FDA Lawyers Blog

By Howard Rosenberg

Last week saw five reported cases of other manufactures' drugs being found in Nurofen Plus packets. The anti-psychotic Seroquel XL had been found in four packets of Nurofen Plus in England and Neurontin, a prescription medicine for epilepsy, had been found in one packet of Nurofen Plus bought from an independent pharmacist in Northern Ireland.

As a consequence Reckitt Benckiser (UK) has now stopped the manufacturing of Nurofen Plus and its distribution has been halted across the UK.

Reckitt Benckiser, recalled the product on Friday night and halted distribution after discovering the issue. The firm estimated 250,000 packets were in customers' hands.
Dr Aomesh Bhatt, medical director for Nurofen Plus said: "We are taking this matter extremely seriously and have decided to recall all packs of Nurofen Plus as the most prudent course of action in the current circumstances."

The UK's health authority, Medicines and Healthcare products Regulatory Agency (MHRA) has issued a class 1 drug alert to healthcare professionals, including General Practioners (GPs).

by Dario Machleidt

The United States Department of Justice ("DOJ") recently fined Google Inc. ("Google") $500 million for permitting Canadian pharmacies to advertise on its search engine to American consumers. The importation of controlled and non-controlled prescription drugs is a violation of federal law, including the Federal Food, Drug, and Cosmetic Act ("FD&C Act"), and, in the case of controlled prescription drugs (those with high chances for abuse) the Controlled Substances Act. Google, despite knowing this fact, permitted Canadian pharmacies to post advertisements directed to United States citizens through its AdWords program. Google's profits stem primarily from AdWords advertising revenue.

The importation or re-importation of prescription drugs into the United States from foreign countries potentially violates several sections of the FD&C Act. Such conduct can violate 21 U.S.C. § 355, which prohibits the introduction of non-FDA approved medications into interstate commerce. This includes foreign versions of drugs approved in the United States and drugs manufactured in the United States but intended for foreign markets. The importation of foreign prescription drugs can also violate 21 U.S.C. § 353(b)(2) which prohibits dispensing a drug without proper labeling. 21 U.S.C. § 331(a), (d), and (i) forbid marketing of misbranded, adulterated, or counterfeit drugs, acts that are difficult to monitor when ex-United States pharmaceuticals find their way into this country. And finally, 21 U.S.C. § 381(d)(1) prohibits a party, except the actual drug manufacturer, from re-importing a drug from a non-United States market.

As early as 2003, Google was aware that companies violated federal law by importing prescription drugs into the United States from foreign countries. Google even blocked pharmacies from various countries from advertising in the United States through Google's AdWords program. Google, however, did not block Canadian pharmacy advertisers from targeting American consumers. In fact, it provided customer support to Canadian online pharmacy advertisers so that they could improve and optimize their AdWords advertisements.

by Andrew S. Wasson

As the East Coast deals with the damage (flooding, wind, or otherwise) left by Hurricane Irene, we note that FDA provides a substantial amount of resources to those wondering whether they can consume food, drugs, or water affected by the storm. Generally, as you can expect, FDA says to generally err on side of caution. The full guidelines can be found here, but a few key guidelines dealing with food, water, and drugs during the aftermath follow. We have also compiled a list of FDA resources at the end of the post. We hope that everyone stayed safe during the storm and that any damage sustained was minimal.

Food
• Do not eat any food that may have come into contact with flood water. If in doubt, throw it out.
• Do not eat food packed in plastic, paper, cardboard, cloth and similar containers that have been water-damaged.
• Discard food and beverage containers with screw-caps, snap lids, crimped caps (soda bottles), twist caps, flip tops and home canned foods, if they have come in contact with flood water. These containers cannot be disinfected.
• Check to ensure that the freezer temperature is at or below 0°F and the refrigerator is at or below 40°F.
• Keep the refrigerator and freezer doors closed as much as possible to maintain the cold temperature.

