FDA Lawyers Blog

by Howard E. Rosenberg, Ph.D.

The general public's expectation for transparency in the regulation and assessment of the safety of medicines is characterized by the number of Freedom of Information Act ("FOIA") requests to FDA asking for detailed information regarding this data and the multitude of blog articles covering this subject matter. To some extent, public postings on FDA's website, particularly Drugs@FDA, has quelled the need for some FOIA requests. In Europe there is the same public pressure and an increasing trend for the release of information contained in the Marketing Authorization Applications ("MAAs") after they are granted. For example the release of clinical and safety data is regularly requested.

Feedback from initial European proposals found that in general the pharmaceutical industry had concerns regarding the release of contractual arrangements between companies, personal data of experts, and clinical and non-clinical data. Pharmaceutical companies also raised special concerns with regard to the disclosure of non-clinical data, while the release of clinical data was supported by most stakeholders.

The European Medicines Agency ("EMA") and the Heads of Medicines Agencies ("HMA") have now adopted a joint guidance document, providing, for the first time, a consistent Europe-wide approach to the identification of commercially-confidential information and personal data in a MAA. This "major step for transparency," will apply in the future to identify which parts of an application dossier can or cannot be released in response to requests throughout the regulatory authorities in the European Economic Area ("EEA"). This policy applies regardless of whether the product concerned was authorized using the centralized, mutual recognition or decentralized procedures.

by Kyle Deighan

FDA is currently exploring the possibility of allowing additional drugs for common health conditions to be sold over-the-counter ("OTC") without a prescription. FDA held public hearings last week to gather input from various groups on the issue, including consumers, pharmacists, and health care community members. Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research ("CDER"), explained, "What we are asking is, should there be more flexibility in the concept of nonprescription drugs? Can we broaden the assistance a consumer gets and increase the types of medicines that might be available over-the-counter?" Drugs that may soon be available OTC without a prescription include cholesterol, asthma, migraine and blood-pressure medications.

FDA may require special conditions to apply before a drug may be sold OTC. These could include requiring patients to speak with a pharmacist before obtaining a medication or undergoing some form of diagnostic test. Or patients may be required to first see a physician to obtain a prescription, but then could obtain refills without needing subsequent prescriptions. FDA has also discussed the use of kiosks in pharmacies or questionnaires on the Internet to help consumers determine whether or not to take a certain drug. Woodcock noted that "the rules for nonprescription status were established in an age when widespread access to information technology did not exist. The world is evolving. It is clear there are now many interactive mechanisms that can help consumers through the process of self-diagnosis and medication selection in a much more comprehensive manner than a few worlds on a fact box."

Supporters argue that making more drugs available OTC would give patients the access they need to necessary medications. According to FDA, the time and cost required to visit a doctor, obtain a prescription, and then fill that prescription may deter patients from ever obtaining medications. An estimated 20 percent of patients with prescriptions do not even bother getting them filled, for example. Proponents argue that more OTC offerings would provide these patients with easier access to necessary drugs. Other benefits highlighted by FDA include "an increase in the appropriate use of medication, decreases in health costs, greater access to health screening ... and better, more consistent treatment of common conditions."

PIV Disputes 2012

Each spring, leading pharmaceutical patent litigators for brand name and generic drug companies gather in New York City at American Conference Institute's (ACI's) Paragraph IV Disputes conference to discuss, debate, and analyze the latest trends, judicial rulings and legislative developments affecting Hatch-Waxman litigation. Come and be part of this industry-leading think tank: meet with the leading legal minds in this area and access the information which will help you master the critical competencies needed for the new era of Hatch-Waxman litigation.

