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# Guide on Post-approval Drug Substance Changes
- URL: https://www.fdaweb.com/guide-on-post-approval-drug-substance-changes/
- Published: 2018-09-10T12:00:00.000Z
- Updated: 2026-09-15T00:30:51.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5142306

FDA has posted a [draft guidance](https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM619947.pdf?ref=fdaweb.com) entitled “Postapproval Changes to Drug Substances.” The document applies to synthetic drug substances and the synthetic steps involved in preparing semi-synthetic drug substances. It covers facility, scale, and equipment changes associated with all steps of drug substance manufacturing; specification changes to starting materials, raw materials, intermediates, and the unfinished and final drug substance; synthetic manufacturing process changes; changes in the source of drug substance; and change to container closure system of the drug substance.