A thousand different excipients can be used when formulating pharmaceuticals and, as a rough estimate, excipients can comprise more than 90% of a medicinal product's weight. Excipients are no longer characterized as simple inert additives to the API, and the need for stringent, quality management of excipients has grown rapidly. In 2010, FDA noted five drug recalls due to dissolution failures ascribed to excipients (1). In one case, FDA issued an import alert and an advisory to drug and dietary supplement manufacturers warning of high levels of peroxide in the excipient crospovidone manufactured in China (2). In the warning, FDA explained that drug manufacturers who used excipients containing high levels of peroxides would observe a loss of drug potency and the formation of excessive impurities during the product's shelf life.
Lack of regulation
Although pharmaceutical excipients are major components of dosage forms—and potential hazards to patients—there is a lack of binding regulation. In recent years, however, several industry standards have been developed. In the United States (US), the recently introduced Drug Safety Enhancement Act includes the following parameters (3):
The role of suppliers
While the move toward more stringent and harmonized regulations continues to make progress, it is incumbent on suppliers and manufacturers to jointly take the lead in ensuring excipient quality. This imperative was reinforced by FDA when the regulator warned about the presence of high peroxide levels in crospovidone, but it should apply to all excipients:
"It is essential that [excipient] users implement robust supplier management programs... Manufacturers should employ sound risk management principles in establishing appropriate scrutiny and actions to take for a given supplier, including but not limited to the following:
In the current regulatory environment, pharmaceutical manufacturers are under increasing pressure to develop better knowledge of their excipient supply chain. At the same time, excipient suppliers must also shoulder a significant responsibility for ensuring quality and mitigating possible risks, which may include excipient variability, trace impurities, the use of an inappropriate grade of materials, contamination, mix-up across the supply chain, and economically motivated adulteration.