FDA Lawyers Blog

On April 1, FDA provided a combined response to three citizen petitions concerning the regulation of over-the-counter ("OTC") nicotine replacement therapy ("NRT") drug products. The petitions were submitted by the Commissioner of Health, New York State Department of Health (Docket No. FDA-2008-P-0116), the Director, Legal Resource Center for Tobacco Regulation, Litigation & Advocacy, University of Maryland Francis King Carey School of Law on behalf of the Association for the Treatment of Tobacco Use and Dependence ("ATTUD") and the Society for Research on Nicotine and Tobacco ("SRNT") (FDA Docket No. FDA-2008-P-0116), and four not-for-profit organizations, the American Cancer Society Cancer Action Network, the American Lung Association, the Campaign for Tobacco-Free Kids, and the American Legacy Foundation (FDA Docket No. FDA-2010-P-0454). For additional background on this topic generally, please see an earlier blog that we posted here about a NRT workshop that FDA held in October 2010 addressing the topics in these petitions.

Written by Brian J. Malkin

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The petitioners asked FDA to consider modifying the labeling of OTC NRTs, certain policy changes, and allowing greater access to the products. While the requests varied, a common theme was that the petitioners wanted consumers to have greater access to NRTs in smaller packages that would permit more flexible use of the products, other than the typical up-to-12-weeks smoking cessation program scenario contemplated by the clinical studies that supported the use of these products. For instance, some of the petitioners suggested that the labeling should include additional risk/benefit information concerning NRTs versus continued cigarette (or other tobacco product) use, including possible concomitant use of cigarettes and NRTs, as well as longer-term NRT use to reduce and perhaps ultimately eliminate an individual's cigarette use. The not-for-profit petitioners wanted FDA to make the development of NRTs a priority within FDA, including certain collaborations with manufacturers of NRTs, such as the development of appropriate trial designs, and to transfer evaluation of NRTs from FDA's drug division for addiction drug products to its division for oncology drug products.

Earlier this week, the U.S. Supreme Court denied GlaxoSmithKline's certiorari petition in a case that would have helped clarify the scope of 35 U.S.C. § 271(e)'s safe-harbor provision. The issue facing the Court was whether section 271(e)(1) applies to postmarketing activity as well as premarketing activity.

Section 271(e), which states that it is not an act of infringement to make, use, offer to sell, or sell a patented invention "solely for uses reasonably related to the development and submission of information under [federal drug laws]," does not include a time limitation. The question about timing was highlighted in two recent Federal Circuit cases. In Classen Immunotherapies, Inc. v. Biogen Idec, 659 F.3d 1057 (Fed. Cir. 2011), the Federal Circuit explained that "§ 271(e)(1) is directed to premarketing approval of generic counterparts before patent expiration." Last year, however, a different panel of judges in Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc., 686 F.3d 1348 (Fed. Cir. 2012) held that post-approval studies performed for the FDA fall within § 271(e)(1)'s safe harbor and explained that Classen held that 271(e)(1) "does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."

Written by Scot B. Pittman

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As previously blogged on here, the Solicitor General had urged the Supreme Court to deny GSK's petition in the Classen case. Despite a belief that the Federal Circuit erred in Classen, United States Solicitor General Donald Verrilli offered the following reasons why the Supreme Court should deny certiorari: (1) the Federal Circuit's Momenta decision sufficiently clarified and narrowed the Classen holding; (2) it was unclear whether the safe harbor applied to the types of patents at issue in the Classen case; and (3) the petitioners were not entitled to the safe harbor protection regardless of the Supreme Court's interpretation of the provision.

On January 2, 2013, barely three months after FDA's new user fee programs go into effect, certain mandated spending reductions, called sequestration, also may go into effect that could prevent FDA from using the user fees it collects from industry. A Congressional Super Committee failed to find the required $1.2 trillion in cuts over ten years by a November 2011 deadline. The combined effect of lost taxpayer and user fees projected by Maryland-based Alliance for a Stronger FDA, would be an initial $294 million out of a $3.65 billion budget.