by Andrew M. Nason

A federal judge in the U.S. District Court for the Central District of California recently rejected an argument that FDA regulation of homeopathic remedies under the Federal Food, Drug, and Cosmetic Act ("FDC Act") preempts claims against the manufacturer under state law. The case, Delarosa v. Boiron, Inc., stemmed from Boiron's claims that its homeopathic product, Children's Coldcalm®, provided relief from common cold symptoms. The plaintiff argued that she found the Coldcalm® pellets ineffective in relieving the common cold, and alleged that by making such claims Boiron violated the California Consumers Legal Remedies Act, the California Unfair Competition Law, and committed common law fraud. Boiron filed a Motion for Judgment on the Pleadings, arguing that over-the-counter homeopathic drugs in compliance with the FDC Act inherently cannot be in violation of the California Consumers Legal Remedies Act or other state laws. Judge Josephine Tucker disagreed, and denied the motion, allowing the case to proceed.

Under the FDC Act, the definition of "drug" includes articles recognized in the non-governmental Homeopathic Pharmacopeia of the United States ("HPUS"), but homeopathic products need not prove safety or efficacy to FDA. Rather, homeopathic drugs must only conform to the standards of strength, quality, and purity set forth in the HPUS. Homeopathics manufacturers must also follow labeling provisions in the FDC Act, register with FDA, and comply with good manufacturing practices.

by Erin A. Lawrence

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

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

by Brian Malkin

Late last week, an online journal, PLoS ONE, published a research article by lead researcher Deborah Korenstein from the Department of Medicine, Mount Sinai School of Medicine, New York, with the objective to systematically analyze adherence to FDA's advertising guidelines to a cross-section of pharmaceutical print advertisements. The authors stated that their study was the first of its kind in nearly 20 years and was designed to help inform FDA's new "Bad Ad" Program.

FDA's Bad Ad Program is FDA's outreach program to help educate health care professionals about how they can help FDA ensure that prescription drug advertising and promotion is truthful and not misleading. The program aims to helps health care professionals who prescribe medications or make prescription selection decisions to better understand how prescription drugs are used by a variety of health care professionals such as physicians, nurse practitioners, physician assistants, and pharmacists to better understand what constitutes appropriate prescription drug promotion and advertising and how to report possible violations.

The authors of the study said that they recognize FDA's Division of Drug Marketing and Advertising ("DDMAC") has been entrusted with an almost impossible task--regulating $58 billion in pharmaceutical advertising with a mere $ 9 million (2008 dollar estimates). FDA's lack of adequate resources, the authors propose, has prevented FDA from properly reviewing each individual piece of pharmaceutical advertising.

by Howard E. Rosenberg, Ph.D.

A recent article in The New York Times highlighted that after many years of discussions and failed attempts, the federal government and the generic drug industry finally reached an agreement that will lead to routine inspections of overseas plants, potentially affecting the pharmaceutical market. More and more pharmaceutical products are now dispensed as generic drugs and for a vast majority of these drugs, the active ingredient ("API") is manufactured outside the U.S. Indeed it appears that over 80 percent of APIs for drugs sold in the United States are made abroad, mostly in facilities in China and India. FDA is overstretched and is unable to regularly visit these facilities, unlike many of the manufacturing sites that are within the U.S. FDA has been working closely with the European and Australian health authorities on a program to improve matters, and the authorizes have just completed a successful pilot where the different health authorities share the information gleaned from the documentation received and the results of plant inspections carried out by the various government health inspectors. This allows each authority to better judge the quality of the facilities without having had to send their own staff. The shared program thus allows for an improvement in both the number of plant inspections carried out and global understanding and standardization of current good manufacturing procedures ("cGMPs") requirements.

Even so, inspections are time consuming and costly and for years the cost of visits has led to a dearth of inspections, which has long been a bone of contention to those manufacturers that do put the time and effort into keeping their plants running to cGMPs. These companies have often pointed out that their competitors that are not being inspected by FDA are potentially cutting corners and not manufacturing to cGMPs and are, in effect, "getting away with it" by saving costs and by not complying with cGMPs. Recent cGMP issues, especially in China, have done a much to justify that position.

by Elizabeth Murphy

Earlier this month, Commissioner Margaret A. Hamburg, M.D. touted FDA as "America's Innovation Agency" in a Wall Street Journal opinion piece. Countering criticism of the agency's approval process as "slow and bureaucratic," Hamburg cited statistics comparing its approval timeline of priority drugs and medical devices with its European counterpart, the European Medicines Agency ("EMA"). According to her calculations, FDA had approved a higher number of new cancer drugs up for approval in less time than EMA during the time period from October 2003 through December 2010. Hamburg also pointed to the fact that lower-risk medical devices, which constitute the majority of all devices reviewed on a yearly basis, reach the U.S. market as quickly, if not more quickly, than they do in Europe.

