FDA Lawyers Blog

by Brian Malkin

On March 18, FDA's Tobacco Products Scientific Advisory Committee ("TPSAC") posted its Report and Recommendations on the Public Health Impact on Menthol Cigarettes on FDA's Internet website. TPSAC was required by the Family Smoking Prevention and Tobacco Control Act ("Tobacco Control Act") to provide its final report to FDA on March 23, 2010. Interesting, while TPSAC's charge was to report on menthol in cigarettes and virtually all cigarettes contain some menthol, the recommendations are phrased in terms of menthol cigarettes, because, as TPSAC rationalized, the Tobacco Control Act asked for a review of menthol as a "characterizing flavor" of a tobacco product or tobacco smoke.

Based on the previously-disclosed chapters that we discussed here, it is not entirely surprising that--despite not finding menthol are inherently more harmful-- TPSAC's overall recommendation was: "Removal of menthol cigarettes from the marketplace would benefit public health in the United States." Following this recommendation, TPSAC cautioned that while a ban on menthol cigarettes could create a demand for contraband menthol cigarettes or mentholation kits, a menthol cigarette ban "could result in a substantial reduction in cigarette smoking." TPSAC reached these conclusions following sufficient evidence that menthol cigarettes, which currently account for about 30 percent of the cigarette market: a) increase experimentation and regular smoking, b) increase the likelihood of addiction and degree of addition for youths (but not necessarily adults), c) result in a lower likelihood of smoking cessation success in African Americans, and d) increase the prevalence of smoking if such cigarettes were not available, among other things. TPSAC qualified these conclusions as "more likely than not" rather than definitive statements.

Commenting on the Report, Center for Tobacco Products Director Lawrence R. Deyton, M.D., M.S.P.H. emphasized that the Report is merely recommendations to FDA and that "receipt of the Report does not have a direct immediate effect on the availability of menthol products in the marketplace." Deyton further noted: "Although there is no required deadline or timeline for FDA to act on the issue of menthol in cigarettes, we recognize the strong interest in this issue among all stakeholders and will continue to communicate the steps the FDA is taking as it determines what future regulatory actions, if any, are warranted. FDA intends to provide its first progress report on the review of the science in approximately 90 days."

According to the Tobacco Control Act, TPSAC's next report, due a year from now, will be on dissolvable tobacco products. As the Menthol Report is now the model, one might suspect a similar approach will be followed, perhaps with a similar set of conclusions and recommendations.

by Brian Malkin

On March 23, a Maryland federal judge dismissed an indictment against a former top attorney, Lauren Stevens, at GlaxoSmithKline ("GSK"), because she withheld information from FDA investigators at the "advice of counsel." The ruling may signal a movement to prevent similar indictments from being filed against corporate individuals, despite an effort by FDA and the Department of Justice ("DOJ") to hold senior officials personally liable for their actions, as we reported FDA announced at the Food and Drug Law Institute's Annual Conference last year.

In essence, Stevens obstructed FDA's investigation of offlabel promotion of Wellbutrin by withholding 28 slides sets from GSK-sponsored events that she herself had identified as promoting off-label use. FDA Lawyers Blog originally reported on this case here last November.

The judge noted "[g]ood faith reliance on the advice of counsel, when proven, negates the element of wrongful intent of a defendant that is required for a conviction." To the extent Stevens relied in good faith on the advice of counsel to withhold certain information from FDA, Stevens reliance, therefore, "would negate the Government's charge that she falsified and concealed documents with the intent to impede, obstruct, or influence the FDA's investigation into the marketing of Wellbutrin . . . [and] . . . would also negate the wrongful intent required to convict Stevens of making false statements," Judge Titus concluded.

All is not lost for federal prosecutors wishing to indict Stevens or similarly-situated top corporate officials who might otherwise avail themselves of the "advice of counsel" card to stay out of jail. Judge Titus dismissed the indictment with prejudice essentially because the Government misinstructed the grand jury about the "advice of counsel", where the Government characterized it as an issue to be raised at defense in the trial rather than "to the heart of the intent required to indict." Eyes are now on the Government to see if it can still obtain an indictment via an appeal or a new indictment with proper court instructions and how this will affect future attempts by FDA to hold corporate officials individually accountable.

by Brian Malkin

During the next two days, FDA's Food Advisory Committee will be hearing testimony whether artificial food dyes can make children hyperactive. Since the 1970s, some physicians and researchers have claimed a link between the colors and hyperactivity. So far, FDA has concluded that a causal relationship between artificial colors and hyperactivity does not appear to exist, but for some children with Attention Deficit/Hyperactivity Disorder ("ADHD"), their condition "may be exacerbated by exposure to a number of substances in food, including, but not limited to synthetic color additives."

The agenda includes members from both sides of the camp. Michael Jacobson, Ph.D., from the Center for Science in the Public Interest ("CSPI") is likely to argue there is a connection for at least some children, following up from their citizen petition dated June 3, 2008 asking for a ban to most artificial dyes. CSPI, known for disclosing the fat and calories in movie-theater popcorn and fast food chains, requested in the petition that FDA, as an interim measure, cease stating that there is no evidence of a connection and include on products containing synthetic colorings a statement such as: "WARNING: The artificial colorings in this food cause hyperactivity and behavioral problems in some children." On the other side, Sean Taylor, Ph.D. and Joseph Borzelleca, Ph.D. from the International Association of Color Manufacturers can be expected to argue that there is no connection or inherent neurotoxic risk with the use of artificial color additives. Other scheduled speakers include individuals with expertise in ADHD and there is a time slot for public comment.

