The goals of the guidance are to:
- Communicate to industry the FDA’s current thinking pertaining to safety data needed to support approval of these drug products
- Increase uniformity within CDER on recommendations for the nonclinical development of reformulated drug products and products being used by an alternate route
The guidance presents general considerations, systemic toxicity considerations, and route of administration considerations. Notable recommendations include:
- The ICH guidance for industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals or S9 Nonclinical Evaluation for Anticancer Pharmaceuticals and the appropriate review division should be consulted regarding the timing of submission of nonclinical data relative to clinical development.
- The adequacy of the available systemic toxicity information should be evaluated based on a comparison of the systemic exposure obtained after administration of a proposed new formulation to the systemic exposure with use of the previously approved formulation.
- In general, durations of the toxicity studies should follow the recommendations outlined in ICH M3(R2) or ICH S9. For a new formulation that will be used by the same route as the previously approved product, shorter duration toxicity studies than those outlined in ICH M3(R2) may be appropriate.
- In addition, the route-specific recommendations should be considered for all new formulations, whether they are proposed for a new route or the same route as a previous formulation.
For further assistance in preparing submissions for reformulated and other drug products, contact RPI.