1. INTRODUCTION

On July 28, 1999, the U.S. District Court for the District of Columbia completed the stunning rebuke that it delivered to Food and Drug Administration ("FDA") a year earlier on the issue of manufacturer dissemination of scientific information on "off-label" uses. Washington Legal Foundation v. Henney, D.D.C., No. 94-1306 (RCL), 7/28/99. Moreover, in Washington Legal Foundation v. Friedman, the court extended its rebuke to Congress by striking down the portions of the FDA Modernization Act ("FDAMA") intended to forge a compromise on the issue.

Congress passed the FDAMA while the Washington Legal Foundation case was being litigated, and the FDAMA was not subject to the initial decision. Section 401 of the law permitted manufacturers to disseminate peer-reviewed articles and medical texts to physicians. However, they had to meet a number of onerous conditions, such as disclosing the off-label nature of the use, and including a bibliography of other scientific articles on the off-label use and filing the material with FDA 60 days before first use. Section 401 also generally required the manufacturer to file, or commit to file, a supplemental application with the FDA for approval of that use. This separate stream of restrictions counteract the effect of the Washington Legal Foundation decision in the opinion of the court.

2. THE HOLDING

The court ruled in Washington Legal Foundation that Section 401 of the FDAMA violates the First Amendment right to commercial free speech, just as the earlier FDA policies did. It struck down the law and again enjoined the FDA from seeking to limit the following activities:

• Journal Articles. Manufacturer dissemination or redistribution "to physicians or other medical professionals" of any article previously published in a "bona-fide peer reviewed professional journal," regardless of whether it focuses on off-label uses.

• Medical Texts. Disseminating or redistributing "to physicians or other medical professionals" any reference textbook "published by a bona fide independent publisher and otherwise generally available in bookstores or other distribution channels where similar books are normally available" regardless of its discussion of off-label uses.

• CME Programs. Suggesting content or speakers to "an independent program provider" in connection with a continuing medical education ("CME") seminar or other symposium regardless of the off-label discussion of the forum.

The court applied virtually the same analysis to FDAMA as it did to the FDA guidance documents in its initial decision. First, it affirmed that promotional activities constitute protected "speech," not unprotected "conduct," although sponsor communications are "commercial speech" and not more broadly protected "pure speech." The court also asserted that restrictions on promotional activities must meet the Central Hudson test for commercial speech. Section 401 of FDAMA did not pass the four-part test, which assesses the following factors:

• The speech is neither unlawful nor inherently misleading. The promotions concern lawful activity (i.e. off-label use of prescription drugs or devices by physicians). The FDA has not shown them to be false or misleading. The First Amendment does not permit restriction of speech merely because it is "potentially misleading."

• The government has a substantial interest. The court identified two government interests: (1) ensuring that physicians receive accurate and unbiased information about drugs; and (2) encouraging drug manufacturers to seek FDA approval for off-label uses. However, only the second is a legitimate interest for First Amendment purposes, based on the government’s interest in protecting health by preventing use of drugs for purposes for which they were not adequately tested.

• The restrictions must directly advance the substantial government interest. The court held that most of Section 401’s requirements (e.g., attaching a bibliography) advanced the interest in safeguarding the information that physicians receive, which is not a legitimate First Amendment interest under Central Hudson. However, the requirement that sponsors seek supplementary approvals for off-label uses did advance the legitimate interest in encouraging such applications.

• The restrictions must be no more extensive than necessary. Section 401 burdens substantially more speech than necessary to advance the desired interest. The court labeled the supplemental application a kind of "constitutional blackmail." It held that this interest could have been advanced by more direct means that did not infringe on a constitutionally protected area. The court noted that substantial incentives already exist to obtain additional approvals, such as manufacturers’ ability to market products more widely; a greater willingness of doctors to prescribe approved products; and protection from future tort claims.

1. SIGNIFICANCE OF THE DECISION

The Washington Legal Foundation decision knocks the FDA even further back in its efforts to regulate the promotional practices of product sponsors. All of the substantial advances of the initial decision are retained, including:

• Burden of proof shifted to the FDA. The burden of proving that this limited class of scientific information is false and misleading is now on the FDA. Data not submitted for agency review is not inherently false and misleading.

• Physician off-label prescribing makes information "legal." The "lawfulness" of a communication was interpreted narrowly, based not on whether the FDA approval is required, but on whether it refers to a legal activity; in this case off-label prescribing by doctors.

