General Variations Guidance Part 1

Disclaimer:
The below guidance has been compiled by an Regulatory Affairs Advisor and serves as an educational resource.

What is a variation?

A change to a drug licence (currently referred to as a Market Authorisation). The change may be requested by the regulator - the MHRA in the UK, or at the request of the Market Authorisation Holder (MAH), or a regulatory agency contracted on behalf of the MAH.

The changes can be diverse covering the active substance, finished product, to the packaging and  even product name.

How are variations classified?

Variations are classified in terms of potential impact with regard to the safety, efficacy and quality of the product. Three classifications currently exist: Type IA, IB and II. The particular change is also ascribed a change code, by way of example a change to the name of a nationally authorised product would be a type IB classification of change code A.2.b.

One of the four possible letter based subcategories are included in the change code; A., B., C., or D where A - Administrative changes. B - Quality changes (changes which are associated with the quality of the product, e.g. changing the manufacturer may impact the quality of the product and hence is classified under a B subcategory. C- Medical changes those concerning the safety or efficacy of the product from a pharmacovigilance perspective. D - changes under this subcategory concern the Plasma MasterFile (PMF); a compendium of information for products containing blood plasma) and Vaccine Antigen Masterfile.

Link to variations guideline for variations:
http://ec.europa.eu/health/files/eudralex/vol-2/2013_05_16_c2804_en.pdf

What is a foreseen or unforeseen variation?

The variations are also divided by the foreseen and unforeseen categories. A variation included in the variations guideline is termed foreseen, as it is a known potential change and therefore is listed. This contrasts with unforeseen variations which are not listed in a guideline, these are less common changes that have not yet been formally classified. All unforeseen variations are requested to be listed under the closest change code (nearest fit), with the letter Z is suffixed, e.g. C.I.z this would be a medical change which does not fall perfectly within any of the available C. change codes.

Important Note:
Unforeseen variations for type IA changes are only acceptable if listed in article 5 of the CMDh, this is currently in the form of an excel spreadsheet (middle option, or most recent option on the following webpage) http://www.hma.eu/293.html. Type IA, unforeseen (Z) change codes submitted which are not listed on this document will be refused.

Z change codes are more commonly submitted as type IB or type II variations. The nature of the change will depend on the classification accepted e.g. if the change is likely to impact the safety, quality of efficacy of the medicinal product, most often a type II classification will be required.