FDA Lawyers Blog

by Richard F. Kurz

On January 25, Senators Herb Kohl (D-Wisconsin) and Chuck Grassley (R-Iowa) reintroduced the "Preserve Access to Affordable Generics Act". Calling "pay-for-delay" agreements "pay-off agreements," the Senators consider settlement agreements between generic and branded pharmaceutical companies to be an "anti-consumer practice." This bill has been referred to the Senate Judiciary Committee, where it awaits further action.

Although settlement agreements are typically encouraged as a matter of policy, various factions are working to change this when pharmaceutical patents are involved. Dubbed "pay-for-delay," there are those who consider settlements between warring pharmaceutical companies anti-competitive. Thus, such agreements are being attacked on several fronts. See some of our previous blogs on "pay-for-delay" here (December 31, 2010), here (December 16, 2010), here (August 3, 2010), and here (May 10, 2010).

Similar bills have been introduced--and died--in Congress in each of the last three sessions. Regarding last year's bill, FTC Chairman Jon Leibowitz commended the Senate Judiciary Committee for their efforts, stating his opinion that "that stopping these pay-for-delay settlements will save consumers about $3.5 billion per year and advance the cause of affordable health care for all Americans." Despite such sentiments, the full Senate never voted on the previous bills.

Indeed, current law supports settlement agreements that end pharmaceutical patent disputes. For instance, the Federal Circuit Court of Appeals noted that such settlements do not violate antitrust laws because the agreements fall within the exclusionary zone granted by patents. Additionally, last year a Second Circuit Court of Appeals panel considered Louisiana Wholesale Drug Co., Inc. v. Bayer AG, affirming (per curiam) a lower court's ruling in favor of such a settlement agreement. Despite that panel's suggestion, the Second Circuit later denied a petition for rehearing in banc. However, the U.S. Supreme Court is currently considering a certiorari petition filed on the Louisiana Wholesale Drug case. In response, several amicus curiae briefs have been filed. If the Supreme Court grants the petition, the case is guaranteed to get a great deal of attention.

No matter how this battle turns out, what is certain is that so-called "pay-for-delay" will continue to be in the news this year.

by Brian Malkin

A few weeks ago, FDA posted a new guidance on Section 905(j) Reports for demonstrating substantial equivalence for new tobacco products, followed by a Federal Register Notice described as a proposed rule for exempting certain tobacco products from the substantial equivalence requirements.

Substantial Equivalence Guidance

According to the Family Smoking Prevention and Tobacco Control Act ("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 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 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.

Timing is everything. First, the waiver process will not be finalized until some time after March 22, 2011. FDA requested comments on the proposed rule by March 22, 2011, and the rule only becomes effective once finalized, which FDA expects to be in July 2011. So, if a product was not marketed prior to March 22, 2011, the waiver process will not be available--at least in the short term. While most tobacco reports to FDA have been by forms, either in paper or electronic format, the substantial equivalence report has no current form--at least not yet. The guidance explains that FDA will provide an update with how electronic submissions may be made. FDA also has a webpage on substantial equivalence for additional updates, which also provides information for small businesses.

Frommer Lawrence & Haug LLP Partner Brian J. Malkin will speak on a key topic essential to patent life cycle longevity--patent term extension on January 27. Mr. Malkin will provide insight that he learned while running FDA's patent term extension program during a greater part of the 1990s. The program is designed to offer practical solutions and in-depth instruction for attorneys servicing the pharmaceutical, biotechnology, and medical device industries to help optimize the length of their patents.

ACI is pleased to offer a discount of $200 to FDA Lawyers Blog readers. Please visit here for further details. For a copy of the conference brochure, see here.

by Howard E. Rosenberg, Ph.D.

Whenever the U.S. or the European Union ("EU") discuss entering into Free Trade Agreements ("FTA") with other countries, they always press for the inclusion in any agreement of a data exclusivity period for pharmaceuticals. The current discussions by the EU with India are no different, and it appears to be one of the proposals that is still holding up any agreement.

The Trade Related Aspects of Intellectual Property Rights Agreement ("TRIPS") requires that data disclosed during registration of pharmaceuticals should remain undisclosed to third parties. TRIPS is an international agreement administered by the World Trade Organization ("WTO") that sets down minimum standards for many forms of intellectual property regulation applied to nationals of other WTO Members that was negotiated at the end of the Uruguay Round of the General Agreement on Tariffs and Trade in 1994. However, the EU is going one step further in requiring a time period restricting use by the Indian pharmaceutical registration authority in accessing the data in support of generic medicines. The EU state in the draft:

The Parties shall guarantee the confidentiality, non disclosure and non reliance of data submitted for the purpose of obtaining an authorisation to put a pharmaceutical product on the market. For that purpose, the Parties shall ensure in their respective legislation that any information submitted to obtain an authorisation to put a pharmaceutical product on the market will remain undisclosed to third parties and benefit from a period of at least [...] years of protection against unfair commercial use starting from the date of grant of marketing approval in either of the Parties.