An experienced faculty comprised of respected and renowned counsel for brand name and generic pharmaceutical companies will help you develop your new plan of attack for 2012 and beyond. They will provide insights on all facets of Paragraph IV litigation: pre-litigation concerns - the commencement of suit - final adjudication - and every step in between. Sessions will address the key elements of Paragraph IV litigation in addition to some of the most pressing and recent controversies surrounding Paragraph IV cases, including:

• The impact of the AIA on Hatch -Waxman litigation
• Carve-outs, use codes and labeling
• Claim construction conundrums
• Prior art obviousness and obvious-type double patenting
• Inducement of infringement and divided infringement
• Inequitable conduct
• Damages

by Richard F. Kurz

On March 26, the United States Supreme Court granted the certiorari petition in Association for Molecular Pathology v. Myriad Genetics, Inc., and remanded the case to the Federal Circuit for reconsideration in light of its newly-issued holding in Mayo Collaborative Services v. Prometheus Laboratories, Inc.

In Myriad, the Federal Circuit previously considered whether certain composition and method claims relating to human genetics were patentable subject matter. The composition claims cover two "isolated" human genes, BRCA1 and BRCA2, and certain alterations, or mutations, in these genes associated with a predisposition to breast and ovarian cancers. An example of one of the composition claims is:

An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2.

All but one of the challenged method claims cover methods of "analyzing" or "comparing" a patient's BRCA sequence with the normal, or wild-type, sequence to identify the presence of cancer-predisposing mutations. An example of one of the method claims is:

A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set forth in Tables 12A, 14, 18 or 19 in a human which comprises analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or analyzing a sequence of BRCA1 cDNA made from mRNA from said human sample with the proviso that said germline alteration is not a deletion of 4 nucleotides corresponding to base numbers 4184-4187 of SEQ ID NO:1.

by Brian Malkin

On March 14, FDA's Office of Prescription Drug Promotion ("OPDP") issued its first Warning Letter this year to Teva for its branded product Copaxone® (glatiramer acetate injection) (solution for subcutaneous injection based on promotional materials sent to FDA on a Form FDA-2253 (pre-dissemination form) as well as its Team Copaxone®" webpage and several associated webpages for "David Kyle" and "Karen Stewart" for Copaxone®.

Team Copaxone

OPDP states in the letter that Teva's promotional materials are false and misleading because they overstate the efficacy, present unsubstantiated claims, broaden the indication of Copaxone®, omit and minimize risk information associated with the drug, present unsubstantiated superiority claims, and omit material facts. OPDP says it finds the violations "concerning from a public health perspective because they suggest that Copaxone is safer or more effective than has been demonstrated by substantial evidence or substantial clinical experience."

Copaxone® is indicated for reduction of the frequency and relapses in patients with Relapsing-Remitting Multiple Sclerosis ("RRMS"), including patients who have experienced a first clinical episode and have magnetic resonance imaging ("MRI") features consistent with multiple sclerosis. MRI is considered one of the best ways to diagnose multiple sclerosis.

by Brian Malkin

On March 23, U.S. District Judge Colleen Kollar-Kotelly for the District of Columbia dismissed without prejudice AstraZeneca Pharmaceuticals LP's ("AstraZeneca's") suit against FDA requesting declaratory and injunctive relief to prevent FDA from granting final approval to generic versions of Seroquel® (quetiapine fumarate) or Seroquel XR® (extended-release quetiapine fumarate). As we reported here, AstraZeneca asserted that FDA could, based on FDA's denial of AstraZeneca's citizen petitions, approve generic versions of both products as early as March 27, 2012 (tomorrow), after the pediatric exclusivity associated with the product expired.

Judge Kollar-Kotelly agreed with AstraZeneca that the Agency's denial of AstraZeneca's two related citizen petitions constituted "final agency action" but disagreed that AstraZeneca's claims were ripe. As the Judge stated in her Memorandum Opinion:

Long has it been established that even a "purely legal challenge" to "final agency action" may not be fit for judicial review. Indeed, the Court of Appeals found that a challenge to the FDA's denial of a citizen petition raising an abstract question that could affect the approvability of related ANDAs [abbreviated new drug applications] submitted by generic competitors, although constituting final agency action, may not be ripe until the agency makes a concrete determination on the related applications. (citations omitted).

