Orphan Drugs

The Orphan Drug Designation program of US-FDA provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders.

What is Rare

  • The World Health Organization (W.H.O.) has suggested that a rare disease should be defined as one with frequency less than 6.5 – 10 per 10,000 people
  • Considering the large population of India, ORDI (Organisation for Rare Diseases in India) suggests a disease to be defined as rare if it affects less than 1 in 5,000 people

A rare disease occurs infrequently in a population, but there is no universal definition.

3 elements to the definition as used in various countries are as follows:

1. The total number of people having the disease

2. Its prevalence

3. Non-availability of treatment for the disorder

  • Authorities in different countries or regions use different cut-off values:
    •  WHO defines an incidence of <0.65-1/1000 as ‘Rare’
    •  US defines <2,00,000 (1/1500) patients as ‘Rare’
    •  EU defines <5/10,000 as ‘Rare’
    •  Japan defines <50,000 as ‘Rare’
    •  Australia defines <2000 as ‘Rare

As of 2014, there were 281 marketed orphan drugs and more than 400 orphan-designated drugs in clinical trials. More than 60% of orphan drugs were biologics. The U.S. dominated development of orphan drugs, with more than 300 in clinical trials, followed by Europe.


  • The Orphan Drug Act (ODA) of January 1983, passed in the United States, is meant to encourage pharmaceutical companies to develop drugs for diseases that have a small market
  • The law is designed to facilitate the development and commercialization of drugs to treat rare diseases
  • The salient features of the act are as follows:
    • Incentives to Pharma companies investing in Orphan Drugs R & D
  • Tax Credits-50% of Clinical Investigations Expenses
  • Protocol Assistance in Drug Development Process
  • Grant Support-Medical Foods and Medical Services also
  • Open Protocols to increase drug availability for patients
    • Faster/Priority clearance of Orphan Drugs Application through FDA
    • Market exclusivity for 7 years for Pharma companies to recover costs

Organisation for Rare Diseases India (ORDI)

  • Launched on Feb. 18, 2014
  • Theoretically, 400 US FDA & 80 European Medicines Agency (EMA) approved orphan drugs are available
  • Practically,  most are either not accessible to most patients in India or are unaffordable
  • It is ORDI’s mission to make these and new approved orphan drugs easily accessible and affordable to patients with rare diseases in India
  • Currently, drug developers in India are receiving no formal incentives from the Government and hence are more focused on developing affordable drugs

How to apply for Orphan Drug Designation

A sponsor shall submit two copies of a completed, dated and signed request for designation that contains the following:

  1. A statement that the sponsor requests orphan-drug designation for a rare disease or condition
  2. The name and address of the sponsor; the name of the sponsor’s primary contact person
  3. A description of the rare disease or condition for which the drug is being or will be investigated, the proposed use of the drug, and the reasons why such therapy is needed.
  4. A description of the drug, to include the identity of the active moiety, all relevant data from in vitro laboratory studies, preclinical efficacy studies.
  5. Where the sponsor seeks approval of an already approved orphan-drug, stating an explanation as to why the proposed variation in his drug may be clinically superior to the first drug.
  6. A summary of the regulatory status and marketing history of the drug in the United States and in foreign countries
  7. Documentation, with authoritative references

After Designation Request Is Submitted…

  • Typical review cycle ~ 90 days (often less)
  • Will either receive:

-Designation Letter OR

-Deficiency Letter

  • Once designated, sponsor is required to submit annual reports until drug is approved

Development of Orphan drugs is costlier because:

  • The limitations of medical and scientific knowledge related to the pathogenesis 
  • A limited market 
  • High research and manufacturing costs (50 to 80 per cent of rare diseases are from genetic origin)
  •  Use of high-tech products, genetic therapies, cellular therapies, recombinant proteins 
  • Impossibility of patenting certain ingredients

Financial incentives available to orphan drug developers in India

  • Currently, drug developers in India are receiving no formal incentives from the Government and hence they are more focused on o developing affordable drugs for more common diseases such as oral insulin, statins for preventing or slowing the progression of cardiovascular disease, vaccines and antibiotics for a number of preventable infectious diseases, etc.
  • Hence, patients with rare diseases in India have to rely on imported drugs from western countries which makes these treatments (even when available) unaffordable.
  • Many infectious diseases qualify for incentives to develop orphan drugs in developed countries

    e.g. Two of the top five infectious disease killers in the world, qualify as rare diseases in developed  nations

  •  Tuberculosis: Rifampicin and Rifapentine  
  • Malaria: Halofantrine, Mefloquine, Quinine sulphate

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