FDA Lawyers Blog

FLH Partner Brian J. Malkin will speak at a pre-conference for ACI's Paragraph IV Disputes Conference on April 26, 2010. He will present A Primer on IP & Regulatory Fundamentals: Patent and IP Overview for Drugs and Biologics: Hatch-Waxman, Trade Dress, and More. Mr. Malkin's presentation will feature an overview of the new Biosimilars Act. The event is co-sponsored by FLH and co-chaired by FLH Partner Barry S. White. A program brochure is here.

by Charles J. Raubicheck

At the April 23 session of the Food and Drug Law Institute's (FDLI's) annual meeting, FDA Commissioner Margaret Hamburg confirmed that the Obama administration is committed to more vigorous enforcement of FDA laws and regulations, even beyond warning letters. FDLI posted on its website a summary of the meeting from its publication, FDLI Update, here.

This theme was echoed at the conference by FDA's Deputy Chief Counsel Rick Blumberg, who emphasized that the agency would be more active in instituting criminal prosecutions. Such cases are governed the strict liability standard, where a responsible corporate official's lack of personal knowledge of an FDA violation is not a defense to criminal liability.

A recent example of stepped-up FDA enforcement is a consent judgment obtained by the agency against Steris Corporation. The company agreed to stop selling an unapproved medical device used to disinfect endoscopes and other heat-sensitive devices. Steris further agreed: (i) to transition to an alternative FDA-approved sterilization device, (ii) to offer customer rebates, and (iii) to destroy used product inventory.

by Brian Malkin

On April 21, FDA announced draft guidance for public availability of advisory committee members' financial interest information and waivers. FDA is advised by almost 50 committees with more than 600 members that provide advice--but do not make decisions--on specific regulatory topics or proposed product approvals. Some meetings have the need for special members with expertise that may have financial conflicts of interest. By law, FDA can grant waivers for such conflicts for about 13% of advisory committee members but reportedly only grants waivers for less than 5% of the members.

The guidance differs from previous agency procedures by not only disclosing that a waiver was granted for a financial interest but also providing the name of the company or institution associated with the financial interest and posting this information on the Internet at least 15 days prior to committee meetings (or as soon as practical if FDA is aware of the information less than 30 days prior to the meeting). FDA must broadly provide FDA's rationale for the waiver--(i) the financial interest is not substantial enough to affect the member's integrity, (ii) the need for the member outweighs the potential for conflict, or (iii) the member's service is necessary to provide the committee essential expertise. The guidance also places would-be advisory committee members on notice the type and extent of information that will be provided to the public.

In mid 2009, FDA held a meeting to solicit comments for ways to increase FDA transparency and currently has a task force making recommendations, posting transparency blogs, and held three additional industry listening sessions in March 2010. FDA has an ongoing task force looking for ways to provide additional information to the public, while protecting confidential information as needed.

FLH partners Charles J. Raubicheck and Brian J. Malkin will be attending the upcoming Food and Drug Law Institute's Annual Conference on April 22-23, 2010 in Washington, D.C. The Conference is scheduled to include updates from all of FDA's centers, including major addresses by FDA Commissioner Margaret A. Hamburg, M.D., FDA's Chief Counsel, Ralph S. Tyler and FDA's lead regulators and enforcement officials.

On April 21, 2010, FLH Partner Brian J. Malkin presented a Post-Conference Workshop - Manufacturers' Working Session - Preparing for and Implementing a REMS (Risk Evaluation and Mitigation Strategy). Mr. Malkin will step in for the scheduled speakers and has developed the presentation for the American Conference Institute's first REMS conference on this topic. The program brochure is here.

by Andrew S. Wasson

On April 14, The Federal Circuit held in Novo Nordisk A/S v. Caraco Pharm. Labs., Ltd. (Fed. Cir. 2010) that Caraco could not compel Novo Nordisk to modify the "patent use code narrative" associated with U.S. Patent No. 6,677,358 ("the '358 patent"), listed in the Orange Book for Prandin® (repaglinide). The '358 patent recites a method for the combined administration of repaglinide and metformin. Caraco submitted its ANDA with a "section viii statement", stating it would not infringe the patent because it had "carved-out" the uses associated with the '358 patent. FDA will approve a "section viii statement" if there is no overlap between the description of the patent scope given by the NDA holder (a "use code narrative") and the proposed ANDA labeling. FDA assigns each use code narrative a "use code number", which is then listed in the Orange Book.

