Concerns About the Safety of Obesity Agents From a Manufacturing Perspective

Abstract

Salt derivatives of active pharmaceutical ingredients (API), such as hydrochloride and mesylate salts, are frequently used during drug product development. Compared with the underivatized API, salt derivatives are often associated with beneficial properties, including improved solubility and better absorption. Although the obesity agent sibutramine was initially approved as the hydrochloride salt, it has also been formulated as a mesylate salt (sibutramine mesylate). In order to qualify as interchangeable, generic products generally must be both pharmaceutically equivalent and bioequivalent to an approved reference product. Because generic versions of hydrochloride salt formulations that have been reformulated as mesylate salts are not pharmaceutically equivalent to the approved reference products, they would not be interchangeable, even if bioequivalent. The safety of APIs and drug products manufactured outside the United States in non-Food and Drug Administration-regulated facilities are of concern, particularly agents that may contain harmful impurities, such as obesity products formulated as mesylate salts.

Keywords:

• bioequivalence
• hydrochloride salt
• mesylate salt
• pharmaceutical equivalence
• sibutramine