As noted in the materials, a United States district court declared several FDA Guidances covering the dissemination of off label information and the regulation of CME, as well as Section 401 of FDAMA and its implementing regulations, to be unconstitutional. In its decision, the Court in the WLF case found these FDA and Congressional efforts to be in violation of the First Amendment of the United States Constitution. The FDA appealed the district court's decision as it related to FDAMA and the Final Guidance on CME and other educational activities.

COURT OF APPEALS DECISION

On February 11, 2000, the U.S. Court of Appeals for the District of Columbia, ruling basically on procedural grounds, vacated the district court's injunction as it related to FDAMA and the Final Guidance. The Court of Appeals ruled, in effect, that the First Amendment issue on which the district court had based its decision was not ripe for decision. Noteworthy, however, was the court's comment in footnote 7 of the opinion that "we certainly do not criticize the reasoning or conclusions of the district court."

The ruling was based on FDA's position, enunciated for the first time during the appeal, that it did not claim authority to regulate the dissemination of information based on FDAMA and the Final Guidance. According to FDA, FDAMA and the Final Guidance merely created safe harbors that could be followed without fear of government action. Moreover, while companies were free to try other mechanisms, FDA stated that if the safe harbors were not followed, a company ran the risk that reprints or CME could be used as evidence in an enforcement action brought against the company for shipping an unapproved drug.

The Court of Appeals decision seemed to raise as many questions as it answered. One question concerned whether the remaining provisions of the injunction were affected by the court's decision. One of the provisions broadly prohibits FDA from interfering with the dissemination of peer reviewed reprints or medical texts. In an effort to have some of those questions answered, the WLF filed a motion with the District Court to "confirm and enforce" its injunction. In a strongly worded opinion critical of FDA and the Court of Appeals for not ruling on the constitutional issues, the Court held that it was constrained to rule that its injunction was "wholly vacated by the Court of Appeals."

While other court actions concerning the issues involved in this case and possibly even additional Congressional action or future FDA Guidances may seek to further define the permissible bounds of regulation in this area, for the time being the WLF decisions establish certain key parameters covering the dissemination of off label information and manufacturer's support of educational activities. Clearly, if manufacturers follow all of the requirements of FDAMA and the Final Guidance there should be no FDA regulatory issue.

The more difficult question relates to situations where not all these requirements are followed. For example, would the mere dissemination of a textbook or reprint containing off label information that did not meet all the requirements of FDAMA (but included an appropriate disclaimer statement concerning the inclusion of off label information and a current package insert) present grounds for a FDA enforcement action? While the answer is not clear, a reasonable interpretation of the WLF decisions would require a pattern of conduct promoting off label use, not just dissemination of an article or textbook. Under such an interpretation, it would be more a matter of degree or number of activities e.g. using the sales force to promote off label uses, a web page with off label information as well as the dissemination of peer reviewed articles. Similarly, a demonstration of the independence of a CME activity regardless of whether all of the factors in the Final Guidance were followed would seem to present an activity that could be viewed as appropriate under the WLF decisions and the First Amendment.(Note to AB-this could also read under the First Amendment deleting the WLF reference)

Due to the degree of uncertainty surrounding some of these issues, legal counsel should be consulted before engaging in any of these activities.

Since the District Court's opinion on the First Amendment issues may become relevant in subsequent litigation, it is discussed in some detail below.

DISTRICT COURT'S OPINION

PEER REVIEWED JOURNAL ARTICLES AND MEDICAL TEXTS
First, the district court decisions related specifically to the dissemination to medical professionals of off label information concerning prescription drugs or medical devices contained in peer- reviewed journal articles or in reference texts (medical textbooks or compendium) or portions of such texts. The dissemination of such information to consumers/patients is not covered, nor is the dissemination of company prepared materials.

The articles must come from "bona fide peer-reviewed journals", those that use "experts to objectively review and select, reject, or provide comments about proposed articles. Such experts must also be experts concerning the subject of the article and be independent from the journal.

Textbooks are required to be "published by a bona fide independent publisher and otherwise generally available for sale in bookstores where similar books are normally available.... " "Bona fide independent publisher" is defined as those that do not have common ownership or other corporate affiliation with a manufacturer "and whose principal business if(s) the publication and distribution of books through normal distribution channels".

Second, the product(s) for which information is being disseminated must have at least one approval by FDA in effect. Once that is the case, the article or medical text can contain significant or even exclusive discussion of off label use. Products awaiting their first approval at FDA are not covered by the WLF decision.

Third, the court recognized that nothing in its opinion will prevent FDA from moving against false or misleading materials. This can be a very broad standard and its application by FDA will be watched carefully by all parties. For example, a situation where there are many unfavorable and only one favorable article about an off label use would seem to present circumstances where dissemination of only the favorable article would be suspect.

Fourth, FDA would be permitted under the court's decision to require companies to disclose that the materials contain references to off label use and the relationship between the company and product and the authors/investigators.s.

CONTINUING MEDICAL EDUCATION

While much of the focus of commentators on the WLF case has been on the dissemination of off label information in peer reviewed journal articles and medical texts, as important was the court's decision invalidating FDA's Final Guidance on Industry Supported Scientific and Educational Activities. In striking down the FDA Guidance, the Court held that FDA could not inhibit a company from "suggesting speakers or content to an independent program provider in connection with a continuing medical education seminar program or other symposium program... " regardless of whether off label uses are discussed. "Independent program provider" is defined by the court:

"as an entity that has no common ownership or other corporate affiliation with a pharmaceutical or device manufacturer, that engages in the business of creating and producing continuing medical education seminars, programs or other symposia and that is accredited by a national accrediting organization pertinent to the topic of the seminars, programs or symposia."

As with the dissemination of peer reviewed articles and medical texts, the prescription drug or medical device must have at least one FDA approval covering the product in effect. Similarly, FDA may act against false or misleading materials and require appropriate disclosure that the use(s) discussed is not approved and of the sponsor's interest in the drugs or devices discussed.

Due to the evolving nature of regulation of the dissemination of off label materials, legal counsel should be consulted about the current status of this matter.