The catch comes from a component of FDA's user fee programs known as the "trigger" that requires a certain baseline of taxpayer funds to go to FDA, so industry user fees supplement rather than fund FDA's operations. FDA's projected funding for fiscal year 2013, set at $2.5 billion, would be cut by an across-the-board, 8% cut in federal government, coined as a "fiscal cliff", imposed to help curb the ever-increasing government debt. While FDA's cut of about $200 million would not normally hit the trigger to prevent FDA's use of user fees, Steven Grossman, Deputy Executive Director of the Alliance for a Stronger FDA, told Anna Edney from Bloomberg that the Obama Administration may still sequester FDA's user fee funds to help with federal spending reduction goals. The exact trigger levels, moreover, are based on formulas that include consumer inflation and past spending, which so far FDA has declined to comment on.

Written by Brian Malkin

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According to Grossman, if this occurs, about $68 million in drug and device user fees and $40 million in tobacco-company payments would be diverted to a U.S. Treasury Department account that would "reduce government because it would reduce what they can do." Faced with the sudden loss of these funds, drug industry experts have speculated that FDA would be forced to lay off personnel and take other measures to reduce costs.

On April 24, at the Food and Drug Law Institute's ("FDLI's") 55th Annual Conference 2012, reflecting on history of the FDA and FDLI, FDA Commissioner Margaret A. Hamburg, M.D., noted that dating back to the first FDLI/FDA informal conference back in 1957, FDA continues to regulate an "enormous scope" of products with a continuing need for more resources. Hamburg said that FDA is now at a "turning point"--there is a need to develop medical countermeasures for biological threats either natural- or terrorism-oriented, such as new antibiotics, and there are needs for new product such as treatments for type II diabetes and obesity. At the same time FDA is poised for various riders expected to be added to the four user fee bills presented to Congress. Some of those riders include new provisions for accelerated approval, increased authorities for FDA to regulate products or component of products made overseas (e.g., 85% of the active ingredients are manufactured outside us and 40% drug products are made outside the United States), increased monitoring for drug shortages, and strengthening FDA's rare disease program. Hoping to create a "brand" for FDA, Hamburg said there is a need for stronger and more sophisticated science to help bolster reliance by the world on FDA's decision-making as the "gold standard."

Following Hamburg, three of FDA's relatively-new Deputy Commissioners discussed key issues confronting each of them. Michael R. Taylor, Deputy Commissioner for Foods, said that he believes resource allocation is important. Taylor's key issues include antimicrobial resistance, nutrition labeling, nanotechnology, chemical contaminants, a new strategic plan for foods and veterinary medicine, and executive leadership management--all with a need to involve stakeholders in the process. Stephen P. Spielberg, M.D., Deputy Commissioner for Medical Products and Tobacco, said that he is excited to be working at FDA at a time when the medical community is better understanding the causes of diseases. He is looking at the potential for more synergies between the centers and also looking at his own responsibilities, including how to help prevent children from initiating smoking and becoming addicted to nicotine. Deborah M. Autor, Deputy Commissioner for Global Regulatory Operations and Policy, said she is interested in "leap frogging" and developing an enterprise management where domestic and foreign inspection are handled the same in an increasingly global environment with statutes and regulations drafted with domestic manufacturing primarily in mind. Autor is hoping that manufacturers take a better look at the supply chain and components that go into their products, while developing better risk analytics to maintain quality.

Written by Brian Malkin

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Following a discussion on FDA regulatory science and a lunch session highlighting FDLI's new upcoming conference in Brazil, each of the FDA centers presented their outlooks for the upcoming year. Presenting for the Center for Drug Evaluation and Research ("CDER"), Deputy Center Director, Douglas C. Throckmorton said that a key priority will be to finalize and implement the requirements of FDA's requested user fees. CDER plans to fill a number of key senior leadership position: an additional Deputy Center Director and directors for the Office of Generic Drugs, the Office of Biostatistics, the Office of Clinical Pharmacology, and the Office for Surveillance and Epidemiology. In addition,

FLH Partner Brian Malkin will attend the Food and Drug Law Institute's ("FDLI's") Annual Conference in Washington, D.C. on April 24-25. For 55 years, FDLI's Annual Conference has been considered the venue for food and drug law lawyers and professionals to hear from FDA and industry about new and emerging topics covering all the products FDA regulates. FDLI has reported that this year's event is expected to draw more than 600 attendees, who will hear directly from FDA's key leaders including Commissioner Margaret Hamburg; Deputy Commissioners Deborah Autor, Stephen Spielberg, and Michael Taylor, various representatives from FDA's six product Centers; newly-appointed Chief Counsel Eliabeth Dickinson, as well as a number of former Chief Counsels. An updated agenda is available here.

