Final Record of Decisions May 10, 2018 Meeting: Innovative Medicines Canada (IMC)

Health Canada - Health Products and Food Branch (HPFB)

Bilateral Meeting Program

1600 Scott Street, Holland Cross, Tower B, 2nd Floor, Boardroom 2048, Ottawa, Ontario

May 10, 2018
(1:00 p.m. to 3:40 p.m.)

IMC Participants

Jared Rhines, Akcea Therapeutics Canada, Co-chair
Keith McIntosh, Innovative Medicines Canada
Wendy Arnott, Bayer Inc.
Lisa Chartrand, Hoffmann-La Roche Limited (by teleconference)
Martin Cloutier, Bristol-Myers Squibb Canada
Samar Darwish, Boehringer Ingelheim (Canada) Ltd.
Loretta Del Bosco, AbbVie Corporation
Rocelyn DelCarmen, AstraZeneca Canada Inc.
Lorella Garofalo, Pfizer Canada Inc.
Neerja Goyal, GlaxoSmithKline Inc.
Laura King, Novartis Pharmaceuticals Canada Inc.
Carrie Ku, Sanofi Canada
Catherine Lau, Janssen Inc.
Dounia Maizi, Servier Canada Inc.
Dave Patel, Takeda Canada, Inc.
Sandra Usik, Eli Lilly Canada Inc.
Sandra Wainwright, Merck Canada Inc.
Sylvie Ducharme, Knight Therapeutics Inc.

Health Canada Participants

John Patrick Stewart, Director General, Therapeutic Products Directorate (TPD), Co-Chair
Celia Lourenco, Interim Senior Executive Director, TPD
Marilena Bassi, Bureau of Policy, Science and International Programs (BPSIP), TPD
Marc Berthiaume, Bureau of Medical Sciences (BMS), TPD
Megan Bettle, Biologics and Genetic Therapies Directorate (BGTD)
Léo Bouthillier, Bureau of Cardiology, Allergy and Neurological Sciences (BCANS), TPD
Mandy Collier, Office of Planning, Performance and Review Services (OPPRS), TPD
Lucye Galand, Bureau of Gastroenterology, infection and Viral Diseases (BGIVD), TPD
Émile Geoffroy, OPPRS, TPD
Stephanie Hardy, BGTD
Melissa Hunt, Bureau of Metabolism, Oncology and Reproductive Sciences (BMORS), TPD
Christine Leroux, OPPRS, TPD
Bruce Randall, Bureau of Pharmaceutical Sciences (BPS), TPD
Jennifer Reid, OPPRS, TPD
Matthew Sanger, Resource Management and Operations Directorate (RMOD)
Andrew Taylor, Policy, Planning and International Affairs Directorate (PPIAD)
Johanne Veenstra, BGTD
Kristen Zorn, BCANS, TPD
Donna Watt, OPPRS, TPD

1. Welcome and Opening Remarks

   John Patrick Stewart, Director General of the Therapeutic Products Directorate (TPD), Health Products and Food Branch (HPFB) welcomed everyone to the meeting.  He thanked the representatives of IMC companies who travel to attend these meetings. Health Canada appreciates the effort made to participate face to face.

   An update on the following organizational changes within TPD was provided. Celia Lourenco has become the Senior Executive Director. Kelly Robinson, previously with TPD, has joined the Biologics and Genetics Therapies Directorate (BGTD) as Director of the Centre for Evaluation of Radiopharmaceuticals and Biotherapeutics.  Melissa Hunt has is now the Interim Director of the Bureau of Metabolism, Oncology, and Reproductive Sciences (BMORS). Craig Simon has become Associate Director of BMORS. Marc Berthiaume is the Director of the Bureau of Medical Sciences (BMS). David Boudreau has joined TPD as the Director of the Medical Devices Bureau (MDB). Jeffrey Skene is the Associate Director of the Bureau of Gastroenterology, Infection and Viral Diseases (BGIVD). Kristen Zorn is Associate Director in the Bureau of Cardiology, Allergy and Neurological Sciences (BCANS). For changes within the Health Products and Food Branch, Rhonda Kropp has become the Director General of the Marketed Health Products Directorate (MHPD).

