Regulatory Affairs

Ever since the implementation of the Generic Drug User Fee Act (GDUFA), Guidance documents are flying out of FDA and landing faster than the planes at Atlanta’s busy Hartsfield airport. One such Draft Guidance was posted yesterday on the FDA web site (here) entitled Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules. While the specific issue addressed in this Guidance is clear, the general issue of something I like to call “functionality” is now being formally addressed through Guidance documents, as opposed to deficiency letters.

Appearing on the FDA’s Paragraph IV database listing on December 3, 2013 is an ANDA filing for Ethinyl Estradiol and Etonogestrel drug-emitting polymeric ring that is used as a contraceptive to prevent pregnancy. What caught my eye and what it interesting about this product is that it is the first of a kind ANDA for an intravaginal contraceptive product of this nature. In addition, its posting date (December 3, 2013) and the ANDA submission date listed as June 17, 2013 (see chart below) suggests that either OGD has a very extensive backlog of ANDAs to process, or that this application presented some unique issues of either bioequivalence or chemistry manufacturing and controls that had to be resolved prior to a decision to receive (file) the application. My guess is that it might be the latter, since OGD has said it was expediting initial completeness and acceptability reviews of ANDAs with Paragraph IV certifications (indicating a challenge to the patent listed for the reference listed drug).

Since the implementation of the Generic Drug User Fee Act (GDUFA), many small facilities have complained about the establishment and facility fees being assessed under the Act. Unlike the Prescription Drug User Fee Act (PDUFA) where establishment (facility fees) are not due or paid until after the respective new drug application (NDA) is approved, GDUFA requires yearly payments of the facility fee while the abbreviated new drug application (ANDA) is pending. With median approval times at about 34 months, that may mean that 3 or more facility fees may be due prior to application approval. At the current rate of $220,152 for domestic facilities and $235,152 for foreign facilities, that could mean close to $700,000 in fees that a facility may have to pay prior to approval of an application that it is named in.

In a letter dated November 27, 2013, the Generic Pharmaceutical Association (GPhA) requested a 60-day extension to provide comments on the FDA’s Proposed Rule – Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products.

Two Federal Register notices that will both publish on November 27, 2013, extend the comment period for 14 days on two separate Draft Guidance documents, due to technical problems that occurred on the Regulations.gov website that made it impossible for some commenters to make electronic submissions to the respective Dockets from November 4-13, 2013.

While Dr. Janet Woodcock, Director, Center for Drug Evaluation and Research (CDER) and Dr. Kathleen Uhl, Acting Director, Office of Generic Drugs (OGD) are kicking around ideas about early communications of deficiencies and potential approvals to firms, the message that OGD is clamping down on phone calls and emails is being heard by Industry loud and clear.

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!

I am stealing a quintessential line from the movie “The Russians Are Coming, The Russians Are Coming”, to explain the emergent nature of the FDA’s proposed revision to its labeling rule to permit unilateral changes in safety information for certain applications for which the Federal Food Drug and Cosmetic Act (FDCA) clearly precludes such changes. So those of you in industry you have a choice – either raise your voices and raise them loudly, or contact your liability carriers and raise your limits and secure good defense counsel.

Speaking at the GPhA Fall Technical Workshop on October 30, 2013, Dr. Kathleen Uhl, Acting Director of the Office of Generic Drugs (OGD) provided a first look at the structure of the new OGD Super Office. There are a number of new organizational blocks that signal to this old former OGDer that not only more changes are on the way, but that emphasis on certain pre- and post-approval issues are going to be beefed up considerably.