US Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER) has issued a draft guidance on chemistry, manufacturing and controls (CMC) which calls for post approval manufacturing changes to drug applicants on the types of changes that are to be included in annual submissions.

According to the draft guidance, the number of CMC manufacturing supplements for new and abbreviated new drug applications (NDAs and ANDAs) has increased greatly over the past few years. The agency, in line with its Pharmaceutical Product Quality Initiative and risk-based approach to CMC review, evaluated the types of changes submitted in CMC post approval manufacturing supplements and 'determined that many of the changes being reported present very low risk to the quality of the product' and therefore no longer should be submitted in supplements.

Certain items that used to be submitted to US FDA in manufacturing supplements now may be reported in annual reports, pending a final guidance document. These items include changes related to the drug product's identity, strength, quality, purity, and potency. A specific list of changes is included in Appendix A of the draft guidance, which is broken down into the sections like components and composition, manufacturing sites, manufacturing process, specifications, container-closure systems, and miscellaneous items.

Specific changes within each section include items like: The elimination of an overage from the drug product manufacturing batch formula that was previously used to compensate for manufacturing losses. The addition of barriers to prevent routine in-process human intervention in a filling area. Changes to filtration process parameters that are within currently validated parameters. The addition of a specification for excipients. The use of a contract manufacturing organization for washing a drug product stopper. Extension of expiry based on real-time stability data from pilot-scale batches.
Post approval changes that must be reported to FDA are included in section 506A of the Federal Food, Drug, and Cosmetic Act. The agency, has noted in the draft guidance that, if the drug applicant is submitting supplemental applications based on recommendations for CMC changes, provided in the 'FDA's Changes to an Approved NDA or ANDA guide, the applicant should now also refer to Appendix A of this draft guidance which will help determine whether a particular change may now be reported in an annual report.

The agency also notes in the draft guidance that applicants must continue to comply with the cGMP for Finished Pharmaceuticals regulations within 21 CFR Parts 210 and 211, and for API manufacturers, with the ICH Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients guideline.

The US FDA is seeking for comments on the draft guidance by the industry by September 23, 2010.

India has the highest number of US FDA plants outside the US and the maximum number of these facilities are in south India. Some of the companies include Strides Arcolab, Micro Labs, Aurobindo, Orchid and Shashun making NDA and ANDA submissions on a regular basis.