Record of Decisions - May 23, 2012, Canada’s Research-Based Pharmaceutical Companies (Rx&D)

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.

Health Canada - Health Products and Food Branch - Bilateral Meeting Program

• Record of Decisions: Canada’s Research-Based Pharmaceutical Companies (Rx&D)
• Location: 1600 Scott Street, Holland Cross, Tower B, 2^nd Floor, Boardroom 2048, Ottawa, Ontario
• Date: May 23, 2012
• Start Time: 1:00 p.m.
• End Time: 4:00 p.m.

Rx&D Participants

Jared Rhines, Ikaria, Chair of Regulatory Affairs Committee (RAC)

Loretta Del Bosco, Abbott Laboratories Limited, Vice-Chair of RAC

Neerja Goyal, GlaxoSmithKline Inc., Member of RAC Executive

Ken Hughes, Rx&D, Vice-Chair of RAC

Samar Darwish, Boehringer Ingelheim (Canada) Ltd.

Rocelyn Del Carmen, AstraZeneca Canada Inc.

Carolyne Desrosiers, Lundbeck Canada Inc.

Vratislav Hadrava, Pfizer Canada Inc.

Franca Mancino, Sanofi-Aventis Canada

Gay Parsons, Janssen Inc.

Maria Perrotta, Novartis Pharmaceuticals Canada Inc.

Sandra Wainwright Merck, Member of RAC Executive

Sandra Usik, Eli Lilly

Keith McIntosh, Sr. Director, Scientific and Regulatory Affairs

Stephen Li, EMD Serono

Bonnie Cockhill, Shire

Health Canada Participants

Barbara J. Sabourin Director General, Therapeutic Products Directorate (TPD), Co-Chair

John Patrick Stewart, Senior Executive Director, TPD

Katie Greenwood, Bureau of Pharmaceutical Sciences (BPS), TPD

Anne Bowes, Office of Patented Medicines and Liaison (OPML), TPD

Gail Gervais, Liaison Office of Business Transformation (OBT), TPD

Janet Brunette, OBT, TPD

Madeleine Marshall, Bureau of Policy, Science and International Programs (BPSIP), TPD

Heather L. McDonald, BPSIP, TPD

Kimby Barton, Bureau of Cardiology, Allergy and Neurological Sciences (BCANS), TPD

Hugh Scheuerman, OBT, TPD

Bruce Randall, OBT, TPD

Marilena Bassi, OBT, TPD

Georgette Roy, Biologics and Genetic Therapies Directorate (BGTD)

Vicky Hogan, Marketed Health Products Directorate (MHPD)

Louise Dery, Policy, Planning and International Affairs Directorate (PPIAD)

Joanne Garrah, PPIAD

Mike Ward, BPSIP, TPD

Christine Marshall, Resource Management & Operations Directorate (RMOD)

Tracey Spack, PPIAD

Observers

Stuart Forestell, Office of Pharmaceuticals Management Strategies (OPMS), Strategic Policy Branch

Barry Jones, OPMS, Strategic Policy Branch

Lynn Hefferton, OBT, TPD

Kelly Robinson, BCANS, TPD

Andy Hua, BCANS, TPD

Genevieve Moore, Food and Drugs Act Liaison Office (FDALO)

Susan Robertson, ORM, TPD

Vikesh Srivastava, Resource Management and Operations Directorate (RMOD)

Alice Hui, OBT, TPD

Celia Lourenco Office of Clinical Trials (OCT), TPD

Isabel Renart-McGowan, BPSIP, TPD

Via Teleconference

Karen Wallace-Graner, HPFB-Inspectorate

Sharron Mullin, HPFB-Inspectorate

1. Welcome and Introductions

Barbara J. Sabourin, Director General, TPD, HPFB, welcomed everyone, and a round table of introductions followed.

Organizational Update

Barbara Sabourin provided an organization update and announced the following changes:

• Barbara Sabourin has now been appointed as Director General for TPD, and John Patrick Stewart, formerly Director of the Office of Clinical Trials, will be the Acting Senior Executive Director for the next few months. Celia Lourenco from OCT has accepted to act on his behalf. As of April 2nd, Marilena Bassi is the new Director for the Office of Business Transformation and Barbara Rotter, Director of the Bureau of Metabolism, Oncology and Reproductive Sciences (BMORS), TPD has retired. Kelly Robinson is now the Acting Director of BMORS.
• Barbara mentioned that TPD came out fairly well with regard to the impact of Budget Implementation 2012. The new cost recovery fee structure put in place last year helped as did our core business priorities. In total, fifteen positions were affected in TPD, some of which were with Schedule F, Regulatory Amendment Group.
• The Policy functions have changed and will be divided into four areas at the Branch level and the best organizational structure will be determined.
• The whole process will unfold in about six weeks. Some employees are now competing for jobs, while those on the surplus list are either looking for another position, retiring or taking advantage of educational leave opportunities.