Frommer Lawrence & Haug Partner Brian J. Malkin will serve as a new committee member on the Food and Drug Law Institute's ("FDLI's") Monograph Editorial Board for a three-year term beginning April 2011. FDLI monographs are designed to provide inside information and proprietary analysis to enable food and drug law practitioners to advise clients or help companies comply with difficult issues, regulations, or guidance. Each report lists specific ways to benefit practitioners and is focused on a current issue in food and drug law. For example, this April FDLI will release two new monographs: "Interactions with Healthcare Professionals in the Field: Compliance in the Current Regulatory Environment" and "Biosimilar Law and Regulation: An Essential Guide". Mr. Malkin will attend his first Board Meeting on April 4 and looks forward to your suggestions how FDLI's monographs can continue to provide you with valuable insight and information..

by Andrew S. Wasson

KV Pharmaceuticals ("KV") is attempting to weather a barrage of bad publicity surrounding the price of its newly-approved progesterone drug, Makena (17-hydroxyprogesterone caproate solution for intramuscular administration). For years, doctors have prescribed injectable progesterone to avoid premature birth. As an unapproved drug, compounded by a pharmacist, progesterone injections typically cost $10 to $20 per injection. Compounding, however, could lead to product variation between pharmacies. KV submitted new drug application ("NDA") for the product and, upon FDA approval, was awarded a seven-year orphan drug exclusivity. This news was welcomed by patients at first before they learned the price tag: $1500 dollars per injection, rounding out to approximately $30,000 per pregnancy.

Not surprisingly, widespread outrage ensued across the spectrum: patients, third-party payers, physician groups, and even Senators have registered their displeasure with KV. Senator Sherrod Brown (D-Ohio) asked KV in a letter to "immediately reconsider this massive price increase," stating that he was "gravely concerned that the exorbitant price increase ... will increase rates of preterm birth nationwide." On March 17, Senator Sherrod and Senator Amy Klobuchar (D-Minn) asked for the Federal Trade Commission to "initiate a formal investigation into any potential anticompetitive conduct" arising from the price increase. The idea of march-in rights under the Bayh-Dole Act has even been suggested, although it is not clear that any patents are in play, and, if they were, that they were supported by federal funding.

This situation presents an interesting study in incentives. FDA is motivated to encourage manufacturers to conduct clinical studies on unapproved drugs to ensure safety, effectiveness and consistency. FDA incentivizes manufacturers to conduct these studies through granting periods of exclusivity. Patients reap the benefits by having access to safe and effective drugs, consistently manufactured. Ostensibly, rational patients should be willing to pay some extra amount for the guarantee of safety, effectiveness, and standardization. In theory, this amount should also allow the manufacturer to recoup the cost of providing these benefits (such as clinical trials) plus a reasonable amount of profit. The problem arises when there is a mismatch between the perceived benefits of standardization, the amount invested by the manufacturer, and the premium paid by patients.

by Richard F. Kurz

Beginning March 17, amicus briefs in the Microsoft v. i4i case before the U.S. Supreme Court began to flow in from pharmaceutical innovators, including Genentech, Roche, Bayer, and the Pharmaceutical Research and Manufacturers of America ("PhRMA"). The Microsoft case questions the standard used by courts when deciding whether to invalidate a patent. Microsoft's argument, which is generally supported by generic pharmaceutical makers (see previous blog here), is that courts should lower the standard (i.e., the burden) required for a challenger to invalidate a patent under particular circumstances. However, pharmaceutical innovators--as well as others, including the U.S. Solicitor General's Office--argue to keep the current standard.

Genentech, Roche, and the California Healthcare Institute note that "[t]o obtain a patent is to enter into a bargain with the public: in exchange for disclosing its invention . . . the patent applicant receives a right to exclude others from practicing that invention in the United States for a limited time." A granted patent gives such companies a property right that is relied upon when deciding whether to dedicate millions of dollars to develop products. Consequently, they argue that the current validity standard provides patent holders "with the necessary level of certainty to support their decisions on whether to invest in new ideas."

Similarly, PhRMA contends that "a ruling lowering [the] standard of proof would dramatically diminish incentives for innovation. This chilling effect would disproportionately affect PhRMA's members, who rely on the incentives provided by strong patent protection when they choose to make extraordinary investments in research and development." Sources cited by PhRMA show that the average cost to bring a new drug to market is approximately $1.3 billion.

As noted in the U.S. Solicitor General Office's brief, the current standard--requiring "clear and convincing evidence" to prove that a patent is invalid--traces its roots back to a U.S. Supreme Court decision in 1934 requiring "'clear and satisfactory' evidence that was 'more than a mere preponderance.'" Microsoft and its supporters now argue that a preponderance is the correct standard, at least when new evidence is presented. Many are watching with interest to see how the current Court views this issue.

The Food and Drug Law Institute's ("FDLI's") Annual Conference starts in just two weeks in Washington, D.C. on April 5-6. As media partner for the program, FDA Lawyers Blog knows the importance of attending this Annual Conference each year.

The Conference is packed full with a range of topics including: a report-out from the Government Accountability Office, the new Consumer Product Safety Commission (CPSC) product safety database, Drug Enforcement Administration (DEA) scheduling, global supply chain integrity, nutrition label regulations and biosimilars regulation.

For more than 50 years, FDLI's Conference has provided the venue for food and drug law professionals to discuss and debate emerging topics, as well as participate in great educational sessions At this year's event, attendees will hear directly from FDA leadership including Commissioner Hamburg, Chief Counsel Tyler and FDA's six product center directors.

Thank you for your support of the FDA Lawyers Blog. We look forward to seeing you at the 2011 FDLI Annual Conference.