Novo Nordisk originally submitted a description of the '358 patent: "use of repaglinide in combination with metformin to lower blood glucose" (U-546). However, Novo Nordisk later requested that the FDA change the use code narrative to read: "a method for improving glycemic control in adults with type 2 diabetes mellitus" (U-968). While Novo Nordisk's request followed a labeling change initiated by FDA in November 2007, it also came immediately after FDA's approval of Caraco's section viii statement with regard to the initial use narrative.

While FDA originally approved Caraco's section viii statement based on U-546, FDA eventually disallowed Caraco's section viii statement based on U-968. In a counterclaim, Caraco requested the court change the use code from U-968 to the original U-546. The district court granted Caraco's request in summary judgment, finding that Novo Nordisk filed an improperly overbroad use code narrative.

by Charles J. Raubicheck

At an April 13 meeting, FDA's Advisory Committee for Pharmaceutical Science and Clinical Pharmacology discussed tighter bioequivalence standards for generic formulations of certain extended-release drugs. The dialogue centered on requiring a demonstration of bioequivalence for partial areas under the curve (AUC), at time intervals when onset of delivery of the active drug ingredient is necessary for early clinical response. For such drugs, in addition to total AUC, bioequivalence would be measured at 3 hours after administration under fasting conditions, and at 4 hours following administration under fed conditions. Such tighter bioequivalence measurements could result in larger subject populations to achieve target confidence intervals.

This approach has been referred to in the industry as "matching the drug delivery curve." The specific drugs mentioned were Concerta® and Ambien CR®. Johnson & Johnson, manufacturer of Concerta®, has requested FDA to take this action in a pending citizen petition.

by Brian Malkin

On April 5, FDA approved a new tablet formulation of OxyContin®, a controlled-release form of oxycodone hydrochloride, which is a potent opioid to relieve pain that may also provide euphoria in higher doses and be abused. OxyContin® contains a large quantity of oxycodone that is released over time. The previous formulation could be easily crushed or chewed or injected to release more drug faster, leading to more euphoria and possibly death, if ingested in high doses.

FDA views the new formulation as only an "incremental" improvement because abusers can simply take more of the drug to provide euphoria. In other ways, the new formulation is a vast improvement, because the tablet is not easily cut, broken, chewed, or crushed and contains a substance that results in a gummy solution that cannot be drawn into a syringe and injected, if an individual attempts to dissolve the tablet in solution. FDA required a risk evaluation and mitigation strategy (REMS) for the new formulation and the manufacturer, Purdue Pharma L.P. (Purdue), is required to conduct a post market study to determine whether the new formulation reduces abuse and misuse. Previously, Purdue pled guilty and paid a fine for over-promoting OxyContin®, including various off-label uses or dosage amounts of the product that led to additional abuse and misuse of the product.

by Brian Malkin

On March 31, U.S. Marshals, acting at FDA's request, seized a variety of consumer products manufactured by a Wisconsin manufacturer of dietary supplements, creams, capsules, tablets, throat sprays, and shampoos. FDA had issued the manufacturer, Beehive Botanicals Inc. ("Beehive"), a warning letter on March 2, 2007, following an inspection conducted in November 2006. FDA's letter provided Beehive with examples of its products that were identified misbranded drugs, devices, and dietary supplements based on their labeling and ingredients and requested a response with an explanation of corrective measures within 15 days. The labeling and promotional materials included claims for "antibiotic, antiviral, and antifungal properties" as well as claims related to the treatment or prevention of cancer, liver or kidney disease, insomnia, bone fractures, and skin disorders. Beehive submitted proposed new labeling for its products that the agency reportedly found acceptable.

During a subsequent inspection between September and October 2009, however, FDA found that drug claims were still being made through related websites and advised Beehive that this was not acceptable. Ultimately, FDA brought the seizure action to make it clear that FDA was serious about its concerns. FDA issued a news release on April 5, including a quote from FDA's Acting Associate Commissioner Regulatory Affairs, Michael A. Chappell, stating: "The seizure shows that the FDA will seek enforcement action against companies that promote therapeutic benefits of products not yet evaluated by the agency for safety and effectiveness."

Postscript: Following the seizure, FDA sued Beehive, resulting in a consent decree enetered on May 14 that prevents Beehive from marketing any new drug unless done in accordance with federal law. Beehive must hire an independent consultant to inspect its products' labelings to certtify that corrections have been made. FDA will continue to monitor and may bring a contempt action against Beehive for any continuing violations.