June 2011

Topic of the Month:  In June, the Supreme Court ruled favorably for drug companies in two decisions expected to have wide-reaching impacts for consumers and interactions with the pharmaceutical industry.  In one case, the court ruled 5-to-4 that the makers of generic drugs are immune from state lawsuits for failure to warn consumers about possible side effects as long as they copy the warnings on brand-name drugs. And in a second, a First Amendment decision, the court, by a 6-to-3 vote, struck down a Vermont law that barred the buying, selling and profiling of doctors' prescription records — records that pharmaceutical companies use to target doctors for particular pitches.

I. Drugs and Biologics Developments

Supreme Court favors pharmaceuticals in twin decisions
On June 23, 2011, the United States Supreme Court ruled in favor of drug pharmaceutical companies in two decisions, one limiting lawsuits from people injured by generic drug products and the other striking down a state law that banned some commercial uses of prescription data.

Failure to warn
In a 5-4 decision, the Court held in Pliva v. Mensing, No. 09-993, that federal statutes and FDA regulations preempted state tort claims requiring the same safety and efficacy labeling for generic prescription drug products. Consolidating two previous cases, Actavis Elizabeth, LLC v. Mensing, No. 09-1039, and Actavis, Inc. v. Demahy, No. 09-1501, patients prescribed a generic version of metoclopramide, a drug commonly used to treat digestive tract problems, had alleged that long-term use of metoclopramide caused their injuries and that the generic drug manufacturers were liable under state tort law for failing to provide adequate warning labels. The U.S. Court of Appeals for Fifth and Eighth Circuits both held previously that state law failure-to-warn claims against generic medication manufacturers were not preempted by federal law.

The Court reversed the appellate decisions, holding that federal drug regulations, as interpreted by the FDA, prevented the generic manufacturers from independently changing their generic drugs’ safety labels. Although the patients argued that the generic manufacturers could have altered the warning labels via (1) the “changes being effected” process, which permits drug manufacturers, without preapproval, to add or strengthen a warning label or (2) “Dear Doctor” letters providing additional warnings to prescribing physicians and other healthcare  professionals, the Court deferred to the FDA’s views that the agency may not have permitted use of either of the processes by the generic manufacturers to unilaterally strengthen their warning labels.
The Court also held that the agency’s views were not plainly erroneous or inconsistent with the regulations, and there was no other reason to doubt that the FDA’s interpretation was fair. If the generic manufacturers had independently changed their labels to satisfy state-law duty to attach a safer label to their generic metoclopramide, they would have violated the federal requirement that generic drug labels be the same as the corresponding brand-name drug labels. Justice Clarence Thomas, writing for the majority, acknowledged that the Court’s distinction between brand name drug manufacturers and generic drug manufacturers would not matter to the eyes of an injured patient, but noted that the Court’s decision followed from the manner in which branded and generic drug companies were treated under federal law. Thus, the state claims were preempted because it was impossible to comply with both state and federal law.

Impact
Almost three-quarters of all prescriptions dispensed in the United States are generics and the decision is expected to impact the number of generic drug lawsuits brought forth by injured patients. Additionally, Congress may undertake legislation in order to unify the current labeling requirements under the Hatch-Waxman Act that led to the Court’s decision.

Protected commercial speech
In a 6-3 decision, with citations to First Amendment decisions outside the realm of commercial speech, the Court also held in Sorrell v. IMS Health Inc., No. 10-779, that a Vermont law that would prevent data mining companies from transmitting prescription drug data violated commercial speech by preventing drug companies from using the prescriber identifiable information to identify a specific audience for their marketing efforts and to refine their marketing messages. According to the Court, although the law initially appeared to impose content-and speaker-based restriction on the sale, disclosure, and use of prescriber-identifying information for all entities, state law exceptions allowed prescriber-identifying information to be purchased, acquired, and used for other types of speech and by other entities.

State arguments that the law directly advanced a substantial governmental interest, including assisting physicians who had an interest in keeping prescription decisions confidential, were rejected, because pharmacies could still share prescriber-identifying information with anyone for any reason except for marketing. Vermont said the current data mining practice invaded medical privacy and helped push up drug spending by improving pharma-industry marketing efficiency. The data companies argued that the state could not make judgments on how the information was used, for example, data allowed to be used to help with recalls had to be available to marketers.

Justice Anthony M. Kennedy, writing for the majority, noted that the case presented fundamental First Amendment issues because it restricted the use of truthful information in private hands based on the identity of the speaker and the content of its speech. The Court noted that while the state may have been displeased with the data mining companies’ effectiveness in promoting brand-name drugs because they had prescriber information, the state could not burden protected expression in order to tilt public debate in a preferred direction.

Impact
Challenges to the FDA’s ban on advertising drugs for off-label purposes, drugs that have been approved by the FDA for treating one disease but not another, were expected as a result of the data mining decision. Drug manufacturers would most likely seek to advertise these drugs for nonapproved purposes. Additionally, the tobacco industry could use the ruling to challenge the new warning labels that the FDA has required the industry to put on cigarette packs. Pliva v. Mensing, ¶39,182 and Sorrell v. IMS Health Inc., ¶39,183

OTC sunscreen products to receive stricter enforcement and modifications
In a final rule that addresses labeling and effectiveness testing for certain over-the counter (OTC) sunscreen products containing specified active ingredients and marketed without approved applications, the FDA addressed labeling and effectiveness testing issues raised by the nearly 2,900 submissions the FDA received in response to a corresponding proposed rule in 2007, which led to several changes from the proposed labeling and testing requirements including the removal of the proposed UVA “star rating” on the principal display panel (PDP).