Register for the FDLI Annual Conference here.

by Erin A. Lawrence

The ongoing legal battle seeking to block U.S. federal funding of research on human embryonic stem cells--meant to protect embryos--is having a devastating effect on the research on lines of stem cells that do not destroy embryos.

Prior to the litigation commencing in 2010, the National Institutes of Health ("NIH") defined stem cells that were eligible for government funds. The agency restricted the definition of eligible stem cells as those derived from a blastocyst. The NIH inadvertently excluded stem cell lines derived from blastomeres. This is a very important distinction because deriving a stem cell line from a blastocyst--an embryo of more than 100 cells--destroys the embryo, however, deriving a stem cell line from a blastomere--a single cell plucked from an eight-celled human embryo--does not destroy the embryo. In 2010, the NIH attempted to redefine stem cells that were eligible for funding as those derived from embryos younger than blastocysts, however, the agency was halted by Judge Lamberth's August 2010 decision halting all stem cell research.

Private funding is not affected by the current stem cell litigation. In fact, the stem cell company, Advanced Cell Technology ("ACT") recently obtained a patent on single-blastomere technology. U.S. Patent No. 7,893,315 issued on February 22, 2011 broadly covers single-blastomere technology that provides a non-destructive alternative for deriving embryonic stem cell lines.

by Howard E. Rosenberg, Ph.D.
[Special to FDA Lawyers Blog, see Events listing here]

Recently the Court of Justice of the European Union ("CJEU") decided that the proposed unified patents court would not be compatible with EU treaties. The ruling focused on only part of the earlier Advocates General Opinion. The CJEU criticized the fact that although the proposed Patents Court would have a mechanism to seek a preliminary ruling from the CJEU, it would operate outside the institutional and judicial framework of the European Union ("EU").

Almost immediately afterwards, the EU Competitiveness Council decided to give the green light to start work on the enhanced cooperation of the unified patent. The European Commission, rather surprisingly, then reported that the CJEU decision was "positive."

This seeming contradiction was explained last Friday by Oliver Varhelyi (Head of Unit D2, DG Internal Market, Industrial Property Rights, European Commission) at the 7th European Generic Medicines Association ("EGA") Legal affairs Forum in Brussels. He began by pointing out that a survey of potential users of any unified patent system required a unified jurisdiction with judges proficient in IP matters. Varhelyi felt that the CJEU judgment and the previous Advocate General's opinion were very helpful and could pave the way for practical solutions to resolve the problems raised by the Court. Indeed, he felt that proposals taking into account both opinions could be put on the table by the end of this month. In addition, the unified patent incorporating twenty-five countries could also be implemented very shortly. Dieter Tzschoppe, Director, Pure and Applied Chemistry Cluster, European Patent Office ("EPO") confirmed that all the mechanisms were in place to add the unified patent to the EPO's list of designated "states" immediately. However, whether the cooperation group's patent would be given a "UP" or "EU" designation was not yet clear.

Varhelyi concluded that he was very hopeful that the new proposals will be successful and that all the pieces would be in place, including the unified patent court, by the end of this year and without the necessity of anything having to be referred back to the CJEU.

by Brian Malkin

On March 17, FDA pitched to the Senate Appropriations Committee on Agriculture, Rural Development, FDA and Related Agencies, FDA's need for proposed funding increases to help fund, among other things, countermeasures needed in the wake of the Japanese Crisis. Despite a general trend for federal agencies to receive less funding in Fiscal Year 2012 and rumors for various Republican members pushing for FDA budget cuts, FDA now appears to be in the driving seat for modest appropriations increases and hefty user fee increases in FY 2012, if President Obama's budget request for FDA is approved.

As members of Congress have been seeking ways to cut the funding of other federal agencies, under the proposed plan FDA would receive $1.3 billion more, for a total of $4.4 billion with more than one-third coming from user fees, including proposed user fees for generic drugs to help reduce the ever-increasing review times. FDA has a lot on its plate in FY2012 with new food safety initiatives and a host of other new initiatives such as the regulation of biosimilars and tobacco products, also in need of additional resources.

FDA's latest plea for more funding, however, appears to focus on the need to develop effective countermeasures. FDA Commissioner Margaret A. Hamburg, M.D. has been identifying various weak links that could benefit from the increased funding, e.g., (1) $70 million for medical countermeasures to respond to chemical, biological, radiological, and nuclear emergencies, (2) $170 million for pandemic influenza research, (3) $324 million to implement the Food Safety Modernization Act, (4) $124 million to develop a pathway for approving biosimilars and , and (5) $49 million to strengthen FDA's core scientific capacity to support FDA's mission and emerging technologies, such as biomarker qualifications.

See our previous blog on the proposed FDA budget here.

by Andrew M. Nason

As we previously reported, the U.S. Senate on March 8, 2011 overwhelmingly in favor of S.23, the "America Invents Act." The House of Representatives expects to complete a draft of a companion bill in the coming weeks. The Generic Pharmaceutical Association ("GPhA"), which represents generic drug manufacturers and suppliers, sent letters to both chambers of Congress leading up to the Senate vote. On March 2, 2011, GPhA mailed a letter to all members of the Senate stating its opposition to the inequitable conduct provisions of the Senate bill. On the same day GPhA sent a similar letter to House Judiciary Committee Chairman Lamar Smith and Ranking Member John Conyers expressing strong objections to any changes to the inequitable conduct provisions in current patent law. Aetna Inc., Apotex Corporation, Hospira Inc., Mylan Inc., Teva Pharmaceuticals and Watson Pharmaceuticals all joined GPhA in signing the letters.

