Regulatory Focus™ > News Articles > Regulators, Industry Weigh in on Proposed EU Orphan Regulation Changes

Regulators, Industry Weigh in on Proposed EU Orphan Regulation Changes

Posted 07 March 2016 | By Zachary Brennan 

Regulators, Industry Weigh in on Proposed EU Orphan Regulation Changes

As the number of orphan drug approvals continues to rise in the EU, the European Commission is now considering feedback from European governments, regulators and industry on how changes to five aspects of the Orphan Regulation may further incentivize the development of drugs for rare diseases.

To date, the commission has authorized 117 orphan medicines, 82% of which consist of new active substances, according to a new report.  And while the number of products authorized as orphan products has grown recently, only 1% of treatments currently cover the more than 5,000 rare diseases.

Proposed Changes

Last November, the commission released a consultation to address five issues with the Orphan Regulation from 2000:

  • How to clarify the definition of what constitutes a “significant benefit.”
  • How to decide whether the development of treatments for communicable diseases that have yet to emerge in the EU (e.g. Ebola) should be granted orphan designations.
  • When to apply some flexibility on the parallel scientific assessments of two orphan medicinal products when the applicants are unable to demonstrate a significant benefit over another medicinal product assessed positively by the European Medicines Agency (EMA) only a month or two prior.
  • How to reassess orphan criteria for a new subset of a condition when a sponsor extends the use of its product after marketing authorization
  • Clarifications on processing the transfer of orphan designations between sponsors.


On Monday, the commission released 30 comments on the proposed changes with EMA, UK’s Medicines and Healthcare products Regulatory Agency, the Dutch government and companies, such as biotech giant Regeneron and generics specialist Teva Pharmaceuticals, weighing in.

On the regulators’ end, EMA made clear that it’s opposed to a proposal supported by some Member States that drugs prepared in a hospital pharmacy should be considered for the purpose of establishing significant benefit, which is one of the requirements for obtaining an orphan designation.

“We would propose that pharmacy preparations are not taken into account for the demonstration of significant benefit as their existence should not dis-incentivize the development of industrially manufactured orphan medicinal products which are subject to a rigorous process for demonstrating their quality, safety and efficacy in the interest of public health,” EMA said. “This situation would introduce an issue of inequality of access to the same standards of treatment and would not address patient needs across the EU.”

EMA also took issue with the idea that a formal review of the orphan criteria should occur every time a Marketing Authorization Holder (MAH) extends the therapeutic indication for an authorized orphan product within the same orphan condition, as that may discourage future rare disease drug development.

“This would add an additional hurdle to maintain the orphan incentive in a situation where, since the granting of the first marketing authorization, market exclusivity already exists,” EMA adds. “If companies lack the certainty that their proposed new indication falling under the same orphan condition as confirmed at time of the initial marketing authorisation will benefit from market exclusivity, they may refrain from further developing the product within the same orphan condition for subsequent new therapeutic indications (in certain cases entailing very small changes in target population). This may in turn promote off-label use rather than stimulating the authorisation of new indications.”

From MHRA’s perspective, the agency said it welcomes the proposal to extend orphan designation to products intended to treat communicable diseases with very low or no prevalence in the EU (e.g. Ebola) so that the region can stay ahead of the curve.

MHRA also said it supports further clarification of when orphan designations can be granted for drugs treating the symptoms of a disease rather than the disease itself.

The European Generic Medicines Association also called on the commission to ensure that orphan drug designations are proportionate to the significant benefit as in some cases, “the conclusion about ‘significant benefit’ seems to be relatively easily granted.”

Regeneron, meanwhile, took issue with “the Commission’s attempt to ensure more objective quantitative measures to demonstrate ‘significant benefit,’” as the company says that “it may not always be possible to demonstrate a ‘quantitative element’ which would allow the Committee for Orphan Medicinal Products (COMP) to measure the magnitude of the effect based on direct or, when not possible, indirect comparative clinical trials with already authorized medicinal products.”

Regeneron also called on the commission to recognize and address situations where “one monoclonal antibody is approved for an oncology orphan indication,” and then “a combination monoclonal antibody product consisting of that same authorized medicine and another monoclonal antibody (and therefore not structurally similar) should be eligible for Orphan designation in the same indication, and be assigned a separate and new exclusivity period upon approval for the Orphan indication, provided that significant benefit as defined by clinically relevant advantage or a major contribution to patient care (Article 3(2) of EC 847/2000) are confirmed.”

European Commission Consultation Document

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