Hamburg also touched on FDA's role within both the domestic and global economy. She first noted that products regulated by FDA currently account for "more than one in five of all dollars spent on consumer products in the U.S." She additionally stated that FDA's approval process, "[b]y instilling confidence in American products and technologies . . . stimulates economic growth, creating jobs at home and opening markets overseas." As evidence, Commissioner Hamburg pointed to the ability of medical device and biopharmaceutical industry players' ability to weather the recent economic downturn of 2006-2009.

Others are less convinced, particularly investors in new and emerging medical technologies. Responses to Hamburg's article suggest that start-up companies aiming to develop innovative treatments often have difficulty securing capital sufficient to cover the expenses imposed by FDA's onerous regulatory hurdles. John Freund, of Skyline Ventures, claimed that FDA requirements are causing investors to focus less on treatments for conditions that affect a large portion of the U.S. population, i.e., diabetes, obesity, and cardiovascular disease, in favor of pursuing orphan designations. As a result, many start-up companies are forced to close or leave the U.S. Kenneth Abramowitz of NGN Capital echoed this sentiment, characterizing FDA's approval process as "a money pit that has driven many small companies to bankruptcy."

by Erin A. Lawrence

On August 11, the American Civil Liberties Union of Northern California ("ACLU") and the San Francisco Bay Guardian (the "Guardian") filed a complaint for injunctive relief under the Freedom of Information Act ("FOIA") seeking that FDA turn over records pertaining to the federal government's role in overseeing or failure to oversee state prisons' procurement of the lethal injection drug--sodium thiopental. The ACLU and the Guardian seek documents that would reveal whether state officials violated any laws in the states scramble to acquire execution drugs from abroad and the role of federal agents in the process.

Currently, lethal injections constitute a cocktail of three drugs--sodium thiopental, pancuronium bromide, and potassium chloride. Sodium thiopental is a fast-acting general anesthetic that puts the inmate to sleep before the deadly drugs are administered. Pancuronium bromide is a paralyzing agent that stops the inmate's breathing and potassium chloride stops the inmate's heart.

States have been struggling to get their hands on the first part of the drug cocktail--sodium thiopental. Hospira Inc. ("Hospira") was the sole American manufacturer of sodium thiopental, however, due to supplier issues, Hospira has not been manufacturing the drug. In response, states sought to import the drug from abroad to continue planned prisoner executions. FDA initially attempted to stop the importation of sodium thiopental, but subsequently cleared the drug for entry. FDA reasoned that they would take a hands-off approach and defer to law enforcement and permit the drug's importation, because the subject falls out of outside of FDA's role in protecting public health.

by Andrew S. Wasson

Facebook signaled a major policy shift in the amount of control that pharmaceutical companies have over their Facebook webpages. The policy change, reported byThe Washington Post last Friday, was said to take effect yesterday. Originally, Facebook allowed pharmaceutical companies to set up pages but allowed them to block public comments on their "walls." FDA has changed its position, however, and will now not allow pharmaceutical companies with this privilege. There are some exceptions. Facebook will still allow a company to block comments on a page about a specific drug. Facebook will also allow a company to delete specific comments.

It should not come as a surprise that the pharmaceutical industry has been slow to embrace social media. The industry waded into social media reluctantly, and only after Facebook allowed it to prohibit wholesale commenting. The highly-regulated pharmaceutical industry faces a number of unique concerns. Looming large among these concerns is the worry that individuals may post a report about side effects that would qualify as a serious adverse event ("SAE") and trigger a duty to report to the Agency. Pharmaceutical companies also worry that posters will advocate the use of pharmaceuticals for off-label uses. Compounding the issue, industry will face the non-trivial task of sifting the bona fide comments from the larks.