According to a recent GPhA press release, "[T]he inequitable conduct defense allows patent challengers to expose [a patentee's] intentional misrepresentations and omissions of material information" during patent prosecution. In the pharmaceuticals context, the group argues the current inequitable conduct provisions enable timely resolution of patent litigation, which in turn enables timely creation of a competitive pharmaceutical market. With generic medicines now representing 76% of all prescriptions dispensed in the U.S., the current scheme has saved consumers, patients, and the health care system a total of $824 billion. This would all change with the introduction of Supplemental Examinations, which would allow a patent holder to gain immunity from the inequitable conduct defense by requesting a second examination from the PTO. In essence, GPhA argues that such a scheme would allow a patent holder to gain immunity from an inequitable conduct defense by engaging in inequitable conduct, i.e., withholding material information from the PTO with the intent to deceive, twice instead of once.

The House has been conducting hearings soliciting expert testimony on patent reform and expects to have a draft bill ready in the next few weeks. Check back often, as we will be reporting on this issue as it develops.

FLH's Scientific Advisor Howard E. Rosenberg, Ph.D will present on "Recent developments on SPCs" covering "The medicinal product - Review of relevant case law" at the 7th European Generic Medicines Association ("EGA") Legal Affairs Forum in Brussels, Belgium. Subtopics include "The medicinal product defined", "Where/when is the first MA (Marketing Authorisation) - problems with EU (European Union) enlargement", and "Combination products / Vaccines and adjuvants". The Forum will be held at the Renaissance Brussels Hotel. Event details may be found here.

by Howard E. Rosenberg, Ph.D.

At the recent Pew Health Group Conference John Taylor, FDA's Acting Principal Deputy Commissioner, told the attendees, "[A]nother public health crisis like Heparin seems inevitable." This being largely due to the fact that not enough foreign inspections of pharmaceutical active pharmaceutical ingredient ("API") manufacturers are being carried out. The cost of implementing and maintaining current good manufacturing practices ("cGMPs") at API plants is significant and for the past few years several groups representing API manufacturers that comply with cGMP have been lobbying hard to level the playing field.

The number of foreign manufacturing plants had grown to more than 3,500 in 2008, from roughly 1,200 in 2001 - a 185 percent increase. In 2001, 20.7 percent of facilities were inspected, but only 8.9 percent in fiscal year 2008 i.e., depth of the problem can be highlighted by the fact that there are nearly 1,000 manufacturers of drug substances eligible for FDA inspection in China alone.

At the conference several suggestions were raised which were designed to help improve the frequency and quality of API plant inspections. One suggestion was for FDA to consider using certified private inspectors with experience to carry out inspections. Another idea was that the agency should develop a system to provide a publically available plant rating scale for manufacturing sites. Brant Zell, who chairs the Bulk Pharmaceutical Task Force, a trade group for API suppliers, stated that the supply chain problem could be improved if FDA were authorized to fine manufacturers and conducted unannounced inspections in India and China. The Society of Chemical Manufacturers and Affiliates has recently asked for mandatory FDA inspections with the sites paying for the cost of the inspections.

Although FDA has moved to halt imports of known violators by issuing warning letters, it was reported that at one site the manufacturer refused an FDA investigator access to its facility. A warning letter was issued, but the episode highlights the limits of FDA's ability to have full access to the documentation and records at foreign facilities. Even where full access is granted, the limited time available for the inspector to carry out inspections (due to cost and limited manpower) may well lead to facilities being given the benefit of the doubt when a more thorough inspection would be appropriate.

by Brian Malkin

On March 15, FDA announced the availability of a new guidance, Planning for the Effects of High Absenteeism to Ensure Availability of Medically Necessary Drug Products. The guidance is intended to encourage manufacturers of medically necessary drug products ("MNPs") and their components to develop contingency plans for use when emergencies cause high absenteeism in their production facilities.

According to the guidance, a MNP is "Any drug that is used to treat or prevent a serious disease or medical condition for which there is no other adequately available drug product that is judged by medical staff to be an appropriate substitute." FDA indicated that high absenteeism may be associated with the emergency situation for which the MNP is indicated, e.g., influenza pandemic, where widespread illness outbreaks could result in production stoppages.

FDA recommends that the contingency plans include mechanisms to attempt to anticipate emergencies that can result in high rates of absenteeism and encourage by increasing inventory of MPNs and components to manufacture MPNs, increase cross-training of employees so they may be reassigned to manufacture MPNs if necessary, performing routine maintenance of equipment to manufacture MPNs and provisions for alternate suppliers of resources and goods to manufacture MPNs. In addition, contingency plans should include mechanisms to activate and deactivate the contingency plans and drills should be run internally to ensure that employees are familiar with the plans and when and how to implement them.

FDA requests that the guidance be provided to all suppliers and contractors associate with MNPs. The guidance provides that it expires on January 31, 2014.

by Andrew S. Wasson

On March 8-9, direct-to-consumer ("DTC") genetic tests were the subject of the Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee ("Advisory Committee"). DTC genetic tests, marketed by companies such as 23andMe, deCode Genetics, and Navigenics can include screening for hereditary diseases, pharmacogenomic tailoring of drug response, and genomic typing to discover ancestral roots. Some have suggested that DTC marketers are selling modern-day snake oil. On the other hand, some proponents of DTC products counter that regulation is an outmoded and paternalistic. Others have alleged that FDA senior official Dr. Jeffrey Shuren made misrepresentations during a Congressional hearing in July 2010.

