FDA Response Time For DTC Ad Advisory Comments Has Doubled, Agency Says

FDA has increased from two to four weeks the time it takes to return direct-to-consumer broadcast ads with advisory comments due to the enlarged volume of submissions, Division of Drug Marketing, Advertising & Communications Branch Chief Nancy Ostrove, PhD, reported Sept. 13 at a Food & Drug Law Institute conference on "Marketing and Promotion in the New Millennium."

The lengthening of time may have to do with an influx of DTC ads for comment in recent months. In June, DDMAC received 32 ads for advisory comments, 16 in July and 26 in August. In addition, 18 new product ads are currently in advisory status, Ostrove said. There are also "in-house revisions" on ads for already aired products.

Ostrove noted that ads are "getting harder" as products with boxed warnings and products that have public health concerns associated with them seek to mount DTC campaigns.

DDMAC may see even more requests for DTC ad review following the Aug. 9 N.J. Supreme Court ruling concerning the promotion of Wyeth-Ayerst's Norplant contraceptive implants. The ruling states that firms that engage in consumer-directed advertising may no longer be able to invoke the "learned intermediary" defense in lawsuits because physicians are less involved in patient education when DTC ads are prevalent (¹ (Also see "DTC Ads Fall Outside "Learned Intermediary" Protections, N.J. Court Rules" - Pink Sheet, 16 Aug, 1999.))

Many participants at the FDLI meeting noted the confusion over product liability resulting from the Norplant case and predicted that firms are likely to increase their submissions to DDMAC for comment and pre-clearance.

Attorney Michael Labson (Covington & Burling, Washington, D.C.) explained that companies conducting DTC advertising incur the duty to warn patients in a palpable way. Pharmaceutical companies should provide risk information and get material cleared by FDA for liability concerns, Labson said. Still, "it is not a complete defense necessarily that you have patient information that's been cleared by FDA."

"The reasoning of the Court was that the base of the [learned intermediary] doctrine...does not apply in today's healthcare environment," he said. "The fact that there is DTC advertising in itself sort of shows that companies can go directly to patients and they [can] give risk information just as well."

Companies could try to preserve the learned intermediary defense by reinforcing the role of the physician in their DTC advertising, Labson added.

FDA's Ostrove outlined some changes in agency thinking regarding advice on drug advertising.

In the past, FDA objected to "reminder" ads that had the same graphic or contextual images as the product-specific ad, Ostrove said. However, FDA does not "worry about the linkages anymore."

"You can use the same graphic in the product ad and the 'reminder' ad as long as they don't make representation about the product." In the past, DDMAC has "taken action" when graphics appeared to imply what a product does, Ostrove noted.

FDA recently sent letters to Merck concerning reminder ads for its osteoporosis drug Fosamax and COX-2 inhibitor Vioxx (² (Also see "Merck Fosamax Reminder Ads Should Be Withdrawn - FDA Ad Division" - Pink Sheet, 23 Aug, 1999.)).

Foreign-language DTC advertisements continue to require that the print ad, brief summary, website and toll free number operators or recording be in the same language as the broadcast, Ostrove said.

Other than a few exceptions for places such as Puerto Rico, the package insert is still required to be in English. Ostrove said that since this disparity "seems kind of silly," DDMAC now suggests that companies include a consumer-friendly translation of the PI in the language of the broadcast ad.

Glaxo Wellcome received a warning letter from FDA regarding the company's failure to disclose risk information in its Spanish-language broadcast ad for the nasal steroid Flonase (fluticasone) (³ (Also see "Flonase Spanish-Language TV Ads Disclose No Risk Info - Warning Letter" - Pink Sheet, 30 Aug, 1999.)).

DDMAC Branch Chief Leah Palmer said that FDA had issued 64 letters in the first six months of 1999. Violation of fair balance was the subject of 61% of the letters and 36% of the letters cited unsubstantiated safety and efficacy claims. Other violations concerned off-label use claims (13%), claims of comparative safety and efficacy (11%) and claims of superior safety and efficacy (9%).

Noting the agency's recent focus on risk management, Palmer focused on the "prominence issue" and how risk information should be presented in DTC ads.

The branch chief gave examples of lack of prominence of risk information in Zeneca ads for its hypertension drug Zestril (lisinopril) and breast cancer treatment Nolvadex (tamoxifen). The ads received a warning letter from FDA in November 1998 (⁴ (Also see "Zeneca Casodex Clinical Trial Excerpts Cited In FDA Warning Letter" - Pink Sheet, 7 Dec, 1998.)).

Palmer also cited Oclassen's Condylox Gel (podofilox), which received an FDA warning letter in December, as an example of "misleading comparisons" to other therapies (⁵ (Also see "Oclassen Condylox Claim Of Faster Clearance Cited In FDA Warning Letter" - Pink Sheet, 4 Jan, 1999.)).

A Merck ad for its ophthalmic beta blocker Timoptic XE was highlighted by Palmer as a "good ad" that included safety information in bullet points alongside efficacy claims.

Palmer said that "there seems to be a lot of confusion in promotional materials" and that FDA is currently working on guidances on fair balance and comparative claims as well as two on economic claims.

CBER Regulatory Review Officer Carole Broadnax discussed recent enforcement actions for biologic product ads.

From Oct. 1, 1998 to Aug. 31, 1999, CBER received 74 complaints about 109 promotional labeling pieces. As a result, one warning letter and 29 untitled letters were issued by the center. Complaints were resolved by phone, fax or memo in 23 cases, 14 complaints are pending action and three were forwarded within CBER or DDMAC, CDER. Four complaints were determined to have no merit.

Of the 29 untitled letters issued by FDA concerning biologic products, 15 were for false and misleading information, seven were for pre-approval promotion, two involved donor incentives and five were for off-label uses, Broadnax said.

Manufacturers, who do not have substantiating data, should avoid the use of the word "superior" in ads for biologic products as it constitutes a comparative claim, Broadnax added. In one case, FDA sent an untitled letter to a manufacturer recommending they change a product's superiority claim to "a total quality system" or similar logo, she noted.