FDA drug advertising letters total 32 for all centers in '03: DTC ad guidance expected by year's end.

Dear Reader,

The three FDA centers that oversee human, animal drug and biologic advertising issued a total of 32 warning and untitled letters in fiscal 2003, which ended Oct. 1.

The statistics are likely to generate even more controversy and criticism, particularly from consumer advocacy groups that believe the agency has lost its zeal in regulating drug marketing.

Before FDA began requiring such letters be pre-reviewed by the Office of Chief Counsel in 2002, the Center for Drugs, alone, was issuing about 100 warning and untitled letters a year.

A major reason for Chief Counsel review was the number of drug advertising letters, as well as repeat warning letters to companies.

Addressing a Food and Drug Law Institute (FDLI) conference in Washington Sept. 11, Thomas Abrams, director of CDER's Division of Drug Marketing, Advertising, and Communications (DDMAC) said his group issued four warning letters and more will be issued before the end of the fiscal year. However, he had no data on the number of untitled letters issued in fiscal 2003, but it is believed to be no more than 11.

With respect to enforcement and the dramatic drop in warning letters, Abrams said the agency is prioritizing offenses and "getting to the most serious first." He added that the number of letters would increase again, and with the added review from the office of chief counsel, companies that receive letters "will know that the full weight of the agency is behind it," he said. "Failure to comply with a warning letter puts the company at risk for enforcement action."

In addition, he contended that enforcement has risen sharply in the last five years for misleading claims made by company sales representatives. In addition, FDA is also being vigilant about advertising distributed at exhibit halls and conferences.

"We are a data-driven agency and we like data," he said. Abrams added that unsubstantiated claims about drugs, such as the terms "fast acting" would not be acceptable. Abrams added that it is much better to take data and give a number to "how fast" than to make comparative or misleading claims.

"Our concern comes when activities are misleading, when claims are not truthful and not balanced," Abrams said. "When sales reps are responsible for volatile action, we will act against them," he said.

Abrams also announced that FDA is expected to issue a draft guidance on direct-to-consumer (DTC) advertising by the end of calendar 2003.

He noted DDMAC conducted two consumer surveys and a physician survey to determine the impact of DTC on public health. Released last month to an agency advisory committee, the data show that DTC ads do not induce patients to demand doctors prescribe certain advertised Rx drugs and that doctors do not feel the ads are harmful. Some members of the panel, however, were skeptical.

"FDA research has illustrated that when consumers are interested, they will read all the information in a brief summary," Abrams added. "The question becomes, how do you present it in a manner that is most beneficial to the consumer?"

Abrams also announced that now that several therapeutic drugs have been transferred from the Center for Biologics to CDER, his division is handling the review of promotional materials for such biologicals.

The four warning letters DDMAC issues were for OxyContin, Xeloda, Viread and Pravachol. Abrams provided examples of those promotional materials and pointed out that for three of the products, significant risks were not listed even though some of the risks are fatal. In fact, one brochure did not list any risk information at all.

In the warning letter to Purdue Pharma, which makes OxyContin, the warning letter stated that the body of advertisements did not present information regarding "limitations on the indicated use of Oxycontin."

Abrams said that in the Oxycontin advertisements, crucial facts were missing related to "potentially fatal risks." He added that one of those crucial facts was that the drug, which is similar to morphine, had the potential for abuse, and this should have been listed as a limitation on the appropriate indicated use. Abrams said this concerned the agency because the "limitations were hidden."

Further, Purdue did not correct the advertisement, so FDA sent a "Dear Health Care provider" letter to alert the health care industry of the potential for abuse.

Abrams said that DDMAC receives about 250 complaints a year related to DTC advertising, most of them from competitors, and some from health care professionals. He said the department tries to acknowledge those complaints within 30 days to inform the company that a complaint has been received while the agency considers what action to take.

CBER's Advertising and Promotional Labeling Branch (APLB) issued five untitled letters and one warning letter in 2002, APLB branch chief Glen Byrd told FDLI.

Of those five untitled letters, two were for therapeutic biologics, one was for tissue plasminogen activator (TPA) and two concerned blood products. The one warning letter issued was for a narrow toxin product, he said.

Byrd encouraged attendees to view FDA's website in order to get a better idea of where FDA is focusing its enforcement efforts. All warning letters are posted on the website, which can be accessed at www.fda.gov/cber/efoi/adpromo.htm.

"Two big areas we want to point out related to safety are unsubstantiated comparative safety claims and minimization of risks," Byrd said. He said FDA also reviews company websites periodically to see if important safety information is omitted.

FDA continues to see overstatements of effectiveness, Byrd said, and will continue to crack down on those. He said the agency would rather see companies substantiate their claims using their database of non-clinical experience.

"We are also seeing misleading superiority claims," he said, "which will continue to get our attention." Another problem area related to enforcement involves "presentation of unapproved indication for use," Byrd said.

FDA's Center for Veterinary Medicine (CVM) reviewed 5,636 promotional items in 2003, according to Martine Hartogensis, DVM, a veterinary medical officer in the Office of Surveillance and Compliance. From those, she said that CVM issued 11 letters. Eight of those letters came from surveillance activities and complaints, while three of them came from FDA's form 2301.

The Center for Devices has not presented to the FDLI meeting for several years, since it closed its promotion and advertising branch in the Office of Compliance.

Sincerely,

The Editors

Presentations from FDA's centers are available for $20.00, Doc. 12670W, plus retrieval.