HealthLawProf Blog

Editor: Katharine Van Tassel
Concordia University School of Law

Thursday, October 8, 2009

A Challenge to the FDA’s Entire Regulatory Scheme for Health Care Products: Botox Manufacturer Files Lawsuit Asserting First Amendment Protection for Off Label Drug Claims

In a move that could undermine the entire FDA premarket approval process for all health care products, the maker of Botox has filed a legal action against the government claiming first amendment protection for the distribution of “truthful, relevant information” to doctors regarding off-label uses of its drugs.


As Natasha Singer of the New York Times reports:


The Food and Drug Administration approves medicines for specific therapeutic indications. Once a drug is approved for a specific use, doctors are then free to use their medical judgment to prescribe the drugs for other unapproved, or off-label, uses. Manufacturers, however, are prohibited from promoting off-label uses to medical providers or advertising such uses directly to the public.


Botox, an injectable drug that can temporarily reduce muscle or gland activity, is approved in the United States to treat crossed eyes, eyelid spasms, excessive sweating, severe neck contortions and wrinkles. But many doctors use the drug for unapproved indications like facial spasms, vocal cord problems and migraine headaches.


‘If you could get a drug approved for one narrow use and then market it for everything else, there would be no incentive or motivation for a company to prepare data to ensure that it meets the standard for safety and efficacy,’ said Marc J. Scheineson, a lawyer specializing in food and drug regulation at Alston & Bird in Washington.


It appears that the Botox suit is claiming free speech protections that are similar to those provided for dietary supplements. See Pearson and Shaw v. Shalala, 1999 U.S. App. LEXIS 464 (Jan. 15, 1999).  However, dietary supplements are targeted to healthy portions of the population to help maintain or enhance health. Drugs are marketed to unhealthy, vulnerable portions of the population claim to aid in an individual’s struggle to return to normal health. This difference should be outcome determinative in the Botox case. 

In an attempt to place this issue in historical context, the following provides a very brief summary of the long history of the relationship between the Food Drug and Cosmetic Act, the FDA and predatory commercial interests which suggests that there are lessons from the past that can assist in the analysis of this current regulatory issue.  


Over the 100 year history of the FDA, Congress has been steadfast in balancing the protection of individual choice in matters involving self-regarding behavior, such as food choices, with the need to protect vulnerable consumers from harm from third parties who are marketing health care products.  It has done so by linking the level of product regulation with the health status of the product’s targeted population. Accordingly, the greatest amount of regulatory protection has been applied when products are targeted at vulnerable, unhealthy populations and claim to aid in an individual’s struggle to return to normal health.  Examples of products that fall into this category include drugs and devices.


For these products, the modern FDCA establishes a premarket enforcement process that places the majority of the cost and burden on the product manufacturer to establish safety and efficacy through the clinical trial process prior to distribution to the public.  Without premarket approval from the FDA, these products will be deemed both adulterated and misbranded as a matter of law.  Conversely, the FDCA requires less regulatory protection when products are targeted to healthy populations for use in maintaining or improving a normal state of health.  Examples of products that fall into this category are foods and narrow categories of functional foods and dietary supplements.  For these products, the FDA  carries the burden of removing an unsafe or ineffective product by proving that it is adulterated or misbranded.


A review of the history of quack medicines supports this public health strategy. The late nineteenth and early twentieth centuries saw a remarkable growth in the marketing of sham products to treat and cure disease. At that time, the rate at which quack medicines were being introduced into the market far outpaced the development of the science necessary to establish the efficacy and identify the risks associated with each new product. This scientific lag time created a period when there was an information void that predatory commercial interests were quick to use to their advantage.  As the FDA carried the burden of proof to show that a product did not work or was unsafe in order to remove the product from the market, during this lag time predatory commercial interests were able to profit from scientific uncertainty to the detriment of public health. 