In general terms the EU's own data exclusivity period is around 10 years with the US around 5 years for new chemical entities.

The EU Commission states it is ready to show the necessary flexibility and fully take into account the specificities of the Indian legal system, the policy developments on this issue within India, its developing country status and the role it plays with regard to production of essential generics for the developing world.

by Charles J. Raubicheck

The U.S. Supreme Court has agreed to hear an appeal by the State of Vermont from a lower court decision ruling that Vermont's law prohibiting dissemination of prescribing data violates the First Amendment.

The law bars the use or sale of information about drugs that physicians prescribe, in connection with pharmaceutical companies' marketing or promotion of their products. Prescribing data are kept by pharmacies, who often sell them to data-mining companies for resale to drug companies. The only exception: if doctors consent.

The lower court found that the law excessively curbs dissemination of commercial information, which the First Amendment protects. The Second Circuit reversed and remanded to the lower court. Vermont maintains before the Supreme Court that its statute reasonably restricts use of prescribing data, since: (i) doctors do not routinely offer this information voluntarily, but are required give it to pharmacies for their patients to obtain drugs, and (ii) the statute properly preserves doctors' and patients' privacy.

by Andrew S. Wasson

For drug products, FDA publishes patent information submitted by the new drug application (NDA) holder in the publication (now electronic) Approved Drug Products with Therapeutic Equivalence Evaluations, generally known as the "Orange Book." For each new drug product with an associated patent, FDA creates an entry in the Orange Book that lists the product, the associated patent number, the expiration date, and other relevant information, such as the patent use code (if applicable, for a method-of-use patent). By contrast, the Biologics Price Competition and Innovation Act ("Biosimilars Act") contains no mechanism for listing patent information. Instead of an Orange Book, the Biosimilars Act proposes a complex and private exchange of patent information between the innovator and proposed biosimilar applicant.

It does not appear that there was much public debate on whether to include a public central repository of patent information like the Orange Book in any proposed biosimilars legislation. Understanding the Orange Book's influence on scientific progress generally will help us understand the implications of leaving a central repository out of the Biosimilars Act. Of course, the Orange Book plays an important role on the incentives set forth by the Hatch-Waxman Amendments. Less attention appears to have been devoted, however, to understanding how the Orange Book generally influences scientific progress in the pharmaceutical arts.

Thus, I ask a simple question: are patents listed in the Orange Book cited more frequently than patents not listed in the Orange Book? The connection to scientific progress is provided by the underlying theory that "the number of times a patent is cited from other patents provides an indication of its technological importance." E.g., Henk F. Moed, Citation Analysis in Research Evaluation 18 (2007). Thus, it may be the case that if Orange Book patents are cited more frequently, then they have greater technological importance. It could be possible that the technologies disclosed by Orange Book patents achieve greater prominence and therefore ostensibly have some stronger directing force on the focus of scientific inquiry.

by Laura Fanelli

Deltex Pharmaceuticals, Inc., ("Deltex") of Rosenberg, Texas, is a manufacturer and distributor of prescription and over-the-counter ("OTC") drug products with a history of considerable regulatory violations. In 2008, after conducting inspections of Deltex's facilities, FDA issued a Warning Letter to Deltex for manufacturing unapproved drugs and for deviations from current Good Manufacturing Practice ("cGMP") regulations. However, after issuance of the letter, the company failed to modify its behavior. As a result, the U.S. Department of Justice filed a complaint detailing Deltex's violations of the Federal Food, Drug, and Cosmetic Act. Specifically, the complaint highlighted Deltex's failure to obtain necessary FDA approval for its prescription drug products, failure to comply with FDA's regulations governing OTC drug products, and failure to abide by cGMP requirements.

On January 18, FDA announced that the U.S. District Court for the Southern District of Texas entered a consent decree of permanent injunction against Deltex, its President, Kabir Ahmed, and Vice President, Mohidur R. Khan. Under the terms of the decree, the defendants cannot resume manufacturing and distributing any drug until Deltex complies with cGMP regulations. Further, the defendants cannot resume distribution of any drug product until it is approved by FDA or it complies with FDA's regulations governing OTC drugs. Additionally, Deltex must recall drugs that were manufactured and distributed since October 31, 2008--the date of FDA's Warning Letter--from their customers, destroy the recalled drugs, and advise their customers to recall products at the retail level. The decree additionally subjects the defendants to penalties of $2,500 per day if they fail to abide by any of the provisions of the decree, and an additional $500 for each violation.

