Post-approval Changes to Drug Substances: FDA Drafts Guidance
Drugmakers looking to make a change to the drug substance manufacturing process during an application’s post-approval period should consult the US Food and Drug Administration’s (FDA) new draft guidance released Monday.The 38-page draft, completed as part of a commitment to the reauthorization of the Generic Drug User Fee Amendments (GDUFA II), provides recommendations to holders of approved new drug applications, abbreviated new drug applications, new animal drug applications, abbreviated new animal drug applications, and holders of drug master files and veterinary master files who may want to make a change to the drug substance manufacturing process during the drug product application postapproval period.
The draft guidance covers facility, scale and equipment changes associated with all steps of drug substance manufacturing; specification changes to starting materials, raw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.
The draft notes that late-stage changes in the drug substance manufacturing process are generally viewed as “more likely to have an adverse impact on the quality of the drug substance and, consequently, on the drug product.
“The responsibility for reporting the types of changes described in this guidance could lie with a single party or with several parties, depending on whether the drug substance synthesis or processing is described in an application or in one or more master files,” the draft explains. “The notification to FDA should include reference to the section of this guidance under which the change is made and all pertinent information to ensure the quality of the drug substance and drug product.”
However, the draft notes that it does not address postapproval changes to “peptides, oligonucleotides, radiopharmaceuticals; or drug substances isolated from natural sources or produced by procedures involving biotechnology; or nonsynthetic steps (such as fermentation) for semisynthetic drug substances.”
Postapproval Changes to Drug Substances: Draft Guidance for Industry