Rather than deal with an "open wall," some companies have decided to take down their pages altogether. For example, AstraZeneca removed its Take On Depression page and Johnson & Johnson removed its psoriasis page Fit In Your Skin. A list of shuttered pages can be found here. Other manufacturers remain undeterred. For instance, Pfizer will maintain the hemophilia pages it sponsors, Our Hemophilic Community.

by Brian Malkin

On August 9, FDA released minutes from three, six-hour Negotiations Meetings held on July 14, 21, and 28 between FDA and industry stakeholders regarding the proposed Generic Drug User Fee Act ("GDUFA") Program. The industry stakeholders included the Generic Pharmaceutical Association ("GPhA"), the European Fine Chemicals Group ("EFCG") and SOCMA's Bulk Pharmaceuticals Task Force ("BPTF"), and organizations that represent active pharmaceutical ingredient ("API") manufacturers. According to FDA, consensus was achieved on many GDUFA issues but others remained to be tackled as soon as another FDA-stakeholder meeting, which was held on August 11.

Some of the consensus points included:

• Industry agreed to fully fund the program in year 1 ($299 million) with standard inflation adjustments each subsequent year with some of the fees in the first year obtained in a one-time fee from pending abbreviated new drug applications ("ANDAs") in the current ANDA backlog.
• Congressional appropriations that currently fund the generics program will not be significantly reduced.
• FDA will not incorporate a work-load adjuster in the fees, which has been part of the pharmaceutical drug user fee act ("PDUFA") program.
• FDA will grant few if any fee waivers or exemptions.
• Facility and application fees will take into consideration extent of foreign manufacturing and need for foreign inspections.
• FDA will provide inspection outcomes on a public website that is updated in a timely manner.
• Sites that make both API and finished dosage forms ("FDFs"), called combination sites, will pay facility fees associated with both operations and API manufacturing information, e.g., if an ANDA contains DMF-type information the applicant would pay fees for both the ANDA and DMF.

by Andrew M. Nason

On August 10, Gilead Sciences, Inc., the world's largest HIV drug maker, announced that FDA has approved Complera™ (emtricitabine/rilpivirdine/tenofovir disoproxil fumarate), a once-daily single-tablet regimen for the treatment of HIV-1 infection in treatment-naïve adults. Complera™ combines Gilead's Truvada®, a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, and Tibotec Pharmaceuticals' rilpivirdine (marketed in the United States by Janssen Therapeutics as Edurant™). FDA previously approved the two treatments in August 2004 (Truvada™) and May 2011 (rilpivirdine) for use as part of HIV combination therapy. Like other AIDS drug cocktails, Complera™ aims to simplify the medicine regimen for AIDS patients. Complera™ is the second once-daily single-tablet regimen for HIV-1 available to treatment-naïve patients. Gilead's Atripla™ (efavirenz/emtricitabine/tenofovir disoproxil fumarate), the world's best-selling HIV drug Gilead markets in conjunction with Bristol-Myers Squibb, is the first.

FDA originally issued a refuse-to-file notice in January 2011 for the NDA Gilead initially submitted in 2010. FDA expressed dissatisfaction with the NDA on the grounds of insufficient data. Gilead re-filed its NDA for Complera™ in February 2011. FDA found support for Complera's™ approval in two Phase 3, double-blind, active controlled, randomized studies Tibotec conducted that evaluated the safety and efficacy of rilpivirine compared to efavirenz among HIV-1 infected adults who had never before received treatment. Gilead's bioequivalence study then demonstrated that the co-formulated single-tablet regimen achieved the same medication levels in the bloodstream as the three drugs administered separately.

by Andrew S. Wasson

FDA provided a window into its thinking on biosimilars last week in the New England Journal of Medicine. The article, titled "Developing the Nation's Biosimilar's Program" co-authored by FDA officials, updated the medical community on the progress of FDA's implementation of the Biologics Price Competition and Innovation Act ("the BPCIA"). While the BPCIA has been in effect for over a year, FDA has kept a low profile so far on biosimilarity standards.

