CBER letters hit ads, Web sites, press releases.

A sampling of advertising untitled letters issued last year by the Center for Biologics Advertising and Promotional Labeling Staff (APLS) showed the agency hitting journal ads, Web sites, press releases and other promos for referencing FDA approval, misrepresenting facts, lack of fair balance and cash incentives.

An 11-page letter to Immunex, Seattle, WA, dated May 13, tore into the company's ad and brochures for Leukine (sargramostim) page by page on 48 points, terming statements false, misleading and lacking fair balance.

Among the agency's concerns about the ad was a statement that "Leukine prevents early death." The letter said that it would be more accurate to state that "there were fewer deaths among patients receiving Leu-kine during remission-induction."

FDA also objected to the presentation of statistical data. For instance, "leukine reduces deaths from infection 54%" should be revised as "the rate of infectious deaths during remission-induction or consolidation was Leukine 3/52 (6%) vs. placebo 11/47 (23%)," or words to that effect, the letter stated.

Other problems involved unsupported claims, large type face that appeared to exaggerate the scope of a footnote's significance, inappropriate use of a blanket statement that Leukine and placebo adverse events were similar and a comparison to a placebo that omitted Leu-kine-related adverse events.

Among violations cited in the brochure were presenting in vitro data to clinicians without identifying the information as non-clinical, misleading presentation of statistical data on infection rates, a lack of fair balance in presenting death rates, a chart and a graph with references to sources that did not support the chart's content, failure to disclose the limitations of a study on costs and incomplete presentation of side effects.

FDA asked Immunex to stop distributing these and any similar materials, "prevent their recurrence" and inform the agency of its planned corrective actions.

Two days later, a second untitled letter to Immunex followed up on the firm's response to previous correspondence faulting press releases for Enbrel.

FDA disagreed with the firm's assertion that the agency was "setting new policy" on two points: the assertion that use of the phrases "statistically significant" and "statistically improved" implied FDA review and acceptance of the data, and the recommendation to add a phrase clarifying the fact that results were based on investigative data not reviewed by the agency. The letter said both points reflected APLS' historical stance.

On the other hand, APLS decided "upon further review," that Immunex did not have to add clarification regarding the small study size in one press release. Regarding a second press release, the agency left to the company's discretion a factual discussion of the product's "fast-track" status.

The letter also noted that adding "the most frequently reported adverse events" would help provide fair balance to a press release, but "a revision date should be added to the press release for clarity."

FDA jumped on a Gamma Biologicals press release and a Web site promos for asserting that the company had received "approval" to market the react Test System, intended for "rapid detection of red blood cell antibodies." The agency advised that devices are cleared, not approved, via 510(k)s and asked for a plan to revise the materials and prevent a recurrence.

In a similar case, Embouchure, of Norcross, GA, ran into difficulties with its Web site promotion of the BIG MultiReader Plus, indicated for hemaglutination and solid phase assays. Instead of referencing "approval" of a 510(k), the firm incorrectly used the term "licensed." The letter asked for corrective and preventive action.

The agency issued a letter to Raritan, NJ-based Ortho Diagnostic Systems, for ads promoting its DiaMed-ID Micro Typing System in the journal "Transfusion."

According to the letter, the statement "for USA/Canada" suggested that the system was available for use in both countries. On the contrary, FDA said, the device was not cleared for marketing in the U.S. The agency asked Ortho to revise the ads.

Genetics Institute of Cambridge, MA, was snagged for a visual aid promoting Neumega (oprelvekin).

FDA said claims had to note usage with high-dose chemotherapy to reflect studies used for licensure. The agency also criticized a journal ad for not giving certain statements redacted from the document adequate prominence.

Palm Beach Blood Bank of West Palm Beach, FL, raised eyebrows when an article on competition in the blood market appeared in the "Palm Beach Post."

The article reported that the blood bank was offering free cholesterol checks, cardiac risk profiles and restaurant gift certificates as incentives.

FDA okayed the medical perks, but thought it easy to convert the restaurant gift certificates to cash.

Consequently, all units collected with that incentive had to be labeled as "paid donors," the agency said.

Immunex, May 13, 1998, Doc. 8009W, $24.50; Immunex, May 15, 1998, Doc.

8010W, $2 (without ad); Immucor, May 20, 1998, Doc. 8011W, $2.50; Gamma Biologicals, May 6, 1998, Doc.

8012W, $2.50; Ortho Diagnostic Systems, May 26, 1998, Doc. 8013W, $3; Genetics Institute, May 11, 1998, Doc. 8014W, $2 (without ad); and Palm Beach Blood Bank, May 26, 1998, Doc. 8015W, $2.50. Please add retrieval fee per order, not per document.