Circulation 60,475 • Volume 14, No. 2 • Summer 1999

Diprivan Maker Adds to Generic Propofol Debate

Sarah Harrison

To the Editor

We appreciate the opportunity to comment on and set straight some misleading and erroneous statements contained in the letter to the APSF Newsletter by Mr. Armand LeBlanc, Vice President for Scientific Affairs for Gensia Sicor Pharmaceuticals. We are troubled that Mr. LeBlanc attributes false motives to Dr. John Tinker’s letter (Spring 1999). Gensia inaccurately suggests that Dr. Tinker’s letter was written at the behest of Zeneca. Gensia ignores the express statement by Dr. Tinker at the conclusion of his letter that he is neither employed nor paid by Zeneca. Dr. Tinker’s motives are clear: “to express my strong concern that many unsuspecting anesthesiologists and CRNAs in the U.S. may soon unwittingly expose their patients to a ‘generic’ propofol that is not the same formulation we have been using for a number of years.” Dr. Tinker wrote to express his personal and professional opinion on an issue of serious public health interest and patient safety.

Gensia’s letter contains other false statements that require correction:

1.) Gensia’s letter calls “grossly misleading” reports of a test conducted by Zeneca that compares Diprivan® (propofol) Injectable Emulsion “against a product formulated by Zeneca” but is “not the Gensia product and does not exhibit the characteristics of Gensia Sicor’s product.” As Gensia knows, because Gensia refused to provide Zeneca with samples of its product, Zeneca initially tested samples of product that Zeneca manufactured using the specifications outlined in Gensia’s product label; once Gensia’s product became available in the marketplace, Zeneca did in fact conduct a “shake” test on the actual Gensia sulfite-containing propofol. (The test results were submitted to the Court, the FDA and Gensia in May, 1999.) As stated in our litigation papers, we believe the test results of Gensia’s actual product demonstrate the intrinsic instability and markedly reduced physical stability of this sulfite-containing formulation of propofol, and raise significant quality, safety and efficacy issues regarding the Gensia propofol formulation.

2.) Gensia claims Dr. Tinker relied on false and misleading information provided by Zeneca and therefore Dr. Tinker’s statements “have no basis whatsoever in fact.” Gensia cites Zeneca’s claims that (1.) the sulfite-containing propofol is “not equivalent” to Diprivan and (2.) Gensia’s product may “crack,” an effect of physical instability. These are, in fact, some of the arguments Zeneca has put forth to the Court that are substantiated by extensive scientific analysis. Rather than address the scientific merits, Gensia has chosen to simply state that Dr. Tinker’s views “have no basis whatsoever in fact.” It would be better for Gensia to respond with its own scientific documentation rather than making such statements. Any such scientific data are what’s needed in this debate for all parties involved – anesthesiologists, pharmacists, nurses and patients.

3.) The FDA has never made any final or formal finding that Zeneca’s distribution of copies of its court documents and the substance of Zeneca’s legal arguments are false and misleading and violate the Federal Food, Drug and Cosmetic Act (FDCA). Zeneca’s legal documents filed in the U.S. District Court for the District of Maryland are not “promotional claims” but serious legal arguments currently under review by a U.S. District Court. The references Gensia uses in its letter are in fact excerpts from a March 23, 1999 Untitled Letter issued by the advertising division of the FDA. An “Untitled Letter” is not evidence that Zeneca’s actions are “willful violations of the FDCA.” According to FDA’s own Regulatory Procedures Manual, an Untitled Letter is neither formal nor final FDA enforcement action. Sending an Untitled Letter demonstrates that FDA itself has currently not determined that Zeneca’s actions rise even to the level of regulatory significance requiring a Warning Letter. On April 5, 1999, we responded to FDA’s letter and strongly defended our distribution of copies of our litigation papers to our customers, because we believe such communication is protected speech under the First Amendment to the United States Constitution.

The Court has recognized the merits of Zeneca’s case and is currently deliberating Zeneca’s request for a permanent injunction to reverse the FDA’s approval of Gensia’s purported generic version of propofol; the Court has indicated that it intends to rule against Zeneca on the interpretation of the scope of Zeneca’s exclusivity right.

As we have stated from the outset of this lawsuit, Zeneca views this matter with the utmost importance. We believe that this case is critical in helping preserve patient safety and the integrity of the drug regulatory review process.

Sarah Harrison Vice President, Pain, Anesthesia and Infection AstraZeneca