May 7, 2012 – Many of the alleged violations cited by the Office of Prescription Drug Promotion (OPDP) in five Untitled Letters and one Warning Letter during the first quarter of 2012 are the same violations the agency has cited in the past. Th

ese violations include:

• Omitting or minimizing risk information
• Making unsubstantiated claims, including superiority claims
• Overstating efficacy
• Omitting material facts
• Promoting unapproved uses
• Broadening indications

Speaking at an April 30 OPDP Webinar on Q1 enforcement actions, OPDP Regulatory Counsel Bryant Godfrey said “quality is improving, but there is still room for improvement across the board. Some companies appear to be getting the message while others don’t.”

The sole Warning Letter issued during this time period was sent to Teva Pharmaceuticals USA for its drug COPAXONE. In the March 14 Warning Letter, OPDP states that exhibit panels and Web pages promoting the drug “are false or misleading because they overstate the efficacy, present unsubstantiated claims, broaden the indication of Copaxone, omit and minimize important risk information associated with the drug, present unsubstantiated superiority claims, and omit material facts.”

Further, the letter states that these alleged violations “are concerning from a public health perspective because they suggest that Copaxone is safer or more effective than has been demonstrated by substantial evidence or substantial clinical experience.”

The FDA took issue with promotional claims related to the duration of treatment experience and years of drug safety for Copaxone, which are not supported on the drug’s package insert (PI). The PI did not support the cited claims, according to OPDP Regulatory Counsel Julie Chronis. “The studies that were cited in the piece did not constitute substantial evidence. These studies were extension, open-label studies,” she said.

OPDP Regulatory Counsel Ernest Voyard further explained that these materials presented information out of context. “This is one of those situations where context kind of matters,” he said. The promotional claims suggested 20 years of use by a single patient not simply that the drug had been on the market for 20 years, he indicated. Chronis added that even when companies cite from the PI, they still have to provide appropriate context.

When asked whether industry should submit diagrams and layout of exhibit booth panels via Form FDA 2253, Godfrey responded, “Yes. The more you can help us out the better.”

One attendee asked why a chart cited in a March 13 Untitled Letter to Biogen Idec regarding AVONEX was problematic, considering that the information used to compare Avonex with other drugs in its class was true. “Even though the information portrayed in the chart was true, it was not complete, because risk information for Avonex and the other drugs was omitted,” Chronis said.

Another member of the audience asked for guidance on when a company could properly discuss a specific use beyond the general indication, a problem cited in a March 30 Untitled Letter to Ferring Pharmaceuticals Inc. for FIRMAGON. “When a drug has a general indication, it can be problematic to discuss those specific uses that have not specifically been approved, for a number of factors,” Voyard said. Companies need to have specifically studied and have substantial evidence to back up those uses, he noted.

Several questions were posed to the

OPDP panel regarding the use of case studies in promotional materials, in light of a Jan. 9 Untitled Letter to Novartis Oncology for GLEEVEC. In the letter, the agency took issue with the use of a promotional case study because although it may have been an accurate representation of one patient’s treatment experience, it found no evidence to suggest that all patients would have a similar experience. “FDA is not aware of substantial evidence or substantial clinical experience to support this suggestion,” the OPDP letter states.

Voyard clarified that patient case studies used for promotional purposes should reflect the general use of the product as listed in the PI. “Companies shouldn’t pick extreme cases that show a clear benefit and hide the risk. It should be an accurate reflection of what patients should expect,” he said. “That being said, it doesn’t have to be a middle-of-the-road patient either, but it should reflect what’s expected.”

Another attendee asked why it was not advisable to discuss a patient that did exceptionally well in a case study. Voyard replied that “the exceptional patient is an outlier, and any outlier can be problematic. A [case study] patient has to experience some of the benefits and some of the risks – not necessarily every benefit and every risk – but the [case study patient] should address the general experience,” he noted. “Outliers are probably dangerous.”

When asked whether companies should stop using case studies, Chronis replied, “We don’t discourage it. We just want to see it done in an appropriate manner.”

Reiterating a sentiment conveyed in the 2011 Q4 OPDP Enforcement Webinar, Godfrey said that “voluntary compliance is key.”