In response to the injunction, FDA's Associate Commissioner for Regulatory Affairs, Dara A. Corrigan, said, "[t]his injunction shows that FDA will seek enforcement action against companies that are identified as being in violation of our manufacturing and drug approval requirements."

by Elizabeth Murphy

On January 17, GlaxoSmithKline ("GSK") announced its plans to set $3.4 billion aside for the settlement of legal claims related to its diabetes drug Avandia® (rosiglitazone maleate).

Avandia®, prescribed for the treatment of Type 2 diabetes, was formerly one of GSK's best selling drugs. In recent years, however, sales have diminished due to safety concerns and regulatory issues. Sales first began to dwindle following the 2007 publication of an article in the New England Journal of Medicine suggesting a link to increased risk of cardiovascular problems. In September 2010, the European Union banned the drug, acting upon a recommendation by the European Medicines Agency ("EMA"). Around the same time, FDA, while stopping short of an absolute ban on the product, nonetheless imposed significant restrictions (for reasons summarized in a memorandum by Janet Woodcock, M.D., Director of FDA's Center for Drug Evaluation and Research). See our previous blog here on the differences between FDA's and EMA's review of the same product.

The majority of the $3.4 billion charge will be put towards "additional provisioning in respect of the investigation by the U.S. Attorney's Office for the District of Colorado into the Group's U.S. sales and promotional practices and for product liability cases regarding Avandia (rosiglitazone)." GSK had previously announced in July 2010 a charge of $2.1 billion to settle legal claims, including those related to Avandia®. According to the company's most recent statement, however, the amount of new product liability claims in the U.S. relating to Avandia® since has been "substantial," thus necessitating the $3.4 billion figure.

by Howard E. Rosenberg, Ph.D.

More drug manufacturers are looking into producing biosimilar versions of expensive biotechnology drugs for the U.S., and they are not just from the generic stable. For example, Merck & Co. ("Merck") recently agreed with Parexel International Corp. to develop copies of biotech medicines. Parexel is a contract research organization that will provide Merck with access to global clinical development services for the biosimilar candidates being developed by the Merck subsidiary, Merck BioVentures. "Parexel has extensive, industry-leading experience with biosimilar development, and we truly understand the scientific complexities, and regulatory pathways involved," Josef von Rickenbach, CEO of Parexel, was reported as saying in a statement. "We are committed to working with Merck BioVentures to assist in advancing its biosimilar portfolio in this rapidly developing market segment for the benefit of patients worldwide."

In the past, Merck had developed a different version of Amgen's Epogen® (epoetin alfa recombinant), which had sales of $3.5 billion in 2009. Merck steered away from the project, because of the need for additional clinical trials. "A year ago we realigned with a focus on the same technology used to produce the drugs now," said Michael Kamarck, president of Merck BioVentures, "[B]y 2012 we expect to have five potential products in late-stage clinical trials." Merck expects its first biosimilar to be a copy of Amgen's Neupogen® (filgrastim), a human granulocyte colony-stimulating factor (G-CSF)‚ produced by recombinant DNA technology. Merck is also conducting clinical trials of a biosimilar to Neulasta® (pegfilgrastim), a pegylated, covalent conjugate of recombinant methionyl human G-CSF (filgrastim) and monomethoxypolyethylene glycollonger, resulting in a longer-lasting version of Neupogen®. Their combined sales were $4.6 billion in 2009.

FDA is being lobbied by trade associations representing largely innovator manufacturers to release guidance on biosimilars before approving any applications, even though this is not required by law. The Generic Pharmaceutical Association disagreed, arguing that this should not be a reason for delay and that guidance already may be already available for biosimilars approved in Europe. (The Pink Sheet, January 17, 2010). With an innovator such as Merck entering the fray, it will be interesting to see how FDA will interpret this lobbying for a guidance delay and how easy Merck and others will find their way through the labyrinthine path of the biosimilar legal process.