FDA had denied AstraZeneca's petitions "without comment on whether [FDA] will take the actions that [AstraZeneca] request[s]." While FDA's actions on citizen petitions are typically considered final agency action, in this case, FDA only has tentatively approved several generic applicants referencing both Seroquel® and Seroquel XR®. FDA has not approved any generic applications to date.

by Richard F. Kurz

On March 20, the United States Supreme Court delivered its long awaited opinion in the Mayo Collaborative Services v. Prometheus Laboratories, Inc. case. The question in the case was whether a patent claiming a method of optimizing therapeutic efficacy for treatment of a disorder is patentable subject matter under 35 U.S.C. § 101. For the specific claims in Prometheus's patents, the answer was "no."

At issue were two patents concerning the use of thiopurine drugs in the treatment of autoimmune diseases, such as Crohn's disease and ulcerative colitis. When a patient ingests thiopurine, the body metabolizes the drug, causing metabolites to form in the bloodstream. Different people metabolize the drug differently, however, which makes it difficult for doctors to determine the proper dose--too high a dose risks harmful side effects, too low and the drug is ineffective. Those in the field did not know the precise correlations between metabolite levels and the likely harm or ineffectiveness of the dose. But, in the research leading to these patents, correlations were identified with some precision. The patents' claims set forth processes that embodied the researchers' findings. An example of one of the claims is:

A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising: (a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and (b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder, wherein the level of 6-thioguanine less than about 230 pmol per 8 x 10(8) red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and wherein the level of 6-thioguanine greater than about 400 pmol per 8 x 10(8) red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

by Howard E. Rosenberg, Ph.D.

Apotex, Canada's largest generic drug manufacturer, claims that as a consequence of action taken by FDA with respect to two Canadian facilities operated by Apotex-Canada, Apotex-U.S. incurred a loss of income exceeding $520 million. Apparently these two facilities produce about 80 percent of the products sold by Apotex-U.S. and an FDA-imposed import alert raised in August 2009 prevented Apotex-U.S. from receiving any drugs produced by these two facilities until the import alert was fully lifted at the end of July 2011.

Apotex alleged that during the relevant time period, FDA accorded more favorable treatment to other U.S. investors and U.S.-owned investments having issues similar to Apotex, in that these other investors were not subjected to a measure as severe as the import alert imposed on the Apotex companies. The problems began for Apotex when their two manufacturing facilities were inspected by FDA that uncovered quality system problems. These issues and the resolution of the issues by a FDA re-inspection were far more protracted to resolve than say those by Teva who, according to Apotex, appeared to have similar or analogous problems. Teva's re-inspection by FDA and the resolution of their quality failures proved to be far quicker than that for Apotex.

According to Apotex, the import alert violated North American Free Trade Agreement ("NAFTA") Article 1102 (National Treatment), Article 1103 (Most-Favored-Nation Treatment) and Article 1105 (Minimum Standard of Treatment). Article 1102 provides, in part, that each Party shall accord to investors of another Party treatment no less favorable than that it accords, in like circumstances, to its own investors with respect to the establishment, acquisition, expansion, management, conduct, operation, and sale or other disposition of investments. Apotex claim that the Import Alert put Apotex Holdings and Apotex-Canada at a clear disadvantage compared to U.S. investors in like circumstances, who were not prevented from applying for authorization of new generic drugs or from benefiting from sales thereof.
Article 1103 extends 1102 by referring to the treatment afforded to third-country investors in like circumstances. Here Apotex pointed to the apparent favorable treatment given to Teva being in stark contrast to what they themselves received. Article 1105 provides that each Party shall accord to investments of investors of another Party treatment in accordance with international law, including fair and equitable treatment and full protection and security.

by Brian J. Malkin

Last week, the U.S. Sentate unanimously passed a bill sponsored by Patrick Leahy (D-VT), S. 1886, the Counterfeit Drug Penalty Enhancement Act of 2011. The Bill increases penalties for trafficking counterfeit drugs.

Currently, it is illegal to introduce counterfeit drugs into interstate commerce, but the penalties are the same as for illegal trafficking other goods, such as electronics or other merchandise. In essence, the penalties for copying a company's logo on a prescription bottle were more severe than for making and selling counterfeit drugs. The Bill targets violators who knowingly manufacture, sell, or traffic counterfeit medicines in the United States.