2. Review of Agenda

Some items were switched on the Agenda in order to accommodate the speakers, and it was then approved.

3. Approval of the Meeting Notes of October 24, 2011

The meeting notes were approved.

4. Auditor General Report

In July 2012, Health Canada will be providing the Public Accounts Committee with an update on the Office of the Auditor General’s Audit of Health Canada’s Regulation of Pharmaceutical Drugs, tabled in November, 2011. The update will include responses to questions posed during the Deputy Minister’s appearance before the Committee in March, 2012 as well as progress made on commitments to address the Auditor General’s recommendations to date. These commitments, which aim to improve the Safety, Timeliness and Transparency of Health Canada’s regulation of pharmaceutical drugs, are relevant to the activities of Canadian drug companies.

Christine Marshall, RMOD, provided the following update:
The recommendations made by the AG in the audit report addressed issues of:

• Safety
• Timeliness
• Transparency

The DM has since appeared at the Standing Committee on Public Accounts in March to report on Health Canada’s progress on addressing the recommendations.

Some accomplishments to date include:

• Safety:
  • Strengthening of Health Canada’s risk-based approaches for monitoring and assessing clinical trial adverse drug reaction reports and selecting clinical trial sites for inspection.
    
  • Progress towards implementing electronic reporting that will capture both foreign and Canadian adverse drug reaction reports. Health Canada will start receiving data electronically in the summer of 2012. This will make it quicker and easier to identify potential drug safety concerns.
• Timeliness:
  • Health Canada introduced its Cost Recovery Initiative in April 2011, which will provide stable funding for the delivery of regulatory services in a timely manner. Health Canada has invested revenue from this project to hire and train new scientific experts and improve business processes and systems.
  • Cooperation has increased between Health Canada and trusted regulators in other countries to share information on inspections and adverse drugs reactions so that timely actions can be taken domestically to protect Canadians.
  • Further, Health Canada is moving towards more formal use of foreign regulatory information to promote more efficient drug authorizations. To this end, a pilot for the use of foreign reviews was initiated in 2011 and an evaluation of the pilot will be completed by March 2014.
• Transparency:
  • In 2011 Health Canada completed a review of the current risk-based approach to select clinical trial sites for inspection which will inform the development of a documented, enhanced site selection process.
  • Health Canada is enhancing public access to information on authorized clinical trials by publishing an annual report on high-level clinical trial inspection summary report findings.
  • New text has been added to Health Canada’s No Objection Letter (NOL), issued when a trial is authorized, to encourage sponsors to register their clinical trials within this 21 day period.
  • The Plain Language Labelling Initiative aims to make labels, including the Product Monograph, easier to read and understand.
  • Finally, through the second phase of the Summary Basis of Decision (SBD) project, to be launched in June, the Department will be incorporating new information on post-approval decisions on marketed health products into documents made available on the Health Canada website. This new information will include approvals with conditions, rejections and withdrawals.
  • Health Canada has committed to provide the Public Accounts Committee with more information on its user fees and performance standards and will report to the Committee in July 2012.

9. Summary Basis of Decision

Gay Parsons, Rx&D advised that in October 2011, phase II of the Summary Basis of Decision Project was initiated through the issuance of a consultation document followed by a stakeholder consultation meeting in November. At the meeting it was indicated that a report summarizing the comments from the November consultation would be issued in December with a target timeline for implementation of phase II by April 2012.

Rx&D would like to get an update on this initiative with respect to:

1. General comments received from stakeholders.
2. Whether any changes to the original proposal are being made and confirmation of the scope of phase II (if revised).
3. Next steps and timelines for implementation.

