A number of publications have recently raised questions about the safety and efficacy of generic drug products, specifically clozapine manufactured by Zenith-Goldline Pharmaceuticals, Inc. (ZGP). ZGP’s clozapine is the generic version of Novartis AG’s (formerly Sandoz’s) brand name drug, Clozaril, used for the management of severely ill schizophrenic patients who either fail to respond to or are unable to take other standard antipsychotic treatments. The Food and Drug Administration (FDA) approved Clozaril® in 1989; a new formulation for Clozaril was subsequently approved in 1997.

One article claimed that ZGP’s product does not work the same nor as well as the brand name drug product, and cited studies conducted by the University of Texas Health Science Center in San Antonio and the Minnesota state psychiatric system. The Food and Drug Administration (FDA) applies very high standards to the approval of both brand name drug products and their generic drug counterparts, and thoroughly reviews complaints about all drug products. In this case, FDA reviewed both of the studies identified in articles to determine if there was a problem with the ZGP product and, if so, to determine the appropriate action to protect the safety of the American public. However, FDA’s review found that the cited studies were not conducted in a manner that could evaluate whether the generic version is unsafe or ineffective. Therefore, FDA does not believe that regulatory action is currently warranted. If FDA finds evidence demonstrating a problem with this or any drug product, it will take necessary action to protect the safety of the American public. In addition, FDA will continue to monitor reports regarding ZGP’s drug product and has recommended that Zenith conduct a new bioequivalence study.

In the case of the study conducted in Texas, it was found that the study was not actually designed to evaluate whether patients responded to the generic version as well as they did to Clozaril, nor could the reported results be interpreted to provide a basis for FDA regulatory action. In addition, FDA’s own inspection of the study site revealed some irregularities in how the study was conducted that cast doubt on the results. The summary report of the Minnesota study also failed to provide evidence that there is a problem with the generic drug product.

During the review of these studies, it became evident that neither medical practitioners nor patients were aware that the brand name drug product formulation had been changed. This lack of knowledge may have contributed to the conclusions reached in the Texas and Minnesota studies. In fact, the same criteria and study requirements applied by FDA to assure the safety and efficacy of Novartis’ new formulation were applied to ZGP’s (and other companies’) generic drug product versions.