by Andrew M. Nason

On January 6, Cody Laboratories, Inc., and Lannett Co., Inc. (collectively "Cody/Lannett"), manufacturers and sellers of morphine sulfate solutions, appealed to the United States Court of Appeals for the Tenth Circuit from the United States District Court for the District of Wyoming's Order granting the government's motion to dismiss for lack of jurisdiction. Cody/Lannett originally complained following FDA's issuance of a 2006 Compliance Policy Guidance. The guidance stated that the grandfathering provisions of the Food Drug and Cosmetic Act ("FD&C Act") of 1938, as amended in 1962, no longer applied to thousands of "unapproved drugs" being sold in the United States, including Cody/Lannett's morphine sulfate. FDA determined that unapproved drugs were now subject to enforcement action as unapproved "new drugs" without any regard to the length of time a particular drug had been in use or the indications for or labeling of such drugs prior to 1938. Cody/Lannett sought a declaratory judgment that FDA's position regarding unapproved drugs was unlawful, and that FDA could not take action to prevent Cody/Lannett from manufacturing, marketing, and selling morphine sulfate, solely because Cody/Lannett do not have an approved New Drug Application ("NDA"). Cody/Lannett alleged that FDA's action violates the Administrative Procedures Act ("APA") and the FD&C Act.

The FD&C Act of 1938 gave FDA the authority to oversee the safety of food, drugs, and cosmetics, and required premarket review of new drugs for safety. The 1962 amendments expanded FDA's premarket review of new drugs to include efficacy. The grandfather provision in the 1938 Act indicates that a drug shall not be deemed a "new drug" that requires approval by FDA "if at any time prior to the enactment of this Act [June 25, 1938] it was subject to the Food and Drugs Act of June 30, 1906 . . . and if at such time its labeling contained the same representations concerning the condition of its use." This wide class of "unapproved drugs" does not, however, exist completely outside of FDA's regulatory authority, because the Food and Drugs Act still categorizes unapproved drugs as "drugs." As such, manufacturing facilities for unapproved drugs are subject to FDA inspection every two years, and manufacturers and others must report adverse events related to unapproved drugs to FDA, which can immediately pull unapproved drugs from the market if they cause harm to the public. FDA issued its 2006 guidance, however, without making formal findings or developing any administrative record.

The District Court found that it did not have jurisdiction to review either FDA's determination that morphine sulfate is a "new drug" or FDA's refusal of priority review to Cody and Lannett's NDAs, because such actions did not constitute "final agency action" as required for review under the APA. FDA determined that morphine sulfate is a new drug in a non-binding industry guidance letter, which the court determined does not constitute final agency action. Furthermore, the court determined that FDA's refusal to grant priority review to Cody/Lannett's NDAs did not constitute final agency action, because it did not create any rights or obligations and no legal consequences flowed from it. Because it found itself without jurisdiction, the District Court dismissed the case without prejudice.

The case could return to the district court level if the appeals court reverses the jurisdictional decision. Even if jurisdiction exists, however, FDA likely will still argue that the court should dismiss the case for failure to state a claim upon which relief can be granted. FDA states that Cody/Lannett relies on the grandfathering provisions of the FD&C Act, which require the labeling and composition of the drug in question to be identical to what it was before 1938. As Cody/Lannett only began marketing five years ago, FDA argues their composition and label could not have existed prior to 1938, and thus the grandfathering provisions do not apply to Cody/Lannett's morphine sulfate solutions. Furthermore, recent safety alerts suggest it may be in the public interest for FDA to take more control of the concentrations in morphine products. If the decision stands, FDA will likely use it to discourage other companies from challenging FDA in court over the Agency's Unapproved Drugs Initiative enforcement plans.

by Dario A. Machleidt

FDA's premarket notification procedure for medical devices (Section 510(k) of the Federal Food, Drug, and Cosmetic Act) has come under fire recently. The 510(k) process has been criticized as unpredictable and slow, thereby preventing patients from having access to new and necessary medical devices, while also permitting unsafe devices into the market. In response, a new survey funded by the Institute for Health Technology Studies ("InHealth") seeks to collect information from individuals and companies familiar with the challenges faced in 510(k) submissions.

In order to collect statistically valid information addressing industry concerns, rather than rely on existing anecdotal evidence, research teams led by John Linehan of Northwestern University and Jan Pietzsch of Stanford University and CEO of Wing Tech launched their survey, titled "A Comprehensive Analysis of the FDA 510(k) Process: Industry Practice and the Implications for Reform," on December 22, 2010. The survey will only run through January 2011, where the short timeframe will hopefully permit the study's sponsors to provide their results to the Institute of Medicine ("IOM") committee that is currently reviewing the 510(k) process (The Tan Sheet, January 10, 2010).