Madeleine Marshall, BPSIP provided responses as indicated:

1. The results from the Phase II Consultation on the Summary Basis of Decision (SBD) were published in a report which was posted online on the Health Canada website on May 7. General comments obtained from stakeholders through the face to face meeting and online consultation process included: overall support for the revision to the SBD documents, questions about the target audience and the level of language used in the SBDs, support for the intention to generate and post the documents more quickly and a range of opinion regarding the post-authorisation/post-licensing activities table.
2. No major changes to the original proposal for Phase II are currently planned. As proposed in the consultation process, the scope for Phase II will remain similar to that of Phase I: New Active Substance New Drug Submissions, and a subset of Class IV medical devices, with the addition of subsequent entry biologics. In Phase II, the Notice of Decision will be eliminated and the SBDs will be written in a question and answer format, with a focus on the benefit/risk section. The documents will be streamlined and will use web functionality to make them easier to navigate. The biggest change in Phase II will be the inclusion of post-authorisation/post-licensing activity (PAA/PLA) information in the form of a table. The PAA/PLA table will provide information for qualifying products on a lifecycle basis, including negative decisions on subsequent submissions. The PAA/PLA will only apply to those products which have an SBD prepared after the Phase II implementation date.
3. Phase II of the SBD project will launch in June, 2012 with the release of a Notice to Stakeholders and documents describing the changes for Phase II published on the Health Canada website. The Phase II process will apply to qualifying products which receive approval as of early fall.

5. Drug Shortages

Ken Hughes, Rx&D began by congratulating Paul Glover on the April 16th letter sent to Market Authorization Holders (MAHs). Rx&D recognizes Health Canada’s support in reaching market authorization holders who are not members of Rx&D or CGPA in order to provice a common understanding of how to report ‘anticipated drug shortages’ publicly.

An update was also provided on the system that has been developed and is being used to report drug shortages in Canada.

Joanne Garrah, PPIAD advised that Health Canada was continuing to try and find ways to deal with drug shortages and hopefully we will have better responses in the future. She also thanked Rx&D members who took the lead in encouraging the working group to develop better notification processes. We appreciate and are very happy with Rx&D’s contributions in this area.

6. Legislative and Regulatory Modernization (LRM): Rare Diseases and Plain Language

Sandra Wainwright, Rx&D advised that Rx&D has been an active contributor to the discussions and consultations regarding Legislative and Regulatory Modernization in the past years and continues to support Health Canada's efforts to achieve appropriate and balanced regulatory frameworks and authorities, similar in scope to other major regulatory authorities.

Rx&D sought:

• Confirmation of the planned release of the Road Map and estimated timing.
• Confirmation of the plan to include Rare Diseases and Plain Language in the first phase of regulatory proposals.
• Common understanding of the future consultation process, particularly for the topics of "Rare Diseases" and "Plain Language".

Joanne Garrah, PPIAD mentioned a recent meeting with Rx&D to update them on the roadmap and modernization. The final draft version of the document has been shared internally and we hope to post it shortly. The detailed structure of the phases/packages will not be included but will be announced individually.

There will be 3 phases:

1. Early deliverables (for example, food additives, labelling).
2. Theme oriented packages tied to efficiencies, RCC, RTR, etc.
3. Reset of all regulations.

This will be a 5-6 year plan.

We are trying to streamline how proposals are brought forward and hope to come up with a charter model for each regulatory package. These should include regulatory policy work, guidance policy work and operational changes for each project - with a lead assigned. However, it may be challenging to accomplish this with some of the larger, more detailed guidances.

7. Foreign Review Pilot

Neerja Goyal, Rx&D indicated that on September 9, 2011, Health Canada issued a draft guidance on the use of foreign reviews and initiated an 18 month pilot starting in October 2011.

Rx&D would appreciate an update on the experiences to date in the pilot across TPD, BGTD and MHPD. This would include aspects such as:

1. Number and type of submissions;
2. Summary of which methods used for which submission components;
3. Successes and challenges.

Louise Dery, PPIAD advised that the Health Products and Food Branch is proceeding with the pilot on the use of foreign reviews in the health product marketing authorization processes. There has been a slow start to the pilot. As of May 16, 2012, we have received 19 requests for the ‘attestation form’, which is an indicator of industry’s interest.

A consultant has been hired to conduct the evaluation of the project and is currently working on refining our data gathering tools to obtain the appropriate information.

Health Canada is also having regular meetings with all implicated directorates to advance this project.

Neerja Goyal suggested possibly expanding the scope of submissions to include: new drug submissions (NDS) (BGTD), safety and efficacy reviews in TPD and Chemistry and Manufacturing reviews within TPD.

Louise Dery, PPIAD also advised that they have entered into discussions to expand the scope and hopefully a revised notice will be provided in the near future.

8. Guidances and Policies

Sandra Usik, Rx&D mentioned that at the previous bilateral meeting, an update on the plans and anticipated timelines for consultations and/or implementation of revised/new guidances was provided by both TPD and HPFI policy groups.