• Enhanced dissemination rights. The ability to disseminate credible peer-reviewed scientific information to physicians is enhanced.

The ruling also changes certain other balances that arose from the FDA’s guidance and the FDAMA provisions. For example, the decision impacts the use of research by another manufacturer. Under Section 401, a manufacturer could not disseminate a reprint about an off-label use based on information derived from clinical research by another manufacturer, unless it had that manufacturer’s permission. This limitation was overturned with the rest of Section 401, giving manufacturers a freer hand to make use of others’ studies. This could reduce the benefits of being the first to publish clinical results on novel uses, as competitors could simply appropriate the publication for their own products.

1. IMPACT ON SPONSORS
1. Permissible Activities For Manufacturers

The Washington Legal Foundation decision took effect on the date of publication. Manufacturers can now undertake the following activities, until or unless the District Court decision is overturned by a decision of the Court of Appeals:

• Distribute Journal Articles. Companies which have had clinical trials, or other scientific information, published in journals which meet the court’s definition of "bona-fide peer reviewed journals" (journals that use qualified, independent experts to objectively review and select, reject, or provide comments about proposed articles) may distribute reprints immediately to doctors, health plans, providers, or to any other "medical professional," regardless of its off-label content.

• Distribute Reference Texts. Manufacturers may distribute independently published reference texts, even if they contain off-label information. The court defined an independent publisher as one with no common ownership or other corporate affiliation with a pharmaceutical or medical device manufacturer, and whose principal business is the publication and distribution of books through normal distribution channels.

1. Impermissible Activities For Manufacturers

The FDA still retains enforcement authority over the promotional activities conducted by a product’s sponsor, distributor, packager, or anyone "acting on behalf of" those entities (e.g., a public relations firm or other promotional agent). In addition to fighting the Washington Legal Foundation decision on appeal, the FDA may choose to concentrate its resources on the many other areas still under its control. The following recommendations highlight areas of likely conflict:

• Don’t Expand the Class of Publications. The Washington Legal Foundation decision is limited to a narrow class of peer-reviewed published scientific information. Manufacturers should not try to expand that class of publications by distributing materials that do not fit this standard.

• Don’t Expand the Class of Information. The court’s ruling only applies to off-label uses. As defined, the term includes only treatment of disease conditions other than those for which the drug was approved, use for different patient populations, or different dosage levels. The drug must have been approved by the FDA for at least one use. Also, claims based on product comparisons, superiority, quality of life, cost-effectiveness, etc. may be beyond the technical reading of the case, although not necessarily beyond the rationale of the decision.

• Don’t Expand the Intended Audience. The decision was premised on communication to an educated audience that can evaluate scientific information for itself. The FDA may scrutinize the composition of the audience to which materials are distributed in an effort to limit the effect of the decision. Manufacturers should be wary of disseminating off-label information beyond "physicians or other medical professionals."

• Don’t Initiate Discussions. The court’s ruling was limited to written materials, and perhaps presentations at CME symposia. Solicited sponsor discussions of off-label uses in the medical literature, outside the formal CME context, is likely still prohibited. Sales representatives should be reminded that they still may not engage in promotional discussions of off-label uses. They may be able to answer questions (unsolicited) concerning the disseminated information, but this remains an unresolved area.

1. Strategies For Manufacturer Response

As the boundaries of the promotional landscape are defined, there are a number of steps that sponsors may take to reduce possible tensions with the FDA:

• Include Prominent Disclosures. Materials circulated pursuant to the Washington Legal Foundation decision should include a conspicuous disclosure that they contain uses not approved pursuant to an application by the sponsor. Other language similar to the FDAMA provision and dissemination regulations should also be considered.

• File Form 2253. Materials distributed should be filed with the FDA at the time of initial dissemination using Form 2253, depending on the existing filing procedures used by the Company.

• Keep the CME Guidance in Mind. A sponsor’s input to a CME symposium is only permitted if the CME provider is independent. While the FDA’s CME guidance was technically invalidated by the court, it still contains criteria relevant in identifying factors that the FDA will consider in evaluating a CME seminar provider’s independence from a sponsoring manufacturer.

Please do not hesitate to contact Marc J. Scheineson. (202/414-9243), David Bloch (202/414-9209), or any other member of the Reed Smith health care group with whom you work if you would like additional information or if you have any questions.