Senator Leahy was clearly pleased with the result and is urging the House to act quickly on the Senate's lead, stating:

We cannot allow the counterfeiting of life-saving medicine to be just one more low-risk venture from which international organized criminals can profit . . . While we should not expect that enactment of this or any legislation will completely deter the serious problem of counterfeit medication entering the American supply chain, it is an important step in the fight. I urge the House of Representatives to act quickly on this legislation.

Worldwide counterfeit medicines are a multi-billion dollar industry, and growing at an alarming pace, especially over the internet. These medicines pose a serious threat to the health and safety of unsuspecting Americans . . .The House should act as quickly as possible to ensure that counterfeit drug traffickers are punished accordingly for putting people's lives at risk with this serious crime.

by Brian Malkin

On March 12, AstraZeneca Pharmaceuticals LP ("AstraZeneca") sued FDA in the District Court for the District of Columbia requesting declaratory and injunctive relief to prevent FDA from granting final approval to generic versions of Seroquel® (quetiapine fumarate) or Seroquel XR® (extended-release quetiapine fumarate). In its complaint (including AstraZeneca's original citizen petitions, FDA response, and other documents related to the Seroquel® products' new drug applications ("NDAs")), AstraZeneca asserts that FDA could, based on FDA's denial of AstraZeneca's citizen petitions, approve generic versions of both products as early as March 27, 2012, after the pediatric exclusivity associated with a product patent expires.

Aside from whether AstraZeneca's arguments have merit, the heart of the issue appears to be whether AstraZeneca has standing to sue FDA when FDA denied its citizen petitions on March 7, 2012. FDA denied AstraZeneca's petitions "without comment on whether [FDA] will take the actions that [AstraZeneca] request[s]." While FDA's actions on citizen petitions are typically considered final agency action, in this case, FDA only has tentatively approved several generic applicants referencing both Seroquel® and Seroquel XR®. Specifically, FDA stated in its response:

FDA has not yet made a final determination with respect to whether to approve or not approve any ANDA relying on Seroquel or Seroquel XR as the RLD. FDA's decision to approve or not approve a specific application will be based on the particular facts that are applicable to that application at the time of the decision. The periods of exclusivity described above for Seroquel or Seroquel XR may or may not apply or be relevant to the Agency's final decisions with respect to any individual application and its labeling depending on the particulars of an ANDA and the timing of its approval. Such decisions are made by the Agency on a case-by-case basis in the normal course of the review process.

by Richard F. Kurz

On March 9, the Drug Enforcement Administration ("DEA") filed its opposition to Cardinal Health, Inc.'s ("Cardinal's") appeal of a recent United States District Court ruling. At issue is the DEA's Immediate Suspension Order ("ISO") revoking Cardinal's Lakeland, Florida facility's registration to ship controlled substances, which has been previously reported here and here. The DEA alleges that Cardinal did not adequately stop diversion of oxycodone, an often-abused pain medication (diversion exists when controlled substances are distributed to an entity that does not have a valid DEA registration). Cardinal is not accused of diversion itself, but instead is accused of not adequately preventing diversion at four pharmacies. Because the ISO was issued prior to an administrative hearing, Cardinal requested that the suspension be halted pending the resolution of this upcoming hearing. The district court denied this request.

Typically, the DEA revokes a distributor's registration after providing the registrant notice of the intent to revoke and a hearing. The DEA may issue an ISO without a hearing, however, when there is an "imminent danger to the public health or safety." Cardinal's appeal argues that the DEA was "arbitrary and capricious" when it issued the ISO because the DEA never met the "heightened standard" Cardinal argues is required to find that the Lakeland facility posed an imminent danger to public health or safety. Additionally, Cardinal argues that it already took remedial measures that obviated any imminent danger, including suspending or sharply curtailing shipments to the four pharmacies specified in the ISO. Consequently, Cardinal argues, issuing the ISO was contrary to law and denied Cardinal its due process right to be heard before the DEA suspended its registration.

