I have been getting lots of calls and questions on my blog post of May 15, 2014 on clarification of the stability guidance particularly on the issue of primary stability batch packaging. Apparently, the Office of Generic Drugs (OGD) has also received e-mails on this issue as well. So to clarify the clarification, here goes!
In a coordinated enforcement action involving the FDA, US Customs and Border Patrol, along with international agencies like Interpol and enforcement and regulatory bodies from 111 countries, action was taken against web sites that “sell unapproved prescription drugs to US consumers.” This is part of an ongoing effort of a program termed Operation Pangea.
An on-site hiring fair is being held in Bethesda as posted on the FDA web page today. So if you are tired of your current job and would like to work at the FDA for a lot less money – then this job fair is for you.
In a petition response issued on May 23, 2014to Hisamitsu Pharmaceutical Company, the FDA partially approved, but mostly denied the requests of the NDA holder for Salonpas (menthol and methyl salicylate 3%, 10%) Patch in a petition submitted on January 6, 2010. While the response did not come as much of a surprise relative to the NDA holders asks, the fact that the petition was submitted in 2010 and is just now being responded to is somewhat a matter of conjecture.
In a May 20, 2014 petition denial to Docket FDA 2013-P-1710 (the second denial on the same subject by the same firm), the FDA made clear that usability studies for transdermal systems are not a requirement for ANDA applicants.
In the Press Briefing Call this morning on the newly revised Q&A document on ANDA stability, three important and significant issues were clarified by the Office of Generic Drugs’ (OGD) Radhika Rajagopalan, Ph.D. that will have important implications for the generic industry.
With about one month to go before the Office of Generic Drugs (OGD) new stability requirements go into effect, a one hour briefing by invitation will be held on May 15, 2014 to discuss the new requirements. It will likely touch on the Draft Questions and Answers Guidance ANDA: Stability of Drug Substance and Drug Products, with (hopefully) an emphasis on any clarifications or revisions that have been made to the final guidance (to be published soon).
The Revised Q&A Guidance on stability for ANDA drug products and drug substances was posted on the CDER web page today (here). While the Agency did a good job in terms of some of the clarifications requested by questions submitted in response to the initial document, there are still some unanswered questions that may require clarification to the clarifications!
On May 13, 2014, the FDA took the third in an unusual series of evaluations to extend the expiration date of certain lots of the drug DuoDote Autoinjectors (atropine and pralidoxine chloride), a drug indicated for the initial treatment of poisoning by organophosphorous nerve agents and insecticides. The manufacturer of the drug product notified FDA of problems relative to under-dosing or failure to activate associated with a small number of its autoinjectors. The FDA responded with a letter (here) indicating that the Agency would exercise enforcement discretion and would, based on information provided by the firm, extend the expiration date for one year beyond the current established expiration date. FDA also noted that the firm would not need to revise the expiration date on the actual packaging.
The issue of when to apply FDA Draft Guidance has always been a bit confusing and sometimes an amusing subject. FDA Guidance (whether in draft or final form) is supposed to represent the FDA’s current thinking on a specific matter. If the Draft Guidance is newly issued and is still within a reasonable comment period, then it may be best to contact FDA to see if the Guidance is likely to change. Sometimes you can look at the comments submitted to the appropriate Docket to see if there appears to be controversial issues raised by the industry or other government components. The real problem comes when a Draft Guidance is issued and the comment period has passed and months or years go by where the Guidance just sits there in limbo before being finalized.
In a (not unexpected) petition denial, the FDA confirmed the statutory requirement that the 5 year New Chemical Entity (NCE) starts on the date of the letter approving the NDA. While this has long been the standard, this case does have a wrinkle that at least two firms, Eisai and UBC, argued in almost identical petition requests. The products in question were substances with abuse potential and also clearly qualified as first time approvals of the drug entity that guaranteed them 5 year NCE. However, because they were controlled substances, there was a need for the Drug Enforcement Administration to formally schedule the product prior to the firms actually being able to market them, even though the firms had final FDA approval in hand.
In a letter issued April 24, 2014 to ANDA applicants for Celecoxib, the FDA explained its rather complicated view of how to treat reissue patents as they relate to 180-day exclusivity and 30-month stays. And, in this case, the FDA did not provide a decision on 180-day exclusivity for any Celecoxib applicant because exclusivity determinations are not made until an ANDA that may be subject to either 180-day exclusivity or may be blocked by such are approved. In the former case, FDA would indicate the eligibility for the 180-day exclusivity, and, in the latter, would issue a Tentative Approval letter indicating that the application (while meeting all other approval requirements) cannot receive final approval due to another applicant being eligible for 180-day exclusivity. As things stand today, there are three firms that have tentative approval letters (Mylan, Teva, and Watson).
The first ANDA for Vivus’s diet drug Qsymia (phenteramine hydrochloride and topiramate) appeared in today’s Paragraph IV new postings. The Paragraph IV database is where first-to-file ANDAs containing Paragraph IV challenges to the reference listed drug are posted. The receipt date reported on the FDA site is July 18, 2013, which is just 6 days more than a year since Qsymia was approved (July 12, 2013).
Qsymia is an extended-release product; thus, the turnaround for generic development, generation of required stability data, conduct of successful bioequivalence studies and putting the ANDA together was almost as much time as FDA took to decide the ANDA was acceptable for receipt (almost 10 months).
For Compounding Pharmacies, there is a new law (Compounding Quality Act) and a sheriff (the FDA) to enforce the law. The new law is an amendment to the Food, Drug & Cosmetic Act (FDCA), which (amongst other things) requires that the drugs must be compounded in compliance with Current Good Manufacturing Practices (CGMP) by or under direct supervision of a licensed pharmacist in a registered facility.
Under this new law, some compounding pharmacies will be categorized as “outsourcing facilities”. Those pharmacies that compound sterile drugs, among others, must register with the FDA as an “outsourcing facility”.
Just when you thought you got it all done, it is time to do it all over again. FDA announced that the new self-identification for facilities named in a generic drug application will begin again soon.