The article replete with guideposts that could help industry stakeholders predict future agency action. It comes as no surprise that FDA advocated the use of a "totality of the evidence" approach to determine biosimilarity and eschewed any "one size fits all" systematic assessment. Indeed, the BPCIA itself appears to require biosimilar applications to include some combination of analytical and clinical studies. The article confirmed that FDA will rely on its past experiences with protein products (both BLA and NDA) as well as the European experience to determine biosimilarity standards.

FDA also appeared to take a sliding scale approach to the balance of clinical versus non-clinical data. For example, the more rigorous the analytical assessment, the less clinical data that the Agency will likely need. Here, FDA cites its experience with enoxaparin, a complex non-biologic low molecular weight heparin product. FDA used highly-sensitive analytic techniques to compare the "fingerprint" of the reference listed drug with the generic enoxaparin. FDA would not go so far as to say that advanced analytical technology would eliminate the need for clinical studies ("for the foreseeable future"), but it would state that using advanced techniques could reduce the clinical burden.

by Dario A. Machleidt

The medical device review procedures of FDA's Center for Devices and Radiological Health ("CDRH"), which have been the subject of significant industry criticism, may see improvement in the near future. As many commentators have noted, including in this blog, a frequent industry complaint regarding the 510(k) and Premarket Approval Application ("PMA") notification processes for medical devices centers on the high FDA reviewer turnover. The 510(k) process is the most common method used by companies to bring new medical devices to market, but has been plagued by problems and perceived inefficiencies. The PMA route takes longer to navigate and is reserved for higher risk devices that are not substantially similar to an existing 510(k) device. As with 510(k) applications, its effectiveness has been widely questioned. For both paths to medical device clearance, a change in key personnel in the middle of the process often resets the review clock, forcing a company seeking approval of an innovative medical device to start from scratch with a new reviewer. This situation leads to inconsistent FDA requirements in an already time intensive and costly process.

Reviewer turnover at the FDA's CDRH division is 8.6 percent, or twice the rate of the FDA's "sister drug and biologic arms." As Jeffrey E. Shuren, M.D., J.D., Director of the CDRH, admits, change is necessary to address this issue and that "[w]e need to find the means to handle the ever-increasing workload and reduce staff and manager turnover." Shuren has also stated that "the majority of my reviewers have less than four years of experience [and that] [m]y front-line managers generally have three years experience or less." To make matters worse, ratios of managers to reviewers range from 1 to 14 on the low side, to 1 to 27 at the higher end, which results in a small number of managers, let alone experienced ones, to train and oversee inexperienced reviewers. Further, the negative impact of the CDRH's high turnover is exacerbated by the fact that innovative medical technologies are becoming increasingly complex and therefore require longer review times even by experienced CDRH personnel.

A solution to the problem surrounding FDA reviewers may be on the horizon. In a recent meeting between the FDA and the Minnesota medical device community, Shuren announced that FDA medical device reviewers will undergo certification and training beginning September 2011. This program will be the first of its kind, and it is aimed at addressing concerns about the inexperience and frequent turnover of medical device application reviewers. Implicit in FDA's decision to implement the program is the hope that standardized training will reduce inconsistencies between individual reviewer decisions.

by Howard E. Rosenberg, Ph.D.

FDA, the European Medicines Agency ("EMA"), and Australia's Therapeutic Goods Administration ("TGA") were very pleased at the outcome of their International active pharmaceutical ingredient ("API") inspection pilot program on drug quality and safety. Based on this positive experience, the agencies have agreed to continue with their collaboration on inspections, taking into account their experiences and lessons learned during the pilot phases.

The report on the API initiative describes how the information-sharing between FDA, TGA, and for Europe, the EMA, France, Germany, Ireland, Italy, the United Kingdom and European Directorate for the Quality of Medicines & Healthcare ("EDQM") proved to be beneficial and useful. Over the course of a two-year pilot phase, they shared their surveillance lists and exchanged considerable amounts of information. They found 97 sites common to all three regions, exchanged inspection reports, and were involved in collaborative inspections. The respective agencies used the reports to decide whether or not to postpone or expedite their own inspections. FDA, for example, also prohibited imports into the U.S. of a firm's products based on the negative findings from a European inspection.

