Off-label Provisions Of The Food And Drug Modernization Act Found Unconstitutional

On July 28, 1999, Judge Royce C. Lamberth, United States District Judge for the District of Columbia, found unconstitutionally restrictive of free speech the provisions of the Food and Drug Modernization Act ("FDAMA") that regulate dissemination of certain types of information about off-label (unapproved/new) uses. See Washington Legal Foundation v. Henney and Shalala, No. 94 CIV. 1306 (July 28, 1999).

On July 30, 1998, the same court had previously found the off-label policies reflected in certain FDA guidance documents unconstitutional, including those concerning the distribution of reprints of articles and reference texts. See Washington Legal Foundation v. Friedman and Shalala, 13 F.Supp. 2d 51 (D.D.C. 1998). Judge Lamberth had also found unconstitutional Food and Drug Administration ("FDA") restrictions on manufacturer involvement in continuing medical education. Because the court denied FDA's request to limit its decision to the guidance documents in effect at the time of the 1998 order, Judge Lamberth raised the issue of the extent to which these policies were reflected in FDAMA and FDA implementing regulations. See Washington Legal Foundation v. Friedman and Shalala, No. 94 CIV. 1306 (Feb. 16, 1999).

This alert describes the court's 1999 decision, which analyzed whether the off-label provisions of FDAMA restricting dissemination of published articles and reference texts unduly burdened free speech, thereby unconstitutionally abridging First Amendment rights.

Restriction of the Dissemination of Information on Off-label Uses

The United States Congress passed FDAMA in November, 1997, and FDA published the implementing regulations for off-label uses on November 20, 1998. See Final Rule, Dissemination of Information for Unapproved/New Uses for Marketed Drugs, Biologics, and Devices. 21 C.F.R. ' 99, 63 Fed. Reg. 64556 (Nov. 20, 1998). The statute and regulations restrict a manufacturer's dissemination of unabridged articles and reference texts to certain health care providers and require the drug or device discussed in the disseminated literature to be legally marketed for some use. FDAMA and FDA regulations also require manufacturers to submit certain information to the Agency 60 days prior to disseminating publications. This submission must include

1. the article or reference publication to be disseminated;
2. a prominent statement disclosing that the material concerns an off-label use;
3. a prominent disclosure that contains, if applicable, that the manufacturer is funding the dissemination, the names of authors who were compensated by the manufacturer, and the name of any person who provide funding for a study of the new use; and
4. a supplemental application, or request for an exemption, for the off-label use.

Within the 60 day period, FDAMA requires FDA to review and decide whether to allow dissemination of information about the off-label use. The manufacturer cannot disseminate the information unless FDA permits it, under FDA's rules implementing FDAMA.

The District Court's Decision

This July 1999 decision confirms Judge Lamberth's 1998 decision that prior restrictions on dissemination of this type of information are unconstitutional . See Washington Legal Foundation v. Friedman and Shalala, 13 F.Supp. 2d 51 (D.D.C. July 30, 1998). The court used the same constitutional analysis in each case, after finding the promotion of off-label uses to be commercial speech. See Central Hudson Gas & Electric Corp. V. Public Service Commission of New York, 447 U.S. 557 (1980).

The Central Hudson test first requires examination of whether the speech is false and misleading. If the speech is truthful and nonmisleading, the government must demonstrate a substantial interest that is directly advanced by the regulation without burdening substantially more speech than necessary. As in his 1998 decision, Judge Lamberth found articles and reference texts not inherently misleading simply because they were distributed by the manufacturer. In fact, FDA acknowledged the same information would not be misleading if distributed in response to a health professional's request, which is expressly permitted by FDA.

Next, the court accepted the government's substantial interest in encouraging the manufacturer to seek approval of off-label uses as part of FDA's broader duty to protect the public health. However, the only requirement that directly advanced this interest was the submission of a supplemental application. Judge Lamberth found this requirement unduly burdensome of free speech because the FDA could have advanced this interest in other ways. The court listed several other means the FDA could have chosen to advance its interest including:

1. banning the prescription of drugs for off-label uses;
2. prohibiting manufacturers from profiting from off-label prescriptions;
3. imposing a fine or other pecuniary penalty on manufacturers for failing to seek supplemental applications; or
4. more stringently enforcing its statutory authority to prosecute misbranding.

Implications of the Decision

This decision represents another failure on FDA's part to regulate commercial speech. See Arent Fox Alert, Pearson v. Shalala, Invalidating Four Dietary Supplement Health Claims regulations (June 20, 1999). FDA appealed that decision and may appeal this case as well, although it is reported there are negotiations within the industry on alternative solutions.

If drug and device manufacturers decide to follow this decision, they may

1. distribute an article published in a bona fide peer-reviewed journal and any independently published; reference textbook on off-label uses of an approved drug or medical device to health care professionals without prior FDA approval; and
2. suggest content or speakers to an independent program provider of medical education regardless of whether off-label uses will be discussed.

The court stated, however, that FDA may require manufacturers who sponsor seminars or provide financial support for disseminating information to disclose:

1. their interest, i.e. whether they have paid for the dissemination of publications, sponsored the research involved, and/or sponsored. the continuing medical education; and
2. the fact that the use discussed has not been approved by FDA. Manufacturers who decide to rely upon this decision should provide these disclosures and should not disseminate false or misleading information.