The District Court, however, stated that "the DEA's issuance of the ISO easily passes the arbitrary and capricious standard of review." The court noted that the DEA considered the following factors: "(1) the rampant pharmaceutical drug problem in Florida, (2) Cardinal Lakeland's history of inadequate anti-diversion controls, (3) the large and increasing amounts of oxycodone distributed by Cardinal Lakeland to the four pharmacies from 2009 to 2011, (4) the sizeable amounts of oxycodone distributed to 25 other pharmacies in 2011 that exceeded state and national averages, and (5) the evidence of Cardinal Lakeland's failure to monitor its chain pharmacy customers, despite clear warning signs of inadequate anti-diversion controls at those pharmacies . . . ." Based on these factors, the court found that the DEA had a reasonable basis to conclude that the Lakeland facility's continued registration posed an imminent danger to public health or safety. This, combined with the DEA's explanation for the action and consideration of Cardinal's remedial efforts, led the court to conclude Cardinal was unlikely to succeed in proving that the ISO was arbitrary and capricious.

by Brian Malkin

On March 12, FDA issued a new draft guidance, "Guidance for Industry: Direct-to-Consumer Television Advertisements--FDAAA DTC Television Ad Pre-Dissemination Review Program." The guidance applies to drugs and biologics and describes how FDA plans to implement a requirement for pre-dissemination review of direct-to-consumer television advertisements ("TV ads") according to Section 503 B of the Federal Food, Drug, and Cosmetic Act ("FD&C Act") as amended by the Food and Drug Administration Amendments Act of 2007 ("FDAAA"). The guidance describes the types of TV ads that FDA plans to make subject to this provision, how FDA plans to notify sponsors that a TV ad will be subject to this provision, and the general and FDA Center-specific guidelines for sponsors to submit their TV ads to FDA for pre-dissemination review.

According to FDAAA, FDA may "... require the submission of any television advertisement for a drug . . . not later than 45 days before dissemination of the television advertisement." Section 901(d)(2), codified at 21 U.S.C. § 353(b). FDA may make recommendations on:

• Changes that are necessary to protect the consumer good and well-being, or that are consistent with prescribing information for the product under review; and


• Statements for inclusion in the advertisement to address the specific efficacy of the drug as it relates to specific population groups, including elderly populations, children, and racial and ethnic minorities, if appropriate and if such information exists.


• 21 U.S.C. §§ 353(b)(1) and (2).

by Brian Malkin

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

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

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

by Howard E. Rosenberg, Ph.D.

The rapidly increasing flow of foreign drugs into the United States is illustrated by the fact that nearly 40% of the drugs Americans take are made overseas, and about 80% of active pharmaceutical ingredients are imported. Approximately half of medical devices used in the United States also come from abroad. These foreign goods often follow complex paths through multi-step supply chains to reach the United States.

This dynamic is very evident in the U.S. trade with China. From 2007 to 2011, the number of shipments of FDA-regulated products from China increased by 62 percent. This represented a fundamental change in both the economic and security landscape, and, as a result, FDA is requesting a budget authority increase of $10 million to strengthen the safety of foods, drug products, and ingredients exported from China to the United States.

The increased budget would allow FDA to improve its food and drug inspection and analytical capabilities by increasing its presence in China with 16 inspectors, and by adding three U.S.-based analysts. The Agency currently has eight staff members working in China. They serve at posts established in 2008 and 2009 in Beijing, Shanghai, and Guangzhou. In addition to inspecting Chinese facilities that manufacture food and medical products for export to the United States, FDA will inspect sites of clinical trials. FDA will also conduct follow-up inspections to ensure that firms continue to manufacture food and medical products under safe conditions.

by Kyle Deighan

Last Wednesday, FDA's Endocrinologic and Metabolic Drugs Advisory Committee recommended that the FDA approve the weight-loss drug Qnexa® (phentermine and topiramate). The same panel, however, voted in 2010 to reject the drug over concerns about the drug's side effects. If allowed, Qnexa® would be the first FDA-approved anti-obesity drug in more than a decade. Qnexa® and FDA's approval standards for weight loss therapies were a hot topic recently at Leerink Swann's Global Healthcare Conference, as we reported here.

