Regulation of Biosimilars in Canada

Transcription

1 Regulation of Biosimilars in Canada Session 2: Global Regulatory Trends of Biosimilars GBC 2018 June 28, 2018 Stephanie Hardy Office of Policy and International Collaboration Biologics and Genetic Therapies Directorate Health Products and Food Branch, Health Canada

2 Outline Regulation of biosimilars in Canada Current issues/challenges Workload and increasing review capacity Improving access to biosimilars Regulatory issues Communicating regulatory decision-making Other key Health Canada activities Biologics naming International collaboration 2

3 Regulation of Biosimilars in Canada Biosimilars are biologic drugs that obtain market authorization subsequent to a version previously authorized in Canada, based on demonstrated similarity to a reference biologic drug Biosimilars are regulated as new biologic drugs and are subject to the Canadian Food and Drugs Act and Part C, Division 8 of the Food and Drug Regulations Flexibility under existing legislation allows for the regulation of biosimilars using the concept of similarity Once authorized, biosimilars are considered stand-alone products Guidance document: Information and Submission Requirements for Biosimilar Biologic Drugs communicates regulatory framework and submission requirements

4 Data Requirements: Key Concepts Reference biologic drug (innovator) Sponsor must independently demonstrate the quality, safety and efficacy Biosimilar The weight of evidence for similarity is provided by extensive side-by-side structural and functional studies comparing the biosimilar and the reference Non-clinical and clinical programs address potential areas of residual uncertainty and show that there are no clinically meaningful differences between the biosimilar and the reference biologic drug Step by step approach tailored to individual product A final determination of similarity is based on the entire submission, including data from comparative structural, functional, non-clinical and clinical studies Physicochemical characterization Biological activity Non-clinical Clinical PK/PD Clinical trials Slide provided by Ally Pen 4

5 Biosimilars in Canada (authorized as of June 1, 2018) Biosimilar Reference Biologic Product Type Date of Notice of Drug Compliance Omnitrope (somatropin) Genotropin Hormone April 20, 2009 Remsima (infliximab) Remicade Monoclonal January 15, 2014 Inflectra (infliximab) Remicade Monoclonal January 15, 2014 Basaglar (insulin glargine) Lantus Hormone September 01, 2015 Grastofil (filgrastim) Neupogen Hematopoietic Agent December 07, 2015 Brenzys (etanercept) Enbrel Cytokine August 31, 2016 Erelzi (etanercept) Enbrel Cytokine April 06, 2017 Admelog (insulin lispro) Humalog Hormone November 16, 2017 Renflexis (infliximab) Remicade Monoclonal December 01, 2017 Lapelga (pegfilgrastim) Neulasta Hematopoietic Agent April 05, 2018 Mvasi (bevacizumab) Avastin Monoclonal April 30, 2018 Hadlima (adalimumab) Humira Monoclonal May 08,

6 History of Biosimilars Regulation in Canada Biosimilar Working Group first formed Draft guidance document released Policy statement on pathway for subsequent entry LMWH published Updated guidance document and fact sheet published Summary Basis of Decision template for biosimilars developed Fact sheet published Final guidance published Biosimilar scientific advice meeting pilot launched Product Monograph template for biosimilars published OMNITROPE somatropin INFLECTRA infliximab, REMSIMA infliximab BASAGLAR insulin glargine, GRASTOFIL filgrastim, OMNITROPE (additional indications) BRENZYS entanercept, INFLECTRA, REMSIMA (additional indications) ERELZI entanercept, ADMELOG insulin lispro, RENFLEXIS infliximab LAPELGA pegfilgrastim, MVASI bevacizumab, HADLIMA adalimumab 6

7 Guidance Document: Information and Submission Requirements for Biosimilar Biologic Drugs - Key revisions - From: Extensive non-clinical data requirements Labelling limited information from reference biologic drug product monograph Extrapolation of indications Review experience, stakeholder engagement, and international collaboration played key roles in the revision process To: In vivo study may not be necessary if comparative structural, functional and non-clinical in vitro studies are considered satisfactory Biosimilar product monograph may include relevant safety and efficacy information from the product monograph of the reference biologic drug Change from extrapolation to Authorization of indications and extensive revision to provide clarity on health Canada s approach 7

8 CURRENT ISSUES/CHALLENGES 8

9 Workload and Review Capacity Building BGTD Annual Performance Reports NDS New Drug Submission (for initial authorization) SNDS Supplemental New Drug Submission (post-authorization changes)

