SUPPLEMENT INDUSTRY EXECUTIVE, Jan/Feb 2000

By Marc Ullman

Since its enactment in its current format in 1938, there has been little doubt that the Federal Food, Drug and Cosmetic Act (FDCA or the Act) grants the Food and Drug Administration (FDA) the power to regulate speech uttered in conjunction with the marketing of products governed by the Act’s provisions. For example, it is beyond dispute that, for regulatory purposes, words can have the effect of changing a product, such as orange juice, from a food to an unapproved new drug.

If you offer a customer a glass of orange juice and tell him to drink it because it contains vitamin C, is good for him and is refreshing, the juice will be considered a conventional food. On the other hand, if you tell your customer to drink the juice because it contains vitamin C and that a recent study published in the New England Journal of Medicine indicated that vitamin C may halt the growth of certain tumors, the orange juice has been converted into an unapproved new drug which is subject to regulatory (possibly even criminal) enforcement action.

One of the earliest, and most prominent, examples of FDA’s ability to regulate speech is found in the Supreme Court’s 1948 decision in Kordel v. United States, which affirmed Kordel’s criminal conviction for marketing misbranded drugs. Kordel’s precise offense arose from his use of circulars and pamphlets making a variety of medicinal claims for “health food products...consisting of vitamins, minerals and herbs” manufactured by Kordel. These materials were distributed to consumers by vendors of the products. Rejecting Kordel’s argument that the pamphlets should be viewed as separate items from his product and thus not render them into unapproved new drugs, the Supreme Court held that literature (i.e., speech) which is distributed as part of an integrated marketing plan can be relied upon by FDA in determining the regulatory status of a product.

In the 50 years following the Kordel decision, FDA’s authority to regulate speech in conjunction with products marketed under the FDCA was virtually absolute.

Last year, however, two federal courts ruled that FDA regulations restricting truthful and nonmisleading speech in conjunction with the marketing of regulated products violated the first amendment. While only one of these cases, Pearson v. Shalala, dealt with the marketing of dietary supplements, and the other Washington Legal Foundation v. Friedman (WLF) addressed restrictions on the marketing of prescription drugs, both have the potential to have a profound effect on the manner in which supplements may be marketed in the future.

The Pearson Case
On January 15, 1999, in Pearson v. Shalala, the United States Court of Appeals for the District of Columbia ruled that FDA’s failure to provide any definition of “significant scientific agreement” and its blanket refusal to consider “qualified” health claims while rejecting four proposed claims submitted to it by dietary supplement marketers in 1993 failed to pass muster under both the First Amendment and the Administrative Procedure Act. This decision was especially significant as it marked the first application of free speech principles to regulations governing the direct marketing of dietary supplements. (Previous decisions had already recognized the First Amendment rights of health food stores to offer books for sale, so long as they were not sold in conjunction with any specific products.)

Plaintiffs Durk Pearson and Sandy Shaw are marketers of dietary supplement products, who, “presumably hoping to bolster sales by increasing the allure of their supplements’ labels” submitted four proposed health claims to FDA, each of which linked the consumption of a particular supplement to the reduction of a particular disease. (Citizens for Health and The American Preventive Medical Association joined Shaw and Pearson as plaintiffs in the case). The four claims:

1. Consumption of antioxidant vitamins may reduce the risk of certain kinds of cancers;
2. Consumption of fiber may reduce the risk of colorectal cancer;
3. Consumption of omega-3 fatty acids may reduce the risk of coronary heart disease; and
4. 8 mg. of folic acid in a dietary supplement is more effective in reducing the risk of neural tube defects than a lower amount in foods in common form.

In addition, the D.C. Circuit ruled that FDA’s routine rejection of the notion that health claims that are based on ongoing scientific research, even where accompanied by disclaimers disclosing the current state of the science supporting the claim, violated fundamental First Amendment Free Speech principles. The primary reason set forth by FDA for this approach had been its view that any claim that did not meet its (undisclosed) definition of “significant scientific agreement” was necessarily misleading.