The study will gather information and perceptions from industry representatives that have been involved in a 510(k) submission within the past three years. The survey's 86 questions cover various aspects of FDA's process ranging from industry experiences with premarket timelines, data requirements imposed by FDA, perceptions on the clarity of those requirements, differences between how companies and FDA interpret process requirements and guidance documents, and challenges with the 510(k) process, such as reviewer turnover.

The Northwestern and Stanford researchers, who will target about three thousand respondents, hope to have a better response rate than that experienced by Josh Makower (Consulting Professor of Medicine, Stanford University; CEO, ExploraMed Development, LLC; Venture Partner, NEA), whose study regarding industry perceptions of FDA's medical device regulatory procedures garnered only two-hundred and four responses out of more than one thousand companies contacted, for a twenty percent response rate. The approximately one-month period during which the 510(k) study will be active may, however, result in fewer responses than the authors would prefer.

by Howard E. Rosenberg, Ph.D.

Last July, the Drugs Controller General of India ("DCGI"), which is akin to FDA, proposed to implement overseas inspections of manufacturing sites as a consequence of the banning of the import of raw materials from ten Chinese drug companies that supplied products without having the mandatory drug manufacturing standards. It has now been reported that in about two weeks the DCGI will begin inspections of manufacturing facilities from where Indian companies source their active pharmaceutical ingredients and intermediates for pharmaceutical production. The pilot program will initially focus on Italy and China and, if successful it will then be extended and introduced for all countries.

The Central Drugs Standard Control Organisation is already in the process of pulling together a team of fifteen to twenty drug inspectors, trained in auditing and inspection of sites in accordance with international standards.

Dr. Surinder Singh, Drugs Controller General of India, said, "Currently there are 1364 sanctioned posts, and around 864 are filled up. We need at least 3,100 drug inspectors in the country." http://www.business-standard.com/india/news/dcgi-plans-to-raise-drug-inspectors-tally-in-india/417975/ Dr. Singh has already pointed out that there was a need for overseas inspections, saying that it is the responsibility of the indenting agents to make the manufacturers aware of the rules and regulations of the country. "As of now they have poor knowledge of the Drugs and Cosmetics Act, poor understanding and interpretation of the drug rules of the country. In fact, surprisingly at times, even their submissions are not complete. It is the responsibility of the indenting agents to make them aware of these laws and also to ensure that these companies follow the rules and regulations of the country if they want to do business in India."

If successful, India's move to inspect manufacturing sites may lead to greater cooperation with FDA inspectors for pharmaceutical products imported from India.

ACI Patent Term Adjustment and Patent Term Extension Conference 2011

ACI, the creator of Maximizing Pharmaceutical Patent Life Cycles and Paragraph IV Disputes (April 2011) is pleased to present its inaugural advanced forum on the "ins and outs" of Patent Term Adjustment and Patent Term Extensions.

We have surveyed our life sciences audience and heard their overwhelming requests for a conference on these very complicated and challenging applications. In response, we have assembled a faculty of the most experienced patent professionals who will show you how to navigate these processes - step-by-step. They will help you:

• MASTER the essentials of PTA from questions of eligibility, calculation, application preparation and redress
• DECIPHER the mysteries of A, B and C-delays
• LEARN to solve the A and B-delay overlap dilemma and B-delay National Stage queries vis-à-vis Wyeth v. Dudas and Japan Tobacco
• AVOID applicant delays and circumvent "failure to engage" findings by the PTO
• NAVIGATE the complexities of PTE in terms of substance and procedure
• COMPREHEND how the key challenges in Wyeth Holdings, Photcure, Lupin and Angiomax will affect PTE determinations in the future
• APPRECIATE how second generation patents and regulatory exclusivities factor into patent term extensions
• EXAMINE the significance of Supplemental Protection Certificates (SPCs) in patent term restoration in the EU

Come to this conference and learn everything that you wanted to know about PTA and PTE and more.

ACI is pleased to offer a discount of $200 to FDA Lawyers Blog readers. Register now by calling 1-888-224-2480, faxing your registration form to 1-877-927-1563, or logging on to here.

by Elizabeth Murphy

FDA continues to mull over various approaches in instituting a human generic drug user fee program. The agency held a public meeting in September (summarized here), soliciting input from industry members. Though the meeting was well-attended by ANDA sponsors, FDA is now reaching out to other entities for feedback, particularly manufacturers of active pharmaceutical ingredients. Compared to innovators, the generic drug applicants rely more heavily on outside manufacturers. Thus, input from various entities along the supply chain is of particular importance, as these players will likely be affected by the user fee scheme ultimately imposed.