The Advisory Committee heard from a number of industry stakeholders and pondered when and how to regulate DTC genetic products. At the March Advisory Committee meeting, the committee members considered the risks and benefits of making genetic tests available to consumers without involving a physician or counselor. FDA also sought to understand whether it was possible to mitigate any results misunderstood by consumers. FDA also considered whether varying evidence requirements would be appropriate over the spectrum of DTC genetic testing uses. While the precise contours of the Advisory Committee's input is being debated, most appear to agree that they will recommend at least some physician involvement. A summary of the proceedings stated that the Panel "could not generalize a recommendation for this whole category of devices," but the Panel did "generally" agree that "several categories or specific genetic tests should be offered solely upon prescription."

And the debate has most certainly turned contentious. In July, at a Congressional hearing before the House Energy and Commerce Committee, FDA Center for Devices and Radiologic Health Director Jeffrey Shuren, M.D., J.D. was asked, "Do these companies have researchers that are adding to the information, that will help us have these breakthroughs for learning more about propensity to disease, how to make medicine more personal? Do they have researchers, are they adding to the scientific knowledge?" Dr. Shuren replied, "From the information we know, they're not adding, they're not doing their own research on the genetic profile, but they're interpreting the studies that have been performed by others." Despite this statement, Dr. Shuren attended a presentation made by 23andMe highlighting one study it had undertaken analyzing genetic information from Parkinson's Disease. FDA has backed Dr. Shuren, stating, "At that time we were not aware of any of the more than a dozen DTC genetic tests making medical claims that were based on results of a company's own research."

by Brian Malkin

On March 9, FDA approved the first lupus drug/biological treatment in over 50 years--Benlysta® (belimumab). Benylsta® is an intravenous infusion human monoclonal antibody manufactured to target B. lymphocyte stimulator (BLyS) protein to reduce the number of abnormal B cells that generally are regarded as the an issue with lupus. Prior to Benylsta®, Plaquenil (hydroxychloroquine) and corticosteroids approved in 1955 an aspirin approved in 1948 were the only drugs to treat lupus.

Lupus is a chronic, serious, and sometimes fatal autoimmune disease affecting from estimates of 300,000 to 1.5 million (latter figure from Lupus Foundation of America) Americans that attaches healthy tissues, including the joints, kidneys, lungs, heart, and the brain. Flaring symptoms often present themselves in the joints or as joint pain, light sensitivity, fever, chest pain, hair loss, and fatigue.

FDA's Curtis Rosebraugh, M.D., M.P.H., Director of the Office of Drug Evaluation II in the Center for Drug Evaluation and Research said, "Benlysta, when used with existing therapies, may be an important new treatment approach for health care professionals and patients looking to help manage symptoms associated with this disease.

According to The New York Times reporter Andrew Pollack, analysts expect Benlysta® sales expect the $35,000/yearly treatment per patient, which could result in sales over $2 billion once insurance companies adjust to the new therapy. Benlysta® is the first FDA-approved therapy developed by Rockville, Maryland-based Human Genome Sciences Inc and will be co-marketed with GlaxoSmithKline PLC. The European Medicines Agency is expected to decide on the marketing approval for Benlysta® later this year.

Frommer Lawrence & Haug LLP Partner Brian J. Malkin Will Speak at the Food and Drug Law Institute's ("FDLI's") Annual Conference in Washington, D.C. on April 4-6. On April 5, Mr. Malkin will speak in a panel on several hot topics concerning tobacco products--classification and reduced risk on April 5.

FDLI has updated the session details as follows:

Title: Development and Regulation of Tobacco Products, Nicotine, and Alternative Tobacco Products under the Family Smoking Prevention and Tobacco Control Act and Beyond

Under the Family Smoking Prevention and Tobacco Control Act ("Tobacco Control Act"), FDA has broad authority to regulate tobacco products, but cannot ban tobacco products or nicotine. Rather than permit FDA to regulate all tobacco, nicotine, and alternative tobacco products in a single center or as its own group of products, the Tobacco Control Act created a regulatory scheme that fragmented these products into different FDA centers of responsibilities-tobacco products, drugs, foods, or combinations of these products. Recently, FDA has faced challenges determining how to classify and regulate e-cigarettes and will undoubtedly face more challenges with definitions created by the Tobacco Control Act such as "cigarette" or "tobacco product", as the tobacco industry creates hybrid products, such as cigarillos, or new products including noncombustible tobacco products, such as dissolvable tobacco. During this thought-provoking session, the panelists will create a dynamic forum for the audience to listen and react to concerns raised by the panelists about the Tobacco Control Act and its effect on the development and regulation of tobacco, nicotine, and alternative tobacco products and proposals for how FDA may address these issues in the coming months and years. In particular, the panel will raise issues about how FDA and Congress can better address the public health concern to develop more reduced risk tobacco, nicotine and alternative tobacco products, as well cope with the requirements set by the Tobacco Control Act to define limits for harmful constituents in tobacco products and ban or reduce the limit of substances used to make tobacco products more addictive or palatable and thereby encourage new or continued use.

Mr. Malkin has been following the Family Smoking Prevention and Tobacco Control Act ("Tobacco Control Act") since it was signed into law on June 22, 2009. Mr. Malkin authored an article for Tobacco Reporter when the Tobacco Control Act was first enacted. Mr. Malkin's article may be found in the Articles tab for FDA Lawyers Blog. A frequent attendee of FDA's Tobacco Products Scientific Advisory Committee ("TPSAC") and other related FDA and industry tobacco meetings, Mr. Malkin also represents a variety of tobacco product manufacturers before FDA.

