ANNEX II: Classification of variations

Location:
Annex
Source:
Eur-Lex
1 The following variations shall be classified as minor variations of type IA:
(a) variations of purely administrative nature that are related to the identity and contact details of:
  • the holder;
  • the manufacturer or supplier of any starting material, reagent, intermediate, active substance used in the manufacturing process or finished product;
(b) variations related to the deletion of any manufacturing site, including for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place;
(c) variations related to minor changes to an approved physico-chemical test procedure, where the updated procedure is demonstrated to be at least equivalent to the former test procedure, appropriate validation studies have been performed and the results show that the updated test procedure is at least equivalent to the former;
(d) variations related to changes made to the specifications of the active substance or of an excipient in order to comply with an update of the relevant monograph of the European Pharmacopoeia or of the national pharmacopoeia of a Member State, where the change is made exclusively to comply with the pharmacopoeia and the specifications for product specific properties are unchanged;
(e) variations related to changes in the packaging material not in contact with the finished product, which do not affect the delivery, use, safety or stability of the medicinal product;
(f) variations related to the tightening of specification limits, where the change is not a consequence of any commitment from previous assessment to review specification limits and does not result from unexpected events arising during manufacture;
(g) variations related to changes to a medical device that is an integral part of or in exclusive use with the medicinal product which have no impact on the quality, safety or efficacy of the medicinal product.
2 The following variations shall be classified as major variations of type II:
(a) variations related to the addition of a new therapeutic indication or to the modification of an existing one;
(b) variations related to significant modifications of the summary of product characteristics due in particular to new quality, pre-clinical, clinical or pharmacovigilance findings;
(c) variations related to changes outside the range of approved specifications, limits or acceptance criteria;
(d) variations related to substantial changes to the manufacturing process, formulation, specifications or impurity profile of the active substance or finished medicinal product which may have a significant impact on the quality, safety or efficacy of the medicinal product;
(f) variations related to the introduction of a new design space, where the design space has been developed in accordance with the relevant European and international scientific guidelines;
(fa) variations related to the introduction of a post approval change management protocol where the protocol has been developed in accordance with the relevant European and international scientific guidelines;
(j) variations related to changes to the active substance of a seasonal, pre-pandemic or pandemic vaccine against human influenza;
(l) variations related to the replacement or, upon agreement of the relevant authorities, addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences for a human coronavirus vaccine;
(m) variations related to the replacement or, upon agreement of the relevant authorities, addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences of a human vaccine that has the potential to address a public health emergency;
(n) variations related to changes to a medical device that is an integral part of or in exclusive use with the medicinal product which may have a significant impact on the quality, safety or efficacy of the medicinal product.