Identification of Drug-related and Formulation-Related Factors that Result in Alcohol Dose Dumping of Modified Release Oral Drug Products (U01) Clinical Trial Not Allowed

Modified release (MR) oral drug products are considered to have a high risk for alcohol dose dumping (ADD) because they contain large quantities of drug(s), designed to release over a prolonged period of time. Accidental exposure of these products to alcohol can result in the relatively rapid release of large quantities of drug with severe side effects, including death. To mitigate this risk, the FDA recommends conducting an in vitro alcohol dose dumping assessment in 0%, 5%, 20%, and 40% alcoholic dissolution media for all prospective generic versions of MR oral drug products. To date, ADD assessments have not been harmonized globally. For instance, the U.S. FDA recommends testing up to 40% alcoholic media while the European Medicines Agency recommends testing up to 20% alcoholic media. This type of difference can present a challenge for formulators designing products for multiple markets, as historical data has shown release from MR oral products do not always follow a linear response (either increasing or decreasing) to increasing alcohol concentrations. In addition, interpretation of an ADD assessment may be limited by the inability of the test to predict in vivo behavior. The purpose of this research is to develop tools that 1) facilitate the development of MR generic drug products that have a low potential for ADD, 2) support regulatory decision making during the assessment of such products, and 3) provide evidence that enables FDA to develop more specific recommendations for efficiently demonstrating a low or comparative potential of alcohol dose dumping for MR oral drug products containing high risk drugs.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The FDA will not accept duplicate or highly overlapping applications under review at the same time per 2.3.7.4 Submission of Resubmission Application. This means that the NIH or FDA will not accept:•A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.•A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.•An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Applicants should review the individual Funding Opportunity Announcement (FOA) issued under this CFDA program to see the specific evaluation criteria that applies.