For a medicinal product that is centrally approved by the European Commission, marketing authorization (MA) for a new therapeutic indication is typically sought by way of a Type II variation under the Variations Regulations (Regulation (EC) 1234/2008). However, there are also cases in which the European Regulatory Framework permits a second MA to be filed under a different brand, which could be advantageous for reimbursement reasons.

While MAs for innovative medicinal products in the EU are usually obtained in the centralized procedure following Regulation (EC) 726/2004, and although the newly introduced health technology assessment (HTA) under the EU HTA Regulation (Regulation (EU) 2021/2282)) provides for a European-wide scientific assessment of medicinal product, the reimbursement decisions in EU Member States remain subject to national legislation. In other words, the approaches of Member States vary on how to incorporate new therapeutic indications for an already-reimbursed medicinal product into the product's existing reimbursement scheme.

If a new therapeutic indication is approved as a "variation" under an existing MA, there can only be one price for the medicinal product, which reflects the often-different benefits of one medicinal product in its various indications (the "mixed price"). This reimbursement price is generally specific to the active substance and not to the indication.

However, if a new therapeutic indication is approved under a separate MA (under a different brand), there is the possibility, in exceptional cases, to obtain a specific price for this therapeutic indication (i.e., "value-based pricing"). For example, in Germany this may be the case if two medicinal products with the same active substance: are approved for two different indications; are available in different strengths and pharmaceutical forms; are not readily interchangeable; and the price level of comparable medicinal product in both indications differs significantly. A pharmaceutical company may wish to assess this pathway in the wider European context if clinical outcomes for different therapeutic indications vary widely.

Obtaining a separate MA for a new therapeutic indication needs to be specifically justified, and is not easily obtained under EU regulations, unless one therapeutic indication has an orphan designation. Under Regulation (EC) 726/2004, an applicant may obtain only one MA for one "specific" medicinal product, unless there are objective verifiable reasons relating to public health regarding the availability of the medicinal products to health care professionals and/or patients, or for co-marketing reasons.

European Commission and EMA guidance indicate that any medicinal product with the same qualitative and quantitative composition in active substance (i.e., the same strength) and same pharmaceutical form is to be considered as the "same" product. This means that when different therapeutic indications translate into different qualitative and quantitative composition in active substance and into the different pharmaceutical forms, there are potential grounds for obtaining a separate MA. In such cases, drug manufacturers should engage early with the EMA to discuss national reimbursement level concerns.