November 2011 Archives

November 28, 2011

Nicotine Vaccine Clinical Trials Begin

by Scot B. Pittman

no smoking sign.jpgMore help could be on the way for those hoping to quit smoking. Selecta Biosciences, a Watertown company founded in 2008 by researchers at the Massachusetts Institute of Technology and Harvard Medical School, began clinical testing on a nicotine vaccine last week. With roughly half of the almost 46 million U.S. smokers looking to quit every year, a potential nicotine vaccine would be a welcome addition to those wanting help. According to John Hughes, a psychiatry professor at the University of Vermont and Selecta consultant, "Only about 5 percent [of those who try] are able to quit forever."

Selecta hopes that SEL-068, the vaccine's current reference identification, will train the immune system to recognize nicotine molecules in the bloodstream and prevent them from entering the brain. Unlike many vaccines that use an actual virus (though typically dead or weakened), SEL-068 employs a synthetic nanoparticle that is designed to appear like a virus. Ideally, the body's immune system will recognize the nanoparticles as foreign and learn to produce antibodies that bind nicotine and prevent it from reaching the brain. Stopping nicotine before it enters the brain could help reduce some of the effects smokers crave, such as appetite suppression, increased focus, and calming.

The clinical trials that started last week are using healthy smokers and nonsmokers. At this stage, Selecta's primary concern is safety. According to Lloyd Johnson, a senior Vice-President, "Safety is the main thing we're looking at, but we'll also be able to see the antibody levels," Scott Kirsner from The Boston Globe, reported. Future clinical trials will determine if the vaccine actually works. They will look to see if the vaccine leads to the production of enough antibodies to absorb nicotine. Those trials will determine whether the vaccine actually helps smokers quit over extended periods of time.

Continue reading "Nicotine Vaccine Clinical Trials Begin" »

November 25, 2011

Medeva and Georgetown Cases--CJEU Decides on Availability of SPCs for Products Where the Basic Patent Does Not Match the Marketing Authorisation

by Howard E. Rosenberg, Ph.D.

CJEU.jpegThese cases concerned attempts at obtaining Supplementary Protection Certificates ("SPCs") for multi-component vaccines. Health Authorities prefer to administer several vaccines combined rather than to have them administered separately. The Medeva case (C-322/10) involved a vaccine comprising multiple active ingredients of which only two were the subject of a combination patent. As a consequence an SPC for this multi-component vaccine was refused, because the patent did not claim the additional active ingredients. SPC protection for a combination of the two active ingredients of the multi-component vaccine that were claimed in the patent was also refused in the United Kingdom, because the marketing authorization ("MA") was granted not for a medicinal product containing the combination of these two active ingredients only, but for the multi-component vaccine comprising other active ingredients.

The Georgetown case (C-422/10), was similar but had only one active ingredient, i.e., the basic patent claims an antigen of a vaccine, whereas the marketing authorization is for a multi-antigen vaccine, including additional antigens beyond the claimed ones. The cases were combined initially at the Court of Justice of the European Union ("CJEU") and were joined for the purposes of the oral procedure and the judgment, but the court decided that in view of the factual differences between the situations at issue in the main proceedings the cases were disjoined for the purposes of the judgment. In both cases the court felt that for a "product" covered, as a medicinal product by a MA, the essence of the SPC Regulation did not in itself rule out the possibility that the MA may cover other active ingredients contained in such a medicinal product and that in accordance with Article 4 of Regulation an SPC was intended to protect the "product" covered by the MA, not the medicinal product as such.

Thus the court's decision: Article 3(b) of Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the SPC for medicinal products must be interpreted as meaning that, provided the other requirements laid down in Article 3 are also met, that provision does not preclude the competent industrial property office of a Member State from granting a SPC for an active ingredient specified in the wording of the claims of the basic patent relied on, where the medicinal product for which the marketing authorization is submitted in support of the SPC application contains not only that active ingredient but also other active ingredients.

Continue reading "Medeva and Georgetown Cases--CJEU Decides on Availability of SPCs for Products Where the Basic Patent Does Not Match the Marketing Authorisation" »

November 23, 2011

SIDS Baby Products Do Not Reduce the Risk: FDA says "Less is More"

by Julie E. Kurzrok

babycrib.jpgSudden Infant Death Syndrome ("SIDS") is the sudden death of an infant, under the age of one, which remains unexplained after a complete investigation and autopsy. Although the cause of SIDS is unknown, it most often occurs in babies who are between two and four months of age, especially in babies who are put to sleep on their stomachs. Other factors that increase the risk of SIDS include: smoking while pregnant, co-sleeping (putting the infant to sleep in bed with the parents), and soft bedding in the crib (e.g., bumpers, pillows, quilts, sleep positioners, or comforters).

