《CMC基础(英文)》.pptVIP

The Basics of CMC Ramnarayan Randad, Ph. D. Chemistry Reviewer DCI Office of Generic Drugs FDA Drug education workshop, Kansas City May 10, 2005 Basics of the CMC -Regulations CMC = 21CFR314.50(d)(1) Additional requirements (ANDA) = 21CFR314.94(a)(9) Detailed information on: Drug substance (API) Inactive ingredients Drug product Master production records and Environmental impact Guidances /cder/guidiance/index.htm Are developed in accordance with FDA’ s Good Guidance Practices (Federal Register Sept. 2000, 56468-56480). Generally serve to meet regulatory expectations on particular topic. Are non binding on both pharmaceutical industry and FDA. Both may deviate with suitable justification. Chemistry, Manufacturing, Controls CMC objective is to sufficiently characterize DS and DP so that important quality, safety, and efficacy attributes are established and controlled. Components and composition API, Excipients controls Manufacturing and controls Batch formulation and records Description of facilities Specs and tests Packaging Stability Basics of CMC – Component and composition Component and composition Describe function, and qualitative and quantitative formulation of DP. List all components regardless of whether or not they appear in the FP (gases, solvents, water, ink etc). Reference to quality standards (USP/NF). Amount; per unit, ANDA, and production batch. Explanatory notes (overage, dosage form, coating, release mechanism etc). Example of composition statement Basics of CMC – Drug Substance DS: How to Submit Information CMC information the about drug substances can be incorporated in the application (NDA, ANDA) or by reference to pertinent information in another application, MF. A written statement that authorizes the reference, signed by the holder of the referenced application i.e. letters of authorization (LOA) should be submitted. DMF’s are not approved. They are reviewed for adequacy. Drug Substanc