Variations to FPPs

Given the rapidly evolving discipline of pharmaceutical science, the manufacture of a finished pharmaceutical product (FPP) is likely to undergo several changes during its life cycle. For example, changes may be made to the product to take into account technical and scientific progress, or to improve or introduce additional safeguards.

Changes to a prequalified FPP, whether administrative or substantive, are commonly termed "variations”. They include changes made to the active pharmaceutical ingredient (API)-related information of a product (that is included in Section 3.2.S of the Common technical document (CTD) ‒ quality (M4Q), as developed by the International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)).

For multisource, generic FPPs WHO has issued guidelines (which apply to APIs and excipients manufactured by chemical synthesis or semi-synthetically, and to FPPs containing such APIs and excipients) to help FPP applicants:

  • determine what type of variation applies in each case
  • understand the documentation that must be submitted when requesting approval or submitting notification.

For multisource (generic) or innovator FPPs prequalified based on approval by a stringent regulatory authority (SRA), WHO should be notified as soon as any variation has been approved by the relevant SRA.