During this long period in U.S. history, the curative claims of predatory sham medicine salesmen were limited only by the gullibility of their targets.  In many cases, the degree of gullibility was proportional to the level of desperation of the individual for a cure. The more dire the condition, the more vulnerable an individual was to the ‘flim flam’ of the greedy snake oil salesman.  And the more dire the condition, the greater the degree of harm when the sham medicine did not work, causing injury over and above the original illness and/or causing a delay in seeking effective medical treatment. Thus, this lag time between initial marketing of a sham product and the development of the science necessary to resolve uncertainties over the new product’s safety and effectiveness was very costly in terms of human suffering and loss of life.

It took a series of highly publicized public health crises [including the thalidomide crisis described below] to create the political will needed to pass legislation to close this ‘space between’ created by scientific uncertainty.  This was accomplished by switching the burden of proof of safety and effectiveness from the FDA and onto drug manufacturers.  As more fully discussed in the following sections, it was not until 1962 that legislation was passed that required manufacturers to obtain premarket approval for new drugs from the FDA by producing “substantial evidence” that the product is both safe and effective for its intended use.  The Drug Amendments of 1962 allowed the FDA to make the transition from its former inefficient and costly police role of enforcing specific statutory prohibitions by removing adulterated and misbranded products from the market, to its current gatekeeper role of preventing those products from entering the market in the first place.  Thus, from 1962 until 1994 [with the passage of DSHEA dealing with dietary supplements], manufacturers were no longer able to ‘play in the grey’ and take commercial advantage of the scientific uncertainty over the safety and effectiveness of a product to the detriment of public health.


See Van Tassel, K.,Slaying the Hydra: The History of Quack Medicine, The Obesity Epidemic and the FDA's Battle to Regulate Dietary Supplements, 6 Indiana Health L. J. 203-251 (2009).

What the manufacturer of Botox wants to achieve is the ability for drug manufacturers to once again promote drugs while there is scientific uncertainty over their safety and effectiveness. They are taking the first step toward this goal by claiming this free speech in the context of communication to physicians. While the debate starts over this question, it will be prudent to recall the lessons taught by the Thalidomide case which occurred prior to the 1962 Drug Amendments and involved the distribution of drug to thousands of patients by doctors while there was still scientific uncertainty over its safety:


Thalidomide was widely distributed in Germany, Japan and the United Kingdom for sedative purposes and for the treatment of nausea in pregnancy for several years. In 1960, William S. Merrell Company, the manufacturer of the American version of Thalidomide, Kevadon, applied for FDA approval. However, it was clear to Dr. Frances Kelsey, one of the FDA officers examining the application, that the drug had not been adequately tested for safety before distribution.  In spite of pressure to approve the drug placed by the manufacturer on both the FDA and Dr. Kelsey individually, Dr. Kelsey insisted that the drug needed additional testing to prove safety before FDA approval could be granted.  In 1961, Dr. Kelsey learned of a possible connection between nerve damage in adults and Thalidomide. [These babies were born with phocomelia, which is a Greek word that combines the words ‘seal’ and ‘limb’ … where the long bones of the infants’ arms had almost completely failed to grow; their arms were so short that their hands extended almost directly from their shoulders. Their legs were less affected but showed signs of a similar distortion of growth . . . .”]. She requested that Merrell provide studies on the use of its Thalidomide product on pregnant women.  In 1962, it was discovered that Thalidomide was causing serious birth defects in children. While the application for Thalidomide was pending for FDA approval, hundreds of severely deformed babies were being born in Germany. [Worldwide, it is estimated that 8,000 severely deformed babies were born because of thalidomide].Without the FDA’s knowledge, Thalidomide had already been provided to 20,000 patients in the United States as part of an “investigational study.”


| Permalink

TrackBack URL for this entry:

Listed below are links to weblogs that reference A Challenge to the FDA’s Entire Regulatory Scheme for Health Care Products: Botox Manufacturer Files Lawsuit Asserting First Amendment Protection for Off Label Drug Claims :


Post a comment