PROGRAM INCLUDES THE REVIEW OF NON-STERILE PRODUCTS
John W. Metcalfe, Ph.D., of the New Drug Microbiology Staff at CDER gave an excellent, informative presentation on “Regulatory Review Perspectives for Non-Sterile Drug Products” at the PDA Global Microbiology Conference on Monday, October 21, 2013 in Bethesda, MD. This presentation presented information on a Pilot Program that includes the microbiological review of non-sterile products.
The New Drug Microbiology Staff (NDMS) within CDER advises physicians and scientists on the risks associated with various manufacturing techniques and dosage forms and provide recommendations as to the suitability of product manufacturing processes and control. While their primary emphasis has been upon the review of sterile products, they began reviewing non-sterile products in the mid-2000s. Historically, the non-sterile microbiology review was performed by chemists with the result that inconsistent microbial limit criteria occurred across various products.
During the past five years, NDMS has continuously increased the review activity of non-sterile drugs. This group has recently instituted a Pilot Program where all new NDAs being received by NDMS are reviewed for microbiology relevance. Some of the rationale for this Pilot Program and its oversight which is now five months into its six month trial period include: 1) an understanding of the dosage form/route of administration with the least microbiological risk to patients, 2) manufacturing process which may contain antimicrobial steps, and 3) low water activity which equals no microbial growth. Areas of concern for which NDMS is concentrating include aqueous intermediate hold times and the potential for the drug product to be adulterated with senescent microbes prior to administration if the in-coming raw materials (components) include bioburden.
The NDMS review focus will include 1) product specifications which include Microbial Limit testing, 2) consistency of the Microbial Limit test with USP<61> Microbiological Examination of Non-Sterile Products, Microbial Enumeration Tests; USP<62> Microbiological Examination of Non-Sterile Products, Test for Specified Microorganisms, 3) are the Microbial Limit acceptance criteria appropriate and 4) is the applicant requesting skip lot Microbial Limit testing? The issue of “Skip Lot” testing will be addressed in a subsequent Blog.