FDA is also considering application-based fees, such as tiered fees (higher fees for more complex applications) and sliding scale fees (the size of the ANDA applicant is commensurate with the fee imposed). Also under consideration is a provision that would do away with the requirement for preapproval inspections in lieu of periodic inspections in limited circumstances.

Heather Bresch, President of Mylan Inc, advocated at the September meeting her proposal for facility-based fees that would aim to level the playing field between domestic and foreign generic manufacturers, by imposing equal regulatory burdens on each. The fees would specifically target overseas drug manufacturing facilities, over which FDA has recently stepped up its scrutiny. In support of her proposal, Ms. Bresch stated in December, "I'm just realistic about the economic situation. Our industry is going to have to subsidize the globalization of the FDA."

Industry is generally in favor of a generic user fee program. Due to the influx of generic drug applications in recent years, the median review time is now around two years, up from what used to be reported as a median about 17 months. In addition, FDA is also currently backlogged by roughly 2,000 new applications. In theory, a generic user fee program would expedite review times and increase predictability.

For more background information on proposed generic user fees, see our blog here.

by Laura Fanelli

Last week, it was announced that effective January 7, Joshua M. Sharfstein would be leaving his post as FDA's Deputy Commissioner. Sharfstein's resignation was the result of his accepting a new role as Maryland's top public health official, Secretary of Health and Mental Hygiene, by Maryland's Governor, Martin O'Malley. Sharfstein has commented that his resignation was not because he was looking to leave the Agency. Instead, he stated, "I was committed to the FDA. But opportunities like this don't come along very often. It's a really great job at a really important moment in time, and with terrific leadership in the state," as reported by Lyndsey Layton and John Wagner of The Washington Post.

As a result of Sharfstein's departure, FDA Commissioner Margaret A. Hamburg, M.D. named John Taylor, FDA's legal counselor to Hamburg since 2009, as Acting Deputy Commissioner. Taylor will be acting in the role for 60 days beginning on January 10. Although Taylor does not have a medical degree, he has expansive knowledge of FDA and the product areas it regulates. This knowledge is the result of his long FDA career, as well as prior positions in the biotechnology, pharmaceutical, and medical device fields.

Hamburg also announced several other personnel changes. (The Pink Sheet, Jan. 5, 2011). The memorandum announcing these personnel modifications suggests that restructuring FDA's senior administrative positions and job responsibilities are approaching. Hamburg stated that she will be consulting with senior FDA leaders to evaluate specific functions and positions. "My top priority is advancing FDA's public health mission, and I want to ensure all our resources--from our programs to our key staff positions--are as efficient and well-organized as possible," Hamburg said.

by Brian Malkin

On December 20, FDA filed a motion to reinstate the preliminary injunction against e-cigarette distributor NJOY that the D.C. Circuit Court of Appeals dissolved on its own motion on December 15. FDA's motion was accompanied by a petition for hearing and rehearing en banc, arguing that the panel's decision rests on a clear error of law and that the preliminary injunction should be reinstated to protect the public health at least until the petition for rehearing is decided. FDA further requested that its petition for hearing be expedited, citing to various inherent dangers in e-cigarettes, such as ingestion or skin contact with the fluid in non-vaporized e-cigarette cartridges or the potential for excess nicotine exposure.

FDA's motion asserts that the panel's decision was erroneous and confuses the "tobacco problem" with a "promising tool in the tobacco control arsenal," because it treated e-cigarettes, which contain isolated nicotine but contain no tobacco, as "tobacco products" under the Family Smoking Prevention and Tobacco Control Act ("Tobacco Control Act"). Instead, FDA argues, the panel should have been guided by provisions in the Tobacco Control Act (21 U.S.C. § 371r(a)(1)) that permit FDA to "fast track research and approval products" under FDA's existing drug and device provisions to "consider approving the extended use of nicotine replacement products (such as nicotine patches, nicotine gum, and nicotine lozenges) for the treatment of tobacco dependence." Whether FDA would go so far as to embrace e-cigarettes as a effective smoking cessation tool, as suggested by a study that we reported on here, has yet to be seen.

FDA further acknowledges that the panel's decision placed e-cigarettes in an unregulated area, because if the panel's decision were followed, e-cigarettes could not be regulated until FDA promulgated regulations deeming them to be subject to regulation under the Tobacco Control Act. FDA's motion is supported in a motion and brief by the amici curiae group of the American Academy of Pediatrics, the American Cancer Society, the American Cancer Society Cancer Action Network, the American Legacy Foundation, the American Lung Association, the American Medical Association, the Campaign for Tobacco-Free Kids, and Public Citizen.

