Big Decisions Loom in 2014 for Generic Applicants

There are a number of dilemmas looming over generic drug firms in 2014 – some with no easy answers, but hopefully firms are considering their choices sooner rather than later. Two of these issues relate to the all-important question “Exactly when should the ANDA be submitted?”. Any generic drug firm knows that that answer is never easy and is dependent on many factors, such as biostudy success, completion of stability testing, facilities being ready for inspection and first-to-file opportunities, just to name a few. And of course, such practical scientific or regulatory deadlines are further complicated by the directed business goal of “the sooner the better”.

Two Watch Outs That May Cost You Dearly!

In trying to read the tea leaves at the Office of Generic Drugs (OGD) and discussing issues that really worry both OGD and industry, I have come across two issues that you need to stay on top of, one during the approval process and the other just after ANDA approval, to avoid a potential delay in approval that you did not see coming or a potential change in the way OGD does business relative to ANDAs subject to the valuable 180-day exclusivity provisions of the Act.

Who’da Thunk?

At the outset of the generic drug scandal uncovered in the late 1980’s FDA developed an administrative Application Integrity Policy. At or about the same time, legislation (the Generic Drug Enforcement Act [GDEA] of 1992), provided for debarment of individuals convicted of certain misdemeanor or felony offenses. During the generic drug scandal, there were 22 criminal convictions of drug companies and 70 convictions of industry and FDA personnel as well as $50 million in fines levied against these organizations and individuals. Eventually there were some 70 individual debarment actions relating to the shenanigans that occurred but to date no firm has been debarred under the provisions of the GDEA. I thought it might be interesting to see what the number of debarments looked like over the last few years.

Warning Letters Continue for Compounding Pharmacies – FDA Cites Five in 2014 So Far

The FDA has stepped up its surveillance of compounding pharmacies and has issued at least 5 Warning Letters to such establishment so far this year. The beat goes on, and now the FDA must begin to integrate with the State Boards of Pharmacy and State Drug Inspectors to determine the evolving definition of what is a compounding pharmacy and what is an “outsourcing” compounding pharmacy.

Revised ANDA Checklist – The New Requirements Keep on Coming

For those of you that may have missed the January 2014 revision of the ANDA Checklist (last revised was 3rd quarter, October 2013), there are some new items that FDA will be looking for in its initial Completeness and Acceptability Review of ANDAs. Failure to include this information could result in a Refuse-to-Receive letter and a penalty of 25% of your ANDA user fee.

OGD’s Paragraph IV Database and Two Interesting Listings

The Office of Generic Drugs (OGD) updated its Paragraph IV Database (PIVDB) yesterday and two new entries caught my eye. An ANDA for glycerol phenylbutyrate oral solution (a copy of the NDA for Ravicti held by Hyperion Therapeutics) was listed as submitted on November 19, 2013 and posted on 3/10/14 or about 4 months after the original submission. In this case, it is not the length of time the ANDA has been at OGD, but rather the exclusivity and patent issues associated with the product and the jump on first-to-file status that at least one generic firm has decided to seek, especially since the original NDA was approved on February 1, 2013, only 9 months prior to ANDA submission. The second listing that got my blood flowing was for Memantine Hydrochloride extended-release capsules, a generic form of Namenda XR Capsules. There was an approximate 10-month period from submission to acceptance of the ANDA. While that is not the longest review time for completeness and acceptability we have seen, it certainly indicates that either OGD had a difficult time evaluating the ANDA for receipt (maybe bioequivalence issues?) or their backlog could be a factor.

A Little Late, But CMC Annual Reportable Postapproval Changes Guidance Hits the Street

The good news is that there is some regulatory relief for the down-regulation of some changes from supplements to Annual Report notifications; the bad news is that the industry will likely spend as much time figuring out the Guidance and trying to position changes such that they can reasonably be read to be covered by the document as trying to get a Regulatory Project Manager on the phone at OGD.

GPhA Testimony on FDA’s Proposed Label Rule – Hearing Delayed but Democrats Balk

The FDA’s Proposed Rule Supplemental Applications: Proposed Labeling Changes for Approved Drugs and Biological Products occupied the podium time of many speakers at this year’s GPhA Annual Meeting and was clearly on the minds of all attendees. Ralph G. Neas, CEO and President of GPhA, was to testify before the House Energy and Commerce Subcommittee on Health on Monday March 3 to explain just what a detrimental impact on the generic industry the Proposed Rule, as currently written, will have on the generic drug industry, patients, and healthcare providers. Unfortunately, the weather postponed the hearing. An article in Insidehealthpolicy.com today was entitled “Democrats: Concerns About Drug Costs Under FDA Generic Labeling Rule ‘Unfounded’”. Well those Democrats should get off Capitol Hill and get out to the drug companies, the pharmacies, talk to healthcare providers instead of speaking or listening only to the Plaintiff’s bar.

Hydrocodone Combination Products a Step Closer to Schedule II

In a Federal Register Notice that published on February 27, 2014 (see here), the Drug Enforcement Agency (DEA) announced the proposed Rulemaking to place all hydrocodone-containing combination products into the more restrictive Schedule II category from Schedule III of the Controlled Substances Act. This process has been going on for several years and now looks like it will swiftly move towards becoming reality. This move has been hotly debated among consumer groups, healthcare providers, drug abuse experts and the like. FDA held a public advisory meeting in January 2013 to meet the requirement established by one of the provisions of Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA). The Advisory Committee meeting was a compromise reached in FDASIA, as changing the schedule of these products was one thing that the Act’s sponsors had considered. The Committee that was charged with making a recommendation voted 19-10 in favor of the rescheduling effort.

With John Dingell’s Departure from Congress, Maybe it is Time to Reflect on the Generic Drugs Scandal

Some 4+ years after the most successful piece of legislation, the Drug Price Competition and Patent Term Restoration Act (more commonly known as the Hatch-Waxman Act), there was trouble in paradise. In late 1987, some firms noticed that certain applicants began receiving reviews and approvals of their ANDAs faster than they did. A simple investigation lead to evidence of wrongdoing by an FDA employee and lead to a widespread and expanded investigation into the industry, and uncovered wholesale fraud at a number of companies and exposed other FDA employees guilty of wrongful acts. This was the beginning of the Generic Drug scandal, which prompted the investigation of the entire industry by Congressman Dingell and two congressional investigators.

What Can Industry Do to Make their Applications of Better Quality? FDA Wants to Know! But, I Have a Different Question!

I received an email yesterday from FDA (as I am sure many of you have) soliciting suggestions on ways to improve the quality of generic applications. FDA has set up a docket to receive your input and also wants to know the best way to share the suggestions with industry….While I will give the FDA credit for the outreach, I also have to speak up for the industry as well. Over the years the requirements for ANDAs has done nothing but increase and increase, while at the same time FDA has been talking about ways to provide regulatory relief for post approval changes and risk- based review of ANDA and risk-based inspection of facilities.