Qnexa®, developed by Vivus, Inc., is designed to decrease appetite and increase satiety, or the feeling of being full. It is a combination of two generic drugs--phentermine, an appetite suppressant, and topiramate, believed to increase satiety. Vivus states on its website that in phase 2 and 3 trials, patients taking Qnexa® have "demonstrated statistically significant weight loss, glycemic control, and improvement in cardiovascular risk factors, when used in combination with a diet and lifestyle modification program."

Peter Tam, President of Vivus said, "We are pleased with the panel's approval recommendation in support of the safety and efficacy of Qnexa . . . We look forward to working with the FDA as they complete their evaluation. Obesity is a serious medical condition, and we are committed to making Qnexa available and providing physicians with a new medical treatment option in their battle with this public health epidemic."

However, serious concerns remain about Qnexa®'s potential side effects, including heart problems and birth defects. Mitchell S. Roslin, M.D., chief of bariatric surgery at Northern Westchester Hospital in New York, for instance, noted, "[W]e don't know if this drug is safe enough for patients to stay on it to maintain their weight loss . . . It clearly works better than other drugs out there, but the questions remain -- at what cost and for how long." Additionally, there are those who doubt the drug's ability to cure obesity at all.

by Richard F. Kurz

On March 2, the United States Court of Appeals for the District of Columbia ordered an administrative stay on the Immediate Suspension Order ("ISO") issued by the Drug Enforcement Administration ("DEA") against Cardinal Health, Inc.'s ("Cardinal") distribution facility in Lakeland, Florida. This stay postpones the ISO while the court considers Cardinal's emergency injunction motion, which would halt the ISO pending Cardinal's separate appeal of the ISO. When granting the stay, the court stated that it had not yet considered the injunction motion on its merits. A decision on the merits will likely come soon, however, because the court ordered an expedited briefing schedule, requiring the DEA's response to the motion by Friday, March 9, followed by Cardinal's reply on Monday, March 12.

The ISO, previously reported here, suspended Cardinal's registration to distribute controlled substances (such as the pain medication oxycodone) from its Lakeland facility to approximately 2,700 customers, including hospitals and pharmacies. Typically, the DEA revokes a registration after providing the registrant notice of the intent to revoke and a hearing. The DEA may issue an ISO without a hearing, however, when there is an "imminent danger to the public health or safety." Here, according to Cardinal, the DEA alleged imminent danger and issued the ISO without notice and a hearing.

Cardinal argues that there was no imminent danger to justify the DEA's action. The ISO did not allege that Cardinal distributed controlled substances to anyone that the DEA had not authorized to receive them. Instead, the ISO alleged that Cardinal sold high aggregate volumes of oxycodone to four pharmacies between 2008 and 2011. But by the time the ISO was issued, Cardinal had already suspended shipments to two of the pharmacies. Cardinal also noted that its shipments to the other two pharmacies had decreased by 80% prior to the ISO, which Cardinal then suspended after receiving the ISO. Consequently, Cardinal argues that its own remedial measures already negated any danger to the public and the ISO is unnecessary pending Cardinal's appeal.

by Richard F. Kurz

On February 29, a federal district court judge issued an Order requiring that Cardinal Health, Inc. comply with an Immediate Suspension Order ("ISO") issued by the Drug Enforcement Administration ("DEA"). The court previously granted a temporary restraining order delaying Cardinal's compliance with the ISO, pending a decision on a preliminary injunction requested by Cardinal. However, the Court denied this preliminary injunction in its Order. Cardinal appealed this decision on the same day as the court's Order.

