Regulatory Update Panel An overview of all Health Canada policies supporting access to Drugs for Rare Diseases, including regulatory pathways and support for innovation, patient engagement, Special Access Programs, aligned HC/CADTH/INESSS, international harmonization, post-market monitoring, support for patient registries, current status and relevance of biosimilars for rare disease patients Rare Disease Day Conference 2020 March 9-10

1. Health Canada’s Regulatory Initiatives
Canadian Organization for Rare Disorders Conference
March 2020

2. Health Canada as the regulator of health products
• Under the Food and Drugs Act,
Health Canada regulates,
evaluates and monitors the
safety, efficacy, and quality of
therapeutic products
– ~14 000 drugs, 36 000 medical
devices
• Includes oversight at all stages
of a product’s life cycle, from
early testing in clinical trials, to
post-market surveillance of
adverse drug reactions, and
compliance monitoring
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3. Clinical trial regulation
• Clinical trials may be conducted either by drug manufacturers, or by independent medical
researchers
• If clinical trials are to be conducted in Canada, a clinical trial application must be made to
Health Canada
• Trials are reviewed quickly as there is a default timeline – if Health Canada does not
object to the application within 30 days, the trial can go ahead
Clinical Trial Applications are not required for:
• Trials that do not involve the sale of a drug (e.g. trials comparing surgical procedures)
• Phase IV trials (for drugs which are already approved in Canada, and used as per their
approved conditions of use)
Trials do not need to be conducted in Canada for a drug to be approved in Canada
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4. Drug Submission Review
• In order to market a drug in Canada, a submission must be filed to Health Canada
• Manufacturers must provide sufficient evidence of the product's safety, effectiveness and
quality for assessment, including
– Manufacturing details and controls to ensure consistent quality
– Pre-clinical data (animal and cell studies) to support safety
– Clinical data to support proposed indication, including “substantial evidence of effectiveness”
– Proposed labels – claims, instructions for use
– Assessment of possibility for name confusion
• Health Canada then reviews the evidence and decides whether the benefits of the
product outweigh the risks, and whether the risks can be managed
• Health Canada continues to receive supplementary submissions after first approval
granted, for any significant change, including:
– New indications
– Manufacturing changes
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5. Regulatory Pathways to Drug Authorizations
New Drug Submission/Supplementary New Drug Submission – review for
safety, quality efficacy
• Target review time – 300 days [similar review for generics = 180 days]
Priority review policy
• Unmet medical need, serious, life-threatening or severely debilitating disease
• Requirement for “substantial” evidence of effectiveness
• Target review time – 180 days
Notice of Compliance with Conditions policy
• Unmet medical need, serious, life-threatening or severely debilitating disease
• “Promising” evidence of effectiveness
• Target review time – 200 days
• Manufacturer agrees to conduct confirmatory studies
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6. Exceptional Pathways to Drug Access
Special Access Program (SAP)
• Access to drugs which are not authorized in Canada, for the treatment of
serious or life-threatening conditions when other treatments have failed, are
unsuitable or unavailable
• Initiated by prescriber for individual patients
• Approximately 150 drugs for rare diseases are accessed via SAP
• https://www.canada.ca/en/health-canada/services/drugs-health-
products/special-access/drugs.html
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7. Drugs for Rare Diseases – Canadian Approvals
• US FDA and the European Medicines Agency have specific programmes to
incentivize the development or submission of orphan drugs, while Canada does
not.
• However, these products are still coming to Canada:
– In 2019, 20 of the 59 new drug submissions approved in Canada were drugs for rare
diseases
– Research published by the Patented Medicines Prices Review Board showed that
Canada has approved 9 out of the top 10 selling orphan drugs
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8. Using flexible regulatory tools to support access
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9. Getting products to patients is a long and complex
process
Drug development, Clinical trials
(years)
INDUSTRY
Regulatory review
(~1 year)
HEALTH CANADA
Health Technology Assessment/ Funding
recommendations
(6-9 months)
CADTH, INESSS and others
Provincial purchasing review and price negotiations
(2-12+ months)
DRUG PLANS and others
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10. Health Canada’s Plan for Transformation
• Objective: An agile regulatory system that supports better access to therapeutic products
based on healthcare system needs
Expanded collaboration with
health partners
• Alignment of the Health
Technology Assessment
(CADTH) Review with Health
Canada Review
• Implementing a Mechanism
for Early Parallel Scientific
Advice
• Use of Foreign
Reviews/Decisions
• International Collaboration
and Work Sharing in
Reviews
More timely access to drugs and
devices
• Expansion of Priority Review
Pathways
• Improving Access to Biosimilars
and Biologics
• Improving Access to Generic
Drugs
• Building Better Access to Digital
Health Technologies
• Pre-Submission Scientific Advice
for Medical Devices
• Special Access Program (SAP)
Renewal
Enhanced Use of real world
evidence
• Leveraging Data for Assessing
Drug Safety and Effectiveness
• Strengthening the use of real
world evidence and regulations
for medical devices
Modern and flexible operations
Common Submission Intake
Appropriate cost recovery framework
Public Release of Clinical Information
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11. R2D2 updates and next steps
Building international partnerships to increase alignment and bring critical
drugs to patients sooner
• ACSS consortium – (as of February) shared review of 3 new drugs completed,
