The Orphan Drug Act and the Development of Stem Cell-based Products for Rare Diseases

19th November 2015 (Last Updated September 14th, 2018 14:54)

Dr. Volker Scherhammer, VS LifeScience Consulting, provides insight into rare disease clinical trials, from a regulatory perspective

The Orphan Drug Act and the Development of Stem Cell-based Products for Rare Diseases

About 30 million people living in the European Union (EU) suffer from a rare disease. Rare diseases are defined as life-threatening or chronically debilitating conditions that affect no more than 5 in 10,000 people in EU. This is equivalent to around 250,000 people or less for each disease.

Sponsors of designated orphan medicines are eligible to benefit from the incentives offered, including:

  • Assistance with development of the medicine;
  • Reduced fees for marketing-authorization applications;
  • Protection from market competition once the medicine is authorized

Rare Diseases at a Glance

  • Rare diseases are life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the EU. Most of these people suffer from diseases affecting less than 1 in 100,000 people.
  • Between 5,000 and 8,000 distinct rare diseases exist, affecting between 6 percent and 8 percent of the population in total - in other words, between around 27 million and 36 million people in the EU.
  • On average, five new diseases are described every week in the medical literature.
  • Symptoms of some rare diseases may appear at birth or in childhood, including spinal muscular atrophy, lysosomal storage disorders, patent ductus arteriosus (PDA), familial adenomatous polyposis (FAP) and cystic fibrosis. More than half of rare diseases appear during adulthood, such as renal-cell carcinoma, glioma and acute myeloid leukaemia.
  • 80% of rare diseases have identified genetic origins, and affect between 3 percent and 4 percent of births. Other rare diseases are due to degenerative and proliferative causes.
  • Medical and scientific knowledge about rare diseases is lacking. The number of scientific publications about rare diseases continues to increase, particularly those identifying new syndromes. However, fewer than 1,000 diseases benefit from even minimal amounts of scientific knowledge. These tend to be the rare diseases that occur most frequently.
  • The EU's Seventh Framework Program for Research and Technological Development (FP7), which is running between 2007 and 2013, will boost research into rare diseases. Its first phase is focusing on innovative and multidisciplinary projects investigating non-infectious, non-cancer rare diseases. The knowledge will provide the basis for future development of new approaches to diagnose, treat and prevent rare diseases.

Application Procedure

Pre-submission Meeting

The EMA strongly encourages sponsors/companies to request a pre-submission meeting prior to filing an application for orphan medicinal product designation. Pre-submission meetings for orphan designation are free of charge and are held mostly via teleconference, unless the sponsor/company has a strong preference to come to the Agency in person. Follow-up teleconferences are also possible.

Sponsors will be invited to take minutes of the meeting, which should be provided to the EMA within two weeks after the meeting.

The Agency will subsequently review the minutes within 2 weeks, and agree the final (amended) minutes with the applicant (sponsor).

Appointment of Coordinators

Two coordinators (1 COMP member, 1 EMA scientific administrator) will be appointed for each application. The sponsor will be informed accordingly via e-mail.

Submission

Deadlines for submission of an orphan medicinal product designation application are published on the EMA website.

Validation

  • The EMA secretariat will complete the validation of the application. In the event that the EMA requires additional data, information or clarification to complete its validation, the sponsor will receive a validation issues letter and will be asked to respond within a 3-month time limit. If no response from the sponsor is received within this time frame, the sponsor will be advised to withdraw the application and consider re-submission.
  • Once the validation process is successfully completed, a timetable to start the procedure for the evaluation will be forwarded to the sponsor for information.

Evaluation

During the evaluation phase the EMA coordinator will work very closely with the COMP coordinator and appointed expert(s). The coordinators may gather information from Committee members on the disease state, availability of treatments, research status, etc.

A summary report will be provided based on the application. The summary report will include data reported in the sponsor's application, a critical review, and a conclusion.

Following agreement between the Agency coordinator and the COMP coordinator, the summary report will be circulated to the COMP members for comments. Members of COMP will forward comments to the Agency in accordance with the adopted timetable.

Following the COMP's first discussion the sponsor may be invited to address the list of questions at the next meeting. The list of questions will be forwarded with the draft summary report to the sponsor after the first meeting. The sponsors may be invited to attend an oral explanation at the next COMP meeting.

The oral explanation lasts around 1 hour and includes the COMP discussion with the sponsor. The outcome of the discussion will be communicated to the sponsor immediately after the Committee has reached a conclusion.

Opinion

The COMP opinion, which may be favourable or unfavourable, is, wherever possible, reached by consensus. If a negative outcome of the review of the application appears likely the sponsor may withdraw the application before the COMP adopts the opinion. In such case the sponsor will be informed immediately about the negative trend and advised on a possibility to withdraw the application by submitting a signed letter requesting a withdrawal by the end of the on-going COMP meeting. If a negative opinion is adopted the sponsor receives the COMP negative opinion with the information about the appeal procedure.

Decision

The decision will be adopted by the Commission, within 30 days of its receipt of the COMP opinion and forwarded to the sponsor.

Following the EC decision on the designation a public summary of opinion on orphan designation will be published on the EMA website.

So far no ATMP for rare disease is approved in the EU.

 

Dr. Volker Scherhammer

VS LifeScience Consulting, Munich-Germany

 

Abbreviations

COMP - Committee Orphan Medicinal Products
EC - Ethic committee
EMA - European Medicines Agency
EU - European Union