Roche's Ticlid (ticlopidine) educational program on the risks of neutropenia and agranulocytosis consists of promotional rather than safety information, Teva Pharmaceuticals maintains in a Jan. 6 letter to FDA.

The Teva letter is in response to a Nov. 27 Roche citizen petition which recommends that FDA require all manufacturers of generic ticlopidine to implement the same postmarketing safety program provided by Roche for Ticlid. Teva received a tentative approval for its ticlopidine ANDA Oct. 29.

Roche's "'educational' documents do not contain any substantive information that is not already present in the package insert and patient leaflet, information which Teva has incorporated into its own labeling," the Teva letter prepared by Geoffrey Levitt (Venable Baetjer, Howard & Civiletti, Washington, DC), states.

"Rather, these documents are essentially promotional in nature, with the alleged 'safety' information Roche highlights being in reality nothing more than required standard fair balance. Accordingly, they do not represent a condition of use for the drug product, and hence cannot be made a requirement for ANDA approval," Teva said.

In the Sept. 21 tentative approval letter for ticlopidine, FDA suggested that the company implement a ticlopidine educational program similar to the one employed by Roche.

"The reference listed drug (Ticlid; Hoffman La Roche) provides educational programs for physicians and patients," FDA said. "In addition, a [complete blood count] monitoring program is offered free of charge. The reason for this monitoring is that ticlopidine can cause life-threatening hematological adverse reactions, including neutropenia/agranulocytosis and thrombotic thrombocytopenia purpura."

FDA suggested a program that would monitor patients hematologically and clinically every two weeks for the first three months of therapy. "The agency also believes that educational programs that alert physicians to the occurrence of neutropenia/agranulocytosis and TTP can enhance the safe use of ticlopidine and strongly encourages you to consider a similar educational program," the letter advises.

In its response to FDA, Teva does not dispute the importance of effective blood monitoring in patients receiving ticlopidine, but strongly disagrees with Roche's assertion that the monitoring be provided free of charge by the manufacturer.

"To be sure, Ticlid's approved labeling does require CBC monitoring - as will the approved labeling of any generic version of Ticlid - but that is not at all the same as a requirement that the sponsor pay for such monitoring, or affirmatively establish a monitoring program through a specific laboratory," Teva said.

In its citizen petition, Roche argued that "the Ticlid postmarketing safety program which provides educational information and the blood monitoring program itself has been deemed essential to the safe use of the product by FDA. Therefore, FDA should require the same postmarketing safety program of all manufacturers."

The Roche petition suggests that if FDA does not feel it has the legal basis to require ANDA applicants to provide educational and blood monitoring program, "Roche will file a supplement to its NDA that would incorporate such programs as a condition of use."

"By unequivocally mandating this program for Ticlid, FDA would eliminate any doubt that it has the basis to require such important postmarketing safety programs of all manufacturers of ticlopidine as a condition of use," the petition suggests.

Teva asserted that the Roche educational program "is so obscure that no one, not even Roche employees responsible for providing medical information to the public, is aware of it."

The company said it had an independent pharmacist contact Roche's Medical Affairs department "on two separate occasions to inquire if such a program existed. Each time, this pharmacist received the same response - no such program existed."

"This account raises the obvious question: Of what possible utility is this postmarketing safety program if, even armed with knowledge of its alleged existence, one cannot obtain substantive information about it from Roche's own Medical Affairs staff?"

Teva claimed to also have contacted FDA's Division of Drug Advertising, Marketing and Communications only to find that "DDMAC did not have any record that such a program existed."

Roche Ticlid Safety Program Is Promotional, Not Educational, Teva Asserts

More from Archive

More from Pink Sheet