A key advantage of the cooperation was that it led to increased levels of understanding between the agencies, and a greater number of inspections of value to more than one authority.

by Erin A. Lawrence

Embryonic stem cell research can continue. On Wednesday, July 27, 2011, Judge Royce Lamberth threw out the lawsuit, Sherley v. Sebelius ("the case"), where scientists, James Sherley and Theresa Deisher ("Plaintiffs"), challenged U.S. government funding of embryonic stem cell research. Judge Lambeth's current decision is decided based on the Court of Appeals for the District of Columbia's binding ruling, on April 29, 2010, that the government could continue to finance embryonic stem cell research.

Plaintiffs are scientists that work with adult stem cells, not embryonic stem cells. Sherley is a former Massachusetts Institute of Technology ("MIT") professor that now works at the Boston Biomedical Institute in Watertown. He alleged racial discrimination against MIT for denying him tenure in 2004. He also executed a hunger strike before leaving MIT in 2007. Deisher is an adult stem cell researcher based in Seattle, Washington.

Initially, on October 27, 2009, the case was dismissed. Judge Lamberth ruled that Plaintiffs' did not have standing because they were not actually harmed by the government's funding of embryonic stem cell research. The Court of Appeals for the District of Columbia overturned Judge Lamberth's decision and stated that the scientists did have standing because they faced increase competition for research funding. When the case returned to Judge Lamberth, Plaintiffs argued that government funding of human embryonic stem cell research violated the Dickey-Wicker amendment that bans funding "research in which a human embryo or embryos are destroyed." Judge Lamberth issued a preliminary injunction in favor of Plaintiffs on August 23, 2010. Judge Lamberth reasoned that the Dickey-Wicker Amendment was unambiguous and that "research" using existing cell lines was the same "research" where the embryo was destroyed. Therefore, he decided that the government must halt government funding for the research.

by Michael W. Harkness

On August 4, FDA approved the biological product Anascorp® (Centruroides (Scorpion) Immune F(ab')2 (Equine) Injection. Anascorp® is the first U.S. government-approved treatment for bark scorpion venom. Bark scorpions, also called Arizona bark scorpions, are the most venomous scorpion in North America, and are common in southeastern California, southwestern Arizona and other parts of the Sonoran Desert in Mexico. About 11,000 people a year are stung by bark scorpions in Arizona alone. Bark scorpion stings can cause severe pain, convulsions, loss of breath, and in rare cases, even death. The Mexican-produced Anascorp® had been available in Mexico before receiving orphan drug status and an expedited review process by FDA. Anascorp®, developed by Mexican company Instituto Bioclon, is created from the plasma of horses that are immunized with bark scorpion venom. In the U.S., the biological license application ("BLA") is held by Rare Disease Therapeutics, Inc., located in Franklin, Texas.

Bark scorpions are an especially dangerous threat to small children. The University of Arizona, working with Instituto Bioclon to get Anascorp® approved, responded by focusing their drug studies on the effectiveness of the drug in children. The University's research team released one of their studies in 2009 that found that most of the 15 children who received Anascorp® after a bark scorpion attack recovered within two hours. Children stung by bark scorpions who did not have access to the drug had to be sedated in order to stop the progression of the drug in the body, and in some cases had to be put on breathing machines in order to overcome the intense pain, loss of muscle control, and breathing problems associated with the stings. The venom acts as a nerve poison, and triggers nerves that cause convulsions and muscle spasms.

