Final Record of Decisions - March 3, 2016, Meeting with Innovative Medicines Canada (IMC)

Health Canada - Health Products and Food Branch (HPFB) Bilateral Meeting Program

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

March 3, 2016 (1:00 p.m. to 4:00 p.m.)

IMC Participants

• Loretta Del Bosco, AbbVie Corporation, Co-Chair
• Keith McIntosh, Innovative Medicines Canada
• Samar Darwish, Boehringer Ingelheim (Canada) Ltd.
• Neerja Goyal, GlaxoSmithKline Inc.
• Sandra Wainwright, Merck Canada Inc.
• Niten Barua, Astellas Pharma Canada, Inc.
• Karen Burke, Amgen Canada Inc.
• Lisa Chartrand, Hoffmann-La Roche Limited
• Jean De Serres, Paladin Labs Inc.
• Rocelyn DelCarmen, AstraZeneca Canada Inc.
• Laura King, Novartis Pharmaceuticals Canada Inc.
• Cathy Lau, Janssen Inc.
• Dounia Maizi, Servier Canada Inc.
• Sandra Usik, Eli Lilly Canada Inc.
• Kathleen Sullivan, Innovative Medicines Canada

Health Canada Participants

• Marion Law, Director General, Therapeutic Products Directorate (TPD), Co-Chair
• Kimby Barton, Senior Executive Director, TPD
• Cathy Parker, Director General, Biologics and Genetic Therapies Directorate (BGTD)
• Marilena Bassi, Office of Performance, Planning and Review Services (OPPRS), TPD
• Megan Bettle, Healthy Environments and Consumer Safety Branch (HECS)
• Rebecca Bose, Bureau of Policy, Science and International Programs (BPSIP), TPD
• Mandy Collier, BPSIP, TPD
• Alice Hui, OPPRS, TPD
• Presho Jesuthasan, Policy, Planning and International Affairs Directorate (PPIAD)
• Laura Johnson, OPPRS, TPD
• Carole Légaré, Office of Clinical Trials (OCT), TPD
• Kelly Lehman, Bureau of Metabolism, Oncology and Reproductive Sciences (BMORS), TPD
• Patrice Lemyre, BPSIP, TPD
• Celia Lourenco, Bureau of Gastroenterology, Infection and Viral Diseases (BGIVD), TPD
• Linda MacDonald, OPPRS, TPD
• Denis Mulhall, Resource Management and Operations Directorate (RMOD)
• Matthew Sanger, RMOD
• Hugh Scheuerman, OPPRS, TPD
• Krishnan Tirunellai, Bureau of Pharmaceutical Sciences, TPD
• Donna Watt, OPPRS, TPD

Health Canada Observer

Heather L MacDonald, BPSIP, TPD

1. Welcome and Opening Remarks

Marion Law, Director General of the Therapeutic Products Directorate (TPD), Health Products and Food Branch (HPFB) welcomed everyone to the meeting. As the new DG, she introduced herself to Innovative Medicines Canada (IMC).

There have been a lot of changes since the last bilateral meeting with Innovative Medicines Canada (IMC) in April 2015 when it was Rx&D. Canada has a new government and a new Health Minister, the Honourable Jane Philpott. As indicated in the Minister's mandate letter, some of issues that will impact HPFB include renewing the health accord with the provinces and territories, and improving access to prescription medication. The government has established an ambitious plan to engage stakeholders and there will be an increased focus on transparency. The Regulatory Cooperation Council (RCC) remains an important initiative and a stakeholder session will be held in Washington, D.C. on May 4-5, 2016.

Action: IMC to provide the Bureau of Policy, Science and International Programs, TPD with suggestions for the Regulatory Cooperation Council consultation.

HPFB is working on renewing the Strategic Plan. TPD continues to meet nearly all of its performance targets and has been dedicating resources to key files such as transparency, Plain Language Labelling implementation and international regulatory harmonization.

Loretta Del Bosco, IMC Co-Chair, welcomed Marion Law. She also wanted to thank Barbara J. Sabourin for the relationship that IMC built with her and TPD. IMC indicated that the bilateral meetings are important and that the agenda item summaries represent the association's priorities. IMC often shares similar goals with TPD and sometimes they have different perspectives but the meetings generate interesting discussions. A roundtable of introductions followed.

2. Review of the Agenda

No changes to the agenda.

3. Approval of Meeting Notes of April 24, 2015 / Previous Action Items

The April 24, 2015 Record of Decisions was approved.