In 1992, the American Academy of Pediatrics ("AAP") released its recommendation that infants be placed to sleep in a non-prone position, preferably on their backs. In response, in 1994 the National Institute of Child Health and Human Development ("NICHD") together with the AAP, launched the "Back to Sleep Public Education Campaign" to educate patents about how a safe sleeping environment, in addition to placing infants on their backs to sleep, can decrease the risk of SIDS. Since 1994, the incidence of SIDS has decreased drastically, however the number of deaths from unsafe sleep environments has drastically increased.

In October 2011, the AAP Task Force on SIDS released a new Guideline, expanding the focus of its 1994 Guideline to include safe infant sleeping environments. The new Guideline aims to reduce all sleep-related infant deaths, including SIDS. The Guideline recommends various ways to reduce the risk of SIDS including, for example, regular prenatal care, avoiding smoke exposure, alcohol, and illegal drug use during pregnancy and after birth, using pacifiers, and breastfeeding.

Continue reading "SIDS Baby Products Do Not Reduce the Risk: FDA says "Less is More" " »

November 22, 2011

Pay-for-Delay Update: The Congressional Budget Office Issues New Report Estimating Near $5 Billion Savings by Banning Pay-for-Delay Settlements

by Kyle Deighan

Thumbnail image for Thumbnail image for Thumbnail image for Money in hand.jpgOn November 9, the Congressional Budget Office ("CBO") estimated that enacting a Senate bill restricting "pay-for-delay" settlements would cut the federal deficit by $4.8 billion over the next 10 years. According to the CBO, the Preserve Access to Affordable Generics Act (S. 27) "would accelerate, on average, the availability of lower-priced generic drugs affected by such agreements and generate savings to public and private purchasers of prescription drugs." Specifically, the CBO estimated that the bill would reduce spending by $4 billion, increase federal revenues by $800 million, and reduce spending subject to appropriation by $400 million between the years 2012-2021. Further, "CBO estimate[ed] that enacting [the bill] would reduce total expenditures on prescription drugs in the United States, on net, by about $11 billion over the 2012-2021 period" (which includes the $4 billion saved by federal programs).

To arrive at their estimates, CBO estimated "that S. 27 would accelerate the entry of generic drugs affected by the bill by roughly 17 months, on average. During that period, CBO estimat[ed] a generic savings rate of about 50 percent--that is, the availability of lower-priced generic drugs would reduce total spending for a given drug by roughly one-half. After accounting for the fact that S. 27 would only restrict settlement agreements entered into after November 15, 2009, CBO estimates that earlier entry of generic drugs affected by the bill would reduce total drug expenditures in the United States by roughly $11 billion over the 2012-2021 period."

The Preserve Access to Affordable Generics Act (S. 27), co-sponsored by Democrat Herb Kohl and Republican Chuck Grassley, was introduced on January 25, 2011 and recently made its way through the Senate Judiciary Committee. It is currently awaiting action in the Senate after being placed on the legislative calendar in late July. As part of its report, the CBO summarized S. 27:

S. 27 would modify how FTC conducts enforcement proceedings against parties to an agreement to settle a claim of patent infringement in specific cases. Under the bill, certain settlement agreements between drug companies would be presumed anti-competitive and unlawful; they would only be allowed if the parties can demonstrate by clear and convincing evidence that the pro-competitive benefits of the agreement outweigh the anti-competitive effects of the agreement. The agreements affected by the bill are ones in which the manufacturer of the generic version of the drug receives anything of value from the manufacturer of the brand-name drug and the generic drug manufacturer agrees to limit or forgo research, development, manufacturing, marketing, or sale of the generic drug for any period of time.

Continue reading "Pay-for-Delay Update: The Congressional Budget Office Issues New Report Estimating Near $5 Billion Savings by Banning Pay-for-Delay Settlements" »

November 21, 2011

National Pharmaceutical Pricing Policy Proposed by Indian Government

by Howard E. Rosenberg, Ph.D.

Indian money.bmpLast week, India proposed a new National Pharmaceutical Pricing Policy. Price control for drugs was first introduced in India in 1963 and over time modified on various different principles but remained broadly based on the principle of effecting control over the prices of essential drugs. The most recent Drug Policy of 1994 focused on controlling bulk drugs. In the Drug Policy of 1994, a list of 74 bulk drugs was identified and those drugs, as well as the formulations, based on these drugs (currently about 1577 in number) were brought under the price control regime.

India is now the 3rd largest producer of medicines by volume but is only 14th in terms of value globally. The industry's production turnover has increased from Rs 51 billion in 1990 to around Rs 1 trillion in 2009-2010 of which Rs 420 billion is exported. After liberalization of the economy and when Foreign Direct Investment in the pharmaceutical sector was brought in, a new pharmaceutical pricing policy was introduced in 2002 but was challenged and thus never implemented, so the 1994 Drug Policy continued in force. However, the National List of Essential Medicines ("NLEM") of 1996 was revised and the list notified as NLEM- 2003 and again in 2011 as NLEM- 2011. Various drug policies adopted from time to time have tried to cope with the challenge of striking a balance between enabling industry to grow and at the same time ensuring affordable and reasonable prices to the consumers, particularly the poorer masses.

