OPDP: There Are “A Number of Things” Companies Can Do to Avoid Enforcement Actions

July 29, 2013 — The FDA’s Office of Prescription Drug Promotion (OPDP) held a Webinar today to discuss and take questions about the seven Untitled Letters it has issued from April through June of this year.

When asked by the Coalition for Healthcare Communication how the drug industry can better avoid enforcement actions, OPDP Regulatory Counsel Julie Chronis stated that there were “a number of things” that companies can do. “As a transparent agency, our relevant materials are available on our Web site – the letters we send and the promotional materials – and we do highly recommend that you take a look at those letters. We also have guidances on our Web site and we do invite you to take a look at those also,” she noted.

“As always, we are looking for voluntary compliance from companies. We’re not out to get companies; we just want companies to do the right thing. If you ever have questions about a piece or about claims you want to make or studies that you want to use, we also invite you to submit those for advisories to us. While that does take some time on occasion, it could be well worth the time invested by you,” she said.

The enforcement actions issued during the three-month period covered by the Webinar cited the following violations:

  • Promotion of investigational new drug
  • Omission of risk information
  • Unsubstantiated superiority claims
  • Unsubstantiated misleading claims
  • Overstatement of efficacy
  • Omission of material facts
  • Inadequate communication of the indication

For example, in an Untitled Letter to Teva Neuroscience Inc. for its schizophrenia drug CLOPAZINE tablets, OPDP stated that an article detailer for the product is misleading “because it makes unsubstantiated superiority and other claims regarding clozapine, omits material facts, and minimizes the risks associated with the drug.”

A Webinar attendee sent in a question about this Untitled Letter, asking why the full page of risk information included on the back page of the detailer was not adequate to convey the risks. OPDP Regulatory Counsel Robyn Tyler replied that although “the article detailer included risk information, some of the serious risks were omitted, and additionally, it did not include all material information necessary to adequately describe each risk that was presented.”

In an Untitled Letter to Johnson & Johnson International Inc., regarding a direct-to-consumer (DTC) print ad for XARELTO – which is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation – OPDP held that the print ad “minimizes the risks associated with Xarelto and makes a misleading claim.” A question sent in to OPDP about this letter asked why the left adjacent page of risk information preceding the ad – as the first information the consumer would read – was not considered prominent enough.

“No, the risk presentation would not be considered prominent enough in this case,” Tyler said. The risk information presented did not use some of the emphasis tools used for the efficacy claims, “like the color scheme, the borders, the layout and the graphics. As a result, the presentation appeared unconnected to the efficacy claim, and not likely to draw the reader’s attention to the preceding page,” she said. “The overall presentation minimizes the risk associated with Xarelto.”

Tyler also noted when responding to a question about an Untitled Letter for Validus Pharmaceuticals LLC’s depression drug MARPLAN that the use of meta-analysis as substantial evidence to support claims of efficacy generally is not considered adequate. “In this case, the meta-analyses were based on a literature review that may have produced a biased sample of studies. Additionally, the clinical studies used to conduct the analyses were done with different doses of the drug in varying clinical conditions.”

OPDP issued an Untitled Letter to Mobius Therapeutics LLC for MITOSOL, which is an adjunct treatment to ab externo glaucoma surgery. OPDP asserts that a professional e-mail for Mitosol is misleading because it “makes representations regarding the use of Mitosol, but omits the full indication and omits and minimizes risks associated with the Mitosol use.”

Tyler explained that the e-mail message “presented general efficacy claims regarding dosing but omitted specific dosing information [that is] material for the safe use of the drug. Specifically, the promotional piece presented the claim, ‘assured dosing,’ however there are several different steps and variables involved with the dosing and administration of Mitosol,” she said.

“This material information was entirely omitted from the promotional piece. Also, the promotional piece presented the claims such as, ‘Eliminate Your Concerns’ and ‘Remove the Variables’ with the word ‘dosing’ in conjunction with the claim,” she explained. “These particular presentations grossly minimize the risks associated with Mitosol by suggesting that there were no safety concerns associated with it. In this case, providing dosing information would not mitigate the misleading presentation.”

Chronis advised industry that the FDA, as a result of a citizen petition, is considering whether or not it should issue guidance on preapproval promotion, which several Untitled Letters have cited as problematic in recent months. Chronis noted that FDA solicited comments on this issue “and we are considering these comments as we contemplate our next steps.” She also responded to a question about the appropriate duration for using terms such as “new,” “new on market” or “now available,” by saying that such claims should be used for “no longer than six months.”

The Coalition also inquired about the status of social media guidance that the agency has been working on for years. “This is an area that is high priority for the office,” said OPDP Senior Lead Regulatory Counsel Bryant Godfrey. “Unfortunately we can’t provide a hard, fast deadline for.” However, he asserted that “it is something we have dedicated resources to help move along.”