According to the University of Arizona pediatrician who led the clinical trials of Anascorp®, Dr. Leslie Boyer, the approval of Anascorp marks the first time that FDA has approved a drug that was made and developed in Latin America. Dr. Boyer is head of the Venom Immunochemistry, Pharmacology and Emergency Response Institute at the University of Arizona, the institute that lead the clinical trials for Anascorp®. The clinical trials were conducted on over 2,000 people at 26 hospitals in Arizona and one in Las Vegas. The reported side effects of Anascorp® from the trial included vomiting, fever, rash, nausea, itchiness, and headache.

by Rachael P. McClure

On July 29, the Institute of Medicine ("IOM") released a report calling for FDA to revamp its 35-year-old approval process for medical devices. At issue is the 510(k) process (based on section 510(k) of the Federal Food, Drug, and Cosmetic Act ("FD&C Act"), which is the most common pathway for bringing medical devices to market. FDA's definition of medical device includes products ranging from simple tongue depressors to pacemakers to laser surgical devices. Under the current 510(k) process, device manufacturers must notify FDA of their intent to market a medical device at least 90 days prior to launch. If FDA determines that the device is substantially equivalent to an existing 510(k)-cleared device or other device that was on the market when the Medical Device Amendments were enacted in 1976, then it may proceed to market. If not, it must undergo pre-market approval as a premarket approval application ("PMA"). For example, FDA received approximately 4,000 501(k) submissions in 2009.

The Agency asked the IOM to review the 510(k) process, specifically requesting consideration of whether the current process best protects patients and promotes innovation in support of public health and, if not, recommendations as to what legislative, regulatory, or administrative changes might be implemented to better achieve those goals. The recently released report calls for a complete replacement of the medical device approval process. An accompanying press release criticizes the status quo as "lack[ing] the legal basis to be a reliable premarket screen of the safety and effectiveness of moderate-risk Class II devices," to the extent that an entire overhaul is needed.

The report suggests that, because a finding of substantial equivalence does not assure a finding of safety and effectiveness, Class II devices should not be granted 510(k) clearance. It recommends that FDA develop and initiate a new dual system of premarket clearance and post-market monitoring to guarantee safety and effectiveness of these moderate risk devices. The report further criticizes underreporting of device malfunctions and unfavorable reactions by device manufacturers under the current system as well as FDA's sluggish progress in reviewing reports of such adverse events.

ACI is proud to announce its Maximizing Pharmaceutical Patent Life Cycles Conference, which has been called the pharmaceutical industry's leading and integral source for information and analysis on patent life cycle management for both small and now large molecule pharmaceutical products. It is the forum where lawyers, executives and policy makers for brand name and generic manufacturers gather each year to prepare for the life cycle challenges they currently face as well as those which they anticipate.

ACI Maximizing Pharmaceutical Patent Life Cycles 2011 NYC

This 12th ACI conference on Maximizing Pharmaceutical Patent Life Cycles promises to bring you the thoughtful and targeted commentary and in-depth analysis that you have come to expect from this industry-leading event, including:

• Presentations from key representatives from the USPTO, FTC and FDA (Invited), who will provide you with direct insights and the logic of these agencies on such pressing life cycle management strategies as:

• Patent reform; PTE and PTA determinations; and reissue and reexam proceedings
• Pay-for-delay update and finings of the FTC Report on the IP Market Place
• Forfeiture determinations

by Dan Constantinescu, Ph.D.

The Federal Circuit handed down its opinion in Association for Molecular Pathology v. Myriad July 29, 2011, reversing, in large part, the district court's holding that the claims are not directed to patent eligible subject matter as required by 35 U.S.C Section 101. The Court made the following holdings with respect to patent eligibility:

(1) Myriad's composition claims to BRCA1 and BRCA2 DNA sequences and to certain alterations associated with a predisposition to breast and ovarian cancers are patent eligible subject matter.

(2) Myriad's process claims for analyzing or comparing a subject's BRCA1 and BRCA2 DNA sequences with wild-type sequences to identify cancer-associated alterations are not patent eligible subject matter.

(3) Myriad's process claim for screening potential cancer therapeutics using transformed cell lines expressing altered BRCA1 and BRCA2 DNA sequences is patent eligible subject matter.