Also, a new panel speaker has been added to this session: David T. Sweanor, JD, Adjunct Professor, Faculty of Law, University of Ottawa. Additional details regarding the agenda for FDLI's Annual Conference will be posted on FDLI's website here.

by Andrew M. Nason

On March 8, the U.S. Senate voted 95-5 in favor S.23, the "America Invents Act." The vote came on the same day retired Federal Circuit Chief Judge Paul Michel criticized lawmakers' efforts that led to the current version of the America Invents Act. Michel said the debate and drafting of the bill has been largely reactive to strong lobbying by a variety of special interests, and consequently focused on what was wrong with the old system, rather than how to create a better system overall. He noted that the system needs to be better balanced to serve the needs of small businesses and venture capital and equity firms that provide capital for inventions, and because the bill does not focus on these issues, it could potentially make the system even slower, weaker, and murkier. Despite Judge Michel's warnings, the Senate overwhelmingly passed the legislation, and patent and industry organizations reacted almost immediately upon the Senate's passage of S.23.

The American Intellectual Property Law Association "applaud[ed] the Senate passage" of a "strong, bipartisan bill that includes the essential patent reform features, including the adoption of a first-inventor-to-file patent system, funding for the [U.S. Patent and Trademark Office] that will bring budget predictability . . . , and the creation of an ever more effective post-grant review procedure." The Biotechnology Industry Organization similarly "commend[ed] the Senate for its overwhelming passage" of S.23, saying that "improvements made by the America Invents Act would benefit all sectors of the U.S. economy by enhancing patent quality [and improving the patent system.]."

The press surrounding the Senate's passage was not, however, all positive. The Innovation Alliance issued a statement noting that it "remain[s] neutral on S.23" in its current version. The group expressed concern over the removal of the gatekeeper compromise on damages achieved in the last Congress, as well as the creation of the transitional post-grant review proceeding for business method patents. The Coalition for Patent Fairness stated in a press release that it "could not support [S.23]'s passage at this time." The organization, which represents a broad range of companies and trade associations, noted that it stands ready to help reach a "consensus on the most efficient way to lessen the growing burden of abusive and unjustified patent infringement claims."

For additional information concerning S. 23, see our most recent blog here. Stay tuned for a blog next week on the Generic Pharmaceutical Association's reaction to S. 23 and related commentary.

by Richard F. Kurz

On February 28, U.S. District Court Magistrate Judge Restrepo handed down an order that may end the controversy Cephalon stirred up in its lawsuit with the Federal Trade Commission ("FTC"). Despite oral arguments tentatively scheduled for March 4, the Court found that the parties' written submissions were sufficient to render its decision denying Cephalon's motion to compel the disclosure of confidential documents underlying two "pay-for-delay" studies previously conducted by the FTC regarding pharmaceutical patent settlement agreements.

Additionally, the Court ordered that the FTC is not precluded from citing its two studies, based upon the FTC's stipulation that these studies would not be offered into evidence and that the FTC's expert witnesses would not be provided with the documentation underlying these studies. Interestingly, the Court added the caveat that while it was not ordering disclosure "at this time," its order is predicated on the FTC's compliance with this stipulation.

As discussed in our previous post, in similar cases the FTC and its expert witnesses typically rely on conclusions drawn from these studies when opining on settlement agreements between brand name and generic companies. Cephalon had surprised many by asking the Court to either disclose the underlying data so that Cephalon could challenge the studies' conclusions or, in the alternative, deny the FTC's use of these studies

Absent further motions by Cephalon, it appears that the remainder of this lawsuit will focus on the FTC's challenge to the actual agreements at issue in this case.

by Andrew S. Wasson

Unapproved oral prescription drugs used for the treatment of cough, cold, or allergy remain in FDA's sights as it declared that shipment in interstate commerce of a large number of such products was unlawful. Starting in 2006, FDA undertook an initiative to address unapproved drugs marketed in the United States. For example, in a Federal Register notice dated March 3, 2011, FDA reached final resolution of five dockets dealing with unapproved cough, cold, or allergy products. More recently, in related subject matter, FDA also denied a Citizen Petition on March 1, 2011 directed to the safety and effectiveness of cough/cold drugs containing tannate salts. The cumulative list of unapproved cough, cold, or allergy drugs can be found here.

To understand how so many unapproved drugs remain on the market, it is necessary to understand the many-layered evolution of drug regulation in the United States. Starting in 1938, the Federal Food Drug & Cosmetic Act ("FD&C Act") required approval for new drugs based on safety (but not efficacy). In 1962, the FD&C Act was amended to additionally require that all drugs be approved with regard to effectiveness as well. Not only that, the efficacy requirement was retrospective: FDA was charged with the task of also evaluating the effectiveness of all drugs approved between 1938 and 1962. For this, FDA enlisted the help of the National Academy of Sciences, which submitted evaluations to FDA by the late 1960s and 1970s (FDA's implementation of these reports is known as the Drug Efficacy Safety Implementation review or "DESI"). DESI determinations also applied to drug products "identical, related, and similar" ("IRS") to approved drugs. FDA granted temporary exemptions to some oral prescriptions used for cough, cold, or allergy symptoms in the early 1970s so FDA could consider the recommendations of the over-the-counter drug panel running in parallel. FDA withdrew most of the exemptions in the early 1980s.

FDA recently has actively addressed lingering issues relating to unapproved prescription drugs for the treatment of cough, cold, or allergy. For example, FDA addressed longstanding requests for hearing related to FDA's revocation of temporary approval exemptions of the early 1980s. FDA gave manufacturers who previously requested such hearings the opportunity to withdraw or affirm their requests in a January 7, 2011 notice in the Federal Register. Not hearing from these manufacturers, FDA deemed the requests withdrawn.

by Charles J. Raubicheck

FDA has granted an extension of time, to February 21, 2012, allowing makers of dietary supplements containing non-esterified (free) phytosterols to submit further data warranting use of the health claim that these products may reduce the risk of coronary heart disease.