The principles surrounding the new proposal for regulation of prices are: (1) Essentiality of Drugs, (2) Market Based Pricing, and (3) Control of Formulations. The new policy is based on regulating the prices of the formulations only. This is different from the earlier principle of regulating the prices of specified Bulk Drugs and their formulations. Bulk Drugs are not considered to fully reflect the "Essentiality" of the actual drug due to the possible applicability of the Active Pharmaceutical Ingredient ("API") in manufacture of various other formulations which may be non-"Essential" for the larger healthcare requirements of the population.

Continue reading "National Pharmaceutical Pricing Policy Proposed by Indian Government" »

November 18, 2011

LIVESTOCK ANTIBIOTIC BAN REJECTED BY FDA

by Scot B. Pittman

livestock.jpgOn November 7, FDA denied two citizen petitions related to the use of certain antibiotics in food animal production. A 1999 Petition, submitted on behalf of the Center for Science in the Public Interest ("CSPI"), the Environmental Defense Fund, the Food Animal Concerns Trust ("FACT"), the Public Citizen's Health Research Group, and the Union of Concerned Scientists, and a 2005 Petition, submitted on behalf of Environmental Defense, the American Academy of Pediatrics, the American Public Health Association, and the Union of Concerned Scientists, requested that FDA rescind its approval of the non-therapeutic use in livestock of any antibiotic used in (or related to those used in) the treatment of humans. Such antibiotics include penicillins, tetracyclines, aminoglycosides, streptogramins, lincomycins, and sulfonamides. According to the petitions, the widespread use of these antibiotics in livestock for disease prevention/control and growth promotion causes a significant increase in the amount of antibiotic resistance in human pathogens.

In its responses (Response to 1999 Petition and Response to 2005 Petition), FDA recognized the concern about using medically important antibiotics in livestock but denied the petitions on statutory grounds. According to FDA, the withdrawal of new animal drug approvals requires providing the new animal drug sponsor with notice and an opportunity for a formal evidentiary hearing. As there have been no formal evidentiary hearings on this matter, FDA determined that it could not mandate a withdrawal and denied the petitions.

To the extent that the petitions asked FDA to initiate formal withdrawal proceedings, the Agency denied those as well. FDA cited its previous experience with formal proceedings and concluded that they were typically overly time consuming and expensive. FDA defended these denials by referencing its 2010 draft guidance, "The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals," as an alternative way to ensure safer uses of antibiotics in livestock.

Continue reading "LIVESTOCK ANTIBIOTIC BAN REJECTED BY FDA" »

November 17, 2011

HEMACORD Gets Thumbs-Up from FDA, Provides Needed Access for Blood Banks

by Fitz Beckwith Collings

Buddy_Blood_Drop.jpgOn November 10, FDA approved HEMACORD, a cord blood biologic, for use in patients with "disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment." The active ingredient in HEMACORD consists of hematopoietic progenitor cells that express the cell surface marker CD34. The potency of cord blood is determined by measuring the number of total nucleated cells ("TNC") and CD34+ cells, and cell viability. Each unit of HEMACORD contains a minimum of 5 x 10(8) total nucleated cells with at least 1.25 x 10(6) viable CD34+ cells at the time of cryopreservation.

Cells expressing CD34 (CD34+ cell) are normally found in the umbilical cord and bone marrow as hematopoietic cells, a subset of mesenchymal stem cells, endothelial progenitor cells, endothelial cells of blood vessels but not lymphatics (except pleural lymphatics), mast cells, a sub-population dendritic cells (which are factor XIIIa negative) in the interstitium and around the adnexa of dermis of skin, as well as cells in soft tissue tumors. Matching for at least 4 of 6 HLA-A antigents, HLA-B antigens, and HLA-DRBI alleles is recommended. The HLA typing and nucleated cell count for each individual unit of HEMACORD are documented on the container label or accompanying records.

Cord blood may used to treat disorders that generally result in diminished or lost capacity to form new blood cells, e.g., following radiation therapy. The undifferentiated hematopoietic cells in cord blood migrate to the bone marrow once inside the body. Once there, they mature and divide, replenishing lost or absent blood cell populations and function, including immune function, of blood-borne cells of marrow origin. In patients with enzymatic abnormalities due to certain severe types of storage disorders, mature leukocytes resulting from HPC-C transplantation may be able to circulate and improve cellular functions of some native tissues. HEMACORD is the first hematopoietic progenitor cell-cord cell therapy licensed by the FDA.

