o EUROPEAN MEDICINES AGENCY S C I E N C E M E D I C I N E S H E A L T H

11 February 2016 EMA/50964/2016

European Medicines Agency comments on the Public consultation paper - Notice from the Commission on aspects of the application of Article 3, 5 and 7 of Regulation (EC) № 141/2000 on orphan medicinal products

The Agency welcomes the European Commission's proposal to review the 2003 Communication on orphan medicinal products to streamline the regulatory framework and to adapt the Communication to technical progress. We would hereby like to provide our views on some of the items under consultation.

Consultation topics:

Consultation item n0l: Clarification of the definition of "significant benefit"

The Agency welcomes the European Commission proposals to clarify the definition of significant benefit and how this should be demonstrated by the sponsors. The Agency would like to take this opportunity to comment on the proposal supported by some Member States that medicinal products prepared in a (hospital) pharmacy should be taken into consideration 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-incentivise 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.

The aim of the orphan regulation is to stimulate the research, development and bringing onto the market of medicinal products for orphan indications. Patients affected by rare diseases deserve medicines of the same quality, safety and efficacy as other patients. Only industrially prepared products which undergo a rigorous assessment process and are finally granted a Marketing

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Authorisation can be said to have a demonstrated quality, safety and efficacy since they have to comply with the Community legislation. In addition, they are subject to rigorous pharmacovigilance requirements.

It should be noted that, medicinal products that are prepared in a pharmacy in accordance with a medical prescription for an individual patient (commonly known as magistral formulations) or in accordance with the prescriptions of a pharmacopoeia (commonly known as officinal formulations) to be supplied directly to the patients are exempt from the requirements of Directive 2001/83/EC and Good Manufacturing Practices (GMP).

Is should also be emphasised that even when pharmacy preparations exist, these may also not be widely available to patients within the same Member State or across the various Member States of the European Union. 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.

For the reasons above the Agency would propose that pharmacy preparations are not taken into account for the assessment of significant benefit.

Consultation item n04: Introducing the reassessment of the orphan criteria for a new subset of the condition when a sponsor extends the use of its product after marketing authorisation

The Agency is committed to the principle of the Orphan Regulation that only products that meet the orphan designation criteria should enjoy the incentives conferred by the Orphan legislation.

The maintenance of the orphan designation criteria is confirmed before granting of the marketing authorisation in order to allow the application of further incentives such as market exclusivity. This assessment is also performed with each extension of indication for an orphan designated product that holds a subsequent new orphan designation for a different condition.

On the basis of the experience acquired by the Agency, we believe that a forma! review of the orphan criteria every time a Marketing Authorisation Holder extends the therapeutic indication for an authorised orphan product within the same orphan condition may discourage development in the area of rare diseases. This would add an additional hurdle to maintain the orphan incentive in a situation where, since the granting of the first marketing authorisation, market exclusivity already exists.

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 in a particular orphan condition and therefore extending the benefit to other groups of patients affected by the same rare disease, which is the objective of the Orphan Regulation.

Alternatively, companies may delay the submission of the application for extension of indication until sufficient data has been generated to justify the significant benefit in the new indication. This would imply a delay in the access of patients to medication which is critical in this area of great unmet medical need, for which the orphan criteria had already been confirmed.

Submission as a separate Marketing Authorisation application for indications that fail to demonstrate significant benefit is a valid possibility from a regulatory point of view. This however may bring

European Medicines Agency comments on the Public consultation paper - Notice from the Commission on aspects of the application of Article 3, 5 and 7 of Regulation (EC) N 141/2000 on orphan medicinal products EMA/50964/2016 Page 2/3

additional regulatory burden on companies to maintain separate Marketing Authorisations for products which would nevertheless be intended for a small number of patients. It is noteworthy mentioning that a new indication falling within the same orphan condition will not be rewarded with new periods of market exclusivity but rather benefit from the remaining period of market exclusivity that was previously granted.

Additionally, this proposal may also have an impact on other European initiatives aimed at promoting early access of medicines for a small indication with subsequent expansion of the therapeutic indication, such as the Adaptive Pathways.

In conclusion, the Agency considers that the introduction of such requirement would not support innovation in the area of orphan diseases and timely availability of medicines.

European Medicines Agency comments on the Pubiic consultation paper - Notice from the Commission on aspects of the application of Article 3, 5 and 7 of Regulation (EC) N 141/2000 on orphan medicinal products EMA/50964/2016 Page 3/3