Phytosterols are plant-derived sterols that reduce cholesterol levels. The agency has proposed to allow the claim for esterified phytosterols (prepared with fatty acids), but is not yet convinced that the non-esterified (free) form is efficacious. Free phytosterols are used more frequently in dietary supplements because they permit the production of smaller, easier-to-swallow pills.

Several trade associations and companies petitioned for the extension. FDA terms its action an "exercise of enforcement discretion."

by Andrew M. Nason

On March 1, Senator Patrick Leahy (D-VT) introduced a "Manager's Amendment" to S.23, the omnibus Patent Reform Bill, and the United States Senate adopted it by a vote of 97-2. The Manager's Amendment, among other changes, re-names the reform bill the "America Invents Act," and includes a provision that would establish a fund to receive PTO fee income for use by the PTO without fiscal year limits or fee diversion. Despite broad bipartisan support for the legislation from lawmakers, the bill still has detractors in the business world.

Edward J. Black, president and CEO of the Computer & Communications Industry Association ("CCIA"), said the bill would leave the tech sector worse off than before. The CCIA letter highlighted several provisions of the bill, including codification of litigation-related provisions concerning damages, venue and inequitable conduct that it said would "lock in statutory language that would be a step backward from current law and prevent evolutionary improvements on these issues" in the courts. The letter came less than a week after Senators received similar mail from a group of nine organizations representing small businesses, start-up entrepreneurs, independent inventors, and technical professionals. The group argued that several provisions of the bill favor large established corporations at the expense of entrepreneurs and individual inventors. Specifically, the group criticized the bill's proposed change from a first-to-invent system to a 'first-inventor-to-file' system and the provisions relating to new post-grant review proceedings.

The Manager's Amendment addressed some of the concerns of the various groups. For example, the Amendment strikes all damages language remaining in the bill, including the gatekeeper provision. It also adds a new provision requiring the Director to charge reduced fees to small entities for the use of accelerated examination, and broadens the definition of "microentity," a status that entitles applicants to reduced fees. The Senate may address other concerns in the coming weeks, as Senator Kirk (R-IL) introduced an amendment to provide a fast lane for small businesses within the USPTO. Following Senate debate, the bill should reach the floor for markup and a full vote in the next few weeks. The House of Representatives continues to debate their own version of Patent Reform legislation in committee.

For additional information concerning the most recent round of patent reform developments, please see our previous blog on this topic here.

by Howard E. Rosenberg, Ph.D.

Last October the Italian Antitrust Authority ("Italy") commenced a procedure against Pfizer Italia Srl and Pfizer Health AB ("Pfizer Italy") for abuse of Pfizer Italy's dominant position with respect to the drug Xalatan® (latanoprost). Pfizer Italia Srl and Pfizer Health AB, are the holders of the Italian marketing authorizations ("MAs") on the product.

Italy was concerned that Pfizer Italy had pursued strategies to artificially prolong a patent for the purpose of preventing or delaying the entry into the market of generic versions of Xalatan®. This procedure was following a complaint filed by Ratiopharm, which seems understandable in light of the recent Enquiry on the Pharmaceutical Sector concluded in 2009 by the European Commission ("EC"). The procedure should be completed on October 15, 2011.

According to the submitted documentation, Pfizer Italy requested and obtained an extension of its patent, by filing an application for a divisional patent, which was followed by an application for a supplementary protection certificate ('SPC") aimed at extending patent protection up to 2011. The divisional patent for which the SPC was granted, however, was recently revoked by the European Patent Office ("EPO") in Munich.

Italy recently announced that it has extended the investigations to Pfizer Inc. ("Pfizer U.S.") based on the information it had collected from Pfizer Italy. Apparently, Italy found documentation "showing that the initiatives relating to the application for divisional patent EP '168 at the EPO in 2002 and the SPC application at the Italian Patent and Trademark Office in 2009, aimed at realigning the expiry of the rights in Italy with the expiry of the rights in the other European countries (from September 2009 to July 2011), were centrally coordinated and managed by the US company Pfizer Inc., either directly or through other European subsidiaries". Hence Pfizer U.S. is also now a party to the proceedings and will need to furnish all requested information to Italy and, presumably, will be subject to the decision made by the Italian Antitrust Authority.

by Andrew S. Wasson

The Bayh-Dole Act was front and center on Monday as the Supreme Court heard oral argument in Board of Trustees of the Leland Stanford Junior University v. Roche Molecular Systems, Inc., Docket No. 09-1159, which centers on a question regarding its interpretation. This is the first time that the Supreme Court has entertained a dispute on the Bayh-Dole Act.

Passed in 1980, the Bayh-Dole Act governs inventions conceived or reduced to practice under a funding agreement with the Federal Government. As a general rule, prior to the Bayh-Dole Act, by default, the Government owned federally-funded inventions. Policy-makers at the time theorized, however, that allowing non-profit institutions like universities to own such inventions would lead to greater commercialization. The thinking was that the universities that carried out the research would be in a better position to coordinate with private industry to develop commercial products than the Federal Government. Those policy-makers were correct in their hypothesis. The Bayh-Dole Act has been wildly successful and some even credit it with creating the biotechnology industry.

