On 26 April 2023 the European Commission published its Proposals to Reform the EU pharmaceutical legislation.[1] We continue our analysis of the Proposals with this focus upon the changes concerning orphan medicines.

1.The current Orphan Regulation (EC) No 141/2000 will be repealed, and the new orphan provisions will be integrated into the general Regulation laying down the EU procedures for the authorisation and supervision of medicines.

2. The orphan designation criteria remain largely unchanged, meaning that for a product to receive orphan designation it still has to be intended for a condition that doesn’t affect more than 5 in 10,000 people in the EU and for which there is no method of diagnosis, prevention or treatment approved in the EU, or if such method exists, the medicine will be of “significant benefit” to those affected by the condition. The orphan designation criterion on the basis of return on investment has been abolished, as it has never been used to date.

3. The definition of “significant benefit” is slightly amended by adding that the clinical relevant advantage or major contribution to patient care required to prove a significant benefit shall benefit “a substantial part of the target population”. It will therefore be harder to demonstrate significant benefit than under the current regime, which does not include this added requirement. How much will depend on what is considered “a substantial part” and how broadly or narrowly the “target population” will be regarded.

4. Orphan designation procedures are simplified, and the European Commission is no longer responsible for granting an orphan designation. The proposal instead foresees that EMA, through the Committee for Medicinal Products for Human Use (CHMP), shall be responsible for granting or refusing orphan designations. The Committee for Orphan Medicinal Products (COMP) is to be downgraded into a working party, as part of an overall effort to streamline and simplify EMA’s structure.

5. The validity of an orphan designation will be limited to 7 years with possibility for extension under certain conditions. At present, the validity of an orphan designation is unlimited and companies can apply for it early in the development process, well before the application for marketing authorisation is made. With this measure, the Commission aims to incite faster authorisation of designated products. What is likely to happen in practice is that companies will apply for orphan designation closer to the marketing authorisation phase.  

6. Orphan market exclusivity periods are reduced and the conditions to obtain an extension are strict:

  • The standard period of orphan market exclusivity is reduced from 10 to 9 years.
  • Well established use orphan medicinal products will be granted 5 years of orphan market exclusivity. This is a new (reduced) period of protection not foreseen in the current legislation.

In exchange for the reduction from 10 to 9 years, additional periods of orphan market exclusivity may be available under specific circumstances:

  • 1 additional year for medicines addressing a high unmet medical need.
  • 1 additional year if the medicine is released and supplied in sufficient quantity and in the presentations needed to meet demand in all Member States covered by the marketing authorisation within two years from the date the marketing authorisation was granted (or within 3 years for SME’s, (groups of) entities with less than 5 centralised marketing authorisations or non-profit entities).
  • 1 additional year for a new indication of an already authorised orphan medicine. This prolongation may be granted twice if the new therapeutic indications are for different orphan conditions.

The possibility to reduce orphan market exclusivity to 6 years, foreseen in the current Orphan Regulation, is abolished.

The Commission is keen to flag that if these conditions are met, orphan market exclusivity periods can add up to a maximum of 13 years, while today the maximum period of orphan market exclusivity is 10 years. However, the requirements to obtain additional periods of orphan market exclusivity are strict and the definitions of unmet medical need, high unmet medical need as well as the requirement to release and supply in sufficient quantity are very restrictive. Moreover, the strength of orphan market exclusivity is mitigated significantly with a striking new rule described in the point below.

7. Orphan market exclusivity becomes a weaker form of protection. Under the current Orphan Regulation, orphan market exclusivity prevents the submission, validation and assessment of a similar medicinal product, during the entire duration of the 10-year period of orphan market exclusivity. Under the Proposal, orphan market exclusivity shall not prevent the submission, validation and assessment of a marketing authorisation application for a similar medicinal product, including generics or biosimilars, where the remainder of the duration of the market exclusivity is less than two years.

This is an important change aimed at facilitating earlier competitor entry. By allowing application and assessment of generics and biosimilars during the last two years of market exclusivity, these products shall be ready to be placed on the market immediately upon expiry of the period of market exclusivity.

8. Definitions of “Unmet Medical Need” and “High Unmet Medical Need” are linked to a “meaningful reduction in disease morbidity or mortality for the relevant patient population”. There is a lot of room for interpretation within these concepts, meaning that extensions of protection periods will be far from secure. Improvement in patient care or technological advancement are excluded from the scope of those definitions and therefore not eligible for an extension of orphan market exclusivity.

Whilst regulatory simplification is welcome, reduction of the standard period of orphan market exclusivity to 9 years and the possibility to assess similar medicines during the last two years of orphan market exclusivity are significant limitations compared to the current regime. In addition, the requirements that need to be fulfilled for an extension of the period of market exclusivity are strict and far from clear so that the claimed accumulation of protection up to 13 years is theoretical at this stage.

The package will now be examined by Council and the European Parliament who may still introduce amendments to these provisions. 

We will continue to keep a close eye on the detail of these proposals as they evolve.

[1] For a general overview of the proposed changes see our previous blog alert, available here.


Els Janssens is a counsel specialised in healthcare life sciences regulatory matters based in Brussels. She has more than 10 years of experience with life sciences industry in the UAE.


Magda Tovar is Senior Knowledge Lawyer for the Healthcare and Life Sciences Industry Group.


Julia Gillert is Of Counsel at Baker McKenzie's London office, and has shaped her practice to focus exclusively on regulatory matters affecting the Healthcare & Life Sciences industry.