Should Medical Food Clinical Trials be Conducted Under INDs? May be  
​[Posted on: Thursday, April 20, 2017]

Last month, FDA issued a Warning Letter to a California medical foods company, Targeted Medical Pharma (TMP), for conducting clinical trials without an IND. This is an interesting case study that highlights common regulatory issues with most companies doing clinical trials, and more specifically medical food and supplement developers. First, FDA regulates products based on the claims made on the label. Hence a product claiming to treat, prevent or diagnose a disease is regulated as a drug. It does not matter if the investigational product is composed of GRAS ingredients. TMP’s clinical trials were to test their products in the treatment of peripheral neuropathy and pain which would classify their products as drugs and not medical food. FDA has in the past issued similar warnings to other food and supplement manufactures who claimed medicinal benefits with their products. Second, when a company wants clarifications regarding the regulatory requirements for its products, it can directly ask FDA. But this inquiry must be made formally in writing. TMP claimed in its response to FDA that one of its employees had contacted FDA but FDA could not find any record of the discussion. Most likely an employee at TMP either just called someone at FDA or met some FDA employees at a conference or other location. Such conversations are not considered formal advice by the FDA. Hence any feedback received at such conversations cannot be used to support decisions made. Third, TMP claimed to have sent Forms 1571 and 1572 to FDA after being told that they need to file an IND but FDA could not find any record to such submissions and the company could not produce any evidence that such forms were sent to FDA. An IND contains the clinical trial protocol, the background information and manufacturing information. The two forms cited by TMP will not suffice in lieu of the IND, assuming that such forms were indeed sent to the FDA. The company should have proof of submission, such as postal records and an acknowledgement of receipt from the FDA. Lacking those two, an IND is not considered to be submitted. Fourth, the company claimed on its website and in its responses to the FDA’s 483 that its products are designated as medical food. A medical food classification requires that there be documented evidence of the link between the medical food and a given disease for which it is intended. Manufacturers usually compile a dossier called the Significant Scientific Agreement (SSA) containing the scientific justification linking the medical food to indication. Lacking it, the manufacturer cannot claim medical food classification. Fifth, a search on clinicaltrials.gov shows that TMP has sponsored 7 clinical trials since 2011 with its medical food products; three of these were completed in 2011. Since they never filed an IND with FDA, it is not clear how FDA got wind of their trials and decided to audit them. This is the second Warning Letter to TMP in 6 months. Their last Warning Letter in Oct, 2016 was regarding non-compliance with registration requirements. So what triggered an FDA audit? It could be a case of whistle blowers telling FDA about these trials or major news about the company. Or may be TMP was just “unlucky” in getting caught in a routine surveillance inspection. Either way, it should be clear to all similar companies, sooner or later, FDA does catch up with violations with negative consequences. While at this time, the maximum penalty FDA can impose is to ask TMP to stop its ongoing trials, it could have long-term consequences when TMP wants to market its “medical food” that FDA considers as “drugs”. This story is still developing but it should already be a lesson to all similar companies flying under the FDA’s radar.