Diagnostics & Imaging Week Washington Editor

WASHINGTON – On the second day of the advertising and promotions conference held by the Food and Drug Law Institute (FDLI; Washington), a number of expert panelists came from law offices, but the primary center of attention was on broader regulatory issue – specifically the impending sunset, on Oct. 1, of Section 401 of the Food and Drug Modernization Act (FDAMA), which loosened the restrictions on promotions of drugs and devices for off-label use.

While the dissemination of journal articles (seen perhaps as often indirectly promoting off-label research and experimentation) may not be profoundly affected in such circumstances, many other aspects of off-label promotion might be impacted – and need considerable clarification.

But the lone FDA representative in the room said that there was little indication from the agency as to how it will proceed on this particular issue after Oct. 1.

Mark DuVal, president of DuVal & Associates (Minneapolis), opened a panel session with an important understatement: that "in our business, you can be quite truthful — but what's left unsaid can get you in trouble" where advertising is concerned.

The session included a series of "what-if" discussions, starting with a look at the information a device maker might provide at a trade show booth.

Posited was a hypothetical company with a pair of premarket approval applications in the works, along with a PMA supplement and a 510(k) — none of which have passed completely through the FDA gauntlet. This fictional company expects approval by now, and one of the devices is an imaging machine, which hospitals and other healthcare providers have to know about beforehand to make budgeting decisions.

Using this hypothetical company as a basis, the discussion turned to investor relations issues, and Deborah Wolf, regulatory counsel at the FDA's Center for Devices and Radiological Health (CDRH), told attendees that "we're not concerned with your investor materials . . . unless they're blatantly false." She noted that the agency does not scan investor pages on company web sites routinely, but that it does so when circumstances seem to warrant such monitoring.

Presenters at a trade show can discuss unapproved uses of a device "if you don't make it appear that a product is approved" for that use, Wolf reminded the audience. However, she noted that "people sometimes get carried away" in crafting their trade show presentations.

The panelists also briefly clarified the role of press releases in product announcements.

Daniel Carmichael, regulatory counsel at Baker & Daniels (Washington) noted that "you can use a press release as a one-time announcement" for a successful 510(k) filing, and that such material can appear on the home page of a web site or in the product section for a day or two. After that, the announcement should be filed in the site's press release section.

DuVal took the idea a step further, cautioning attendees that web sites that prompt the viewer to find the release with Flash technology or other means of drawing attention to the release are flirting with regulatory pushback. In such a case, he said, "you've covered something that was lawful with something that is not."

Of particular urgency to attendees, as noted above, was the Sept. 30 expiration of Section 401 of FDAMA, signed into law in 1997.

Section 401 allows manufacturers to discuss off-label uses of devices, drugs and biologics with health plan managers, doctors, payers, pharmacy benefits managers and others, on the proviso that:

• the sponsor send copies of the material to the agency at least 60 days before the event,
• that such dissemination will pose no threat to public health,
• and that any such materials will "prominently display" a statement that the applications discussed in those materials are not cleared by the agency.

Section 401 does not call for imposing corrective action on the part of the sponsor for relatively harmless violations, but in more serious cases, the FDA has often required manufacturers to write and publish "Dear Doctor" letters clarifying the situation and, when appropriate, take out advertising offering clarification.

Warning letters to such effect have been sent in the past, including a June 29, 2004 warning letter to TherMatrx (Northbrook, Illinois) for unapproved promotion of its TMx 2000 system.

Wolf acknowledged that FDA "does not yet know what we're going to do" about the sunset of Section 401.

DuVal pointed out that as a result of the suit successfully filed against the FDA by the Washington Legal Foundation (Washington) in 1998, "if you complied with 401, you could count on" staying in the clear for use of journal article reprints and a variety of other materials, including abstracts."

However, he asked rhetorically: if industry "can still disseminate reprints, are we limited to [journal article] reprints?"

One attendee asked about communications to pharmacy benefits managers outside the context of a trade show.

DuVal responded by saying that, for the most part, materials sent out upon request are not limited in the same way by regulations, but he recommended that the materials include some notification that the discussed use is off- label, as well as a bibliography.

Another conduit of communication, that of medical science liaisons (MSLs), was also discussed.

Such personnel are typically employed to handle scientific communication, but in the "what-if" discussion, MSLs were described as possibly presenting information to hospitals and managed care organizations with three-ring binders stuffed with presentation materials. One attendee remarked that in such a proactive, organized circumstance, these liaisons served as a sales force.

Kelly Reeves, an attorney with law firm King & Spaulding (Washington) pointed out that disclaimer stickers are often used in other print material contexts to indemnify the sponsor from legal liability, but added that "the sticker does not make the fact that this is promotional material go away."

DuVal added that in the past, he has found that, generally speaking, FDA is "typically okay with a reprint binder" of journal articles and that MSLs will not create problems by having them so long as discussions are of a scientific nature.

He added that drug and device makers are under some pressure to get their information out quickly because a lot of hospitals and plans get upset if they get the news about a new product from patients before the maker contacts them about it, especially when the news comes in shortly after a fiscal year begins and the PBM has committed all the organization's formulary budget.