Company Responds To Writer’s Questions On Generic Preparation

Armand J. LeBlanc

[Editor’s Note: Published here is an abridged version that captures the spirit of nine pages (including the attachments) of text that was received too late to be included in the Spring issue as companion counterpoint to Dr. Tinker’s letter to the editor.]

To the Editor:

Thank you for allowing us to respond to the letter to the editor (APSF Newsletter, Spring 1999), regarding our Propofol Injectable Emulsion 1% with Sodium Metabisulfite 0.025% from John H. Tinker, M.D. of the University of Nebraska Medical Center.

We are surprised and troubled that the APSF Newsletter would publish such a letter that is, by its own admission, a recounting of documents prepared by Zeneca and its lawyers which we believe were designed to disparage Gensia Sicor’s new generic drug. There is no mention, however, of the more recent fact that FDA has examined the Zeneca "court" documents relied upon by Dr. Tinker and that FDA found these same documents to be in part false and misleading, and to violate the Federal Food, Drug, and Cosmetic Act. Dr. Tinker’s parroting of such promotional claims is shameful and your publication of such misleading promotion irresponsible.

Dr. Tinker’s letter restates promotional assertions found in two written communications from Zeneca.

The first, dated February 8, 1999, recounted statements made by Zeneca’s lawyers in a lawsuit filed by Zeneca against the FDA over the approval of Gensia Sicor’s Propofol ANDA. Zeneca’s lawyers allege, among other things, that our Propofol formulation is unsafe and ineffective because it contains a commonly-used preservative, sodium metabisulfite. Also, Zeneca finds individuals to speak on behalf of Diprivan®. The second communication, dated March 12, 1999, contained further statements from Zeneca supporters, including grossly misleading reports of testing conducted by a Zeneca employee that compared Diprivan® against a product formulated by Zeneca and described by Zeneca as the formulation approved in Gensia Sicor’s ANDA. In fact, the product used in the Zeneca study is not Gensia Sicor’s product and does not exhibit the characteristics of Gensia Sicor’s product.

On March 23, 1999, an FDA Regulatory Review Officer in the Division of Drug Marketing, Advertising and Communications sent a letter to Zeneca charging Zeneca with violations of the Federal Food, Drug, and Cosmetic Act. The letter includes:

"…We have concluded that these promotional labeling pieces are in violation of the Federal Food, Drug, and Cosmetic Act …, and thus misbrand Diprivan®. Your February 8, 1999, letter and glossy promotional brochure states or suggests that Gensia Sicor’s formulation of Propofol Injectable Emulsion is not therapeutically equivalent to Zeneca’s Diprivan® (propofol) injectable emulsion. Such suggestions are false or misleading. As you know, FDA has reviewed Gensia Sicor’s application and has determined that Gensia Sicor’s propofol and Zeneca’s Diprivan® are therapeutically equivalent, and therefore, was granted an "A" rating. This rating means that these products are bioequivalent and therapeutically equivalent, and can be substituted with the full expectation that the substituted product will produce the same clinical effect and safety profile as the prescribed product.

"You allege in your promotional materials that Gensia Sicor’s propofol product is not therapeutically equivalent to Diprivan and should not be substituted for Diprivan because Gensia Sicor’s product contains sodium metabisulfite as a preservative whereas your product contains EDTA. You also allege that Gensia Sicor’s product is neither safe nor effective. These allegations are false or misleading.

"In the March 12, 1999, letter and brochure, you allege various types of stability problems associated with Gensia Sicor’s product. Since Gensia Sicor’s product was not available to Zeneca, you prepared a product that you allege is similar to the approved product. You conducted some tests on the product you prepared and state or suggest that the results you obtained are representative of quality, safety, and efficacy issues regarding the Gensia Sicor propofol formulation. Such allegations are clearly false or misleading and misbrand Diprivan®…."

(Excerpt from letter available at: http://www.fda.gov/cder/warn/mar99/032399_zeneca.pdf)

FDA called on Zeneca to "immediately cease" the dissemination of such materials that "state, suggest, or imply that Gensia Sicor’s product is not equivalent and substitutable for Diprivan®."

Zeneca has fared no better in its lawsuit challenging FDA’s approval of our Propofol Injectable Emulsion. The court rejected Zeneca’s attempt to introduce statements of its supporters and denied Zeneca’s motion for a preliminary injunction against FDA in its ruling of March 26, 1999.

Dr. Tinker admits his letter is based on submissions by Zeneca’s lawyers in this lawsuit. Dr. Tinker repeats statements deemed misleading by the agency, such as: (1) Gensia Sicor’s product is not "equivalent" to Diprivan®; (2) Gensia Sicor’s product may "crack" under use, an effect of physical instability; and (3) FDA’s generic drug approval process is a "fast track" process, subject to pressure to quickly approve products to reduce drug costs and thus permits unsafe generic products on the market without rigorous testing such as human clinical trials.

Dr. Tinker’s letter was based upon false and misleading information provided by Zeneca. FDA, an authoritative scientific body, evaluated the information from Zeneca and deemed the information to be false and misleading. Therefore, Dr. Tinker’s statements have no basis whatsoever in fact.

Dr. Tinker also raises the issue of fairness by asserting FDA reneged on its commitment with respect to three years of market exclusivity granted to Zeneca for its Diprivan® with EDTA formulation. FDA simply implemented the law passed by Congress which specifically intended that market exclusivity be limited in scope to specific changes which required clinical studies to support approval. Zeneca requested exclusivity for the innovation of the addition of disodium edetate to propofol and FDA granted Zeneca three years of market exclusivity since FDA determined that clinical trials were necessary to demonstrate the safety of EDTA in the Diprivan® formulation.

We ask that you withdraw the publication of Dr. Tinker’s letter and/or issue a retraction concerning its publication. Regardless of our concerns over your publication of Dr. Tinker’s letter, we appreciate the opportunity in allowing us to respond.

Armand J. LeBlanc Vice President, Scientific Affairs Gensia Sicor Pharmaceuticals, Inc., Irvine, CA