The final rule has requirements for the PDP, drug facts labeling and the SPF test parameters including water resistance. Until the final sunscreen monograph becomes effective the FDA is directing the industry to a concurrently published draft guidance document on the enforcement policy. The final rule does not address issues related to sunscreen active ingredients or issues regarding the GRASE determination for sunscreen products. 

Additionally, the maximum labeled SPF value for over-the-counter (OTC) sunscreen drug products would be “50+” under an FDA proposal. The proposed rule comes after a data review which showed that there is not currently sufficient data to indicate that there is additional clinical benefit above SPF 50. Although SPF tests can be accurately and reproducibly performed for sunscreen products with SPF values as high as 80, the FDA did not find adequate data demonstrating that a sunscreen product with an SPF value over 50 provides an increase in clinical benefit over a sunscreen product with an SPF value of 50.   FDA Order, ¶40,431 and FDA Proposal, ¶46,170

Cigarette graphic images to be required in warnings
A Final Rule specified the color graphics that must be used to depict the negative health consequences of smoking that will accompany nine new textual warning statements as required by the Family Smoking Prevention and Tobacco Control Act (P.L. 111-31) which amended the Federal Cigarette Labeling and Advertising Act (FCLAA).

The Final Rule required that the new warnings appear prominently on cigarette packages and in advertisements, occupying at least 50 percent of the area of the front and rear panels of cigarette packages and the top 20 percent of the area of advertisements; and a reference to 1-800-QUIT-NOW will appear as part of the warnings.

The Final Rule also included: (1) it will be unlawful for any person to import for sale or  distribution within the United States any cigarettes that fails to bear one of the required warnings on both the front and rear panels; (2) distributors are obligated to ensure that the products they receive from manufacturers, importers, and other distributors which they will subsequently distribute or sell comply with the law, including checking whether the packages include the required warning on the front and rear panel; (3) retailers, however, are not in violation if they display or sell a cigarette package that includes a health warning, even if it is not one of the nine required warnings, as long as other statutory requirements are met; the retailer exemption will be limited to situations where the cigarette package contains a health warning supplied by a licensed or permit-holding tobacco product manufacturer, importer, or distributor that was not materially altered by the retailer; and (4) the list definitions included in the proposed rule will not be revised except for the term “importer.”  FDA Order, ¶40,432

Nanotechnology application draft guidance published
A draft guidance titled “Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology” will provide the industry with information on whether FDA-regulated products contain nanomaterials or involve the application of nanotechnology.  The points to consider in the guidance will apply broadly to all FDA-regulated products and in the future the FDA may issue specific guidance to be used for specific product areas.

There are two points the FDA wants the industry to consider: (1) whether an engineered material or end product has at least one dimension in the nanoscale range (approximately 1 nm to 100 nm); or (2) whether an engineered material or end product exhibits properties or phenomena, including physical or chemical properties or biological effects, that are attributable to its dimension(s), even if these dimensions fall outside the nanoscale range, up to one micrometer. These considerations will apply to both new products and when manufacturing changes alter the dimensions, properties, or effects of an FDA-regulated product or any of its components. In addition, theses considerations will be subject to change as new information becomes available and refinements are made in product-specific guidance documents.  FDA Notice, ¶42,114

Lung cancer drugs’ clinical trial endpoints draft guidance issued
A draft guidance issued by the FDA and titled “Clinical Trial Endpoints for the Approval of Non-Small Cell Lung Cancer Drugs and Biologics” discusses the agency’s recommendations to applicants on endpoints for lung cancer clinical trials submitted to support effectiveness claims in new drug applications, biologics license applications, or supplemental applications. The draft guidance is a companion to the guidance for industry “Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics.” 

The endpoints discussed in the draft guidance are for drugs to treat patients with lung cancer, which were considered by the agency during discussions regarding lung cancer endpoints presented at previous Oncologic Drugs Advisory Committee meetings; however, the guidance does not address endpoints for drugs to prevent or decrease the incidence of lung cancer.

Applicants are encouraged to use the guidance to design clinical trials for the treatment of lung cancer and to discuss protocols with the FDA.  FDA Notice, ¶42,115

II. Medical Devices Developments

Classification of a product as drugs or device draft guidance issued
The FDA’s current thinking on approaches for classifying products as drugs and devices, as well as additional product classification issues, was published in a draft guidance by the agency. Titled “Draft Guidance for Industry and FDA Staff: Classification of Products as Drugs and Devices and Additional Product Classification Issues,” the draft document addresses three topics: (1) obtaining formal classification determination for a medical product; (2) presenting the agency interpretation of the statutory definitions of device and drug, other than the term “chemical action,” addressed in a separate draft document; and (3) presenting the status of published  intercenter jurisdictional agreements, current regulations establishing classifications, and classifications the agency has otherwise previously made for specific products.  FDA Notice, ¶42,117