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.
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.
In a follow-up to my post on this issue early this morning, GPhA announced that 21 pharmacy groups were signatory to a letter to Commissioner Margaret Hamburg, imploring her to reconsider the Proposed Rule on labeling changes in its current form.
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.
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.
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.
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.
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.
Then FDA is looking for you! The implementation of the Generic Drug User Fee Act (GDUFA) has created about new 930 positions in the Center for Drug Evaluation and Research (CDER). With first year hiring over, there are still about 600 positions left to fill and FDA is aggressively recruiting.
At a Pharmaceutical Quality Assessment Workshop held in October 2005, Janet Woodcock, MD, Director, Center for Drug Evaluation and Research (CDER), spoke about CDER’s Vision: “A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products without extensive regulatory oversight.” CDER’s Vision was considered the desired state after the successful implementation by a manufacturing firm in accordance with FDA’s Initiatives: Pharmaceutical Quality for the 21st Century (initiated in 2004). In order to meet the Agency’s vision and ultimately, the desired state, FDA envisioned firms moving forward to establishing an effective pharmaceutical quality system, adopting a “Quality Culture”, proactively monitoring products and processes using risk-based approaches, ensuring a stable supply chain and investing in continuous improvement.
