FDA releases draft guidance for post-approval changes to drug substances

The US Food and Drug Administration (FDA) have released new draft guidance for drug manufacturers who are looking to make a change to the drug substance manufacturing process during an application’s post-approval period.

The draft guidance, which was completed as part of a commitment to the reauthorisation of the Generic Drug User Fee Amendments (GDUFA II), contains recommendations for holders of approved new drug applications, abbreviated new drug applications and holders of drug master files, who may want to make a change to the drug substance manufacturing process during the drug product application post-approval period.

The draft guidance details information regarding the following:

  • facility, scale and equipment changes that are 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
  • change to container closure system of the drug substance.

The draft guidance states that late-stage changes in the drug substance manufacturing process may be “more likely to have an adverse impact on the quality of the drug substance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 the guidance may 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 The draft guidance also states that “notification to FDA should include reference to the section of this guidance under which the change is made and all pertinent information to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.”

To read the draft FDA guidance on post-approval changes to drug substances, please click here.