Communications regarding medicines in development – often referred to as “investigational compounds” can be particularly challenging. On the one hand, there are data milestones and advancements for the product through the regulatory cycle about which there is great interest. On the other hand, a compound that is being investigated through clinical study for possible approval by FDA should not be promoted nor should it be implied by any means that it has both safety and efficacy for a medical use for which it has not yet been approved. When does the line get crossed?
Specifically FDA regulations state that “A sponsor or investigator, or any person acting on behalf of a sponsor or investigator, shall not represent in a promotional context that an investigational new drug is safe or effective for the purposes for which it is under investigation or otherwise promote the drug. This provision is not intended to restrict the full exchange of scientific information concerning the drug, including dissemination of scientific findings in scientific or lay media. Rather, its intent is to restrict promotional claims of safety or effectiveness of the drug for a use for which it is under investigation and to preclude commercialization of the drug before it is approved for commercial distribution.” (21 CFR 312.7 (a) )
So how often has it happened that FDA has taken action when it perceives that there has been promotion of an unapproved compound and under what circumstances has it occurred?
It turns out that while the omission or minimization of risk information is the most common of all violations that have been cited by FDA over the years, promotion of an investigational compound has not been all that common. Looking back to all of the violations cited by FDA’s Office of Prescription Drug Promotion (OPDP) recently, and back when it was called the Division of Drug Marketing, Advertising, and Communications (DDMAC) through 2004, I have counted only nine letters (out of the total of 309 letters issued during that period) that addressed this particular violation.
Of the nine letters,
- 5 involved products being investigated for use in oncology
- A website was the communications vehicle involved in the violation in 7 out of the 9 circumstances
- The 2 others included one brochure and one involving spoken word where an investigator gave interviews to the media that FDA deemed in violation.
- All of the letters involved small companies.
- While the search looked at the years 2004-2016, the first one showed up in 2008.
- Eight of the nine letters were untitled letters – only 1 was a warning letter.
- Finally, and perhaps most importantly, a violations cited in these letters are not predicated on a single statement. Rather the letters cite multiple statements made about the efficacy and safety together create an impression that a compound is safe and effective when cited. That is not to imply that an individual statement could not be the subject of a letter, particularly if it were brazen enough, but that the recent letters have looked at more than one statement and the totality of a presentation within the context of the communication.
And here is one interesting note – while letters from OPDP/DDMAC regularly cover more than one violation in a letter, each of the nine involving promotion of an investigational compound shared one characteristic. They were single issue letters, meaning that the promotion was the sole reason the letter was generated.
If you are interested in seeing each one individually, here are links:
- 2008 – Website – Oncology product –
- 2010 – Spoken word – Dermatological product
- 2011 – Brochure – ADHD product
- 2011 – Website – Oncology product
- 2011 – Website – Oncology product (warning letter)
- 2012 – Website – Oncology product
- 2012 – Website – Gastrointestinal product
- 2013 – Website – Oncology product
- 2015 – Website – Scan marker
While this posting is not meant to be a tutorial, reading the letters in combination will give one a good idea of the kind of language that runs outside of regulatory parameters in the eye of FDA. Those parameters allow for the exchange of scientific information – so sticking to factual data during pre-approval is important while characterizing outcomes or position of a product in the marketplace takes you away from that.