Continue reading "HEMACORD Gets Thumbs-Up from FDA, Provides Needed Access for Blood Banks" »

November 16, 2011

Legislation Seeks to Ease Barriers to Medical Device Approval

by Andrew S. Wasson

Covered_Stent_Graft.jpgSenators Al Franken (D. Minn) and Lamar Alexander (R. Tenn.) introduced yesterday a bill that would amend 21 U.S.C. § 360j(m) and 21 U.S.C. § 379d-1, both relating to medical devices, titled the "Patient Access to Medical Innovation Act." According to Senator Franken, the aims of the legislation are to: (1) "[p]romote the development of devices to treat patients with rare diseases", (2) "[h]elp improve the federal Food and Drug Administration's (FDA) approval process for medical devices by allowing the agency to more easily consult with experts," and (3) "[l]ift the current profit cap on "humanitarian use devices"-- devices that treat rare conditions-- that go through a special approval process."

The bill seeks to amend 21 U.S.C. § 360j(m) which governs the "Humanitarian Device Exemption." The currently-effective law authorizes the Secretary of Health and Human Services to grant an exemption from certain effectiveness requirements for medical devices as long as (i) the device is designed to treat or diagnose a disease or condition that affects fewer than 4,000 individuals in the United States, (ii) the device would not be otherwise available, and (iii) the device will not expose patients to "an unreasonable or significant risk of illness or injury" with the benefits of use outweighing the risks. This provision also mandates that devices authorized under the exemption could not be sold "for an amount that exceeds the costs of research, development, fabrication, and distribution" except for the treatment of pediatric patients. The proposed bill appears to enlarge the exception to cover all uses, regardless of whether the intended population is pediatric patients.

The bill also seeks to amend 21 U.S.C. § 379d-1, which deals with conflicts of interest for advisory committee members. As a default, the currently-effective law prohibits participation by advisory committee members who have "a financial interest that could be affected by the advice given to the Secretary with respect to such matter." The Secretary is authorized to waive this requirement if it is necessary to provide a committee with "essential expertise." Critics of the current law argue that entirely unencumbered experts are difficult to find. The proposed bill strikes the prohibition and replaces it with a broader directive to the Secretary to consider "the scope and magnitude of the financial interest" balanced against the "public health need for the expertise" of the committee member in question. Opponents of the revision argue that reducing the safeguards may lead to biased advice.

The Franken-Alexander bill is not the only bill to target medical devices recently. Senators Amy Klobuchar (D-Minn.), Richard Burr, (R-N.C.), and Michael Bennet (D-Colo.) proposed the Medical Device Regulatory Improvement Act in October which also seeks to amend 21 U.S.C. § 360 et seq. While both bills seek to reduce restrictions on advisory committee members, one key difference appears to be that only the Franken bill seeks to amend the humanitarian device exemption provision.

November 15, 2011

Graphic Cigarette Warnings Blocked by Initial Lawsuit by Tobacco Companies

by Erin A. Lawrence

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

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

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

Continue reading "Graphic Cigarette Warnings Blocked by Initial Lawsuit by Tobacco Companies" »

November 14, 2011

Health Information Technology--Who Should Regulate?

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EMR.jpgOn November 8, the Institute of Medicine ("IOM") released a report, "Health IT and Patient Safety: Building Safer Systems for Better Care". The IOM Committee had been charged with summarizing existing knowledge of the effects of health information technology ("IT") on patient safety, making recommendations to the Department of Health and Human Services ("HHS") regarding specific actions federal agencies should take to maximize the safety of health IT-assisted care, and making recommendations concerning how private actors can promote the safety of health IT-assisted care, and how the federal government can assist private actors in this regard.

The IOM Committee concluded that current market forces are not adequately addressing the risks associated with the use of health IT. No federal agency is currently charged with monitoring the safety of health IT, i.e., the software, hardware, and systems that record and manage patients' health information. The Report recommended that HHS should publish an action and surveillance plan within twelve months that includes a schedule for working with the private sector to asses the impact of health IT on patient safety and minimizing the risk of its implementation and use. The Report also recommended that HHS fund a new Health IT Safety Council, which would operate within an existing voluntary consensus standards organization, to evaluate criteria for assessing and monitoring the safe use of health IT to enhance safety. All health IT vendors should be required to publicly register and list their products with the Office of National Coordinator for Health IT ("ONC"), the Report continues, and HHS should establish a mechanism for reporting health IT-related deaths, serious injuries, or unsafe conditions.

Continue reading "Health Information Technology--Who Should Regulate?" »

November 11, 2011

Hill Dermaceuticals Challenges FDA's Approval of Identi Pharms ANDAs on Products Containing Peanut Oil

Koeh-163.jpgby Scot Pittman

Hill Dermaceuticals, Inc. has sued the Food and Drug Administration in the District Court for the District of Columbia over the approval of three Abbreviated New Drug Applications ("ANDAs") submitted by Identi Pharms, Inc. Hill seeks the immediate withdrawal or suspension of FDA's approval of the alleged generic equivalents to Hill's Derma-Smoothe/FS® (fluocinolone acetonide) (Scalp Oil), Derma-Smoothe/FS® (fluocinolone acetonide) (Body Oil), and Derm-Otic® Oil Ear Drops.

