Conclusions How Will Excipients Be Evaluated for Potential Use in Glp Gmp and GCP Evaluation

The collected data suggest that historical decision trees for the use of excipient in toxicology investigation are rapidly becoming obsolete. This has prompted a search for additional approaches and solubilizing formulation adjuncts. A possible way forward in trying to assess what excipients are useful may include: (1) Determine the type of excipient based on novelty, compendial status and expected duration of dosing. (2) Assess whether the excipient is GRAS listed, is present in a marketed product or has been evaluated by the JECFA or other agencies. Assess dose, duration of administration, route and specific patient population to see if this is consistent with its intended use and if this is different from the suggested Phase I investigation. (3) Assess whether the excipient is considered a residual solvent and note the class and if appropriate the PDE. Critically assess the nature of the data provided and compare this with the use of these solvent in marketed formulations with regard to dose, duration, route and patient population. (4) Design the GLP toxicology studies in a balanced way using data generated to support human clinical testing. While risk increases with the novelty of the excipient, it should not be a matter of policy to automatically exclude an excipient. (5) If risk-benefit analysis deems it necessary, a novel excipient may be characterized in keeping with published guidelines and monographs (Steinberg et al., 1996).

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