Worldwide Orphan Medicinal Designation Workshop: an enlightening experience
A workshop on orphan product designation and grants took place on 10 March 2014 at the European Medicines Agency (EMA). Jointly organised by the EMA, the US Food and Drug Administration (FDA) and for the first time the Japanese Ministry of Health, Labour and Welfare (MHLW) and Pharmaceuticals and Medical Devices Agency (PMDA), this one day workshop was an effort towards bringing more treatments for rare disease patients faster.
This one-of-a-kind workshop brought together the regulatory authorities from three large regions with legislation encouraging orphan medicinal product development: the United States (US), European Union (EU) and Japan. The agencies representing these areas, with contributions from Canada and Australia, have worked jointly over the years to improve the quality and number of orphan designations as well as encourage parallel submission for orphan medicinal designation.
The workshop aimed at enhancing efficiency and avoiding ambiguity between the agencies and sponsors by highlighting 3 areas, the process of granting orphan medicine designation by the FDA, MHLW/PMDA and EMA, the post designation incentive programmes (accessible after receipt of designation) and the grants available through the FDA, European Commission and NIBIO (Japan) intended to boost research and development in the therapeutic management of rare diseases. Finally the sponsors also had a chance to attend 40 minute face-to-face sessions with the 3 agencies to discuss their individual concerns or comments.
Orphan Designations around the world
Following the explanation of the legal basis for orphan designations in Europe, the centralisation of the designation process and its assessment as well as the review strategy at the time of marketing authorisation (MAA) was clarified by speakers Agnes Mathieu and Stina Aarum. The progress so far on the provision of orphan designations and MAA of the orphan medicinal products (80 until December 2013) along with its distribution in different areas of medicine was also furnished.
The speaker from FDA (RAC) James Reese informed the audience about the orphan designation process as well as New Drug Application (NDA)/ Biological Licensing Application (BLA) approval, delineated by FDA. Also explained was when a drug can be authorised based on scientific rationale alone due to the paucity of human studies and the Final rule - which included amendments to the Orphan Drug Act. The number of orphan drug designations and approvals (33 in 2013) by the FDA were also provided.
Yasuko Inokuma from MHLW recounted the conditions of the Orphan Designation System in Japan. The criteria required by a product to be designated as an orphan product was explained in detail along with the importance of the preparing for consultation of the application to obtain the designation. The intricate relationship between the sponsor, MHLW and the PMDA and PAFSC was elucidated.
Orphan Designations incentives and grants around the world
During this session highlighting the framework of grants provided in the 3 regions, the role and goal of IRDiRC – working towards 200 therapies and means to diagnose most by 2020 - was expounded. Irene Norstedt presented EU policies towards sharing and collaborative research, establishing standards in research as well as participation by patients and/ or representatives in research and the efforts taken towards fulfilling these. A description of some of the current projects, earmarked funding, and future funding opportunities was furnished.
Erica McNeilly, presented the grants programs in Office of Orphan Product Development (OOPD), which includes the Pediatric Device Consortia Grant Program and OPD Clinical Research Grants (R01) for Orphan Diseases. Along with the grant application and review process, data on the number of applications and grants bestowed each year was provided. Information on other federally funded, patient advocacy group funded and grants provided by IRDiRC members were described.
In Japan the funding body is the National Institute of Biomedical Innovation (NIBIO) who, according to Hirofumi Kusunoki, provide grants after a product is granted an orphan drug designation. Only Japanese companies are eligible to apply for this grant which is for a maximum of 3 years and contributes half of the actual costs required to develop the drug.
Incentives and regulatory considerations
The incentives and regulatory considerations given after a product receives an orphan designation in EU are spread over several pieces of legislation. The presenter Segundo Mariz detailed the incentives covered in Europe, which include support for product development, small to medium enterprises, licensing and post licensing (10 year market exclusivity + 2 year market exclusivity with endorsed Paediatric Investigation Plan) along with specific regulatory considerations for biosimilar orphan medicines. Exclusive to sponsors applying in the EU is the availability of scientific advice and protocol assistance.
FDA incentives include access to the Orphan Products Grants Program, tax credits, fee waivers and market exclusivity. Additionally, John Milto from FDA described auxiliary incentives that can be obtained through the Rare Pediatric Disease Priority Review Voucher and Breakthrough Designation.
The means to obtain five major incentives for development of orphan drugs in Japan was demonstrated by Hiroshi Takeda from PMDA. These include subsidy payment, guidance and development, preferential tax treatment, priority review and extension of re-examination period.
Overall, this workshop was an illuminating experience to all rare disease stakeholders that attended, which will greatly benefit in the future from the insights provided by the various speakers from the agencies of the three large regions. The slides of each presentation of this workshop will be shortly available on the EMA website.
Read the Workshop Agenda
Further information on the workshop
Due to the availability of low-cost genome sequencing, the identification of the molecular cause of hundreds of rare genetic disorders can be an achievable goal. However, the discovery of disease-causing variants requires confirmation of the mutation in multiple unrelated individuals. Additionally, an even larger number of genetic disorders remain unsolved due to the difficulty of identifying second families. It is therefore critical to establish effective and secure data-sharing techniques that allow clinicians and scientists to identify additional families via phenotype and genotype searches. 
The prestigious Eva Luise Köhler Research Prize for Rare Diseases has been granted this year to Prof. Dr. Dr. hc mult. Niels Birbaumer of the Institute of Medical Psychology and Behavioral Neurobiology , University of Tübingen for his groundbreaking work on "Combined brain-machine interface for communication in amyotrophic lateral sclerosis brain”. This award was presented to Prof. Birbaumer by Eva Luise Köhler on 13 March, 2014 in the presence of her husband, Prof. Dr. Horst Köhler and the Health Minister Hermann Gröhe. 
China’s Food and Drug Administration (CFDA) has acted to impose regulatory constraints on the provision of clinical genetic tests. The announcement appeared vague as although the ban on prenatal DNA testing is unambiguously stated, it is not known whether the ban would apply to other kinds of testing as well (for e.g. screening/testing for cancer). In effort to uphold the ban, CFDA has also prohibited the continuance of all current projects except those approved by the government relating to clinical genetic testing. They will now require all related medical devices to be licensed by the government “before they can be manufactured, imported, sold or used, potentially covering the world’s most popular gene-sequencing equipment, made by San Diego-based Illumina, Inc”. There is also an overwhelming possibility that this move could significantly restrict the efforts of the Chinese genome sequencing giant 
A press release from the newly formed 
A paper published in Procedia - Social and Behavioral Sciences describes selected results of an extensive study monitoring the quality of life of caregivers of a child with a rare disease. The authors evaluated questionnaires from parents of children with the following diseases: cystic fibrosis (CF), spinal muscular atrophy (SMA), mucopolysaccharidosis (MPS), group of metabolic disorders (MP) and achondroplasis (ACH), confirming that most monitored areas deteriorated during the care. The showed that the socio-economic status of the these caregivers deteriorated considerably and their outlook of the future was fairly grim. This difference was statistically significant between the respondents from the groups: caregivers who care for a family member with a rare disease and persons who care for a child without disability or disease - the control group - were confirmed. The authors recommend that considering the immense financial and social strain on these families, it is necessary to focus on better support of caregivers as well. 