Rx&D sought an:

1. Update on Health Canada’s schedule for issuance of draft guidances or policies including:
   1. any being developed/revised in relation to the Regulatory Modernization.
   2. an update on the status/ timing of Environmental Assessment Regulations.
   3. an understanding of Health Canada’s position on the new European Union (EU) Pharmacovigilence Regulations and International Conference on Harmonisation (ICH) guidance E2C (R2) on Periodic Benefit-Risk Evaluation Reports.
2. Update on the timing for release of GUI-0080 Guidance on good manufacturing practices (GMP) Compliance of Foreign Sites for comment (was expected at the end of 2012).
3. Understanding of how Rx&D’s comments are being addressed and timing for finalization of draft documents such as:
   1. Common Technical Document (CTD) guidance;
   2. Labelling guidance;
   3. Clinical Trial Application (CTA) guidance.

Joanne Garrah and Tracey Spack, PPIAD and Vicky Hogan, MHPD provided the following information for item 1.

• 1. a. Regulatory Modernization
  • OLRM will provide an overview of the modernization agenda, including the process that will be used to sequence regulatory packages and align development of regulations with guidance development.
    
    
• b. Environmental Assessment Regulations
  • Health Canada has been exploring legislative options for the promulgation of the regulations and are currently pursuing a regulatory framework for “Class 1 substances” (medicinal ingredients) under the Food and Drugs Act.
    
    Work on guidance development is expected to begin this fall at which time we will be seeking input from stakeholders for both Class 1 and Class 2 substances.
    
    
• c. EU Pharmacovigilence Regulations and ICH guidance
  • A slide deck was provided by Vicky Hogan to update this issue.

Karen Wallace-Graner, HPFB-Inspectorate provided the following update for item 2:

• 2. Timing for Release of GUI-0080 Guidance on GMP Compliance of Foreign Sites for comments.

Preparatory work on revisions to GUI-0080 has commenced. The target for “Release for comment” has been amended to Q3-4 of Fiscal Year 2012-2013. Due to this delay, communication of minor process changes not requiring consultation will be occurring via mail notification to DEL holders and periodic Health Canada internet postings. RX&D members are encouraged to monitor the “What’s New” page of the Health Canada Compliance and Enforcement area of the website.

Additionally, an updated list of the status of Good Manufacturing Practices and Post Market and Reporting Compliance documents identified for review or modifications this year is being provided as a separate accompanying document.

Heather L. MacDonald, BPSIP, provided this update for item 3:

• 3. a. CTD guidance
  • The Draft Guidance Document: Preparation of Drug Submissions and Applications in the Common Technical Document (CTD) Format was posted on the Health Canada website for internal and external consultation in August 2011.
    
    
  • It is anticipated that the final Guidance Document: Preparation of Drug Regulatory Activities in the Common Technical Document (CTD) Format and the Issue Analysis Summary will be posted in June 2012.
    
    
• b. Labelling guidance
  • The draft label guidance has been revised taking into consideration all comments received curing the consultation period. The most common issues of concern for stakeholders were the sections of the guidance on final labels and font size. Other comments were received requesting more clarification and explanation and these comments have been reflected in the revised final guidance.
    
    
• c. CTA guidance
  • The 90 day consultation period for the Draft Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications ended in February 2012. Comments received are being reviewed with the guidance being revised as necessary. The expected date of completion for the final CTA guidance is Winter 2013.

9. This item was discussed earlier in the meeting.

N/A

10. Metrics: 2011 Annual Performance Report

The metrics working team comprised of both Rx&D and HPFB members has agreed on a series of common metrics for HPFB’s performance. In addition, with the implementation of the new Cost Recovery scheme, Health Canada developed new metrics/data presentation to track performance in relation to Cost Recovery.

Health Canada provided an update on:

• 10.1) the consolidated TPD and BGTD 2011-12 annual performance metrics up to March 31, 2012 (comparison to the 2010-11 FY performance metrics).
• 10.2) the new cost recovery metrics based on the fiscal year April 1, 2011- March 31, 2012.
• 10.3) the schedule for the 3 year review of the cost recovery framework. Opportunities for stakeholder input.

Anne Bowes, OPML provided a handout on consolidated TPD and BGTD 2011-12 annual performance metrics. Hugh Scheuerman, OBT presented a deck on new cost recovery metrics and discussed some of the fee lines, expected revenues, performance statistics and forecasting challenges. Further information on the 3 year review of the cost recovery framework was provided by Isabel Renart-McGowan, BPSIP.

11. Pipeline

TPD is continuing to solicit pipeline information from Rx&D member companies and will provide an update to Rx&D on how the information is being used within the organisations. TPD is also soliciting pipeline information from other industry associations to obtain pipeline data and planning to approach other companies not affiliated with associations.