These products are topical corticosteroids approved by FDA for treatment of certain skin diseases. They use a highly refined peanut oil to deliver the fluocinolone acetonide to the affected area, and thus carry a risk of allergic reactions. As such, prior to their approval, FDA required Hill to undertake stringent testing to ensure that the products were virtually free of peanut protein, as well as include warnings about the peanut oil on the labels.

The current lawsuit follows a citizen petition (CP) Hill filed with FDA on September 30, 2004, and a previous motion to stay filed with the District Court for the District of Columbia in March 2007. Hill's CP requested that approval of any ANDAs for generic versions of Derma-Smoothe® be withheld absent a showing of identical active ingredients, labeling, and conditions of use. After more than two years and only a non-substantive response from FDA in 2005, Hill filed the motion to stay seeking to prevent FDA from approving any generic versions of its Derma-Smooth® products. The 2007 Motion was denied on November 27, 2007 because Hill had failed to satisfy the elements requiring a stay. Namely, Hill could not show a likelihood of success on the merits, nor could it show sufficient harm to itself or the public.

Continue reading "Hill Dermaceuticals Challenges FDA's Approval of Identi Pharms ANDAs on Products Containing Peanut Oil" »

November 10, 2011

Drug Approvals Up FDA Reports

by Kyle Deighan

Last Thursday, FDA released a report, entitled "FY 2011 Innovative Drug Approvals" touting the number of drugs it approved over the past 12 months. The report boasts, "FDA's performance during the most recent fiscal year . . . demonstrates that the FDA continues to lead the world in rapid, high-quality drug reviews." The report indicates that FDA approved 35 new medicines in the past year, the second-highest number of approvals in a single year in the past decade. Only 2009 saw more approvals, with 37.

FY2011

Margaret A. Hamburg, M.D., FDA Commissioner, stated that "we approved a set of drugs that are truly medically important, and in fact did so in a way that made these drugs available to Americans before other places around the world." According to the report, FDA approved almost 70% (24 of 35) of the new drugs before they were approved in other countries, including the European Union. To help bring about the speedy review process and subsequent increase in approvals, FDA utilized an accelerated review and approval process and streamlined the requirements for clinical trials to allow for smaller, shorter, or fewer studies where possible. However, FDA was careful not to take too much recognition. "We're not taking credit for these innovative medicines, but we are trying to demonstrate that by working closely with industry and the broader biomedical research community, we can produce the kind of innovative medicines the American public needs," Hamburg stated.

The report indicates that many of the new approvals are groundbreaking drugs, including "the first new drug to treat Hodgkin's lymphoma in 30 years and the first new drug to treat lupus in 50 years. The 35 novel drugs are noteworthy for their contributions to the health of Americans and their scientific innovation." The drugs are designed to treat a variety of ailments, including "hepatitis C, late-stage prostate cancer, lupus, drug resistant skin infections, pneumonia and other serious and life-threatening diseases," in addition to various advances in cancer treatment and heart attack, stroke and kidney transplant rejection therapies.

Continue reading "Drug Approvals Up FDA Reports" »

November 9, 2011

Prescriber Education Blueprint in Draft Form for Class-Wide Opioid REMS Posted

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morphinepills.jpgLess than a week after the Centers for Disease Control and Prevention ("CDC") reported on the growing epidemic of opioid pain reliever ("OPR") overdoses, which we reported on here and asked for FDA to take action, FDA announced in a Federal Register Notice that FDA had developed a draft blueprint entitled "Blueprint for Prescriber Education for the Long-Acting/Extended-Release Opioid Class-Wide REMS" ("Blueprint") . FDA has obviously been thinking about ways that its class-wide opioid Risk Evaluation and Mitigation Strategies ("REMS") can have an impact on the growing prescription drug abuse crisis. FDA's latest Blueprint appears triggered, at least in part, by a report released by the Obama Administration on April 19, 2011 entitled, "Epidemic: Responding to America's Prescription Drug Abuse Crisis", which we reported on here.

As indicated in FDA's Notice, FDA issued letters to application holders for long-acting and extended-release innovator and generic opioid drug products requiring them to submit a REMS within 120 days and providing certain elements that had to be included in each of the REMS. FDA's "central component" was the requirement for a cost-free, drug education program for prescribers, yet there is no prerequirement for training for prescribing. Instead, FDA requested that application holders set goals for numbers of prescribers trained, collect information about the number of prescribers who took the courses, and report the information to FDA as part of the required periodic assessments for REMS.

FDA's Blueprint is meant to provide the basic outline and core messages for continuing education that should be offered to all prescribers of long-acting and extended-release opioids, suggesting that the message be delivered in 2-3 hours. According to the Notice, the outline requires information weighing the risks and benefits of opioid therapy, choosing patients appropriately, managing and monitoring patients, and counseling patients on the safe use of these drugs. The education must also include information how to recognize evidence of, and the potential for opioid misuse, abuse, and addiction.

