What is an Orphan Drug?

Orphan drugs are medicinal products that are meant for the prevention, diagnosis, or treatment of rare diseases or orphan diseases. Due to their limited market, very few pharmaceutical companies engage in the research and development for such drugs.

Pharmaceutical companies are generally not interested in developing orphan drugs under normal market conditions. This is because the costs related to the drug development process and marketing costs cannot be retrieved by the anticipated sales of medicines without providing incentives.

What is an Orphan or Rare Disease?

A rare or orphan disease is a condition that affects a relatively small number of people and has different definitions for different regions. In the United States, an orphan disease is a condition that affects not more than 200,000 persons. In the European Union (EU), an indication that affects 1 in 2,000, or a maximum of 250,000 individuals, is termed as an orphan indication. For Japan, an indication is designated as an orphan disease if it affects less than 50,000 people.

Symptoms of some orphan diseases might be observed at birth or during childhood. Some of the rare diseases include spinal muscular atrophy, patent ductus arteriosus (PDA), lysosomal storage disorders, cystic fibrosis, and familial adenomatous polyposis (FAP). Over half of orphan diseases occur during adulthood, for example, glioma, renal-cell carcinoma, and acute myeloid leukemia (AML).

• In the US, the FDA (Food and Drug Administration) is responsible for the authorization of orphan drugs.
• In Europe, the European Medicines Agency (EMA) performs a central role in assisting the development and authorization of medicines for rare diseases. Almost 30 million citizens in the European Union (EU) suffer from an orphan or rare disease.
• In Japan, the Ministry of Health, Labour and Welfare (MHLW) manages the designation of orphan drugs/diseases.

As rare diseases are a global concern, the agencies work closely together on the designation as well as the assessment of orphan medicines.

What is an Orphan Drug Designation?

The Orphan Drug Act (ODA) provides a special status or designation to a drug or biological product for treating a rare or orphan disease at the application of a sponsor. This status is known as orphan drug designation or orphan drug status. In the United States, the orphan drug status is also applicable for medical devices and dietary products.

Orphan drug status gives pharmaceutical companies exploring cures for orphan diseases the exclusive right for manufacturing drug or treatment for a specific condition. Orphan drug designation can be granted for new drugs, and drugs that are already approved and in the market. However, in the case when the drug is already approved, the sponsor must submit a reasonable assumption on how the drug is clinically superior to former drugs or undeveloped drugs.

Orphan Drug Designation in the United States

Granting orphan drug status may enable the sponsor to obtain the following advantages for the development of the product in the United States-

• A 50% tax credit on the cost of clinical trials undertaken in the US.
• Seven years of marketing exclusivity after the marketing approval.
• Some recommendations by the FDA regarding clinical as well as preclinical trials to be completed to register the new drug.
• A fast-track process for the FDA for evaluation of registration files.

Orphan Drug Designation in Europe

In the European Union (EU), applications for orphan drug designation are examined by the EMA's Committee for Orphan Medicinal Products, using the network of specialists that the Committee has built up. The evaluation takes a maximum of three months from validation.

• Sponsors who obtain an orphan designation from EMA getbenefit from protocol assistance and market exclusivity once the medicine is available in the market.
• Fee reductions are also available depending on the status of the sponsor and the type of service needed.

Orphan Drug Designation in Japan

In Japan, drugs & medical devices are designated as orphan drugs or medical devices based on Article 77-2 of the Pharmaceutical Affairs Law. Medicines are designated by the Minister of Health, Labour and Welfare (MHLW) based on the judgment of the PAFSC (Pharmaceutical Affairs & Food Sanitation Council).

After receiving applications for ODD application from the applicants, MHLW may give the orphan designation to drugs or medical devices after assessing the drug against the following points:

• The number of patients.
• Medical requirements.
• Possibility of development.

What is the Orphan Products Development (OOPD) Program?

The Orphan Products Development (OOPD) mission of the FDA is to advance the evaluation as well as the development of products such as drugs, biologics, medical devices, or foods used to diagnosis and/or treatment of orphan or rare diseases.

The program offers incentives for sponsors to develop products for rare diseases. Since 1983, this program has facilitated development and commercialization of over 600 drugs and biologic products for orphan indications.

The OOPD program provides orphan status to medicines and biologics that are described as those meant for the treatment, prevention as well as diagnosis of a rare condition or disease.

In the United States, a sponsor seeking orphan designation for medicine or device must submit an application for designation to OOPD with the information necessary in 21 CFR 316.20 and 316.21.

Sponsors requesting designation of a similar drug for a related rare disease or condition as a previously designated product must submit their information to support their designation request.