Partially at issue in this dispute is the question of who is responsible for stopping diversion, a form of illegal sales of controlled drug substances. Diversion is distributing controlled drug substances to an entity without a valid DEA registration. In this case, diversion of the prescription pain killer oxycodone allegedly took place at pharmacies supplied by Cardinal's Lakeland, Florida distribution facility. Cardinal states that it has a system in place to stop diversion and that it is ready and willing to suspend shipments to any pharmacy that the DEA identifies as likely to be engaged in diversion. The DEA, however, states that the Lakeland facility has a continuing, affirmative obligation to police its retail customers to ensure that the controlled drug substances it provides are not being unlawfully diverted--and the Lakeland facility fell short of its legal and contractual obligations.

According to a Complaint filed by Cardinal, the ISO requires the Lakeland facility to immediately halt shipments of all controlled drug substances to about 2,700 pharmacies, hospitals, and other customers to prevent alleged imminent danger to the public health or safety. Notably, only Cardinal's Lakeland facility is subject to the ISO. The DEA, however, does not allege that Cardinal itself distributed controlled drug substances to any entity not permitted to purchase them. Instead, the ISO was issued because four pharmacies that were supplied by the Lakeland facility have allegedly distributed oxycodone for illegitimate uses.

by Charles J. Raubicheck

FDA Commissioner Margaret Hamburg has announced Elizabeth ("Liz") Dickinson was appointed as the Chief Counsel of FDA, effective March 12, 2012.

The new Chief Counsel has had a long and distinguished career at FDA since she joined the agency in 1994. She has principally served as legal counsel to FDA's Center for Drug Evaluation and Research, providing advice in such key areas as Hatch-Waxman generic drug approvals, pediatric exclusivity and orphan drugs. She has also worked closely with the Department of Justice representing FDA in many court cases. Liz is well respected by both her colleagues at FDA and outside lawyers representing companies in FDA-regulated industries.

Among the imminent issues that Liz will face at FDA include generic drug user fees, drug shortages, and regulations/guidances for the Agency's implementation of new statutes on food safety and tobacco products.

Liz received her B.A. in Economics from the University of Massachusetts, and her J.D. from Northeastern University. She clerked for Judge William B. Bryant at the U.S. District Court for the District of Columbia.

Mark Raza will continue to serve as the Acting Principal Deputy Chief Counsel.

by Howard E. Rosenberg, Ph.D.

Today, FDA held its first-ever Rare Disease Patient Advocacy Day, because of its recognition of the need for therapies for rare diseases. The day was designed to help patients and caregivers engage with the FDA on issues related to drug and medical device development for rare diseases and conditions. Debra Lewis, Deputy Director of FDA's Office of Orphan Products Development ("OOPD"), said, "Today gives rare disease patient advocates the opportunity to meet with FDA staff and learn more about how FDA works. And, as we come together with colleagues, families, patients and advocacy groups, it gives FDA a moment to reflect on recent news in helping people with rare diseases." She also highlighted a new study published in Pediatrics by Chandana Thorat et. al. which carried out a ten-year analysis of the effect of the Orphan Drug Act of 1983 ("ODA"). The study reports that from 2000 to 2009, 1138 "orphan" drugs were designated and 148 received FDA approval, of which 38 were for pediatric diseases. The proportion of approvals for pediatric products increased from 17.5% in the first half of the decade, to 30.8% in the second.

Stephen C. Groft, Pharm.D., Director, NIH Office of Rare Diseases Research, gave an overview of the available resources to researchers and patients alike in this area and highlighted that the considered best approach to carry out research and to look into solving the problems of these rare diseases is to engage in collaborative efforts. Thus the use of disease specific steering committees between academic research investigators and medical specialists, together with the patient advocacy groups and philanthropic foundations and working with offices such as the Office of Rare Diseases Research is the right way to achieve the goals, Groft explained.

The ODA has been viewed as the single biggest catalyst for encouraging research for orphan drug diseases with FDA approving more than 390 orphan products for the treatment of rare diseases since the legislation came into effect. EU legislation followed in 2000 and has also helped to incentivize research. Further, as we reported here, FDA has decided to expand OOPD's staff to reflect the increasing proportion of orphan drug applications that the Agency has been receiving lately, reflecting over a third of new drug applications in 2011, as we reported here.