjective, given the fact that some reviewers may be more detail-oriented than others.  Remember 10 or more minor deficiencies earn you a RTR letter.  Don’t be tricked by or expect a guarantee that any pre-review will result in avoiding a RTR letter; the best anyone can do is reduce the risk of receiving one.  Correcting problems in the application prior to submission will also reduce, but not guarantee that there will not be deficiencies upon review of the application.  But keeping the number of deficiencies to a minimum will certainly lessen the burden of responding to the OGD’s first Complete Response Letter or may even give you a chance, and I emphasize chance, for a first-cycle approval.

The bottom line is the firms that get on board with improving the quality of their submissions and pay attention to the quality issues may avoid a seat in the penalty box, and will ultimately be the victors in the race for approval. For any additional regulatory questions, or to find out how Lachman Consultants can assist in reducing your risk for a seat in the penalty box, please contact Joan Janulis (