European Commission clarifies orphan drug regulation

The European Commission (EC) has, following a consultation, issued a notice clarifying some grey areas of the EU’s Orphan Regulation. A number of key issues have been addressed:

  • Clarification of the meaning of “significant benefit”
  • Orphan designation in cases where two MAAs for two products for the same indication are assessed in parallel
  • Applying the Orphan Regulation to emerging diseases, such as Ebola and Zika, that are not present within the EU
  • Reassessment of a product’s orphan designation when a sponsor extends the use of its product after the initial marketing authorization
  • Transfer of orphan designations between sponsors

Significant Benefit – The meaning and interpretation of the term “significant benefit” has caused much debate. It is defined in Regulation (EC) No. 847/2000 as “a clinically relevant advantage or major contribution to patient care” so a medicine may be designated as an orphan product even if a treatment exists, provided the new product confers “significant benefit”. The notice makes it clear that “significant benefit” based on clinically relevant advantages mean improved efficacy or a better safety profile compared to existing treatments, or a major contribution to patient care, such as a switch from hospital to self-administration or new pharmaceutical form that has been shown to improve patient compliance.

Helpfully but not doubt to the disappointment of some potential sponsors, the notice states that significant benefit should not be based on improved product supply or availability due to shortages or because existing products are authorised in only one or a limited number of Member States. However, exceptions may be possible if the sponsor can demonstrate evidence of patient harm in such circumstances. Other situations that do not meet the definition of “significant benefit” are superior pharmaceutical quality of a product in compliance with relevant Committee for Medicinal Products for Human Use (CHMP) guidelines or a new pharmaceutical form, a new strength or a new route of administration per se, unless it brings a major contribution to patient care; or an alternative mechanism of action. However, in exceptional cases consideration may be given to those developments at the time the designation is granted. At the time the criteria are reviewed for the purposes of granting the marketing authorisation, this must translate into a clinically relevant advantage or a major contribution to patient care.

Parallel Marketing Authorisation Applications – The notice also describes maintenance of an orphan designation when two MAAs for two products for the same orphan indication are being assessed by EMA at the same time. In such situations, it is not necessary for the sponsor of the second product to demonstrate significant benefit over the first, because limited information is likely to be available. However, the Commission says that the sponsor of the second product will need to demonstrate significant benefit over the first product if the notification of marketing authorisation for the first product has been published in the Official Journal of the EU by the time the Committee for Orphan Medicinal Products (COMP) reconsiders the second product’s designation criteria. This requirement may be met by performing an indirect comparison.

Prevalence of a Disease not Present in the EU – The notice has addressed how to handle orphan designations for conditions that do not affect the EU population, e.g., the Ebola outbreak in 2014, which affected very many people in West Africa, but was not spread within the EU. Such diseases qualify for consideration as orphan products because the prevalence of the disease within the EU, not outside of it, is the consideration for orphan designation. However, for conditions with, at the time of application, zero prevalence within the EU, sponsors should consider the risk that people within the EU may become affected by the disease in the future.

Designated Condition versus Authorised Indication – The Commission has also clarified that an orphan product’s designation must be reassessed when there is a change to its indication. This will ensure that the marketing authorisation for an orphan product only covers indications that meet the criteria for an orphan product.

Transfer of Orphan Designation – Whilst it is possible to transfer an orphan designation between sponsors, the Commission has spelled out that it is not possible to transfer an orphan designation to a sponsor who already has a marketing authorisation for the same medicinal product and condition.

Click here to read the full communication.

If you require any support with your EU orphan designation, from protocol assistance, to preparation and submission of the designation application, please contact our Regulatory team.