Written by Ezra de Leon

Orphan drugs are drugs that treat rare diseases that are life-threatening, seriously debilitating, or cause serious and chronic conditions that affects only a relatively small number of patients.

Rare or ‘orphan’ diseases in Canada are those which affect less than 5 in 10, 000 people. About 6,000 to 8,000 rare diseases have been identified worldwide. Most (~80%) are genetic disorders and the remainder are from either viral or bacterial infections or are caused by environmental factors.

orphan drugs

A patient with a rare disease target for orphan drugs

Over half begin early in childhood and are degenerative and life-threatening. These diseases are called ‘orphans’ because the number of people affected is so small that research on treatment would not be profitable for the  pharmaceutical industry. The cost of developing an orphan drug is the same as for other pharmaceuticals. This is why incentives were developed to encourage vital and necessary orphan drugs research.

Canada’s Orphan Drug Policy

Canada adopted an Orphan Drug policy on October 3, 2012. This made it the last developed country to adopt an orphan drug policy. In July 2011 the orphan drug Soliris, now available through restricted access, received funding from the pan-Canadian Pharmaceutical Alliance, which negotiates drug prices for all provinces and territories in Canada.

Health Canada will  launch a regulatory framework for orphan drugs soon.

The proposed framework has 6 key features:

  • Designation: The regulations under development will include criteria for orphan drugs and rare diseases. Health Canada will review applications for orphan drugs and decide whether or not a candidate drug can be designated an orphan drug.
  • Clinical trials: Clinical trials for orphan drugs will be carried out under the existing clinical trial framework (Part C, Division 5 of the Food and Drugs Regulations). Clinical trials are also required to be publicly listed on a site such as clinicaltrials.gov.
  • Scientific recommendation: The company that holds an orphan drug designation can request scientific advice from Health Canada for help in designing and implementing clinical trials on orphan drugs.
  • Post-market plan: An application for an orphan drug must include a post-market plan that the manufacturer is obligated to follow. The plan will be customized according to the benefits, harms, and uncertainties with the orphan drug.
  • International collaboration: The proposed framework will be harmonized with existing frameworks in other jurisdictions to ensure ease when collaborating with other systems. In practice this would mean a close alignment with the US and EU regulations.
  • Patient collaboration: Patient input at the designation stage will be required. Patient input will also be requested during the drug review stage, ensuring that information gathered at the designation stage is still applicable. Health Canada plans to model its patient input process on that developed by the Canadian Agency for Drugs and Technologies in Health which allows patients to formally give their views on issues related to the disease.

It is impossible to discuss orphan drugs in Canada without also looking at the US. The 1983 Orphan Drug Act, the first of its kind in the world, defined rare diseases and outlined incentives for research on their treatment. Orphan Drug Designations are assigned to drugs in clinical trials for rare disease indications. Once the drug has received FDA approval it becomes an official Orphan Drug. Since the establishment of the act 511 orphan drugs have been approved by the FDA, out of 3280 Orphan Drug Designations.

Orphan Drugs and other New Drugs

Orphan drug patent holders have the same intellectual property rights as with other drugs. An orphan drug sponsor will receive market exclusivity for a period of 20 years from the filing of the earliest US or international (PCT) application for which priority is claimed but extensions are possible under the Hatch-Waxman Act. Once a patent has lapsed or is rendered invalid in court, generic orphan drugs become possible. In 2010, of the 108 orphan drugs that received an NDA between 1984 and 1989 and were still being marketed, 55 percent were generics. Patent laws in Canada also protect the innovator companies until the patent expires.

Incentives for developing Orphan Drugs

Health Canada has proposed the following incentives to encourage research on orphan drugs: advice on scientific and clinical protocols, priority review, fee reductions for small to medium enterprises, and market exclusivity for 8 years and 6 months – the same period of exclusivity for innovative drugs with pediatric studies. These are based on incentives in the US: 7 years of market exclusivity, tax credits up to 50% of R&D costs, R&D grants, waived NDA/BLA fees, assistance with protocols, and possible clinical trial tax incentives.

Proposed Canadian Orphan Drugs framework

Once the Canadian framework is enacted a sponsor can apply for an orphan drug designation. The sponsor must sign and date the application and must include:

  • The sponsor’s name, address, and telephone number, and the fax number and email address of the sponsor (if applicable) or, in the case of a foreign sponsor, the sponsor’s representative in Canada;
  • Information regarding the company that manufactures the drug if the sponsor does not do so;
  • The proposed indication;
  • The medicinal ingredients that will constitute the drug;
  • Sufficient information showing that the requirements for orphan drugs are met;
  • An explanation of the phase of drug development, including usual indications;
  • A synopsis of the regulatory condition of the drug in Canada and in other countries, as well as current investigational uses, previous authorizations to market the drug, designation for orphan drug status, and any regulatory actions taken.

The format and information for market authorization would be the same as for a New Drug Submission for other drugs. The only additional information required is a copy of the Orphan Drug Designation, information on its designation in other countries (if applicable), and a post-market plan that is customized according to the benefits, harms, and uncertainties associated with the orphan drug candidate and which the sponsor is obligated to follow.

Orphan Drug Designations and Applications in the US

An Orphan Drug Designation application in the US is substantially similar, as the Canadian process is based on it. A rare disease in the US is one that affects less than 200,000 Americans. An orphan application can be filed at anytime during drug development – even before filing of the IND. A sponsor submits two copies of a completed, dated, and signed request for a designation, with the FDA taking roughly 60 days for a decision. Once a designation is received an annual report is required to update the FDA on any progress. FDA Form 3671 can be used to apply for an orphan drug designation. There is no specific form for an orphan drug market authorization application but information similar to an NDA is required, with additions being:

  • A statement that the sponsor requests an orphan drug designation for to a rare disease or condition that is precisely identified;
  • If a sponsor requests that a drug be designated an orphan drug and that drug is meant for a subset of persons with a particular disease or condition that affects more than 200,000 people, a demonstration that, due to the properties of the drug, other people with such a disease or condition would not be suitable users of the drug;
  • Documentation, with included references showing that the disease or medical condition for which the drug  was developed affects less than 200,000 people living in the USA  or, if the drug was intended to be used as a vaccine, for diagnosis, or for the prevention of disease, the target persons in the US to whom the drug will be administered number less than 200,000 per year.

Between 1983 and 2007, orphan-designated drugs had a shorter average review time than non-orphans: 1.6 years versus 2.2 years. It is important to note that US orphan drug manufacturers must satisfy the same GMP requirements as for non-orphan drugs.

Health Canada is expected to introduce the National Orphan Drug Framework soon. Until then, this article reflects all of the currently available information and has outlined the likely requirements.



Radke, James. “Proposed Orphan Drug Framework for Canada.” Rare Disease Report. Rare Disease Report. 15 April 2014. Web. 6 January 2016. http://www.raredr.com/news/Proposed-Orphan-Drug-Framework-Canada

 Sheppard, Catherine. “Health Canada Orphan Drug Policy – A Long Overdue Need.” Ask-Cato.com. Cato Research. 19 November 2012. Web. 6 January 2016.

 Orphanet website Canadian entry point. Orphanet-Canada. 2012. Web. 6 January 2016. http://www.orpha.net/national/CA-EN/index/homepage/

Wong-Reiger, Durhane. “Canada’s long journey toward and Orphan Drug Framework.” Advocate Vol 20, Issue 2. Canadian Organization for Rare Disorders. Summer 2013. Web. 6 January 2016.