Here, Stanford sued Roche for the infringement of three patents and Roche defended on the basis that it was also an owner of the patents. One of the inventors, Mark Holodniy, joined the staff at Stanford, but also received training at Cetus Corporation (eventually acquired by Roche). Holodniy's agreement with Stanford provided that he "agreed to assign" all inventions to Stanford, however, he also signed a "Visitor Confidentiality Agreement" assigning Cetus all right in inventions created "as a consequence" of Holodniy's access to Cetus. Roche argued that Stanford lacked standing to sue because Roche was also an owner of the patents-in-suit.

by Brian Malkin

Today and on March 17-18, FDA's Tobacco Products Scientific Advisory Committee ("TPSAC") will continue to receive updates from TPSAC's Menthol Report Subcommittee.

On the one hand, briefing materials for today's meeting (chapter on "Effects of Menthol on the Disease Risks of Smoking") suggest TPSAC will conclude evidence is insufficient to conclude that menthol affects tobacco-related diseases. However, another chapter on "The Physiological Effects of Menthol Cigarettes" suggests that TPSAC will conclude that menthol: (1) has a cooling or anesthetic effect that makes cigarette smoke more palatable, (2) menthol makes low-tar, low-nicotine cigarettes more acceptable to smokers, (3) it is "at least as likely as not" that menthol inhibits the metabolism of nicotine, and (4) it is biologically possible that menthol makes cigarette smoking more addictive.

Missing from the briefing materials are draft chapters that the tobacco industry and menthol cigarette consumers want to know--TPSAC's recommendations on menthol cigarettes and their regulation to FDA, which is due by March 23, 2011, and was mandated by the Family Smoking Prevention and Tobacco Control Act ("Tobacco Control Act"). One could conclude, however, that based on the conclusions from the chapter on physiological effects, TPSAC will seek to reduce or ban menthol in cigarettes to help make cigarettes less palatable or addictive.

Just last Friday, two lead manufacturers of menthol cigarettes, Lorillard Tobacco Company and R.J. Reynolds Tobacco Company, sued FDA and the Department of Health and Human Services, charging them with assembling a biased TPSAC in an attempt to block FDA from "receiving or relying on" TPSAC's recommendations. It seems the Tobacco Control Act battle between FDA and the tobacco industry is just beginning. Stay tuned as we continue to report on these developments.

by Brian Malkin

On February 25, FDA released a draft guidance entitled Medication Guides--Distribution Requirements and Inclusion in Risk Evaluation and Mitigation Strategies (REMS). FDA stated that the guidance addresses when FDA intends to exercise enforcement discretion for distribution of certain Medication Guides and when Medication Guides will be required as part of a risk evaluation and mitigation strategy ("REMS"). Medication Guides are a form of enhanced labeling that provides additional risk- or safety-related information about a drug or special directions of use that are deemed critical to the safe and effective use of a drug. REMS is the new term for risk management programs required by the Food and Drug Administration Amendments Act of 2007 ("FDAAA"), when necessary to ensure that the benefits of a drug outweigh the risks. "Drug" in this context also includes biologics.

Medication Guides--Distribution Requirements and Inclusion in Risk Evaluation and Mitigation Strategies (REMS)

FDA said that questions have arisen whether a Medication Guide needs to be distributed every time the drug is dispensed and whether every time a drug has a Medication Guide, distribution of the Medication Guide needs to be included in a REMS, when there are no elements to assure safe use of a drug as part of a REMS. In the Guidance, FDA states that between March 25, 2008, when the REMS provisions of FDAAA took effect, and January 1, 2011, FDA has approved over 150 Medication Guides as part of a REMS, of which 108 were Medication Guide-only REMS.

FDA determined that FDA will continue to have Medication Guide-only REMS, if FDA determines that having a Medication Guide without a REMS will not be sufficient to ensure the benefits of the drug outweigh the risks. FDA will exercise enforcement discretion of a Medication Guide in certain circumstances--primarily when a drug is dispensed in an inpatient setting, such as a hospital under the supervision of a healthcare professional, or when dispensed to a healthcare professional for administration to a patient in an outpatient setting, such as a clinic. FDA, however, believes distribution of a Medication Guide is still mandatory whenever: (1) the Medication Guide has been materially changed, (2) it is requested by a healthcare professional or patient, (3) the drug is dispensed in an outpatient setting without direct supervision of a healthcare professional, e.g., retail pharmacy, and (4) the first time the drug is dispensed to a healthcare professional for administration to a patient in an outpatient setting.

The Guidance further provides that applicants with a REMS that does not include elements to assure safe use of a drug may submit a prior approval supplement to eliminate the Medication Guide from the REMS--but still to remain as part of the approved labeling--consistent with the Guidance, which must be accompanied by a REMS assessment in certain circumstances. Based on FDA's new Guidance, it appears that FDA is trying to trim its Medication Guide-only REMS to drugs that truly require such a program and to reduce its workload to police distribution of Medication Guides in general.

Frommer Lawrence & Haug LLP Partner Brian J. Malkin Will Speak at the Food and Drug Law Institute's ("FDLI's") Annual Conference in Washington, D.C. on April 4-6. Specifically, Mr. Malkin will speak about several hot topics concerning tobacco products--classification and reduced risk on April 5.

Mr. Malkin has been following the Family Smoking Prevention and Tobacco Control Act ("Tobacco Control Act") since it was signed into law on June 22, 2009. Mr. Malkin authored an article for Tobacco Reporter when the Tobacco Control Act was first enacted. A frequent attendee of FDA's Tobacco Products Scientific Advisory Committee ("TPSAC") and other related FDA and industry tobacco meetings, Mr. Malkin also represents a variety of tobacco product manufacturers before FDA.

Additional details regarding the agenda for the presentation will be posted on FDLI's website here.