As mentioned yesterday, there was a virtual drip of warning letters out of DDMAC during this past quarter, in line with the very low numbers of recent years. There were also interesting comments entered by readers on that front in yesterday’s posting.
Today, we’ll review the substance of the FDA warning letters for the first quarter of 2007 to see if there are any lessons to be gained:
- De Facto Omission of Risk Information – One compound had several contraindications in its label, including patients with uncontrolled asthma, known hypersensitivity to the makeup of the drug and in glaucoma. There were also specific warnings for people with cardiovascular disease, pulmonary disease and ocular conditions as well as precautions advising patients to be informed of other potential, specific adverse events. However, promotional materials in the form of a dry erase board and wall calendar. While risk information was included, it was printed on the back of the wall calendar and dry erase board.
- Unsubstantiated Claims – A two-page promotional piece produced for a product that is an adjunct therapy in cancer patients fails to disclose the full indication if it does not specifically state that it is adjunct therapy. The agency also felt it was an unsubstantiated claim to say that the treatment was effective beginning Day 1 of treatment as the only studies cited were animal studies.
- Broadened Indication – A promotional piece regarding a drug that is approved to treat narcolepsy and other sleep-inducing disorders was considered by the FDA to have broadened the indication when it it suggested that the product had "utility" in the treatment of disorders not considered on the label, including neurologic and psychiatric disorders. The warning letter noted that this was particularly troublesome since the company had received a "not approvable" letter regarding some of these indications.
- Inappropriate Reminder Ad and Omission of Risk Information – Reminder ads are exempt from having to state risk information, and a ten-second ad for an insomnia medication the company did omit the information. (A reminder ad calls attention to the name of the drug product, but does not include the indication or dosage of the drug product.) The reminder ad, ten seconds long, showed a back to school situation and the voice-over stated that it was Back to School time and to see if the drug might be right for you. Because the drug does not have a pediatric indication, the FDA considered the ad inappropriate.
- Summary of Lessons Learned? - First – Needless to say, including the risk information on material where it will not be seen does not count. Risk information must be where people can read it, otherwise, FDA perceives it to be omitted. Second – Animal studies cannot substantiate a claim in humans. Third, stick to the label on indications – the label is your guide to promotion - not your aspirations. Fourth, risk information can only be omitted in a reminder ad if, in fact, the drug is being promoted by the ad in a way that does not suggest it can be used by a population outside of that for which it is indicated.
That’s it for the quarter. Frankly, I’m relieved that there were only four letters this quarter, as it makes my job easier. And while these letters did provide some important insights, particularly the one regarding the reminder ad, the lack of letters now is still troublesome. As painful as a warning letter is, they at least provide guideposts for industry to follow. With a nearly mute DDMAC, those guideposts become far less certain.