Most action items from the April 24, 2015 meeting have been completed. The only outstanding Item is 14 - ICH Update: IMC (formerly Rx&D) to provide TPD with feedback and concrete examples on the value of Health Canada's membership in the International Conference on Harmonization (ICH). In response to IMC's question as to whether Health Canada still required the information, Celia Lourenco, Director, Bureau of Gastroenterology, Infection and Viral Diseases noted that TPD is doing a return on investment so the information would still be useful. Cathy Parker, Director General of the Biologics and Genetic Therapies Directorate indicated that she is interested in presenting the analysis in June 2016.

Action: IMC to provide feedback to the Bureau of Policy, Science and International Programs, TPD on the value of Health Canada's membership in the International Conference on Harmonization (ICH) by the end of March 2016.

4. Introduction to Innovative Medicines Canada

Keith McIntosh, IMC, outlined how Canada's Research-Based Pharmaceutical Companies (Rx&D) changed its name on January 4, 2016 to become Innovative Medicines Canada (IMC) in order to better reflect its values and mandate. In addition to the name change, the association has undergone a complete structural change to focus on priorities that the IMC Board has set and to rethink how to approach the challenges the sector faces.

5. Performance Reporting / Pipeline Initiative

Hugh Scheuerman, Manager, Performance Reporting and Review Services, Office of Planning, Performance and Review Services (OPPRS), TPD provided a presentation on updated performance metrics for TPD including a performance summary for User Fee Average Days for fiscal year 2015/16, received vs forecasted submissions, performance details and a pipeline data summary.

Action: Marion Law indicated that an update on cost recovery (user fees refresh) will be provided at the next bilateral meeting.

6. HPFB Transparency and Openness

Laura Johnson, Office of Planning, Performance and Review Services, TPD and Rebecca Bose, Bureau of Policy, Science and International Programs, TPD presented the item. In January and February 2016, TPD and the Biologics and Genetic Therapies Directorate (BGTD) conducted an external consultation on several of its transparency-related initiatives. The consultation included an external session via WebEx on January 27, 2016, and an external survey that was available on the Health Canada website until February 19, 2016.

TPD/BGTD provided an overview of the feedback received from the external consultation and informed IMC of next steps in the development of transparency initiatives. One of the comments that were received at HPFB's consultation with stakeholders this year was that HPFB should maintain an open dialogue with its stakeholders on the transparency initiatives and any potential new items should be communicated in advance.

7. C-17 and the Disclosure of Confidential Business Information

Innovative Medicines Canada requested an update on Health Canada's Bill-C17 regulations especially in the disclosure of Confidential Business Information (CBI) and the status of the guidance on the procedure of sharing CBI.

Denis Mulhall, Executive Director, Business Informatics Section, Information Management and Technology, RMOD, addressed the item. A draft guide for Confidential Business Information will be posted for a 75 day consultation on the Health Canada website by the end of April 2016. Each line of text will be numbered so that stakeholders can make specific comments. A presentation about the draft guide was made at the January 27, 2016 Webex mentioned above.

Innovative Medicines Canada indicated that the companies want assurance that the information is being managed appropriately. The association also noted that it is not opposed to matching what is being done in other jurisdictions for CBI. IMC expressed concern that confidential information that it provides to a Health Canada reviewer could be subject to an Access to Information request. The association requested that an industry-only WebEx/Meeting be organized.

Action: RMOD agreed to invite industry to one of the WebEx meetings on the draft guide for Confidential Business Information. Update: Action item complete - The consultation was held on April 27, 2016.

8. Plain Language Labelling

IMC requested clarifications around TPD's approach regarding the implementation of Plain Language Labelling (PLL). The association also indicated that it is interested in discussing ways to smooth the implementation of the regulations.

Alice Hui, Manager, Regulatory Project Management Division, Office of Planning, Performance and Review Services, TPD and Rebecca Bose, Bureau of Policy, Science and International Programs, TPD addressed this item. Health Canada indicated that it is open to continuing the discussion on Plain Language Labelling with IMC. A Working Group has been formed to discuss areas of concern and explore, over the coming months, potential options to address them. TPD will continue to inform Innovative Medicines Canada of changes to its implementation approach. TPD and the Biologics and Genetic Therapies Directorate are working together to implement Plain Language Labelling in a consistent manner. Any changes to approach will be the result of collaboration between the two directorates.

IMC indicated that the updates to the Plain Language Labelling Questions and Answers document posted on the Health Canada website are useful.

