Virtual Companies Beware – FDASIA Ratchets Up the Heat

In 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) inserted a statement into Section 501(a)(2)(B)of the Food, Drug and Cosmetic Act that expanded the meaning of current good manufacturing practice (cGMP). FDASIA’s legislative history tells us that one intention was to require drug manufacturers to employ adequate controls over the materials they purchase. Most would agree that the hazards of unsafe materials justify the need for effective controls and oversight by manufacturers, and most companies are well aware of their responsibility to oversee safety and quality of materials used for manufacturing. FDA’s web page describing FDASIA promises that requirements of the enhanced 501(a)(2)(b)will be reflected in revised CGMP regulations. FDA’s 2014 Regulatory Agenda targets November for issuing a proposed rule. However, enforcement has already begun, and virtual companies are a target.

OGD Seeking Comments on How to Improve ANDAs

In a Federal Register Notice to publish on January 23, 2014, OGD is seeking comments and suggestions on how to improve the quality of submitted ANDAs and associated amendments to those applications. In addition, OGD is asking about what specific difficulties firms are having when preparing their ANDAs, so that FDA might help “provid[e] more or better information” to industry.

FDA Moves to Finalize Plans to Limit Acetaminophen in Prescription Combination Products

Three years has come and gone since FDA published its Federal Register Notice (here) requiring drug companies to reformulate their acetaminophen (APAP)-containing combination drug products to contain no more than 325mg of APAP per dosage unit. FDA gave manufacturers three years to make the change or face withdraw of approval of their applicants. In an announcement posted at the very end of the day yesterday, FDA gave final notice that “[I]n the near future we intend to institute proceedings to withdraw approval of prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit that remain on the market.”

Let’s Clean This Up!

Today, FDA announced the issuance of a 137 page Proposed Rule designed to investigate whether antibacterial hand soaps are any more safe or effective than washing with simple bar soap. FDA is taking this action to evaluate the safety and effectiveness of these products due to the continued concern about the potential development of bacterial resistance from the widespread use of these agents. The Proposed Rule does not cover does not cover hand sanitizers, wipes or antibacterial products used in the healthcare setting. Rather, it is targeted towards the multitude of bar and liquid soaps used by consumers in routine daily hand and body washes that are advertised as, and contain an antimicrobial agent.

Getting Ready for October 1, 2014 – the Reality Check is Coming!

Having previously written about the need for Generic companies to step up the quality of their submissions to avoid refuse-to-receive (RTR) letters as well as avoiding time review penalties for major amendments or multiple minor or unsolicited amendments, I must take a moment to perform a reality check on what happens when the Generic Drug User Fee Act’s (GDUFA) metric kick in on applications submitted after October 1, 2014. As we know, there are no metrics for ANDAs submitted in years one and two of GDUFA; however, years three through five must be looked at with intense scrutiny in light of the good, the bad and the (potentially) ugly aspects of the metrics themselves.

The Issue of Functionality – And a New Draft Guidance Hits the Street

Ever since the implementation of the Generic Drug User Fee Act (GDUFA), Guidance documents are flying out of FDA and landing faster than the planes at Atlanta’s busy Hartsfield airport. One such Draft Guidance was posted yesterday on the FDA web site (here) entitled Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules. While the specific issue addressed in this Guidance is clear, the general issue of something I like to call “functionality” is now being formally addressed through Guidance documents, as opposed to deficiency letters.

New Revised Bioequivalence Guidance Clarifies Requirements

FDA issued a newly revised Draft Guidance entitled Bioequivalence Studies with Pharmacokinetic Endpoints for Drug Submitted Under an ANDA. The new Guidance document is specific to abbreviated new drug applications (ANDAs) and combines part of two previous guidance documents on general bioequivalence (BE) and BE for fed studies for ANDAs. The document does not address bioavailability (BA) or BE for investigational new drug applications (INDs) or for studies required to support BE for new drug applications (NDAs).

First Nuvaring Generic Equivalent Filed with a Paragraph IV Certification

Appearing on the FDA’s Paragraph IV database listing on December 3, 2013 is an ANDA filing for Ethinyl Estradiol and Etonogestrel drug-emitting polymeric ring that is used as a contraceptive to prevent pregnancy. What caught my eye and what it interesting about this product is that it is the first of a kind ANDA for an intravaginal contraceptive product of this nature. In addition, its posting date (December 3, 2013) and the ANDA submission date listed as June 17, 2013 (see chart below) suggests that either OGD has a very extensive backlog of ANDAs to process, or that this application presented some unique issues of either bioequivalence or chemistry manufacturing and controls that had to be resolved prior to a decision to receive (file) the application. My guess is that it might be the latter, since OGD has said it was expediting initial completeness and acceptability reviews of ANDAs with Paragraph IV certifications (indicating a challenge to the patent listed for the reference listed drug).

The Hardship of GDUFA Facility Fees

Since the implementation of the Generic Drug User Fee Act (GDUFA), many small facilities have complained about the establishment and facility fees being assessed under the Act. Unlike the Prescription Drug User Fee Act (PDUFA) where establishment (facility fees) are not due or paid until after the respective new drug application (NDA) is approved, GDUFA requires yearly payments of the facility fee while the abbreviated new drug application (ANDA) is pending. With median approval times at about 34 months, that may mean that 3 or more facility fees may be due prior to application approval. At the current rate of $220,152 for domestic facilities and $235,152 for foreign facilities, that could mean close to $700,000 in fees that a facility may have to pay prior to approval of an application that it is named in.