Opposing FDA's motions, NJOY argues that FDA has not met its burden to point to a law or facts that the panel misapprehended. In particular, NJOY notes that FDA's hypothesis that the panel's decision undermines incentives for nicotine replacement therapies is "unsupported" and "wrong" and that FDA's "risk to public health" argument merely restates generalized warnings found on NJOY's website into a threat that has "no indication of imminent public harm." NJOY asserts, moreover, that FDA's decision to not regulate e-cigarettes under the Tobacco Control Act, even provisionally, undercuts FDA's public health argument. As we noted in our previous blog on this topic, FDA appears to have lost valuable time with its initial regulatory approach to block e-cigarette imports and deem the products to be unapproved drug/devices.

by Howard E. Rosenberg, Ph.D.

Monitoring the effect of last technical revision (Directive 2007/47/EC), has resulted in the European Commission ("EC" or "Commission") suggesting that it should be reviewed, arguing that the current system has not always offered a uniform level of protection of public health. New and emerging technologies have challenged the current framework, highlighting gaps and pointing to a certain scarcity of expertise. The Commission would like the European Community regime to further converge on to the Global Harmonisation Task Force for Medical Devices ("GHTF") model. In addition, they note that "the legal system has been criticised as being too fragmented and difficult to follow and is fraught with national variation."

The European Commission services consulted stakeholders on the revision of this legal framework for medical devices ("recast") between May 8 and July 2, 2008. The Commission received 200 responses to the public consultation, whereas the previous consultation, 2004-2007, received only 80 responses, reflecting the huge increase in interest. Respondents agreed that elements of centralization would be useful. However, the suggestion to expand the role of the European Medicines Agency ("EMA") was rejected by the vast majority, mainly based of the fear that EMA's involvement would represent a move towards adopting pharmaceuticals-like regulations and may also result in undue delays and higher costs, which would have an adverse effect on small and medium-sized enterprises, which make up around 80% of the sector.

Another public consultation on the technical aspects for the revision of the In Vitro Diagnostic Medical Device Directive 98/79/EC was also carried out. The EC believes that since 1998, in vitro diagnostics have significantly evolved technologically. The Commission considers it necessary, to introduce, among other things, clearer definitions and requirements for safety and performance.

The next step is for a high-level conference to be organized in March 2011 which will bring together regulatory authorities, healthcare professionals, patients, industry, academics and other interested parties to discuss the specific aspects.

by Howard E. Rosenberg, Ph.D.

This year, 2011, may provide some useful guidance (or even a decision or two) in a couple of key Court of Justice of the European Union ("CJEU") cases regarding European Supplementary Protection Certificates (SPCs)--Europe's version of patent term restoration in the U.S. One case concerns the type of marketing authorization that enable a product to qualify for an SPC and the other case is about the meaning of the term "product" being protected by a basic patent in force.

The first case is actually the combination of two cases (galantamine in Generics [UK] Ltd. v. Synaptech and memantine in Synthon v. Merz), where each drug was marketed for many years in one or more member states prior to the later filing of dossiers which included the full regulatory details and studies that are required by the European Economic Community Directive 65/65/EEC. These subsequent EU-wide authorizations were compliant with 65/65/EEC, and SPCs were obtained based on the new 65/65/EEC authorizations. The combined case before the CJEU raises questions to clarify what constitutes an acceptable marketing authorization (i.e., approval under a national law or only under 65/65) and/or whether products marketed for the first time in the EEC without going through the administrative procedure Directive 65/65 actually fall within the scope of SPC law at all.

The second case concerns the availability of SPCs for Medeva's multi-disease vaccines. The UK has generally rejected applications for SPCs where the applications have been based upon a marketing authorization for a product containing a combination of active ingredients, but where the basic patent has explicitly claimed only one of the components. Recently, the UK court has acknowledged that there may be some doubt as to whether the words "protected by a basic patent in force" in Article 3(a) of the SPC Regulation (EC 469/2009) requires a "direct protection" test (the active ingredients of the authorized product must be both disclosed and claimed in the basic patent) or just an "infringement" type test (does the patent claim at least one of the authorized products and thus a third party would infringe that claim).

The Medeva case, referred to the CJEU, specifically asks what is meant in Article 3(a) of the SPC Regulation by "the product is protected by a basic patent in force" and what criteria should be used in deciding it. It also includes an Article 3(b) question as to whether an SPC is available for an approved medicinal product containing a single active ingredient or combination of active ingredients together with one or more other active ingredients which is the first marketing authorization that places the single active ingredient or combination of active ingredients on the market.