While the Blueprint goes a long way to provide valuable information to the prescribers who choose to be educated, it remains unclear why FDA is not mandating the prescriber education for all prescribers as a precondition to dispensing the medication to patients or more effectively targeting the perceived source of the problem. At least suggested by CDC's report, the majority of OPR overdoses seem to be attributed to a relatively small percentage of OPR prescribers with more loose prescribing practices. How could FDA's mandated REMS reach the prescribers who would most benefit from the training? One might think then it would make sense to either mandate the education for all prescribers (i.e., an even-playing-field approach) or at least mandate the training for prescribers who have had documented instances of OPR misuse or abuse (i.e., a more targeted approach to save resources). How, for example, will FDA's requirement lead the prescribers who need the training to take it rather than provide more information to the majority of prescribers who are already being cautions about prescribing OPRs? Also, why should the training exclude immediate-release OPRs? CDC's report did not single out extended-release and long-acting opioids as the only source of the problem with OPRs.

FDA's mandated REMS and Blueprint also does not seem to go far enough in its recommendations. For example, while the Blueprint describes the possibility for patient prescriber agreements ("PPAs") (i.e., agreements signed at the time of prescribing providing mutual commitments and goals in the treatment between prescriber and physician) and suggests a treatment plan, why are these PPAs only something prescribers should be "aware of"? Without making PPAs a requirement, it would seem most prescribers may choose to operate without them. Similarly, it would seem that other voluntary elements such as patient treatment plans, reassessments whether OPRs are still necessary, and plans to withdraw patients from OPRs including tapering doses, as well as the risks associated with diversion should be reconsidered as elements of the mandated class-wide REMS.

State legislators should consider passing complementary regulations to help provide pharmacists with the appropriate tools to be "gatekeepers" to prevent addictive OPRs from getting in the wrong hands. In Delaware, for example, new laws have been passed to require special "tamper-proof" prescription pads and prescribers will soon be able to electronically prescribe controlled drugs directly to a patient's pharmacy--measures designed to help prevent counterfeit prescriptions and to collect more detailed information about every prescription for controlled drugs written by Delaware doctors.

FDA has asked for comments on their draft education Blueprint by December 7, 2011.

November 8, 2011

Therapeutic Cancer Vaccines the Subject of Recent FDA Guidance

By Andrew S. Wasson

Red_White_Blood_cells.jpgFDA recently issued a Guidance for Industry titled "Clinical Considerations for Therapeutic Cancer Vaccines" which describes factors relevant to the design of clinical trials for a cutting-edge class of cancer treatments: therapeutic cancer vaccines. Therapeutic vaccines are different from preventative (or prophylactic) vaccines. While preventative vaccines are intended to prevent the development of disease in healthy people, therapeutic vaccines work toward strengthening the immune system to help the body fight an existing disease. FDA's recent Guidance finalizes a Draft Guidance dated September 2009.

The development of therapeutic cancer vaccines poses a number of difficult issues compared to conventional chemotherapeutic therapies. Most therapeutic cancer vaccines work on a longer timetable than conventional therapies. In many therapeutic cancer vaccines, tumor-specific antigens are presented by antigenic determinants via APCs (antigen presenting cells) to T cells. The T cells, now programmed to recognize a tumor, will attach tumor cells expressing the antigenic determinants. This sensitiziation, however, takes time, especially compared to conventional therapies. Throughout the Guidance, FDA presents factors relevant to the design of clinical trials which speak to this critical difference.

FDA presented considerations relevant to (1) both early and late phase clinical trials, (2) early phase clinical trials alone, and (3) late phase trials alone. Determining the appropriate patient population is one consideration applicable to both early and late phase trials. For example, cancer treatments were often tested against a wide variety of tumors in order to find the maximum tolerated dose, optimum dosing schedule, and clinical activity. In traditional therapies, evaluating the desired effect can be accomplished in relatively short time periods, such as during the first eight weeks of treatment. Therapeutic cancer vaccines, however, require much long time periods in order to see possible effects - time periods on the order of 2-3 months.

Along the same lines, FDA discussed the advantages and disadvantages of clinical trials involving patient populations with relapsed or recurrent metastatic cancer versus patient populations showing no or little evidence of disease. On the one hand, patients with relapsed or recurrent metastatic tumors often have employed multiple therapies, including those which may interfere with immune response. Because the immune response is key to the mechanism of action for therapeutic cancer vaccines, these other therapies may interfere with the effectiveness of the studied vaccine. On the other hand, studying patients with no or little evidence of disease would avoid the confounding effect of other therapies, but would require longer study times to allow for relapse monitoring.

