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 Container Closure System of the Medicinal Product initiate the following variations that have to be reported to the competent Health Authorities:

• B.II.e.1 Change in immediate packaging of the finished product
  • a)   Qualitative and quantitative composition

    • 1. Solid pharmaceutical forms

    • 2. Semi-solid and non-sterile liquid pharmaceutical forms

    • 3. Sterile medicinal products and biological/immunological medicinal products

    • 4. The change relates to a less protective pack where there are associated changes in storage conditions and/or reduction in shelf life

  • b)   Change in type of container or addition of a new container

    • 1. Solid, semi-solid and non-sterile liquid pharmaceutical forms

    • 2. Sterile medicinal products and biological/immunological medicinal products

    • 3. Deletion of an immediate packaging container that does not lead to the complete deletion of a strength or pharmaceutical form

• B.II.e.2 Change in the specification parameters and/or limits of the immediate packaging of the finished product

  • 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.II.e.3 Change in test procedure for the immediate packaging of the finished product

  • 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 authorised

• B.II.e.4 Change in shape or dimensions of the container or closure (immediate packaging)

  • a) Non-sterile medicinal products

  • b) The change in shape or dimensions concerns a fundamental part of the packaging material, which may have a significant impact on the delivery, use, safety or stability of the finished product

  • c) Sterile medicinal products

• B.II.e.5 Change in pack size of the finished product

  • a)   Change in the number of units (e.g. tablets, ampoules, etc.) in a pack

    • 1. Change within the range of the currently approved pack sizes

    • 2. Change outside the range of the currently approved pack sizes

  • b) Deletion of pack size(s)

  • c) Change in the fill weight/fill volume of sterile multi-dose (or single-dose, partial use) parenteral medicinal products, including biological/immunological medicinal products

  • d) Change in the fill weight/fill volume of non-parenteral multi-dose (or single-dose, partial use) products

• B.II.e.6 Change in any part of the (primary) packaging material not in contact with the finished product formulation (such as color of flip-off caps, color code rings on ampoules, change of needle shield (different plastic used))

  • a) Change that affects the product information

  • b) Change that does not affect the product information

• B.II.e.7Change in supplier of packaging components or devices (when mentioned in the dossier)

  • a) Deletion of a supplier

  • b) Replacement or addition of a supplier

  • c) Any change to suppliers of spacer devices for metered dose inhalers