   Pat Stewart added that it continues to be an active time in TPD with a high number of key ministerial and branch priorities underway, including: Regulatory Review for Drugs and Devices (R2D2); The Federal Action Plan on Antimicrobial Resistance and Use; the Federal Action on Opioids; the proposed approach to the Regulation of Cannabis; Public Release of Clinical Information; and the Cost Recovery Renewal Initiative. Pat Stewart thanked IMC members for providing valuable feedback on the many recent and important consultations in the Health Products and Food Branch.

   Jared Rhines, IMC Co-chair, indicated that the association members also value these bilateral meetings. Most of all, IMC members value the transparent and open discussion. As an industry, IMC has increasing concerns about the broader ecosystem within health. The association struggles with current initiatives because it is not sure that they will be relevant in a few years. IMC met with Simon Kennedy, the Deputy Minister of Health Canada about the Regulatory Reform for Drugs and Devices initiative.  Simon Kennedy indicated that there were further ways for industry to engage on R2D2. IMC expressed confusion because industry CEOs returned from the meeting with the impression that IMC was not engaging. IMC indicated that it believed that it was actively participating in any opportunities. IMC requested a discussion on any ways to engage with Health Canada that it might be missing.

2. Review of the Agenda

   There were no changes to the agenda.

3. Approval of Meeting Notes of October 5, 2017 / Previous Action Items

   The Record of Decisions from the previous bilateral meeting on October 5, 2017 was approved. The action items from the meeting were all completed.

4. Regulatory Reform for Drugs and Devices (R2D2)

   Innovative Medicines Canada (IMC) requested an update on the status of the Regulatory Reform for Drugs and Devices (R2D2) including progress on specific projects. Megan Bettle, Director, Biologics and Genetic Therapies Directorate, provided a presentation on the topic. R2D2 includes 15 projects under a number of pillars. Three pillars to improve the pharmaceutical system are: access, appropriate use; and affordability.  BGTD outlined a plan for improved access which includes: Alignment of the Health Technology Assessment (HTA) Review with the Health Canada Review; early parallel scientific advice; use of foreign reviews/decisions, international collaboration and worksharing; expansion of priority review pathways; improved access to biosimilars and biologics; improved access to generic drugs; Special Access Programme (SAP Renewal); strengthening the use of real world evidence for drugs; and building better access to digital health technologies.

   Health Canada indicated that if it could be involved in providing early scientific advice on submissions along with the Canadian Agency for Drugs and Technologies in Health (CADTH), it could contribute to the process. Health Canada indicated that this process would not be for all products as they have limited resource capacity and so it would only be available for specific products. IMC noted that alignment with other regulators is valuable and the sense that Health Canada does things differently makes Canadian submissions more challenging. IMC indicated that in Canada, market size is a consideration and that it is not so much the regulations as the interpretation of the regulations that can lead to mis-alignment with other major Health Authorities. Industry understands that Health Canada may have a different perspective. BGTD noted that there are situations where products have not been registered in Canada but Health Canada would like to bring them to the Canadian market. For Health Canada to use a foreign decision for a regulatory drug approval, a regulatory amendment would be required.

   BGTD indicated that the consultation for the healthcare system needs questionnaire was open for a month and 1,100 responses were received. The comments are currently being analysed.

   In terms of international collaboration and work-sharing, Health Canada is working with other regulators and there have been a number of pilot projects. Health Canada now has a candidate for an innovator product to do a review at the same time as Australia. It is a challenge do a review with more than one regulator at the same time.

   BGTD is interested in receiving more feedback from IMC members about R2D2 initiatives and is seeking ways to engage association members. There is a dedicated webpage for the R2D2 initiative which includes project summaries, timelines and upcoming opportunities for consultation.

5. Health Technology Assessment Organization (HTA)/Health Canada Aligned Reviews

   Mandy Collier, Director, Office of Planning, Performance and Review Services (OPPRS), Therapeutic Products Directorate (TPD) provided a presentation on the alignment of the Health Product and Food Branch’s reviews with the Health Technology Assessment Organizations’ (HTAs) reviews. As part of Health Canada’s “Regulatory Review of Drugs and Devices” initiative, HPFB and HTA organizations will formally offer aligned reviews for certain submissions in order to minimize the time between Health Canada market authorization and HTA funding recommendation.