FDA Lawyers Blog is a Media Partner of FDLI's 55th Annual Conference. Prior to FDLI's Annual Meeting, Mr. Malkin will participate in a FDLI Monograph Committee Meeting on April 23 and will be working out of Frommer Lawrence & Haug LLP's Washington, D.C. office next week. Mr. Malkin looks forward to seeking you and catching up at FDLI's Annual Conference this year.

For more than 50 years, the Food and Drug Law Institute's ("FDLI's") Annual Conference has provided the venue for food and drug law professionals to discuss and debate emerging topics, as well as participate in valuable education programs. At this year's event, more than 600 attendees will hear directly from FDA leadership including Commissioner Hamburg; Deputy Commissioners Autor, Spielberg, and Taylor; representatives from FDA's six product Centers; Chief Counsel Dickinson and former Chief Counsels.

Programming at the Conference addresses a range of topics including: regulatory science; global developments and emerging markets; economic, legal and regulatory challenges of innovation; social media and mobile apps.

Join FDLI for the largest networking opportunity for food and drug law professionals. We look forward to seeing you at the 2012 FDLI Annual Conference next week.

FDA Lawyers Blog is a Media Partner of FDLI's 55th Annual Conference.

by Brian Malkin

On March 7, FDA announced in a Request for Comments in the Federal Register a two-day public hearing to obtain feedback and suggestions regarding ways that FDA can modernize its regulations, policies, and practices that apply to the conduct of clinical trials for FDA-regulated products. FDA hopes that with this input it can modernize the regulatory framework that govern clinical trials and form approaches for good clinical practice ("GCP") providing for greater effectiveness and efficiencies in the process.

FDA explained in its Request for Comments that FDA's clinical trial regulations are now more than twenty-five years old and has been showing its age. In the past years, clinical trial management has changed dramatically, including increased size and complexity of clinical trials, increased number of clinical trials performed globally, greater use of contract research organizations ("CROs"), increased participation of "vulnerable" populations (children, individuals with orphan-designated diseases, others), and numerous scientific and technological advances, including increased use of the Internet. FDA has learned in various forums that FDA's current regulations and compliance policies may not facilitate the use of innovative methods to improve clinical trial quality, the Request for Comments observes. For example, CROs or other clinical investigators may continue to use older data collection methods given the uncertainties involved in using new procedures that may not be aligned with FDA's older guidances and recommended procedures.

FDA said that its focus is on good clinical practice, including enhanced clinical protocol design to take advantage of newer technologies to ensure reliability of data, safety surveillance reporting, quality control processes including auditing, data integrity, and human subject protection. FDA is interested in workshops or strategic alliances that may help to encourage the implementation of innovative methods in clinical trials including risk-based methods in the design, oversight, and conduct of clinical investigations.

by Howard E. Rosenberg, Ph.D.

The recent editorial in the British Medical Journal ("BMJ ") by Richard Lehman and Elizabeth Loder, highlights the authors' grave concerns about missing clinical trial data, data which by now should have been published. This lack of information is perceived in the editorial as being a distinct threat to the integrity of evidence-based medicine.

As the authors point out, clinical research aims to reduce clinical uncertainty by performing experiments on groups of people who consent to run the risks of such trials in the belief that the resulting knowledge will benefit others. Their concern was voiced particularly after the publication of a study in the BMJ by Andrew Prayle, Matthew Hurley and Alan Smyth, which examined the compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the Food and Drug Administration Amendments Act ("FDAAA") legislation.

The study by Prayle et al. takes as its premise that the key principle in the good conduct of clinical trials is that a summary of the trial protocol should be freely available while the study is ongoing and that, on completion of the study, the results should be readily accessible to all in a timely fashion. As they point out in their paper; in February 2000 the Food and Drug Administration Modernization Act ("FDAMA") prompted the creation of a national clinical trials registry in ClinicalTrials.gov. FDAAA required the registration of summaries of trial protocols for "applicable clinical trials" (i.e., clinical trials that are covered by the FDAAA). These are clinical trials that (1) have at least one site in the United States, (2) are of a drug, device, or biological agent; and (3) are "initiated or ongoing as of September 2007," excluding phase I studies and early feasibility trials of devices.

by Brian Malkin

On December 16, a group of Senators sent FDA a letter urging FDA to prohibit the use of flavorings in cigars. The letter was signed by Senator Frank Lautenberg (D-N.J.) joined by Senators Dick Durbin (D-Ill.), Sherrod Brown (D-Ohio), Jeff Merkley (D-Ore.), and Richard Blumenthal (D-Conn.).

