Pharmaceutical excipient development: the need for preclinical guidance

Pharmaceutical excipients have a vital role in drug formulations, a role that has tended to be neglected as evidenced by the lack of mechanisms to assess excipient safety outside a new drug application process. Currently, it is assumed that an excipient is "approved" when the new drug formulation, of which it is a constituent, receives regulatory acceptance. Existing regulations and guidelines indicate that new (novel) excipients should be treated as new chemical entities with full toxicological evaluation. No guidance is available for potentially useful materials (essentially new excipients) available from other industries, e.g., food additives or for established excipients with a new application, e.g., dose route change. However, despite this situation, drug companies are actively evaluating new materials or applying new uses to established excipients. Recently developed excipients (e.g., materials giving "sugar-free" status to medical preparations, the cyclodextrins, and the hydrofluoroalkane inhalation propellants) and excipients undergoing development (e.g., chitosan, various enteric coating substances, liposomes, polymers derived from glycolic and lactic acids, and vaccine adjuvants) are all discussed. In light of many other areas of drug development having recently benefited from new or updated regulatory guidance, specific guidance to assist companies in the development of their excipients is urgently needed. Also, an excipient testing strategy would be an excellent topic for inclusion for International Conference on Harmonisation (ICH) consideration. Such guidance/discussion would complement the current advances in pharmacopoeial standardization of excipient quality. As a consequence, it may be possible to have excipients reviewed by a committee of an international pharmacopoeia with the safety data assessed by elected experts and published.