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 Finished Product initiate the following variations that have to be reported to the competent Health Authorities:

• B.II.d.1 Change in the specification parameters and/or limits of the finished product

  • a) Tightening of specification limits

  • b) Tightening of specification limits for medicinal products subject to Official Control Authority Batch Release

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

  • d) Deletion of a non-significant specification parameter (e.g. deletion of an obsolete parameter such as odour and taste or identification test for a colouring or flavouring material)

  • e) Change outside the approved specifications limits range

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

  • g) 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

  • h) Update of the dossier to comply with the provisions of an updated general monograph of the Ph. Eur for the finished product  (8)

  • i) Ph. Eur. 2.9.40 Uniformity of dosage units is introduced to replace the currently registered method, either Ph. Eur. 2.9.5 (Uniformity of mass) or Ph. Eur. 2.9.6 (Uniformity of content)

• B.II.d.2 Change in test procedure for the finished product

  • a) Minor changes to an approved test procedure

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

  • c) Substantial change to, or replacement of, a biological/immunological/immunochemical test method or a method using a biological reagent or replacement of a biological reference preparation not covered by an approved protocol

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

  • e) Update of the test procedure to comply with the updated general monograph in the Ph. Eur.

  • f) To reflect compliance with the Ph.Eur. and remove reference to the outdated internal test method and test method number  (9)

• B.II.d.3 Variations related to the introduction of real-time release or parametric release in the manufacture of the finished product