The issue of when to apply FDA Draft Guidance has always been a bit confusing and sometimes an amusing subject.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 If the Draft Guidance is newly issued and is still within a reasonable comment period, then it may be best to contact FDA to see if the Guidance is likely to change.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 The real problem comes when a Draft Guidance is issued and the comment period has passed and months or years go by where the Guidance just sits there in limbo before being finalized.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.
Are you thinking of making a monoclonal antibody and hoping that your product is different enough than another already approved to gain 7 years of Orphan Drug Exclusivity (ODE)?
Had trouble getting hold of someone at the Office of Generic Drugs (OGD) lately? Just wait until next week! The long awaited OGD move to White Oak starts next week and will stretch over at least three weeks.
As of April 11, 2014, the FDA has received and processed requests for 37 compounding pharmacies as outsourcing facilities. In October 2014, outsourcing facilities will be required to pay a fee. The fee schedule will be published in August 2014, and any facility that registers on or after fees are due will have to pay the registration fee at the time of registration.
On April 10, 2014, FDA responded to a petition from Teva Respiratory LLC approving it in part and denying it in part. Teva requested that FDA refuse to approve any rescue inhaler (generally metered dose inhalers (MDIs) of short-acting beta agonist like albuterol), brand or generic, unless it has a dose counter, and that FDA implement a plan to transition all currently approved rescue inhalers to versions incorporating a dose counter.
Six months into Fiscal Year 2014 and some staggering submission numbers should send a chill up the old OGD spine. So far, this FY OGD has received 597 new original ANDAs based on numbers released on April 11, 2014. That number reflects activity through the end of March 2014. On the other hand, OGD has approved 392 ANDAs in the first 6 months of this FY. So let’s look at the numbers a bit more closely.
OGD approved another “complex” drug product and brings a happy closure to an ANDA submitted in November 2008. By no means a record in terms of length of approval, this ANDA has been percolating for 65 months since submission and represents another in a string of complex products that OGD has tackled and approved. Thus, the first generic for Lovaza will likely hit the market soon as Teva’s ANDA # 091028 for Omega-3 – Acid Ethyl Esters gained approval on April 7, 2014.
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”.
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.
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.