   For aligned reviews, TPD would welcome comments from IMC as to what its members would consider to be valuable. The Bureau of Metabolism, Oncology and Reproductive Sciences (BMORS) and pan-Canadian Oncology Drug Review (pCODR) pilot project for oncology pharmaceuticals was completed in December 2017. The findings of the pilot continue to inform the development of the broader alignment initiative. Both the Canadian Agency for Drugs and Technologies in Health (CADTH) and the L’Institut national d’excellence en santé et en services sociaux (INESSS) now accepting submissions up to 180 days prior to an anticipated Notice of Compliance (NOC), which is an important change to enable aligned reviews.

   Jared Rhines, IMC, indicated that the association has been tracking when early HTA submission filing is used and when it is not used and offered to share the information with TPD.

6. Pause the Clock

   Stephanie Hardy, Co-Lead, Office of Policy and International Collaboration, Biologics and Genetic Therapies Directorate (BGTD) presented this item. She indicated that Michèle Chadwick, BGTD, is the other co-lead for Pause the Clock and Johanne Veenstra is a key analyst on the file. To ensure that only Health Canada’s active review time is counted against performance target standards, there is a need for a pause the clock mechanism to be in place. A triggered pause clock model is being considered that consists of only pausing the clock during the review process when pre-specified conditions are met (triggers). BGTD noted that the “Pause the Clock” process would be rarely used.

   As it relates to drugs, proposed triggers being explored, include the following:

   • Request for extensions to respond to a Clarifax
   • Clarifaxes occurring simultaneously in all review streams
   • Expert Advisory Panel advice sought

   BGTD indicated that this initiative was originally called Stop the Clock. Health Canada currently has no mechanism available to pause and resume a review. During the pause, all review activity would stop. The clock would start again when a response has been received from the sponsor. BGTD asked IMC to provide feedback on the proposed pause the clock triggers.
   Update: Since the meeting was held, this has evolved based on stakeholder input requesting continuation with the review during a pause.

   IMC indicated that this is the first time the association has seen this. From an industry perspective, association members are not interested in driving unnecessary penalties in the review process. The association added that with other regulators, the stop clock mechanism is associated with other predictability mechanisms. IMC indicated that if the pause the clock mechanism is being built as a penalty management tool, it does not meet industry’s needs. But if pause the clock avoids unnecessary approval delays (i.e. reducing 2nd cycle reviews), it could work for industry. The association noted that the proposal that is presented today does not meet with industry’s needs as it introduces greater unpredictability into the review process.

   BGTD clarified that if a company is given two days to reply to a Clarifax and asks for an extension, Health Canada would not pause the clock. Other regulators that have stop clock mechanisms need to work with established timelines (controlled intake) and they have a significant amount of work up front (advance filing notification). During consultations, Health Canada has heard that there is continued value in the Clarifax process as sponsors appreciate the opportunity to interact with reviewers during the review period. 

   IMC noted that the majority of the review requests (Clarifax) are received during the last one to two months of a review and frequently with responses requested with shortened timeframes (less than 15 days).  However, performance targets are generally being respected and the predictability of the review period is important to IMC member companies.  The association expressed concern that the proposed pause the clock process is not about improving access but is financially driven instead to avoid incurring a penalty for not meeting the performance target. Health Canada confirmed that the Pause the Clock triggers will apply to all regulated activities with a performance target.  IMC expressed concern that removing the predictability of these review processes will have a negative impact on the ability of manufacturers to manage supply chain, activities that are critical for avoiding drug shortages.

   Of note, the Regulatory Operations and Regions Branch is developing a separate pause the clock proposal specific to the Establishment Licensing process.

   BGTD indicated that this process does not replace the need for submission planning and project management exercises. BGTD asked IMC members for examples of situations where pause the clock would be valuable for industry and where it would make sense for members to have more time. IMC members responded that they are usually given less than 15 days to respond to Clarifaxes (2-5 days). TPD indicated that it would look at options such as providing a range of time (eg. 60 days before the end of the review) where stop the clock would not be appropriate. TPD indicated that it needs to keep to its performance on-time standards.

