Expert Patient Advocates & 21st Century Therapies Forum Nov 19 - 20, 2015

1. The
Orphan
Drug
Framework
for
Canadians

2. What is an orphan drug used for?
Orphan drugs are used to treat rare diseases which:
• are life-threatening, seriously debilitating or both serious and chronic in nature
• affect a relatively small number of patients (less than 5 in 10 000, but typically
closer to 1 in 100 000)
• are often genetically based, onset at birth or early childhood, lead to a
shortened life-span
• reduce quality of life and place a heavy burden on caregivers and the
healthcare system
• are difficult to study because of the small patient population
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3. Objectives of the Orphan Drug Framework
• channel orphan drugs into a federal regulatory pathway designed to improve
market availability in Canada
• draw on new post-market and transparency powers from Vanessa’s Law
• reflect Canada’s legislative and regulatory context, while aligning where
possible with other international regulators’ orphan drug frameworks
• encourage the generation of knowledge regarding rare diseases in drug
development through an open and transparent regulatory environment and the
provision of advice to companies developing orphan drugs
• allow for accelerated market authorization
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4. Key Components of the Framework
Orphan drug designation certificate
• The designation process will:
– publicly identify medically plausible drugs for rare diseases (orphan drugs)
– enable early consideration of medically plausible drugs by payers for purposes of
improving patient access
• Alerting the health care system that the drug is promising
• Allowing early consideration of evidentiary needs for the system and transmission of them to
drug developers (federal – clinical trial and market authorization requirements; provincial –
reimbursement)
– align with key international pathways and have a special pathway for drugs that have
already received designation for the same indication from the United States Food
and Drug Administration (US FDA) or the European Medicines Agency (EMA)
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5. Key Components of the Framework
Regulator’s Advice
• Drugs with orphan designation will be eligible for formal, written regulator’s advice for
clinical trials, the potential balance of pre- and post-market evidence requirements, and
the development of post-market plans
• Health Canada will facilitate joint advice where possible and requested by sponsors
– with international regulators
– with Canadian health technology assessment (HTA) bodies
Market Authorization Applications
The market authorization application process promote an abbreviated pathway for
drugs for ultra-rare diseases that are already approved by the US FDA or EMA under
existing framework for use of foreign reviews:
– A disease is considered ultra-rare if it affects not more than 5 in 100,000 persons in Canada
– Abbreviated data requirements for market authorization applications for these drugs
– Health Canada’s review of drugs for ultra-rare diseases will be based on the regulatory decisions
made by the US FDA or EMA in their reviews
– Aims to encourage manufacturers to submit applications for drugs and improve the availability of
drugs for patients suffering from extremely rare diseases
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6. Key Components of the Framework
Post-authorisation market plans
• application will include a post-authorization plan to:
Ø characterize, monitor and continue to identify and assess the harms and benefits associated with
the orphan drug, and
Ø manage the uncertainties relating to those harms and benefits
• Includes: enhanced post-market surveillance procedures, regular
monitoring of the terms and conditions associated with market
authorization, risk management plan, confirmatory studies, etc.
• Timelines for fulfilling the measures, reporting on progress and submitting
results to Health Canada
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7. Key Components of the Framework
Transparency
• Transparency throughout the life-cycle of the drug:
– at designation: screened-in application for a named disease and anticipated
therapeutic benefit; name of company and drug upon issuance of designation
– at market authorization: screened -in application of named drug from named sponsor
for named indication; at issuance, additional details including summary of post-
market plan and any terms and conditions imposed on the market authorization
– post-market: transparency at key points, such as amendments to the market
authorization, post-market plan, and terms and conditions
– positive and negative regulatory decisions and the reasons for them, including:
issuance and refusal of a certificate of designation, issuance and refusal of a market
authorization, reassessment, suspension or revocation of a market authorization
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8. Patient Involvement
• The Orphan Drug framework seek public input into the review of
submissions for orphan drugs.
• In December 2013, Health Canada endorsed a patient
involvement pilot project:
– What it is:
• A simulation of how patients, caregivers, health care professionals and patient
groups could be involved at the anticipated market authorization stage for orphan
drugs
• Allow Health Canada to manage expectations and gauge stakeholder (patients,
caregivers, patient groups, health care professionals, drug sponsors) and
reviewer satisfaction with the pilot project and make adjustments as necessary
• Help minimize the risk of errors and contribute to the Department’s readiness to
use patient involvement information

9. Patient Involvement Pilot Project
• A simulation of how patients will be involved at the market authorization
stage
• Two sponsors/drugs (one pharmaceutical and one biologic)
• Surveys posted on Health Canada’s consultation website (access
limited to pilot participants)
• Recruited patients, caregivers, health care professionals and patient
groups through Canadian Organization for Rare Disorders (CORD) and
other disease specific patient groups.

10. Life-cycle Approach
What is known about the potential/actual benefits, harms and
uncertainties associated with a drug changes over time
Current:
Limited point-in-time oversight based on applications for clinical trials and
marketing authorizations.
Future:
Expanded and continuous oversight beginning at early development stage
with medical plausibility and encompassing a greater ability to define post-
approval information gathering.
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11. The Orphan Drug Life-Cycle
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12. Vanessa’s Law
• Vanessa’s Law amends the Food and Drugs Act improving Health Canada’s
ability to:
– collect post-market safety information
– take appropriate action when a serious risk to health is identified
• These amendments are particularly important in the rare disease context
where often times:
– many of the patients impacted are vulnerable paediatric populations
– information on the drug and the disease is sometimes limited
• Powers that will be incorporated into the Orphan Drug Framework
– Terms and conditions on a market authorization
– Transparency including making positive and negative regulatory decisions publicly available
• Opportunities for structured patient involvement
– Reassessment
– Mandatory label changes
– Mandatory notification of foreign risk information
– Tests and studies
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13. Next Steps
• Briefings to Minister’s Office on project
• A Guidance Document on new framework has been completed
• Timelines for consultations not yet confirmed
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14. Thank You/Merci!
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