IMC indicated that the requirement for second language labelling at the time of filing is delaying prescription drug submissions. TPD responded that the inclusion of the second-language labels at the appropriate time allows a full assessment of the safety of the drug for all Canadians. TPD believes that providing labels in both official languages contributes to the overall safety of health products. TPD is committed to supporting the inclusion of English and French labels at the time of filing a product submission.

Health Canada noted that it has taken stakeholder comments into account, that the requirement for mockups and second-language labelling was a challenge for Notifiable Changes (NCs) and post-authorization Division 1 changes (PDCs). As a result, NC and PDC submissions will no longer require mock-ups of the Product Monograph (PM), package insert, or inner and outer labels as part of their submission package.

Action: As Rocelyn DelCarmen of AstraZeneca Canada requested an offline conversation to further clarify some details of the Plain Language Labelling regulations, it was suggested that she contact Marilena Bassi, Director of the Office of Planning, Performance and Review Services, TPD.

9. Guidances and Policies Update

IMC requested an update on any upcoming guidance or policy changes or consultation, including the International Conference on Harmonization (ICH) workplan. Krishnan Tirunellai, Senior Scientific Advisor, Manufacturing, Bureau of Pharmaceutical Sciences, TPD and Patrice Lemyre, Director, Bureau of Policy Science and International Programs, TPD addressed this item. Minor revisions to the Health Canada Post-Notice of Compliance (NOC) Changes Quality Guidance were released on July 20, 2015. A significant number of Active Pharmaceutical Ingredients (APIs) are sourced from countries where Health Canada has minimum collaboration with the local regulatory authority. If the (new) API source and synthetic path have not been reviewed by Health Canada or a Memorandum of Understanding (MOU) partner (e.g., the European Directorate for the Quality of Medicines (EDQM), the risk of implementing the site change as an Annual Notification is considered high.

The first version of the Post-NOC Guidance for Change #2 included a condition that allowed sponsors to make a site change as an Annual Notification, provided they had complete information on the open and closed part of the API, and the change involved only the site address of the company. However, the condition was misunderstood by stakeholders and was applied to new API sources/Drug Master File (DMF) holders that had never been reviewed by Health Canada. This has the potential to significantly impact patient safety. To address this gap, all API site changes (except those which a Certificate of Suitability (CEP) from EDQM) are to be filed as supplements. IMC members indicated that they were not aware of the changes to the Guidance and requested that they be informed of changes before they are released in the future. Health Canada responded that consultations were held on this change and that it would be open to discussing ways to reduce communication issues.

Action: Krishnan Tirunellai, Bureau of Pharmaceutical Sciences, TPD to share the comments with IMC on the revisions to the Post-Notice of Compliance (NOC) Changes Quality Guidance. Action item complete.

An update was provided on the following guidance documents and notices:

• Draft Guidance Document: Drug Master File (DMF) - This consultation is posted on the Health Canada Website and is open for a 60-day comment period starting February 15 until April 14, 2016.
• Final Guidance Document: Product Monograph Parts I & II - A consultation has taken place and comments have been considered. It is expected that the guidance document will be finalized in summer 2016.
• Notice Regarding Dear Health Care Professional Letters for Notice of Compliance with Conditions - it is anticipated that this will be posted on the Health Canada website by the end of April 2016.
• Notice on Equivalence Standards for Highly Variable Drug Products - Posting of this notice on the Health Canada website is expected by the end of April 2016.
• Draft Good Label and Package Practices Guide - this is a Marketed Health Products Directorate lead. The online consultation is closed and it is anticipated that it will be finalized in summer 2016.

For the International Committee on Harmonization, Celia Lourenco, Director of the Bureau of Gastroenterology, Infection and Viral Diseases indicated that now that Health Canada is a member of the Steering Committee, any potential issues for regulatory changes will be examined. If any issues are found, consultations will be held in the same way as for regular consulations.

10. Regulatory Priorities of Innovative Medicines Canada

Keith McIntosh presented the regulatory priorities of Innovative Medicines Canada under its new structure. The Board of IMC has adopted a new set of organizational objectives centered on improving patient access to medicines, strengthening intellectual property rights in Canada and developing alliances with stakeholders.

Loretta Del Bosco, IMC Co-chair, indicated that the one-day workshop that was held with the Biologics and Genetic Therapies Directorate (BGTD) was very useful. The workshop broke off into working teams to generate solutions to challenges. IMC would be interested in a joint meeting with TPD and BGTD in 2017. TPD showed interest in joining BGTD for the meeting.