The Court, however, found that this approach failed to satisfy the notion of Commercial Free Speech contained within the First Amendment. Indeed, the D.C. Circuit noted that: “As best we understand the government, its first argument runs along the following lines: that health claims lacking ‘significant scientific agreement’ are inherently misleading because they have such an awesome impact on consumers as to make it virtually impossible for them to exercise any judgment at the point of sale. It would be as if the consumers were asked to buy something while hypnotized, and therefore they are bound to be misled. We think this contention is almost frivolous. See Peel, 496 U.S. at 105 (rejecting paternalistic assumption that the recipients of a letterhead are ‘no more discriminating than the audience for children’s television’). We reject it.”

FDA has also consistently rejected the notion that truthful, non-misleading health claims may be qualified in order to inform consumers of the preliminary nature of the scientific research supporting the health information they seek to convey. In support of this position, the Agency has argued that “there would be a question as to whether consumers would be able to ascertain which claims were preliminary [and accompanied by a disclaimer] and those which were not.” In FDA’s analysis, the use of disclaimers would therefore render any health claim accompanied by any limiting disclaimer inherently “misleading.”

The Court in the Pearson case also rejected this notion, stating: “The government disputes that consumers would be able to comprehend appellants’ proposed health claims in conjunction with the disclaimers we have suggested -- this mix of information would, in the government’s view, create confusion among consumers. But all the government offers in support is the FDA’s pronouncement that ‘consumers would be considerably confused by a multitude of claims with differing degrees of reliability.’ Although the government may have more leeway in choosing suppression over disclosure as a response to the problem of consumer confusion where the product affects health, it must still meet its burden of justifying a restriction on speech -- here the FDA’s conclusory assertion falls far short.”

The WLF Litigation
Once a new drug has completed what is probably the most rigorous testing and review process in existence and been approved for its indicated use in the United States by the FDA, physicians may prescribe the drug for any medical condition they deem suitable. The legitimacy of this practice, known as prescribing for “off-label use,” is well accepted as one of the privileges attendant to the right to practice medicine. While FDA asserts that it has the right to prohibit physicians from prescribing off-label, it has never taken action against the practice, and it is questionable whether the Agency would succeed if it attempted to do so.

During the past decade, many pharmaceutical companies have recognized that off-label prescribing presents a potential new market for drugs that are already marketed pursuant to a New Drug Application (NDA) for an entirely unrelated indication. One obvious attraction of such marketing is the opportunity to increase sales of a drug product without undergoing the vast expense associated with obtaining formal approval from FDA. In response to increased off-label marketing efforts which it perceived as an effort to circumvent the NDA process, FDA adopted two Guidance Documents essentially prohibiting manufacturers from promoting off-label uses to physicians. Of course, information on such uses continued to be available in medical journals and through other outlets, including Continuing Medical Education Seminars (so long as they were independent of the drug manufacturer).

This entire regulatory scheme was upended, however, in two decisions last year which held that it unreasonably suppressed truthful and nonmisleading speech in violation of the First Amendment to the Constitution. Those decisions by Judge Royce C. Lamberth of the United States District Court for the District of Columbia in WLF v. Shalala, both reaffirm the right of companies to communicate important, truthful and nonmisleading information and the concomitant right of the public to receive that information.

In the first WLF decision, Judge Lamberth overturned the two FDA Guidances. As an initial matter, Judge Lamberth ruled that there is a substantial government interest in encouraging drug manufacturers to develop and obtain approval for new on-label uses for their products -- an essential requirement where the government seeks to regulate commercial speech. Compliance with all of the rigorous procedures associated with obtaining FDA approval for on-label indications promotes public safety and confidence in prescription drug products marketed in the United States.

However, FDA could put forth no rational basis for completely suppressing the right of drug manufacturers to communicate information in published studies and journal articles on off-label use to physicians. In reaching this decision, Judge Lamberth rejected FDA’s contention that the regulations were necessary in order to ensure that physicians were not confused by information disseminated by drug companies.

Of particular note, his decision stated: “If there is one principle in the commercial speech arena, it is that a ‘State’s paternalistic assumption that the public will use truthful, nonmisleading commercial information unwisely cannot justify a decision to suppress it.’ To endeavor to support a restriction upon speech by alleging that the recipient needs to be shielded from that speech for his or her own protection -- which is the gravamen of FDA’s claim here -- is practically an invitation to have that restriction struck.”

