Paragraph 1 InterpretationF1

In this Schedule—

• “change of, or addition of a new, route of administration”, in relation to parenteral administration, includes any change or addition as between intra-arterial, intra-venous, intramuscular, subcutaneous and any other route;

• “extension of a UK marketing authorisation” or “extension” means a variation which consists of—

  1. (a)

     a change to one or more active substances that involves—

     1. (i)

        replacement of a chemical active substance by a different salt, ester, complex or derivative, with the same therapeutic moiety, where the efficacy and safety characteristics are not significantly different,

     2. (ii)

        replacement by a different isomer, a different mixture of isomers, of a mixture by an isolated isomer (for example, racemate by a single enantiomer), where the efficacy and safety characteristics are not significantly different,

     3. (iii)

        replacement of a biological active substance with one of a slightly different molecular structure where the efficacy and safety characteristics are not significantly different, with the exception of changes to the active substance of a seasonal, pre-pandemic or pandemic vaccine against human influenza,

     4. (iv)

        modification of the vector used to produce the antigen or the source material, including a new master cell bank from a different source, where the efficacy and safety characteristics are not significantly different,

     5. (v)

        a new ligand or coupling mechanism for a radiopharmaceutical, where the efficacy and safety characteristics are not significantly different, or

     6. (vi)

        change to the extraction solvent or the ratio of herbal drug to herbal drug preparation where the efficacy and safety characteristics are not significantly different; or

  2. (b)

     a change to strength, pharmaceutical form and route of administration that involves—

     1. (i)

        change of bioavailability,

     2. (ii)

        change of pharmacokinetics, for example change in rate of release,

     3. (iii)

        change or addition of a new strength or potency,

     4. (iv)

        change or addition of a new pharmaceutical form, or

     5. (v)

        change or addition of a new route of administration;

• “holder” means UK marketing authorisation holder;

• “major variation of type II” means a variation which is not an extension and which may have a significant impact on the quality, safety or efficacy of the medicinal product concerned namely—

  1. (a)

     variations related to the addition of a new therapeutic indication or to the modification of an existing one;

  2. (b)

     variations related to significant modifications of the summary of product characteristics due in particular to new quality, pre-clinical, clinical or pharmacovigilance findings;

  3. (c)

     variations related to changes outside the range of approved specifications, limits or acceptance criteria;

  4. (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;

  5. (e)

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

  6. (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 international scientific guidelines; or

  7. (g)

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

• “minor variation of type IA” means a variation which has only a minimal impact, or no impact at all, on the quality, safety or efficacy of the medicinal product concerned namely—

  1. (a)

     variations of purely administrative nature that are related to the identity and contact details of—

     1. (i)

        the holder,

     2. (ii)

        the manufacturer or supplier of any starting material, reagent, intermediate, active substance used in the manufacturing process or finished product;

  2. (b)

     variations related to the identity, location and contact details of the qualified person for pharmacovigilance, or the location of the pharmacovigilance system master file;

  3. (c)

     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;

  4. (d)

     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;

  5. (e)

     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 British Pharmacopoeia, where the change is made exclusively to comply with the pharmacopoeia and the specifications for product specific properties are unchanged;

  6. (f)

     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;

  7. (g)

     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;

• “minor variation of type IB” means a variation which is not a minor variation of type IA, a major variation of type II nor an extension; and

• “urgent safety restriction” means an interim change in the terms of the UK marketing authorisation due to new information having a bearing on the safe use of the medicinal product.