If you are interested in SPCs or patent term extension in the U.S., FDA Lawyers Blog's own Brian J. Malkin will be speaking at an inaugural American Conference Institute event focusing on patent term adjustments, patent term extension, and SPCs later this month. For more information and an FDA Lawyers Blog reader discount, see here and here.

by Elizabeth Murphy

On January 4, President Barack Obama signed into law the Food Safety Modernization Act, the first major overhaul of the nation's food safety system in over 70 years. A day before the bill was signed, FDA Commissioner Margaret A. Hamburg, M.D. posted a statement on the White House Blog stating: "The historic legislation the President will sign tomorrow directs the Food and Drug Administration, working with a wide range of public and private partners, to build a new system of food safety oversight - one focused on applying, more comprehensively than ever, the best available science and good common sense to prevent the problems that can make people sick."

The legislation has been enacted as a response to a spate of food contamination outbreaks in recent years, most notably: bagged spinach (2006), peanut butter (2007 and 2009), peppers (2008), cookie dough (2009), and eggs (2010). FDA's ability to respond to these crises was somewhat hampered by their limited resources and authority. The new law, however, allows the agency to be more proactive in preventing these sorts of large-scale outbreaks, providing FDA with increased authority to inspect food processing facilities more frequently, implement stricter standards, and recall contaminated foods in the event of an outbreak.

The bill signed on Tuesday has been under debate for quite some time. The House was the first to pass a version of the bill, passing H.R. 2749 in July 2009. It took the Senate until November 2010 to pass its version, S. 510. After a lengthy series of objections, procedural delays, one constitutional snag, and threats of filibuster, the Senate and House finally reached an accord late in the waning lame duck session of Congress.

See our other posts detailing Congress' sustained efforts in passing the Food Safety Modernization Act here (December 21), here, (December 12), and here (November 23).

by Elizabeth Murphy

Each year, the beginning of January inspires in some a commitment to end unhealthy habits in the New Year. Those looking to quit smoking (a perennially popular New Year's resolution, according to USA.gov) in 2011 may find hope in the results of a recent study conducted in connection with the Boston University School of Public Health. The study, performed in part by Dr. Michael Siegel, community health sciences professor at the school, reports that electronic cigarettes ("e-cigarettes") are a much safer alternative than conventional tobacco-based cigarettes. According to the study (and perhaps, unsurprisingly), e-cigarettes appear to be only 1/1,000 as carcinogenic as their conventional counterparts. The study further indicates that e-cigarettes pose no greater risk than other nicotine replacement devices currently regulated by FDA, such as nicotine patches, gum, inhalers, lozenges, and nasal sprays.

E-cigarettes have become increasingly popular in recent years as smoking cessation aids, although they are not legally marketed as such. An e-cigarette is essentially a battery-operated nicotine inhalation tube designed to mimic the look and feel of smoking a conventional cigarette. The key difference between an e-cigarette and a conventional cigarette, however, is that the former delivers to the user a vaporized nicotine solution and the latter the byproducts of tobacco leaf combustion, e.g., tar and other carcinogenic compounds.

Since their 2007 introduction to the U.S. market, the regulation of e-cigarettes has been a source of controversy. FDA has taken the position that e-cigarettes should be regulated as drugs or devices under the Federal Food, Drug and Cosmetic Act ("FD&C Act"). In September, the agency sent warning letters to five popular e-cigarette manufacturers to that effect. See our blog here on that topic.

by Mark P. Walters

On December 29, the United States Department of Agriculture ("USDA") published new rules in the Federal Register to require meat packers to include labels listing calories, calories from fat, total fat, saturated fat, cholesterol, sodium, protein, and vitamins for forty of the most commonly purchased cuts of beef, poultry, pork, and lamb. In addition, the rule provides that, when a ground or chopped product does not meet the regulatory criteria to be labeled "low fat," a lean percentage statement may be included on the label or in labeling as long as a statement of the fat percentage that meets the specified criteria also is displayed on the label or in labeling. The new rules are set to take effect January 1, 2012.

First required on many foods in 1993, "Nutrition Facts" labels were not required on meat except under a voluntary provision. By publishing the rule in the Federal Register, the USDA's Food Safety and Inspection Service ("FSIS") has begun the process of making them mandatory. The labels either will need to be attached to meat packages or made available to consumers at the point of purchase.

In the notice, FSIS states that "[n]utrition labeling continues to be an integral part of USDA's efforts to educate consumers concerning nutrition and diets," and that "[t]he information FSIS is requiring would ... assist consumers in following the advice in the Dietary Guidelines for Americans, 2005."