According to the letter, more than 13 million Americans smoke cigars, including an estimated 1.8 million high school students and 475,000 middle school students. Unlike cigarettes, which FDA regulates under the 2009 Family Smoking Prevention and Tobacco Control Act ("the Act"), FDA has so far chosen not to regulate cigars as "tobacco products."

Cigars and little cigars or "cigarillos" are like cigarettes because they contain tobacco and are intended to be smoked, so they arguably contain the same ingredients that were described in the Act as "inherently dangerous and cause cancer, heart disease, and other serious adverse health effects" and are addictive because they contain nicotine, "an addictive drug." Another purpose of the Act was to reduce smoking by "young people," including minors, who may be tempted to smoke, particularly when tobacco products contain non-tobacco-type flavors.

by Erin A. Lawrence

On November 9, 2011, U.S. District Court for the District of Columbia, Judge Richard Leon, ruled that it is likely that tobacco companies will succeed in their lawsuit to block the new graphic warning labels proposed by FDA. Tobacco companies were supposed to begin distributing cigarettes with the FDA's graphic package warnings on October 22, 2012. However, pursuant to Judge Leon's decision, the companies will no long have to meet this requirement at least until the lawsuit is decided. (See our most recent blog on this topic here).

The tobacco companies did not challenge FDA's proposed textual warnings; they only opposed the graphical warnings. The tobacco comanies argued that the warnings are unconstitutional, because they do not simply convey facts to inform people's decision whether to smoke. Instead, the labels force the companies to display the government's anti-smoking advocacy and, therefore, violating their first amendment rights by compelling speech.

FDA argued that the public interest in conveying the dangers of smoking outweighs the companies' free speech rights. FDA said Congress gave it the authority to require the new labels because existing warnings dating to 1984 were going unnoticed and, therefore, health warnings were not being conveyed effectively.

by Kyle Deighan

On September 16, FDA argued that its required graphic warnings on cigarette packages next year should not be blocked by a preliminary injunction because the tobacco companies' free speech rights would be outweighed by the public interest in disclosing the dangers of smoking.

In June, FDA mandated that labels showing graphic warnings about the risks associated with smoking appear on packs of cigarettes. The labels show images such as a sewn-up corpse, a man smoking through a hole in his throat, and a picture of a black diseased lung. The pictures are accompanied by warning messages regarding smoking, such as "Cigarettes are addictive" and "Smoking can kill you." Cigarette-manufacturers are required to print the labels on the top-half of cigarette packs, both front and back. Additionally, the warnings must occupy at least 20% of each cigarette advertisement. According to an FDA timeline, cigarette manufacturers are not allowed to distribute cigarettes in the U.S. after October 22, 2012 without the required warnings.

Tobacco companies, including R.J. Reynolds Tobacco Co. and Lorillard Tobacco Co., filed suit against FDA in August in the U.S. District Court for the District of Columbia. The tobacco companies argued that the labels violate their free speech rights, force them to engage in anti-smoking advocacy for the government, and will cost them millions of dollars. They also argued for a preliminary injunction to stop the labeling requirement while the free speech suit is decided. A representative of the companies stated: "The notion that the government can require those who manufacture a lawful product to emblazon half of its package with pictures and words admittedly drafted to persuade the public not to purchase that product cannot withstand constitutional scrutiny."

by Erin A. Lawrence

The 2009 Family Smoking Prevention and Tobacco Manage Act calls for color warnings covering the top half of the front and back panels of cigarette packages. Under the Act, each cigarette package and advertisement must bear one of nine textual warnings. Tobacco companies want to put a stop to these new graphic warnings. Four of the five largest U.S. tobacco companies sued the federal government on Tuesday, August 16, 2011 saying that the newly required warnings violate their First Amendment free speech rights. The companies included R.J. Reynolds Tobacco Company, Lorillard Tobacco Company, Commonwealth Brands, Inc., Liggett Group LLC, and Santa Fe Natural Tobacco Company ("the tobacco companies"). The tobacco companies filed the lawsuit in the U.S. District Court for the District of Columbia.