November 7, 2011

GlaxoSmithKline to Pay a Record $3 Billion to Settle Civil and Criminal Investigations

by Julie E. Kurzrok

Thumbnail image for drugmoney.jpegOn November 3, GlaxoSmithKline ("GSK") tentatively agreed to pay $3 billion to the U.S. government to settle pending investigations regarding its sales and marketing practices. This sets a new record for the highest settlement paid by a pharmaceutical company to the U.S. government, surpassing the $2.3 billion paid by Pfizer and the $1.4 billion paid by Eli Lilly in 2009. GSK was accused of illegally paying doctors and altering medical research to promote its diabetes drug Avandia® (rosiglitazone). On September 23, 2010, the EMA banned the use of Avandia® in Europe and the FDA severely limited access to it in the U.S through additional labeling and restrictions, including a Risk Evaluation and Mitigation Strategy. Other countries have either already taken or are in the process of taking similar action. On February 7, 2011, the FDA again changed the Avandia® labeling and restricted its use to either patients already taking rosigliazone-containing medication or to new patients who have either tried other diabetes medications to no avail, or who will not take pioglitazone or pioglitazone-containing medications.

The $3 billion settlement also covers payment for the U.S. Department of Justice's investigations of GSK's Medicaid pricing practices and reimbursement fraud, and the Colorado U.S. Attorney Office's investigation of the sales, marketing, and off-label use of nine of GSK's other drugs from 1997 to 2004, and its asthma treatment Advair® (fluticasone and salmeterol).

Critics believe that these settlement agreements between the government and pharmaceutical companies are too lenient, arguing that while the numbers are large, they fail to make any significant impact on the these companies' yearly revenues. For example, GSK's revenues in 2010 were close to $50 billion, and during the 4th quarter of 2010, GSK set aside several billion dollars in anticipation of this settlement and other legal issues. The critics request stiffer penalties including, for example, prison sentences for corporate officials. The terms of GSK's settlement are still tentative and GSK plans to finalize the settlement in 2012.

November 4, 2011

Mobile Style Sheets for FDA Lawyers Blog Finalized

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Thumbnail image for FrommerLawrence512k size (large).jpgFDA Lawyers Blog is pleased to announce that its style sheets for iPhones and Android smartphones are now complete. These style sheets are In addition to mobile apps for iPhones and Android smartphones that can be downloaded directly from the Apple App Store and the Android Market free of charge. Together, FDA Lawyers Blog's mobile style sheet and iPhone and Android apps provide a new global level of accessibility and usefulness for professionals in the field of FDA law.

As we previously mentioned, the mobile style sheets make FDA Lawyers Blog more readable on your iPhone or Android smartphone. First, the style sheets provide you with an initial pop-up to choose to download the iPhone app, the Android app, or to go directly to the mobile style sheets for the blog ("TAP HERE TO CLOSE"). You should only see this pop-up once unless you clear your browser's cache (cookies and data).

Once you enter FDA Lawyers Blog's mobile style sheets, you are provided with a similar but somewhat different interface than the full version of FDA Lawyers Blog. Recognizing that individuals utilizing FDA Lawyers Blog on the move may want to locate particular blog items quickly, we moved a search bar up to the top (as opposed to a separate "Search" tab in the full blog). The most recent blog appears as it does on the full version of the blog, whereas older blog items are truncated after about a paragraph to make scrolling to blog items easier with "Continue reading" features to permit readers to view the full blog. To make reading the blog items easier, the mobile version focuses on the text in the blog, increasing its font size to permit readability in an upright mode without the need to flip the phone on its side or increase font size on the screen.

Following the most recent blogs are other features found on the full version of the blog. First, there is the contact screen, then subject headings to locate particular blogs by subject, then the "Events" and "Articles" tabs that feature FDA Lawyers Blog contributors on FDA-related topics.

Towards the bottom of the screen is a button "View Full Version" that permits readers to toggle to the full version of FDA Lawyers Blog on an iPhone or Android smartphone. When you want to go back to the mobile version, towards the bottom right-hand corner of the full version is a button "View Mobile Version" that permits readers to toggle to the mobile style sheets once again.

We hope that you enjoy both the mobile style sheets and iPhone or Android smartphone apps. Please continue to watch for additional updates as we listen to your comments about what you need to be more productive with regard to FDA news and updates.

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November 3, 2011

2012- A Happy New Year for Generic Drug Companies

by Julie E. Kurzrok

Thumbnail image for Thumbnail image for Generic Labeling.jpgSeveral of the top-selling drugs in the U.S. will be losing their patent protection within the next 14 months, resulting in a potential savings of 40-80% for consumers. This will be the largest group of pharmaceuticals to go generic. Most notably, as of November 30, 2011, generic versions of the cholesterol-lowering medication Lipitor® will be available. Lipitor® (atorvastatin calcium) is the highest-selling drug in the U.S., with 2010 U.S. revenues of $5.3 billion. On November 30, 2011, it is anticipated Watson will release its authorized generic version of Lipitor®, and with FDA approval, Ranbaxy would be able to release its generic Lipitor®. There are at least nine other generic companies that could potentially launch generic Lipitor® on May 28, 2012, after the expiration of Ranbaxy's 180-day exclusivity as the first applicant with a patent challenge. For this product alone, the potential generic competition could cut consumers' spending by $6 billion by the year 2015.