7. TPD Performance Reporting

   Christine Leroux, Supervisor, Planning and Reporting Unit, Office of Planning, Performance and Review Services (OPPRS), TPD provided a presentation on updated performance metrics for TPD including key messages, a cost recovery performance summary for fiscal year 2017-18, TPD on-time performance, received vs forecasted submissions, and a pipeline data summary.

   Loretta Del Bosco, IMC, suggested that the association would be pleased to present further details of its Time-to-NOC (Notice of Compliance) analysis. IMC asked TPD if there is an opportunity for the association to be provided with milestones in order to plan resources. TPD responded that it is looking at that and has made significant investment on the quality side.

8. Public Disclosure of Clinical Information

   Draft regulations have been published in Canada Gazette 1 outlining a framework for the public release of clinical information.  IMC expressed concern that its member companies in Canada will be significantly impacted by these regulations and therefore the association has been actively engaged in all consultations on the topic.  Matthew Sanger, Resource Management and Operations Directorate (RMOD), addressed this item. The proposed regulations were open for comment for a 75-day period that ended on February 22, 2018.  Over the course of the consultation period, HPFB received twenty submissions on the proposal from six stakeholder groups.  HPFB is carefully analyzing the comments to see if any changes need to be made to the regulatory proposal published in Canada Gazette I.

   IMC shared some of the comments that it will be providing to Health Canada and indicated that its biggest concern is with the intent to include submissions previously approved/rejected in scope for release. The association believes that the proposal for the treatment of previously filed submissions is different than Policy 43 in the European Union. IMC noted that there needs to be more flexibility in timelines for these older submissions as there are aspects that are unique to Canada. The association has heard from colleagues that it takes approximately six months to ensure Personal Private Information is protected and limited remaining Confidential Business Information (CBI) redacted.  For previously filed submissions, IMC would like to see something that guards against one company being inundated with multiple requests at the same time. Because of the backlog in the European Union, it is likely even prospectively filed submission documents will be processed for Health Canada release first. IMC is also interested in having the process include an opportunity for the sponsor and Health Canada to discuss and agree upon the scope of the documents to be released and that this concept be embedded in the guidance document so that there are no surprises at end period allotted for document processing.

   RMOD indicated that IMC’s comments were constructive. The criteria in the framework are geared to reflect public health interests. RMOD agreed that there is a need to guard against a particular manufacturer being inundated. IMC expressed concern about retrospective releases being Canada only. RMOD noted that it is working closely with the European Union and that their process is also in evolution. The goal is to protect private information.

   IMC indicated that it is interested in providing broader input into the language of the Guidance Document. The association noted that its submission on the draft regulations in December 2017 was limited by the fact that the draft guidance had not been released yet. The draft guidance document has now been released and there will be a technical briefing on it the week of May 14, 2018. It is anticipated that the guidance will go for Canada Gazette approval in Fall 2018.  Health Canada indicated that there is still time for IMC to provide further input into the Guidance Document. IMC indicated that it would provide comments.

   IMC asked TPD if there would be a transition phase as not all companies have a European presence so the regulations would be a challenge for them. RMOD indicated that it has taken that into account.

9. Round Table

   a) Opioid Action Plan Update
   Léo Bouthillier, Director, Bureau of Cardiology, Allergy and Neurological Sciences, TPD addressed this item. TPD indicated that despite the efforts being made, people are still dying from overdoses and it hopes that Health Canada initiatives will have an impact. IMC recently received a letter from Simon Kennedy, the ADM of HPFB on the topic. In order to better inform Canadians about opioid risks, Health Canada will require that a mandatory warning sticker be applied on containers and an information handout be provided to patients, for all dispensed (prescription) opioids. The sticker plan will be published in Canada Gazette, Part III, and a six-month implementation is anticipated to begin in October 2018. Class labelling of opioids are on track and is expected to be completed in November 2018.  TPD indicated that it is seeking IMC’s assistance to find solutions to the problem. IMC requested information on how TPD would process a potential new chemical entity that would reduce opioid use. TPD indicated that it will look at expediting any product that would help.

