Based on the legislatively defined sets of "basis for change" documents, changes in the definition of a Medicinal Product - Preparation Production Chain related to the Control of Excipients of the Medicinal Product initiate the following variations that have to be reported to the competent Health Authorities:

• B.II.c.1 Change in the specification parameters and/or limits of an excipient
  

  • a) Tightening of specification limits

  • b) Addition of a new specification parameter to the specification with its corresponding test method

  • c) Deletion of a non-significant specification parameter (e.g. deletion of an obsolete parameter)

  • d) Change outside the approved specifications limits range

  • e) Deletion of a specification parameter which may have a significant effect on the overall quality of the finished product

  • f) Addition or replacement (excluding biological or immunological product) of a specification parameter with its corresponding test method, as a result of a safety or quality issue

  • g) Where there is no monograph in the European Pharmacopoeia or the national pharmacopoeia of a Member State for the excipient, a change in specification from in-house to a non-official

• B.II.c.2 Change in test procedure for an excipient

  • a) Minor changes to an approved test procedure

  • b) Deletion of a test procedure if an alternative test procedure is already authorised

  • c) Substantial change to or replacement of a biological/immunological/immunochemical test method or a method using a biological reagent

  • d) Other changes to a test procedure (including replacement or addition)

• B.II.c.3 Change in source of an excipient or reagent with TSE risk

  • a)   From TSE risk material to vegetable or synthetic origin

    • 1. For excipients or reagents not used in the manufacture of a biological/immunological active substance or in a biological/immunological medicinal product

    • 2. For excipients or reagents used in the manufacture of a biological/immunological active substance or in a biological/immunological medicinal product

  • b) Change or introduction of a TSE risk material or replacement of a TSE risk material from a different TSE risk material, not covered by a TSE certificate of suitability

• B.II.c.4 Change in synthesis or recovery of a non-pharmacopoeial excipient (when described in the dossier) or a novel excipient

  • a) Minor change in synthesis or recovery of a non-pharmacopoeial excipient or a novel excipient

  • b) The specifications are affected or there is a change in physico-chemical properties of the excipient which may affect the quality of the finished product

  • c) The excipient is a biological/immunological substance