Based on the legislatively defined sets of "basis for change" documents, changes in the definition of a Marketed Substance - Production Chain related to the Marketed Substance Container Closure System initiate the following variations that have to be reported to the competent Health Authorities:

• B.I.c.1 Change in immediate packaging of the active substance

  • a) Qualitative and/or quantitative composition

  • b) Qualitative and/or quantitative composition for sterile and non-frozen biological/immunological active substances

  • c) Liquid active substances (non-sterile)

• B.I.c.2 Change in the specification parameters and/or limits of the immediate packaging of the active substance

  • 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) Addition or replacement of a specification parameter as a result of a safety or quality issue

• B.I.c.3 Change in test procedure for the immediate packaging of the active substance

  • a) Minor changes to an approved test procedure

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

  • c) Deletion of a test procedure if an alternative test procedure is already authorized