Based on the legislatively defined sets of "basis for change" documents, changes in the definition of a Medicinal Product related to the Medicinal Product Safety, Efficacy and Pharmacovigilance Changes initiate the following variations that have to be reported to the competent Health Authorities:

• C.I.1 Change(s) in the Summary of Product Characteristics, Labelling or Package Leaflet intended to implement the outcome of a Union referral procedure

  • a) The medicinal product is covered by the defined scope of the procedure

  • b) The medicinal product is not covered by the defined scope of the procedure but the change(s) implements the outcome of the procedure and no new additional data is required to be submitted by the MAH

  • c) The medicinal product is not covered by the defined scope of the procedure but the change(s) implements the outcome of the procedure with new additional data submitted by the MAH
    

• C.I.2 Change(s) in the Summary of Product Characteristics, Labelling or Package Leaflet of a generic/hybrid/biosimilar medicinal products following assessment of the same change for the reference product

  • a) Implementation of change(s) for which no new additional data is required to be submitted by the MAH

  • b) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH (e.g. comparability)

• C.I.3 Change(s) in the Summary of Product Characteristics, Labelling or Package Leaflet of human medicinal products intended to implement the outcome of a procedure concerning PSUR or PASS, or the outcome of the assessment done by the competent authority under Article 45 or 46 of Regulation (EC) No 1901/2006

  • a) Implementation of wording agreed by the competent authority

  • b) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH

• C.I.4 Change(s) in the Summary of Product Characteristics, Labelling or Package Leaflet due to new quality, preclinical, clinical or pharmacovigilance data

• C.I.5 Change in the legal status of a medicinal product for centrally authorised products

  • a) For generic/hybrid/biosimilar medicinal products following an approved legal status change of the reference medicinal product

  • b) All other legal status changes

• C.I.6 Change(s) to therapeutic indication(s)

  • a) Addition of a new therapeutic indication or modification of an approved one

  • b)Deletion of a therapeutic indication

• C.I.7 Deletion of:

  • a) a pharmaceutical form

  • b) a strength

• C.I.8 Introduction of, or changes to, a summary of pharmacovigilance system for medicinal products for human use

  • a) Introduction of a summary of pharmacovigilance system, changes in QPPV (including contact details) and/or changes in the Pharmacovigilance System Master File (PSMF) location

• C.I.9 Change(s) to an existing pharmacovigilance system as described in the detailed description of the pharmacovigilance system (DDPS)

  • a) Change in the QPPV and/or QPPV contact details and/or back-up procedure

  • b) Change(s) in the safety database and/or major contractual arrangements for the fulfilment of pharmacovigilance obligations, and/or change of the site undergoing pharmacovigilance activities

  • c) Other change(s) to the DDPS that does not impact on the operation of the pharmacovigilance system (e.g. change of the major storage/archiving location, administrative changes)

  • d) Change(s) to a DDPS following the assessment of the same DDPS in relation to another medicinal product of the same MAH

• C.I.10 Change in the frequency and/or date of submission of periodic safety update reports (PSUR) for human medicinal products

• C.I.11 Introduction of, or change(s) to, the obligations and conditions of a marketing authorization, including the risk management plan

  • a) Implementation of wording agreed by the competent authority

  • b) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment by the competent authority is required

• C.I.12 Inclusion or deletion of black symbol and explanatory statements for medicinal products in the list of medicinal products that are subject to additional monitoring

• C.I.13 Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority