Based on the legislatively defined set of some of the above specified "basis for change" documents, changes in the definition of a Marketed Substance - Production Chain initiate following variations that have to be reported to the competent Health Authorities:

• B.I.e.1 Introduction of a new design space or extension of an approved design space for the active substance, concerning:

  • a) One unit operation in the manufacturing process of the active substance including the resulting in-process controls and/or test procedures

  • b) Test procedures for starting materials/reagents/intermediates and/or the active substance

• B.I.e.2 Introduction of a post approval change management protocol related to the active substance

• B.I.e.3 Deletion of an approved change management protocol related to the active substance

• B.I.e.4 Changes to an approved change management protocol

  • a) Major changes to an approved change management protocol

  • b) Minor changes to an approved change management protocol that do not change the strategy defined in the protocol

• B.I.e.5 Implementation of changes foreseen in an approved change management protocol

  • a) The implementation of the change requires no further supportive data

  • b)The implementation of the change requires further supportive data

  • c) Implementation of a change for a biological/immunological medicinal product