Plavix® (clopidogrel bisulfate), the most prescribed drug to prevent heart attack and stroke, is another top-seller that will lose U.S. exclusivity in May 2012. Additional examples of drugs set to lose patent protection in 2012 include the antipsychotic Seroquel® (quetiapine fumarate) and the asthma drug Singulair® (montelukast sodium). While the patent on the type II diabetes drug Actos® (pioglitazone hydrochloride) has already expired, Takeda, the drug's manufacturer, has an agreement with several generic companies that they will not market generic versions until August 2012. While the damages to innovator drug manufacturers may be substantial (e.g., between 2010-2012 Pfizer will lose patent protection for drugs currently accounting for about 42% of its revenue), the influx of generic drugs into the market is positive news for both consumers and generic drug companies.

For example, the generic company Mylan, which in 2012 plans to introduce generic versions for Plavix®, Actos®, and for Lipitor® in Europe, along with 500 other products, stands to increase its sales by $800 million. The savings for consumers will be substantial considering the average retail drug costs of some of these brand-name blockbusters (Plavix® at approximately $750 per month, Actos® at approximately $250 per month, Lipitor® at approximately $150 per month). As more generic versions of these popular innovator products become available to consumers, consumers and their insurance providers win by reduced costs.

November 2, 2011

Opioid Painkiller Overdose Epidemic--Need for Effective REMS Evident

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morphinepills.jpgOn November 1, the Centers for Disease Control and Prevention ("CDC") published in its publication, Morbidity and Mortality Weekly Report ("MMWR"), the results of a study that confirmed the epidemic of overdoses of opioid pain relievers ("OPRs") has continued to worsen particularly from 1999-2008. OPR deaths now account for more drug overdose deaths than heroin or cocaine combined and represent nearly 75% of all prescription drug overdose deaths. Drug overdose deaths (36,450) are now almost as high as the number of deaths from motor vehicles (39,973), which is the leading cause of injury death in the United States.

What is also alarming is that the OPR overdose rates have continued to rise despite increased warnings and recommendations over the past decade for voluntary education of health-care providers about more cautious use of OPRs. According to the MMWR, the death rate of drug overdoses of 11.8 per 100,000 population (nearly 100 people per day) is about three times the rate in 1991. Since 1999, most of the drug overdose increases have been attributed to prescription drug overdoses. In 2009 alone there were 1.2 million emergency department visits related to misuse of pharmaceuticals, which represented a 98.4% increase from 2004, compared to 1.0 million for use of the illegal drugs heroin and cocaine.

According to the MMWR, sales of OPRs quadrupled between 1999 and 2010 so that by 2010 enough OPRs were sold to mediate every American adult with a typical dose of hydrocodone every 4 hours for 1 month. Increased use of OPRs has contributed to overall increases in overdose death and nonmedical use. Yet the total number of prescribers responsible for the increase appears to be small: one study found only 3% of physicians accounted for 62% of the OPRs prescribed. Once prescribed, OPRs may be diverted for nonmedical uses (i.e., to patients for whom the drug was not prescribed or for other uses not attributed to pain for whom the drug was prescribed) or sold on the street. In 2010, 4.8% of the U.S. population 12 and older reportedly used OPRs nonmedically. This, in turn, cost insurance companies up to $72.5 billion in health-care costs.

Continue reading "Opioid Painkiller Overdose Epidemic--Need for Effective REMS Evident" »

November 1, 2011

Vaccine Immunization Exemptions May Be Putting Children at Risk--What Should FDA Do?

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childimmunization.jpegOn October 31, a preliminary report of a new California study was presented at the American Public Health Association in Washington, D.C. that appears to demonstrate that state vaccination "personal belief exemptions" are resulting in "hot spot" zones where children are at greater risk of exposure to preventable infectious diseases such as measles, mumps, and rubella.

The new California study analyzed state health department statistics for personal belief exemptions among kindergartners. Personal belief exemptions are affidavits signed by parents indicating that "all or some immunizations are contrary to my beliefs," which permits children to avoid otherwise mandated vaccines. Twenty states allow personal belief exemptions including California.

According to the study, in 2010 for every 100 children in a California kindergarten, 2.3 had skipped immunizations because of one or more personal belief exemptions. Interestingly, the exempted children tended to cluster in certain schools, where an average of 16 out of 100 of their peers also claimed exemptions. Some schools had one in five kindergartners with parental exemptions for vaccinations. More than 7,000 kindergartners across California attended these schools, including 2,700 who were exempted.

Continue reading "Vaccine Immunization Exemptions May Be Putting Children at Risk--What Should FDA Do?" »