Rather, Judge Lamberth suggested that FDA consider adopting a number of other regulatory alternatives that would allow drug manufacturers to disseminate truthful and nonmisleading information, such as journal articles concerning off-label use, while simultaneously encouraging application to FDA for approval for on-label indications. Such a scheme, which could mandate disclosure of the preliminary nature of study results and any limitations inherent in the study, would seem to address both FDA’s concerns and the Constitution’s preference for free speech.

Thus, Judge Lamberth noted: “The most obvious alternative is full, complete, and unambiguous disclosure by the manufacturer. Full disclosure not only addresses all of the concerns advanced by the FDA, but addresses them more effectively. First, it assuages concerns that the message communicated is potentially misleading...that the use discussed therein had not been approved by the FDA would be readily apparent... Second, permitting this limited form of manufacturer communication still leaves more than adequate incentives compelling drug manufacturers to get new uses approved by the FDA... Third, to the extent that physicians look to FDA approval as an important (or exclusive) indication of effectiveness...manufacturers will seek to obtain FDA approval... Fourth, the Court must again note that off-label prescriptions, presently legal, do constitute the most effective treatments available for some conditions.

Because the Guidance Documents suppressed truthful, nonmisleading speech where a less restrictive regulatory scheme encouraging full disclosure of all potential issues attendant to off-label marketing could advance FDA’s objective of ensuring that physicians are not misled and encouraging manufacturers to obtain on-label approval, the Guidance Documents were declared unconstitutional.

Shortly after this decision, FDA adopted a new regulatory scheme controlling off-label marketing under FDAMA. This new structure allowed off-label marketing involving distribution of published studies and journal articles under certain conditions, including:

1. The drug must be the subject of a previously approved NDA;
2. The information disseminated must be unabridged, not false or misleading, and not pose a significant risk to public health;
3. The information must not be derived from clinical research by another manufacturer without that manufacturer’s permission;
4. FDA must be provided an advance copy of any information to be disseminated;
5. The manufacturer must submit a supplemental new drug application (SNDA) for the off-label use, or certify that one will be submitted within six months, unless FDA determines that it would be prohibitively expensive or unethical to conduct the necessary research;
6. The disseminated material must include a prominent disclosure that:
   
   
   (a) FDA has not approved the off-label use; (b) the material is disseminated at the manufacturer’s expense; (c) identifies the authors of the information; (d) includes current approved labeling; (e) where appropriate, the existence of other, approved products for the off-label use in question; (f) identifies the parties funding the study being distributed; and (g) contains a bibliography of other scientific articles on the off-label use.

In this instance, he found both the regulations and the relevant portions of FDAMA fatally flawed because they failed to advance the government’s interest in encouraging drug manufacturers to obtain approval for on-label indications for off-label use. Rather, he concluded that almost all of the requirements were designed to force a “balanced” presentation of information to physicians in order to prevent them from potentially being misled. Potentially misleading speech, however, is not proscribable under the First Amendment. Only where speech is more likely than not to mislead do First Amendment protections fall away. Moreover, the validity of FDA’s professed concern over the ability of article reprints to mislead physicians is belied by the ability of physicians to freely exchange articles amongst themselves, and FDA’s position that it is permissible for manufacturers to distribute the same information in response to a physician inquiry.

Judge Lamberth also struck down the new requirement that requires filing of an SNDA for any off-label use promoted by a manufacturer for its products, stating that it “amounts to a kind of constitutional blackmail -- comply with the statute or sacrifice your First Amendment rights. It should go without saying that this tactic cannot survive judicial scrutiny.” Once again, he urged that the best, constitutionally acceptable, approach for FDA to take would be to mandate full disclosure in connection with any off-label promotion. Adoption of a regulatory scheme requiring disclosure of all relevant facts, including the fact that FDA has not approved the off-label use and any issues that might effect the scientific reliability of the study in question, would ensure that the only truthful and nonmisleading information is disseminated, while encouraging manufacturers to pursue on-label approval.