In June 2011, FDA released nine graphic warnings that must be prominently displayed on every cigarette package in the United States by September 2012. By October 2012, cigarette manufacturers will be banned from distributing cigarettes without the required warnings. FDA feels that these warnings are necessary because "[t]obacco use is the leading cause of premature and preventable death in the United States, and claims over almost half a million lives each year." FDA also states that "[r]equiring larger, more prominent warnings on cigarette packaging and advertisement is part of a broader strategy to help tobacco users quit and prevent young people from starting." FDA is requiring that the health warnings be placed on the top 50 percent of both the front and the rear panels of each cigarette package and on the upper portion of each cigarette advertisement, occupying at least 20 percent of the area of the advertisement.

by Brian Malkin

On July 5, FDA announced in the Federal Register that it had finalized its draft exemptions from substantial equivalence requirements. The purpose of the final rule is to "establish procedures for requesting an exemption from the substantial equivalence requirements of the Family Smoking Prevention and Tobacco Control Act ("Tobacco Control Act"). The effective date of the rule is August 4, 2011.

Final Rule on Exemption for Substantial Equivalence

On January 6, 2011, FDA issued its notice of proposed rulemaking, which we blogged on here. According to the Tobacco Control Act, new products not marketed prior to February 15, 2007, require some form of premarket clearance or approval prior to marketing. For products marketed prior to March 22, 2011, the Act requires premarket approval or filing a 905(j) substantial equivalence report, unless FDA later determines the product is not substantially equivalent to a predicate (similar) tobacco product. A predicate product must have been marketed as of February 15, 2007. For products that a company intends to market after March 22, 2011, the Tobacco Control Act requires either a premarket approval, a finding of substantial equivalence, or a waiver for finding the product substantially equivalent prior to marketing. For all products not on the market as of June 22, 2009 (The date the Tobacco Control Act became law.), the Tobacco Control Act requires that FDA be provided with a list of ingredients in the product at least 90 days in advance of the intended marketing date.

Despite the promise for a waiver process, the process outlined in the final rule is only effective August 4, 2011. This means that for products not marketed until March 22, in theory they have not been able to take advantage of the waiver process yet. While most tobacco reports to FDA have been by forms, either in paper or electronic format, the substantial equivalence report has no current form. The final rule states, however, that an exemption for substantial equivalence must be filed electronically. FDA also has a webpage on substantial equivalence and associated exemptions for additional updates, which also provides information for small businesses.

by Brian Malkin

On May 9-10, the Institute of Medicine's ("IOM's") Board on Production Health Practice held a meeting on the Scientific Standards on Modified Risk Tobacco Products. The agenda provided that on the first day, which was a public session, stakeholders could present their views. Industry stakeholders included a familiar round of players, Altria Client Services, British American Tobacco, Lorillard Tobacco Company, R.J. Reynolds Tobacco Company, and Swedish Match. Public health representatives were also on hand from FDA, the National Cancer Institute, and various representatives from academia and other associations, such as the American Cancer Society, the American Heart Association, and the Campaign for Tobacco-Free Kids. Many of these presentations are available on IOM's website, as provided above.

IOM's Board is meant to help review and present recommendations to FDA about standards for scientific studies to permit the marketing of modified risk tobacco products, as well as post-marketing studies for these products. The Board's mission is outlined in Section 911 of the Family Smoking Prevention and Tobacco Control Act of 2009 ("Tobacco Control Act"). The Board is chaired by former FDA Commissioner Jane Henney, M.D., who is now a Professor at the University of Cincinnati's School of Medicine. IOM's Board plans to submit its recommendations to FDA by late summer or early fall this year.

During the public session, representatives presented their viewpoints on the appropriate preclinical and in vitro studies, as well as clinical studies including biomarkers, risk perception, and population communication. Many of the speakers referred to IOM's guidelines in "Clearing the Smoke", and the need for consumers to understand the risks associated with modified risk tobacco products, which in the past have been misunderstood. While industry representatives were concerned about consumer acceptance and and use of these products, public health advocates were concerned about their potential impact on smoking initiation, cessation, and failed attempts to quit the use of tobacco products. At this point, FDA still reports that is has not received a modified risk tobacco product to review and proposes that it would take a year to review the first product that meets this definition. For additional thoughts regarding modified risk tobacco products, please see a previous blog here discussing thoughts presented at FDLI's Annual Conference last month.