Breaking Barriers: Exploring Rare Diseases and Orphan Drug Regulations in Canada

Rare diseases, often referred to as orphan diseases, affect a small percentage of the population. Despite their rarity, these conditions collectively impact millions of lives. In Canada, as in many other countries, the regulation and development of treatments for rare diseases present unique challenges and opportunities.

What are Rare Diseases?

A rare disease is defined as a condition that affects a small number of individuals within a given population. In Canada, a disease is considered rare if it affects fewer than 1 in 2,000 people. Estimates of the number of people living in Canada with a rare disease vary widely; There are over 7,000 known rare diseases according to the National Institutes of Health (NIH), and they can be chronic, debilitating, and life-threatening. Examples include cystic fibrosis, CNS drugs for Huntington’s disease, and certain types of neurodevelopmental disorders and muscular dystrophy.

The Challenge of Rare Diseases

The primary challenge with rare diseases is their low prevalence, which often translates to limited knowledge and research. Patients frequently face long diagnostic journeys, misdiagnoses, and a lack of effective rare diseases drugs. The economic incentives for pharmaceutical companies to invest in the development of drugs for such small patient populations are limited, leading to a scarcity of available therapies.

What are Orphan Drugs?

Orphan drugs are medicinal products intended for the diagnosis, prevention, or treatment of rare diseases drugs. As a result of a small market, these drugs are often not profitable without government incentives. This is where orphan drug regulations come into play, providing support to encourage the development and commercialization of these essential therapies.

Orphan Drug Regulation in Canada

In Canada, the regulatory landscape for orphan drugs has been evolving. The Canadian government, through Health Canada, has been working to create a more supportive environment for the development of orphan drugs ensuring better health outcomes and access to cutting-edge treatment options for those living with rare diseases.

To bring a drug to market in Canada, especially those targeting rare diseases, the manufacturer must first submit a detailed application to Health Canada. This submission includes comprehensive information on the drug’s intended use, as well as extensive data on its safety, efficacy, and dose proportionality to ensure it works across different patient groups. 

Health Canada then thoroughly reviews this information. If the assessment concludes that the benefits of the drug outweigh its potential risks, Health Canada grants authorization for the drug to be sold. This rigorous process ensures that orphan drugs meet high standards of safety and effectiveness before reaching patients.

Existing tools for drug sponsors which can also be applicable to orphan drugs

When filing submissions for a drug for a rare disease, some of these resources can be applied as indicated in Health Canada website:

Advice on Clinical Trials

Canada’s regulatory framework for orphan drugs seeks to improve access to treatments for rare diseases. While Canada lacks a specific orphan drug designation like those in the U.S. or Europe, Health Canada offers guidance and support to pharmaceutical companies working on these treatments. Sponsors are encouraged to seek regulatory advice from Health Canada before submitting their applications, with recommendations tailored to the drug’s stage of development. Requests for advice should be directed to the relevant Bureau or Centre Director, as listed on the Pre-Clinical Trial Application Consultation Meeting website. View our Regulatory Inspection History here.

Accelerated Review Pathways

Priority Review: Health Canada offers priority review status to drugs intended for serious, life-threatening conditions, including rare diseases. This can significantly shorten the review process, bringing essential therapies to patients more quickly.

Data and Patent Protection, including 6-Month Pediatric Data Extension

In Canada, data protection grants 8 years of market exclusivity for drugs that qualify as “innovative.”

An additional 6-month pediatric extension to this 8-year exclusivity period is available if certain criteria are met. Pediatric clinical studies must either be:

• Submitted with the innovator’s New Drug Submission, or
• Included in a supplement filed within 5 years of the issuance of the Notice of Compliance (NOC) for the New Drug Submission.

The Minister must determine that the clinical trials were designed and conducted to enhance knowledge of the drug’s use in pediatric populations including the effectiveness of topical drugs, and that this knowledge offers a health benefit to those populations. 

Innovators may apply to have patents listed on Health Canada’s Patent Register for approved drugs. These patents are assessed to ensure they meet the regulatory criteria for listing. The Patented Medicines (Notice of Compliance) Regulations ensure that a Notice of Compliance is not issued for a subsequent entry drug (generic or biosimilar) until the patents listed on the Patent Register have been addressed. To qualify for a Certificate of Supplementary Protection (CSP) , the drug must meet criteria including “first authorization” and “timely filing.” CSPs provide up to 2 additional years of protection for patented drugs.

Access to Certain Drugs through the Special Access Programme (SAP)

The SAP allows manufacturers to sell drugs that are otherwise not approved for sale or distribution in Canada. When conventional treatments have failed, are unsuitable, or unavailable, health care providers treating patients with serious or life-threatening conditions can request access to these rare disease drugs through the SAP. This program covers a range of products, including pharmaceutical, biologic, and radiopharmaceutical drugs

Fee Mitigation Options

In some cases, fee payers may qualify for fee mitigation or deferral to lessen the financial burden of paying the required fees. Fees can be deferred for one to two years if the company has not yet completed its first full fiscal or calendar year of operations. Additionally, fees may be capped at a percentage of the product’s sales.  As of April 2019, Health Canada proposed new fee mitigation measures designed to assist small businesses.

