ABSTRACT

During the investigational new drug (IND) process for a new drug application (NDA), the safety of inactive ingredients in a topical drug product should be documented by specic studies or may be based on a prior history of successful use in the same amount administered via the same route of administration in an approved product. The requisite safety studies to establish the safety of a new excipient during the IND process should be discussed with appropriate review staff at the Food and Drug Administration (FDA). For an abbreviated NDA (ANDA), the safety of inactive ingredients in an ANDA can be based on a prior history of successful use in an NDA or ANDA. If the inactive ingredients in an ANDA are not the same as the reference listed drug (RLD), the applicant should demonstrate to the agency that the change(s) does not affect the safety and/or efcacy of the proposed drug product. In some instances, a comparative bioavailability (BA) study will satisfy this recommendation. If preclinical or clinical studies are needed to demonstrate the safety of inactive ingredients(s) in the generic drug product, the ANDA may not be approved. In this circumstance, the applicant may wish to resubmit their application as an NDA under the provisions of 505(b)(1) or (b)(2) of the Act.