Commission Regulation (EC) No 1234/2008Show full title

ANNEX II Classification of variations

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.

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;

(e)

variations related to modifications in the manufacturing process or sites of the active substance for a biological medicinal product;

(f)

variations related to the introduction of a new design space or the extension of an approved one, where the design space has been developed in accordance with the relevant European and international scientific guidelines;

(g)

variations concerning a change to or addition of a non-food producing target species;

(h)

variations concerning the replacement or addition of a serotype, strain, antigen or combination of serotypes, strains or antigens for a veterinary vaccine against avian influenza, foot-and-mouth disease or bluetongue;

(i)

variations concerning the replacement of a strain for a veterinary vaccine against equine influenza;

(j)

variations related to changes to the active substance of a seasonal, pre-pandemic or pandemic vaccine against human influenza;

(k)

variations related to changes to the withdrawal period for a veterinary medicinal product.