Ever since I began my career at FDA in 1985 and straight through until today, I have heard the Agency criticized for failing to respond to patients needs regarding to access to new life saving treatments. There are new initiatives being discussed relative to patient’s ability to access new and unapproved treatments for serious, life threatening conditions, but the same arguments of ethics still hang visibly on each side of the issue. Over the weekend, I stumbled across something I had not seen before on the CDER web page; it was a link to the Expanded Access Submission Receipts Report.
While the number of new molecular entities (NME) filed in 2013 (a subset of all NDAs filed) was lower than in 2012 (36 vs 41), there are some interesting facts associated with how CDER did on approvals. For instance, of the 36 NMEs filed in 2013, FDA approved 27. This compares with 39 of the 41 submitted in 2013.
In a blog post on August 12, 2014, I raised the question of why there have been so many recalls of parenteral products related to visible particulate matter. There are a multitude of factors that lead to the formation of particulate matter, some of which have to do with formulation, some with storage, some with handling, some with manufacturing equipment and the like as was discussed in the blog referenced above.
As part of its GDUFA commitments the FDA has issued a Draft Guidance entitled Guidance for Industry – Controlled Correspondence Related to Generic Drug Development. FDA makes clear in this document that controlled correspondence (CC) does not include Citizen Petitions, petitions for reconsideration or stay requests.
The FDA’s paragraph IV (PIV) database is designed to give applicants and potential applicants information relative to first-to-file opportunities. FDA does this for two reasons: 1) it gives applicants assurance that their product is a first-to-file if the acknowledgement date (date acceptable for filing) on their letter from FDA officially receiving their application matches the date of submission in the PIV database. This has eliminated the many calls to the Office of Generic Drugs (OGD) to find out if their submitted application holds a potential first-to-file seat; 2) the listing also informs potential applicants that at least one ANDA has been submitted with a PIV certification and allows others to decide if they wish to enter the fray and expose themselves to litigation.
Over the last few days, FDA has posted information on new and updated drug shortages with 6 new shortages listed over the last week. We have noted the problems that drug shortages create in previous posts and we have all followed the media accounts of the problem; however, it still seems that, while many of the causes of drug shortages have been identified, stopping them from happening in the first place appears to be more elusive than any regulation, required notification or interaction with regulatory bodies can resolve.
With what seemed like the entire industry trying to beat the June 20, 2014 submission deadline ahead of the ANDA new stability requirements set to take effect that day, a record of 635 ANDAs were submitted in June. Now it looks like there will be some reload time before OGD sees the normal flow of ANDAs coming in.
Last week while waiting for my flight home at an airport on the east coast, I decided to look at the recalls listed on the CDER web page. I realize that I have read about a number of recalls of parenteral products recently and those recalls were for a number of different firms, but what caught my attention was that 12 of 25 recalls listed were for visible particulate matter (including glass particles).
While I am not a manufacturing expert by any stretch of the imagination, I started to wonder why this might be.
Having heard about an important announcement made by OGD last week, I was fortunate enough to receive a copy of an internal email issued by Cook from the CDER trade press office. I read it once, and then reread it about 5 more times. “More changes at OGD” was the bottom line message, and then a question popped into my head. Is this message good news? If it results in more consistent actions coming out of OGD quicker, the answer is yes!
The 2 new MaPPs: 5200.4 Criteria and Procedures for Managing the Review of Original ANDAs, Amendments and Supplements and 5240.3 (a revision of the old 2006 MaPP entitled Review Order of Original ANDAs, Amendments and Supplements) Prioritization of the Review of Original ANDAs, Amendments and Supplements were released today by FDA. These two MaPPs describe how the Office of Generic Drugs (OGD) will prioritize review of ANDAs.
Although Office of Generic Drugs (OGD) total activity numbers (including issuance of Complete Response Letters (CRLs), etc.) will not be posted until about 2 weeks after the close of the month, it is disappointing that the number of approvals this late in the month appears only in the teens.
While there are many things going on at OGD (training of new staff, Guidance and Policy development, the reorganization to a Super Office, among other important things) the bottom line for industry is the number of approvals that OGD issues and the number and timeliness of OGD deficiency responses it receives. But approvals rule the roost in terms of industry importance because, after all, you cannot sell products that receive CRLs.
In previous post earlier this week, we were hoping to discover the Agency position on this particularly important issue. Thus, the Agency has decided to make a bright line of June 20, 2014 as the start date for the requirement for 3 batches with 6 months room temperature and 6 months of accelerated stability at time of original submission.
The Office of Generic Drugs’ (OGD) elevation to a Super Office in the Center of Drug Evaluation and Research has come at a challenging time for the Generic Drug Program. The new Office structure is presented below and represents a dramatic organizational change to us old timers. But this is progress and represents the need to move the program in a different direction for today’s environment.
If you are one of the about 600 ANDA applicants submitted in the first 19 days of June, or have one of the additional ~ 100-200 ANDAs that have not yet received notification of acceptance for ANDAs submitted prior to June 2014, a decision is expected soon on what stability requirements you will need to meet upon resubmission.
With 9 months gone in FY 2014 and the June Generic Drug Activity Report just released, things don’t look so good! The June ANDA submissions not only beat any previous one-month total ever, but shattered the previous record by almost 275%. The big problem when looking at the numbers in the Activity Report is not only seen in the number of ANDAs submitted, but also in the disturbing trend in the numbers in general.