Action: A joint TPD/BGTD meeting to be organized with IMC in 2017.

11. Controlled Substances - Status Confirmation and Scheduling Review Processes

Megan Bettle, Director, Office of Drug Science and Surveillance, Controlled Substances Directorate, Healthy Environments and Consumer Safety Branch presented this item. The Controlled Substances Directorate (CSD) has initiated a new governance structure supporting the review of substances for scheduling under the Controlled Drugs and Substances Act. New active substances which may have central nervous system effects, or may be structurally related to known controlled substances, should be assessed for scheduling by CSD as early as possible, in a process that is separate from review under the Food and Drugs Act, in order to ensure that the appropriate regulatory framework is applied.

Industry is welcome to contact CSD for any questions as to whether their substance is a controlled substance. Best practices for engaging with CSD early in product development were discussed. Once a recommendation is made to control a substance, then the regulatory process begins. It can take from 18 to 24 months from the time the recommendation is made to control a substance to the time that it is controlled. There is a possibility that this will be built into TPD pipeline questionnaires.

A presentation was provided with information on how substances are controlled under the Controlled Drugs and Substances Act. The address to contact to determine if a substance is a controlled substance is: status@hc-sc.gc.ca.

Other questions about CDSA scheduling review can be directed to ODSS.BSSD@hc-sc.gc.ca.

12. Obtaining Drugs via the Special Access Programme

Dr. Carole Légaré, Director, Office of Clinical Trials, TPD presented this item. The Special Access Programme (SAP) allows practitioners to request access to drugs that are unavailable for sale in Canada for patients with serious or life-threatening conditions when conventional therapies have failed, are unsuitable or unavailable. The intent of the "sale of new drugs for emergency treatment" section of the Food & Drugs Regulations (under which SAP operates) was to allow access to drugs not marketed in Canada to treat medical emergencies.

The scope of the SAP has gradually expanded to address requests for a broader range of unauthorized drugs which has gone beyond the original intent of the regulations. On average SAP receives approximately 16,000 requests per year. Approximately two thirds of the total annual authorizations are for approximately 40 products which were requested and authorized more than 100 times per year. Most of these drugs have been on the programme for over 10 years. The SAP intends to reach out to various manufacturers over the next few months to move these drugs to a regulated pathway and is requesting the support of IMC.

Keith McIntosh indicated that the objective of the Board of IMC is to bring new products to Canada. One of the association's regulatory objectives is to remove barriers to filing so IMC would be willing to discuss the issue. TPD indicated that the approach will be gradual and will be tailored on a case by case basis.

13. Round Table

1. Bioanalytical Method Validation Craig Simon, Associate Director, Bureau of Pharmaceutical Sciences (BPS), TPD updated that on October 8, 2015, a notice regarding clarification of bioanalytical method validation procedures was posted on the Health Canada website. This notice caused concern among sponsors. TPD has taken the feedback into account and will post an addendum to the notice. Companies should contact TPD if there is doubt as to whether they have the requirements in the notice.
2. Good Manufacturing Practices (GMP)/ Drug Establishment Licence (DEL) Screening of Drug Submissions Craig Simon, Associate Director, Bureau of Pharmaceutical Sciences (BPS), TPD indicated that Health Canada is on track to reduce the time to 90 days from 250 days for new sites and activities. Health Canada is still looking for evidence of GMP compliance in order to accept a submission.
3. Orphan Drug Framework Presho Jesuthasan, Office of Legislative and Regulatory Modernization, Policy, Planning and International Affairs Directorate updated that the orphan drug framework continues to be under review and development.
4. Inspectorate to Move to a New Branch The Inspectorate will be moving from the Health Products and Food Branch to a new Regulatory Operations and Regions Branch (RORB) that is being launched on April 4, 2016. After three years with HPFB, Anne Lamar will be leading RORB as Assistant Deputy Minister. The Inspectorate will continue delivering its national compliance and enforcement program.

14. Closing Remarks & Adjournment

Marion Law, Co-chair, thanked everyone for participating in the meeting.

Loretta Del Bosco, IMC Co-chair, indicated that IMC truly appreciated the robust discussions and everyone's time.

The meeting was adjourned at 4:00 PM.

15. Next Meeting

The next bilateral meeting will be held in October 2016.

Original signed by
Marion Law
Director General
Therapeutic Products Directorate