4 more ongoing, others in planning stages
• Project Orbis – parallel review of oncology drugs with the US FDA
• EMA partnerships – participation in expert committees and cluster meetings to
share expertise
Working with domestic health system partners to speed up access to drugs
and devices
• Aligned reviews with CADTH and INESSS – process implemented since 2018,
evaluation of first 18 months of full implementation ongoing
• Early parallel scientific advice pilot launched in March 2019 – supporting drug
development plans that will meet regulatory and HTA needs – two early advice
processes completed, more being planned, processes to be finalized after initial
trials
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12. R2D2 updates and next steps (cont’d)
Building significant new review capacity in key scientific areas
• Additional scientific staff hired and trained to ensure ongoing technical capacity
Modernizing review processes to meet healthcare system needs
• Completed consultations on expanded priority review policy
• Completed consultations on draft revised regulations supporting Special Access
Program
Developing ways to better use information from real world use to assess and
monitor drug and device safety and effectiveness
• Working with health system partners to optimize the use of information
gathered from variety of sources throughout the product life cycle
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13. Australia, Canada, Singapore, Switzerland
(ACSS) Consortium
• A cooperation of medium-sized regulatory authorities facing similar challenges focused on
concrete information and work sharing initiatives
─ 4 sub-groups focusing on new active substances, generics, complementary health products, and IT
architecture
• Goal of maximising international cooperation, reducing duplication, and increasing the capacity
of regulatory authorities to ensure consumers have timely access to high quality, safe and
effective therapeutic products
• Recent results (New Active Substance Working Group; Australia – Canada worksharing):
─ ERLEADA (apalutamide) - treatment of prostate cancer – NOC July 3, 2018
─ VERZENIO (abemaciclib) - treatment of metastatic breast cancer – NOC April 05, 2019
─ ZEJULA (niraparib) - maintenance treatment for ovarian cancer – NOC June 27, 2019
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14. Project ORBIS
• FDA Oncology Center of Excellence (OCE) initiative that allows for the concurrent submission
and review of oncology drugs between international partners
• Enables regulatory agencies to share information, expertise and analysis, to allow for the more
effective review of submissions and identification of any regulatory divergence across
jurisdictions
─ Concurrent submissions are filed in each jurisdiction
─ Each jurisdiction reviews the applications independently, but shares data, questions, and conclusions
─ Each jurisdiction comes to a decision independently and is responsible for the development of its own
drug labelling (approaches may differ across jurisdictions)
• Results to date:
─ LENVIMA (lenvatinib) in combination with KEYTRUDA (pembrolizumab) - treatment of certain
advanced endometrial carcinomas – NOC September 20, 2019
─ CALQUENCE (acalabrutinib) – treatment of adult chronic lymphocytic leukemia – NOC November 28,
2019
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15. More action required to adapt to changing health context
Data
Data-generating and data-
reliant systems for all
aspects of health
Information and resources
to manage individual care
Citizen Agency
Individualization of systems
and services
Precision &
Personalization
Product
Complexity
Innovations that blur
product lines and defy
standard classification
Local, connected, and
accountable manufacturing
and supply chains
Production &
Distribution
New technologies, R&D
practices, and trial designs
challenge review processes
Evidentiary
Standards
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16. Regulatory Innovation Agenda for Health Products
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To have better,
safer, and more
trials in Canada
To ensure a
flexible
approach for
innovative
products that
do not fit within
the current
system
To make sure
regulations
align with the
nature and
lifecycle of
health products
To make sure
there is
appropriate
oversight while
enabling
innovation
To be the user-
friendly
authoritative
source for
information
Modernized
clinical trials for
drugs and
devices
A better way of
communicating
with Canadians
A pathway for
Advanced
Therapeutic
Products
Agile licensing
for drugs
Modernized
medical device
oversight

17. Patient involvement
• Including the patient voice in expert panels – e.g., scientific advisory committee
on health products for women
• Direct patient/consumer adverse drug event and medical device incident
reporting
• Patient-reported outcomes as part of clinical trials and drug submissions
• International collaborations and best practices
– Participation in ongoing collaboration between major regulators on how to engage
with patients
– Contributing to development of international guidance (CIOMS) on best practices
• Consultations on policies and regulations - Register here:
https://www.canada.ca/en/health-canada/corporate/about-health-canada/public-
engagement/stakeholder-registry.html
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18. Providing information for Canadians
Submissions under review lists- what’s currently under review
https://www.canada.ca/en/health-canada/services/drug-health-product-review-approval/submissions-under-
review.html
Summary basis of decisions and regulatory decision summaries – what was the basis for a
drug approval or rejection?
https://hpr-rps.hres.ca/reg-content/summary-basis-decision.php
Drug product database – product monographs
https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-
database.html
Annual highlights report – overview of activities and new products approved
https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/drug-medical-device-
highlights-2018.html
Public release of clinical information – clinical trial data received in drug submissions
https://clinical-information.canada.ca/search/ci-rc
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19. THANK YOU/ MERCI
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