Preclinical Testing for an Established Excipient

Established excipients are those with a history of use in drug formulations and thus are known to the regulators. Indeed, many appear in pharmacopeias and can be referenced as such in new drug applications in which they occur in the formulation. Thus, in theory, preclinical testing should not be needed. However, there is a common misconception that once an excipient is used in an approved product, it is automatically assumed to be safe for use in any product thereafter that involves the same route of administration and level of exposure (17). In reality, even in such cases, the level of toxicity information may need to be brought up to current 

Even for established excipients, regulators will look carefully at their presence in new drug formulations because they are not necessarily inert materials and some have well-established activity and/or toxicity. Clinically relevant adverse reactions are known for well-known excipients and the subject is covered elsewhere in the published literature (2,20,75-81). Findings tend to be uncommon compared to the overall prevalence of adverse drug reactions and often involve hypersensitivity reactions that are not likely to be predicted by conventional toxicity studies. 

---