   b) Urgent Public Health Need (UPHN)
   Marilena Bassi, Director, Bureau of Policy, Science and International Programs (BPSIP), TPD, provided an update on UPHN. Health Canada has been building on its work about the opioid crisis. This topic was raised at the April 20, 2017 bilateral meeting. TPD noted that a number of drugs on the UPHN list are now being imported into the country. At the one year anniversary of the listings, Health Canada is working with jurisdictions to see if products still need to be on the list as this was not meant to be long-term. One of the drugs that was on the UPHN list will now be receiving a Notice of Compliance (NOC).

   c) Policies and Guidance Update
   Marilena Bassi, Director, BPSIP, TPD indicated that TPD had provided a written policies and guidance document update.

   d) Annual HPFB Stakeholder Session
   Marilena Bassi, Director, BPSIP, TPD, provided a heads up to IMC that the annual HPFB stakeholder engagement session specific to health products will be held on June 27, 2018. It is HPFB’s main forum to engage with a broad range of stakeholders and there will be Webcasting this year for those unable to attend. The main themes for the event will involve better understanding health innovation, future states, and the evolving role of the regulator. There will also be breakout sessions specific to current and future challenges for regulation and regulatory and legislative modernization efforts.

   e) Antimicrobial Resistance (AMR)
   Lucye Galand, Director, Bureau of Gastroenterology, Infection and viral Diseases, TPD, provided an update.  Health Canada has posted a class labelling notice that will be updated regularly. This initiative was started in 2015 and is being done in parallel with generics. The list includes close to 350 innovator products. In April 2018, Health Canada released a Notice of its intent to prioritize bacterial pathogens. Health Canada needs to prioritize the submission of innovator products. TPD is seeking confirmation from stakeholders that the list is sufficient. Also, Health Canada will lead an innovation working group to leverage additional submissions on the part of sponsors as well as to guide development.  There is a sustainable momentum for antibacterials to be made available.

   f) Bureau of Metabolism, Oncology and Reproductive Sciences (BMORS) Cluster Teleconference - Melissa Hunt, Interim Director, BMORS, TPD, provided an update. BMORS has been involved in the Canadian Agency for Drugs and Technologies in Health (CADTH) pan-Canadian Oncology Drug Review (pCODR) pilot that has now become a process. Health Canada participates in meetings that are held by phone or videoconference with other regulators in clusters (areas of cooperation focusing on special topics). BMORS liaises regularly with international counterparts: the European Medicines Agency (EMA), the United States Food and Drug Administration (FDA), Switzerland, and is exploring work-sharing with the Australian Therapeutic Goods Administration. These initiatives have resulted in setting international standards on quality of life.

   g) Foresight Project Update
   Andrew Taylor, Policy, Planning and International Affairs Directorate (PPIAD), presented an update on HPFB Regulatory Foresight Activities. An internal network has been established to guide foresight work and has been engaged with horizon scanning. PPIAD is working on creating an external network and anticipates presenting at the next HPFB Stakeholder Event in June 2018. PPIAD is working with international counterparts to determine how to collaborate on horizon scanning. The Directorate is looking at products that will be a challenge for international systems as well as Health Canada systems. IMC, along with other stakeholders will be asked to identify where the system might have challenges. IMC indicated that it is looking forward to the opportunity for engagement.

   h) Bureau of Pharmaceutical Sciences (BPS) Update
   Bruce Randall, Director, Bureau of Pharmaceutical Sciences, provided the update that Stéphanie Parra is the new manager of the New Drugs Quality Division in BPS. Krishnan Tirunellai will be retiring in July 2018.

10. Closing Remarks & Adjournment

    John Patrick Stewart, TPD, thanked everyone for participating in the meeting. Jared Rhines, IMC Co-chair, indicated that a separate discussion on ways to engage would be welcome. IMC is willing to engage as early as possible and noted that the meetings with Health Canada are useful. IMC suggested that more time be added to the agenda of future bilateral meetings for topics that are critical to its members. The association is also willing to participate in workshops on specific topics.

    The meeting was adjourned at 3:40 PM.

11. Next Meeting

    The next bilateral meeting is expected to be held in Fall 2018.

    Original signed by:
    John Patrick Stewart
    Director General
    Therapeutic Products Directorate