On 6 February 2014, the EMA released an amended Q&A document on the implementation of the new Variations Guidelines of 2013, which provides details on the different variation categories and the operation of procedures laid down in Commission Regulation 1234/2008 concerning the examination of variations to the terms of marketing authorizations for human and veterinary medicinal products.
In its press release, the EMA notes that the Q&A document has been amended in agreement with the European Commission and these amendments aim to clarify specific points related to the new (as of August 2013) variation categories to the terms of marketing authorizations. This concerns, in particular, category C.1. 11 on the introduction of, or changes to, the obligations and conditions of a marketing authorization (including the risk management place) and category C.1.13. on other variations not specifically covered by the Variations Guideline which involve the submission of studies to the competent authorities.
According to the EMA, the adjustments clarify the following points:
(1) Submission of paediatric studies pursuant to Art. 46 of the Paediatric Regulation 1901/2006 (P46 studies) will be handled as:
- a post-authorization measure if the marketing authorization holder (MAH) considers that no changes to the product information (PI) are warranted (instead of a type II variation as was suggested in the initial Q&A document from the EMA);
- an implementing variation category C.1.3 if the assessment of the EMA Committee for Medicinal Products for Human Use (CHMP) identifies amendments to the PI;
- variation category C.1.4 if the MAH concludes that changes to the PI are necessary based on data from the P46 study at the time of submission.
(2) Studies in the context of environmental risk assessments (ERA) for human medicines should be assessed during the initial marketing authorization or relevant post-marketing procedures, such as extension applications. If they are exceptionally submitted on a stand-alone basis, they will be handled as type IB C.1.z variations (instead of type II variations), as they do not include information relevant to the quality, safety and efficacy of the medicines.
(3) MAH requests to amend due dates of conditions of a marketing authorization or of measures in a risk management plan will be handled as type IB variations (instead of a type II variation).
The adjustments made to the Q&A document will be retrospectively applicable from 1 January 2014. They will have significant, and positive, financial implications for the pharmaceutical industry. Type II variations are very costly (general fee of EUR 82 400, as compared to a general fee of EUR 6 900 for a type 1B variation, or no fee at all for the post-authorization measure) and were not justified in some cases initially covered by the EMA Q&A (such as for the submission of a P46 study, which does not require any change to the PI).