Guidance on the Use of Foreign Reviews and Third-Party Data

• Use of Foreign Reviews
  In certain cases, Health Canada may consider using information from foreign regulatory counterparts to inform its review process. However, all health products must still meet Health Canada’s regulations and standards to be authorized for sale in Canada.
• Use of Third-Party Data
  Submissions that rely on third-party data are classified as New Drug Submissions (NDSs) and Supplements to New Drug Submissions (SNDSs) that primarily depend on literature and market experience for support.

The Canada Revenue Agency’s Tax Incentives for Research and Development in Canada

Incentives for orphan drug development in Canada include fee waivers, tax credits, and grants. These measures are intended to reduce the significant costs of research and development, encouraging companies to invest in the creation of orphan drugs.

The Canada Revenue Agency (CRA) manages the Scientific Research and Experimental Development (SR&ED) Tax Incentive Program, the largest source of federal support for R&D in Canada. The SR&ED program offers cash refunds and/or tax credits for eligible R&D work conducted in Canada, contributing approximately $4 billion annually to companies of all sizes. This permanent program includes key features such as:

• Refundable tax credits
• R&D expenditures that can be carried forward indefinitely
• Coverage for salaries, materials, contracts, and incremental overhead
• Tax-deductible capital equipment for R&D
• Tax incentives for research performed in Canada and funded by non-residents

Other Federal Government Department Incentives

In Canada, there are additional incentives for developing new treatments for rare diseases which are accessible through various programs based on:

• • The nature of the product
  • The stage of research in the drug development process

The Government of Canada invests in key research and development initiatives through several departments and programs, including Genome Canada and the Canadian Institutes of Health Research (CIHR). Small and medium-sized enterprises (SMEs) can also receive guidance from the National Research Council’s Concierge service, with further industry support available from Innovation, Science and Economic Development Canada.

Advancing Therapies

CIHR plays a critical role in advancing research on rare diseases and leads important international research efforts, such as the International Rare Disease Research Consortium (IRDiRC). This consortium, which includes over 40 organizations from 17 countries, aims to accelerate medical breakthroughs for individuals affected by rare diseases. By 2016, it had contributed to the development of therapies for 222 rare diseases. The consortium’s new goal is to deliver 1,000 new therapies over the next decade.

Advancing Diagnostics

CIHR and Genome Canada also support the Care for Rare project, which leverages new gene sequencing technologies to identify the genes responsible for many rare diseases. This project advances genomic research and supports the development of personalized medicine—treatments tailored to patients based on their unique genetic makeup. To date, the project has recruited over 4,000 patients and family members, studied 950 different rare diseases, diagnosed over 1,500 patients, identified 135 novel rare disease genes, and is working on three experimental therapies.

Advancing Collaborative Research

Canada is also involved in E-Rare, the European Union’s primary instrument for funding research related to rare diseases. This initiative fosters international collaboration among scientists on interdisciplinary research projects with a strong translational approach. The European Research Area Network (ERA-Net) “E-Rare” has entered its third phase, “E-Rare-3” (2014-2019), which further coordinates research efforts and implements the objectives of IRDiRC. CIHR has been a member of E-Rare-3, supporting 25 projects since 2012 through five Joint Transnational Calls.

Advancing Resource Hubs

Canada is an active participant in Orphanet, an online resource providing specialized information for people with rare diseases and healthcare providers. Orphanet collects data from around the world on:

• Biobanks
• Registries
• Researchers
• Clinical trials
• Expert centers
• Specialized clinics
• Medical laboratories
• Patient organizations

Patient Involvement

Patient advocacy groups play a crucial role in shaping orphan drug policies in different countries around the world These groups work closely with regulatory agencies, providing valuable input on the needs and challenges faced by patients with rare diseases. Their involvement ensures that the patient perspective is considered in policy development and drug approval processes.

Recent Developments and Future Directions

Canada has made significant strides in improving the regulatory environment for orphan drugs, but there is still work to be done. Recent initiatives include increased funding for rare disease research and efforts to streamline the regulatory process further.

Looking ahead, continued collaboration between the government, pharmaceutical companies, healthcare providers, and patient advocacy groups will be essential. By working together, these stakeholders can ensure that patients with rare diseases have timely access to the treatments they need.

Rare diseases present a unique set of challenges, but with a robust regulatory framework and continued support for orphan drug development, Canada is making progress in addressing the needs of this underserved population. The journey is ongoing, and sustained efforts are required to ensure that all patients, regardless of the rarity of their condition, have access to effective and life-changing treatments. By fostering innovation, encouraging collaboration, and putting patients at the center of policy-making, Canada is paving the way for a brighter future for those living with rare diseases.

Written By:

Negar Gharavi

Senior Director, Medical Writing & Regulatory Affairs

BioPharma Services, Inc., a HEALWELL AI and clinical trial services company, is a full-service Contract Clinical Research Organization (CRO) based in Toronto, Canada, specializing in Phase 1 clinical trials 1/2a, Human Abuse Liability(HAL) and Bioequivalence clinical trials for international pharmaceutical companies worldwide. BioPharma Services conducts clinical research operations from its Canadian facility, with access to healthy volunteers and special populations.