The Court concluded that the composition claims to isolated DNA sequences are patent eligible because the claims "cover molecules that are markedly different--have a distinctive chemical identity and nature--from molecules that exist in nature." The Court observed that isolated DNA is different from native DNA as found in a cell because "[i]solated DNA has been cleaved (i.e., had covalent bonds in its backbone chemically severed) or synthesized to consist of just a fraction of a naturally occurring DNA molecule." The Court also distinguished isolated DNA from the lines of cases dealing with purified natural elements, noting that "isolated DNA is not purified DNA. Purification makes pure what was the same material, but was previously impure. Although isolated DNA must be removed from its native cellular and chromosomal environment, it has also been manipulated chemically so as to produce a molecule that is markedly different from that which exists in the body."

"Revisiting the Debate on an Orange Book for the Biologics Price Competition and Innovation Act" by Andrew S. Wasson was published in the latest edition of FDLI Update. In comparing the Biologics Price Competition and Innovation Act ("BPCIA") to the Hatch-Waxman Amendments, commentators are quick to point out that the laws differ in many ways. Commentators often cite that the BPCIA lacks the patent information machinery contained Hatch-Waxman which would eventually lead to the Orange Book. In the article, Mr. Wasson hoped to carefully think through the role of patent information in Hatch-Waxman, understand the relationship between the original statutory language and the Orange Book in its present form, and evaluate whether the exclusion of patent information from the workings of the BPCIA would have any effect.

Wasson Associates Corner

Mr. Wasson concluded that patent information does play an important role in Hatch-Waxman. He hypothesized that a legislative scheme lacking a central repository of patent information may discourage competition, insofar as potential biosimilar manufacturers might be less likely to invest without some upfront certainty to the relevant patents. He also concluded that some of the initial concerns that militated against an Orange Book-like publication might be unfounded. For example, worries about gaming the system have less force where publication of patent information is separated from any effect on stay of approval. Further, proponents of a regime without an Orange Book made several critical assumptions about patenting patterns (i.e., that biologic products are subject many more extensive layers of patents compared to small molecule drugs). This may or may not be true.
His goal remains to gather statistics on patents per product for both drug products as well as biologic products. Because of the Orange Book, it would be relatively straightforward (albeit tedious) to gather the data on small molecule drugs. It appears less straightforward to gather the data on biologic products. Thus, it does not seem that such an empirical comparison will be forthcoming in the near future.

by Howard E. Rosenberg, Ph.D.

Case C-195/09 Synthon v Merz Pharma
Case C‑427/09 Generics [UK] v Synaptech

On July 28, the Court of Justice of the European Union ("CJEU") handed down decisions on two cases. The first between Synthon and Merz concerning the medicinal product, memantine and a second similar issue concerning galantamine. The CJEU followed the Attorney General's opinions and decided that the Supplementary Protection Certificate ("SPC") for both memantine and galantamine were invalid.

Memantine had been on the market in Germany (and approved in Luxembourg) without going through the now currently accepted safety and efficacy testing as required by the European Union ("EU") Directive 65/65. However a new marketing authorization was submitted for a second medical use and approved. This new authorization contained the safety and efficacy data required by the Directive. Subsequently the original product was withdrawn, the new product launched and an SPC applied for based on this new authorization.

The High Court of Justice (England and Wales) had doubts as to both the scope of Regulation No 1768/92 and the definition of 'first authorisation to place ... on the market in the Community', within the meaning of Articles 13 and 19 of that regulation, and referred questions to the Court of Justice for a preliminary ruling:

(1) For the purposes of Articles 13 and 19 of [Regulation No 1768/92], is an authorisation a "first authorisation to place ... on the market in the Community" if it is granted in pursuance of a national law which is compliant with [Directive 65/65], or is it necessary that it be established in addition that, in granting the authorisation in question, the national authority followed an assessment of data as required by the administrative procedure laid down in that directive?

(2) For the purposes of Articles 13 and 19 of [Regulation No 1768/92], does the expression "first authorisation to place ... on the market in the Community" include authorisations which had been permitted by national law to co-exist with an authorisation regime which complies with [Directive 65/65]?

(3) Is a product which is authorised to be placed on the market for the first time in the EEC without going through the administrative procedure laid down in [Directive 65/65] within the scope of [Regulation No 1768/92] as defined by Article 2?

(4) If not, is an SPC granted in respect of such a product invalid?