Impact of Pearson and WLF
While the Pearson and WLF decisions are of particular note for their ground-breaking application of First Amendment principles to FDA regulation of speech directly connected with the marketing of Agency regulated products, it is important to keep in mind that neither decision fundamentally alters FDA’s regulatory abilities.

While Pearson requires FDA to define the term “significant scientific agreement,” either through an affirmative rule-making procedure, or through a case-by-case explanation, Agency pre-approval of all health claims is still required. Though the decision required FDA to consider the viability of qualified health claims, Pearson did not alter the regulatory structure surrounding the health claim process or alter FDA’s authority to commence enforcement actions against products that are marketed in conjunction with unapproved health claims.

Similarly, while the WLF decisions clearly establish FDA’s long-standing paternalistic view that it is necessary to restrict the free flow of truthful and nonmisleading information in circumstances where the Agency determines that consumers must be protected from themselves, Judge Lamberth’ s decisions do not authorize the wholesale mailing of clinical studies, much less abstracts or non-scientific articles to consumers. On their face, these decisions merely state that FDA cannot prohibit the dissemination of published journal articles to physicians.

Having said this, the long-term impact of these cases may be significant indeed. At a minimum, it seems that FDA will now be required to consider fundamental First Amendment Free Speech principles in any future rule-making that restricts speech. The Agency will be required to explain its rationalization for the restrictions imposed, and justify the scope and force of those restrictions in relationship to the ends it seeks to achieve. Any regulation adopted without this analysis should be vulnerable to challenge in federal court.

In accordance with the Pearson decision, on December 22, 1999, FDA issued a Guidance Document setting forth its view of the meaning of “significant scientific agreement” and the process by which it proposes to determine if that standard is satisfied by future health claims. Among the noteworthy provisions in that document are:

• FDA’s assertion that the standard must be satisfied primarily through publicly available data -- proprietary studies will be given much less weight;
• While interventional studies in a randomized clinically controlled trial are the “gold standard,” other types of data will be considered including observational studies, case reports and meta-analyses. Animal and in vitro studies can also be used to support data presented in human studies, but cannot support a health claim on their own.
• Significant scientific agreement represents the agency’s best judgment as to whether qualified experts would likely agree that the scientific evidence supports the substance/disease relationship that is the subject of the proposed claim. This is intended to be a strong standard that provides a high level of confidence in the validity of the claim, but does not require that a consensus exist.
• The opinion of a federal government scientific body such as the National Institute of Health or the Centers for Disease Control will be relevant to determining if such agreement exists. The opinion of certain independent expert entities such as the American Heart Association or the Amer ican Cancer Society will also be relevant.

Additionally, it appears that the Pearson and WLF decisions have not altered FDA’s desire to restrict the flow of truthful and non-misleading information concerning the health benefits of dietary supplements as the Agency has rejected a proposed health claim linking consumption of saw palmetto to improvement in cases of benign prostate hypertrophy. FDA’s stated concerns with the proposed claim dealt not with its truthfulness, but with the notion that a health claim might properly discuss curative rather than merely preventative effects. This ruling has already been challenged in court by some of the same plaintiffs that participated in the Pearson decision. At first blush, their challenge to FDA appears to have great merit.

Additionally, while the precise scope of the WLF rulings may be narrow on their face, one logical extension of their reasoning would permit dietary supplement marketers to provide copies of published studies to physicians, without worrying whether their dissemination complies with the complex set of rules governing “Third Party Literature” under DSHEA. If physicians are educated enough to read, understand and evaluate such studies in connection with prescription medications, it is difficult to see why they cannot review studies relating to supplements with similar skill and care. Taking the logic of these decisions even further, it is possible that they may be used to lay the groundwork for a legal attack on the notion that FDA is justified in suppressing any truthful and nonmisleading information concerning dietary supplements, or any other health related product.

(Marc S. Ullman is a partner in the New York City firm Ullman, Shapiro & Ullman, LLP, which specializes in the handling of matters relating to the natural products industry. The practice includes the counseling of clients in matters concerning the FDA, FTC and DEA. Ullman and partners Steven Shapiro and Robert Ullman can be reached at 212-571-0068, or by e-mail at usu@usulaw.com. Marc’s direct e-mail is msu@usulaw.com)