10 Improving Access to Biosimilars The number of biosimilar submissions is expected to continue increasing as patents/data protection for leading biologics expire Almost every submission has a pre- submission filing meeting and possibly pre-clinical trial application meetings (scientific and regulatory advice) Increased interactions between regulator and sponsor for many biosimilar submissions new pathway, new companies, and companies new to biologics manufacturing Improving access to biosimilars is one sub-project under Health Canada s Regulatory Review of Drugs and Devices (R2D2) Initiative Focus on building capacity (hiring and training new staff) to meet the demand 10

11 Access as a Priority Research & development Health Canada review / authorization Minister of Health mandate letter (2015) Expectations related to improving access to necessary prescription medications and making them more affordable to Canadians. Minister of Health mandate letter (2017) Reinforced need to improve access and affordabilityhttps://pm.gc.ca/eng/ministerhealth-mandate-letter Health Technology Assessment Patented Medicine Prices Review Board (PMPRB) Hospitals pan-canadian Pharmaceutical Alliance (pcpa) Increased collaborations and information sharing with health care system partners, such as health technology assessment bodies to support improved access Provincial/Territorial Drug Plans Patient Access 11

12 Regulatory Issues New sponsors or sponsors with limited biologics regulatory experience Regulatory roadmap for authorization of Biologic (Schedule D) Drugs in Canada (under development) Submission checklist for biosimilars (under discussion) Intellectual Property hold a unique issue Upon completion of the review of a submission, authorization of the biosimilar will not be issued until all matters under the Patented Medicines (Notice of Compliance) Regulations have been resolved. Until this time, the biosimilar submission is placed on "Patent Hold". Scientific advice meetings Health Canada launched a pilot program in 2015 specific to the quality comparability package for biosimilars Very little uptake; evaluation needed as to what type of meetings are most valuable for the Canadian context 12

13 Frequently Asked Questions 1. How do the development and regulatory review processes for innovators and biosimilars differ? 2. Why are traditional clinical studies not needed in each indication? What is the role of clinical studies for biosimilars? 3. Are biosimilars as safe and effective as the originator products? 4. How does Health Canada align internationally? 5. What are Health Canada s positions on switching and interchangeability? 13

14 Communicating Regulatory Decision Making Several activities underway to enhance understanding of and build confidence in Health Canada s regulatory framework and the basis for biosimilar authorization fact sheets, workshops, webinars Health Canada publishes Summary Basis of Decision documents for authorized products. A separate template specific to biosimilars was recently developed to better reflect the decision-making process. Change in order, with more focus on demonstration of analytical similarity Addition of section on Authorization of Indications Contribution to the development of the IPRP template - Public Assessment Summary Information for Biosimilars (PASIB) 14

15 OTHER KEY ACTIVITIES 15

16 Naming scheme Example No international consensus Biologics Naming EMA US FDA Japan Australia HC Trade name and common name (INN) INFLECTRA Infliximab Proper name: core name (USAN) & designated suffix proposed by manufacturer for FDA approval INFLECTRA Infliximab-dyyb Reference INN [Reference INN biosimilar 1*] * Denotes order of approval Infliximab (Genetical Recombination) [Infliximab Biosimilar 1] Trade name and ABN (INN) INFLECTRA infliximab Brand name and common name (INN) INFLECTRA Infliximab Scope All biologics All biologics Biosimilars All biologics All biologics Notes Still deciding on naming of interchangeable products and policy for retrospective application of suffixes consultation. Decided not to implement a suffix. Both trade and non-proprietary names mandatory for adverse event reporting biologics naming consultation. Brand nameand suffixbased approaches under consideration. 16

17 Biologics Naming Calls for a naming convention that distinguishes between biologic drugs that share the same common name to facilitate accurate prescribing, dispensing and surveillance Differing approaches internationally National public consultation launched early 2018 in collaboration with the Institute for Safe Medication Practices (ISMP) Canada to help inform development of a Canadian policy Request for input on preferences and impacts of implementation of different naming approaches 362 responses received; large proportion of respondents represent pharmacy Analysis is currently underway 17

18 International Collaboration Regular Biosimilar Cluster teleconferences (FDA-EMA-Japan- Canada) International Pharmaceutical Regulators Programme (IPRP) Biosimilars Working Group WHO biosimilar guideline drafting groups Australia-Canada-Singapore-Switzerland (ACSS) Biosimilars Working Group Newly established interim WG To facilitate information sharing, share expertise and explore feasibility of work-sharing

19 Biosimilars Landing Page Guidance document Fact sheet Product Monograph template Links to relevant documents Drug Product Database Resources Product specific information including product monographs Submissions under Review Informs Canadians that a drug has been accepted for review Regulatory Decision Summaries (RDS) and Summary Basis of Decisions (SBD) Explain Health Canada's decisions for drugs including biosimilars Summary Safety Reviews Results of safety reviews for marketed health products Health Canada New Drug Authorizations Annual publication identifies biosimilars approved in the previous year 19

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