In brief the information has been used to:

• plan, specifically in the areas of workload management and determining the need for external scientific experts;
• forecast revenue;
• identify responsible Bureau for products for which the filing is “unknown”;
• providing feedback to sponsors in regard to accuracy of forecasts.

Bruce Randall, OBT advised that information provided to Health Canada needs to be as accurate as possible and to advise us as soon as possible of any known adjustments. A call will be going out in December/January for next fiscal year’s information.

Barbara Sabourin, TPD added that last year we did not get the revenue we projected due to overestimation on two or three fee lines. The forecasts had been created before pipeline data from sponsors was available, using a 5-year weighted moving average applied to historical data to estimate future submission volumes. The more accurate the pipeline information we receive the better our forecasts will become as this helps us to project our workload and required budgets. This process is evolving as we now hope to get other associations involved in this initiative.

12. eReview Products/FDA Gateway

Bruce Randall, OBT provided background information as well as the status of these 2 projects.

eReview 2.0 is a key IT modernization initiative lead by HPFB. Drivers supporting eReview include:

• modern regulatory review environment;
• operational excellence;
• cost recovery;
• end-of-life IT systems; and
• international data standards.

Two key projects within eReview include electronic forms development and FDA Electronic Submission Gateway.

1. Electronic forms development;
2. FDA Electronic Services Gateway.

FDA Electronic Services Gateway

Background:

• HPFB requires a secure means to share protected information electronically with stakeholders. A near term priority is the capacity to exchange submission content with submission sponsors via a secure electronic gateway.
• This Initiative will improve the ability to share protected information in support of timely reviews to meet performance targets for Cost Recovery.
• Enhancing electronic exchange capacity will also increase the efficiency and timeliness of the delivery of regulatory information, thus minimizing unnecessary delays in bringing safe health products to the Canadian marketplace.

Current Status

• With our technology partner, Information Management Services Directorate (IMSD), we have:
  • Stood up a Health Canada gateway to connect with the FDA Electronic Submission Gateway.
  • Successfully completed connectivity tests with the FDA.
  • Begun a series of load tests and exchanges of messages with the FDA.
  • Currently drafting a formal agreement with the FDA in order to proceed with a pilot in Fall.

Next Steps

• Finalize formal agreement with FDA.
• Initiate pilot of ESG with industry.

Electronic Forms

Background

• As part of the drug product and medical device registration process, HPFB has a number of required forms which are currently either in a paper-based format or are using a proprietary standard such as Microsoft Word or WordPerfect.
• A fully electronic environment requires conversion of existing forms into an Extensible Markup Language (XML) - based format such as Portable Document Format (PDF). XML-based forms offer improved functionality such as business rules that can be incorporated into the form to improve the quality and structure of information being captured.
• The conversion existing forms will increase the quality and accuracy of incoming information in the short term leading to less review and correction effort for front-line workers. Higher quality information and more accurate capture in HPFB systems will support the productivity goals of cost recovery and long term goals of the eReview 2.0 Initiative.

Current Status

• With Information Management Services Directorate (IMSD), established a pool of experienced resources for delivery of eForms.
• Ran a successful test of four eform mockups with members of joint HPFB-Industry Group on Electronic Regulatory Affairs (GERA).
• Joint effort with GERA to define the test parameters.
• Over 100 recommendations received and being incorporated into first release.
• First release now in final cycle of development and planned to be completed by end of Q1:
  • 21 smart-forms in 4 priority groups for drugs and medical devices.
  • 15 fillable eforms.

Next Steps

• Update eforms as needed and complete User Acceptance Testing.
• Conduct controlled production pilot for consumption of eforms into regulatory systems.
• Enhance eforms to establish connectivity to the forms to improve the quality of information captured on the eform.

13. Roundtable

1. Therapeutic Products Directorate Forward Planning Initiatives
   Heather L. MacDonald (BPSIP), outlined the initiatives that are currently active and which will require industry input in the near future. Where possible, the anticipated timing of the projects was provided to facilitate the coordination of member input by Rx&D. A handout was circulated.
2. Changes in Drug Master Files (DMF) Fees
   Anne Bowes, OPML advised that there would be revised DMF fees as of April 1st with a reminder that these updates are done every two years.
3. ICH membership
   Mike Ward, BPSIP advised of an urgent matter in regard to discussions on the future of OCH. A significant discussion would be taking place at the upcoming meeting in Japan in regard to possible changes in governance procedures and increased transparency. Subsequent discussions could have implications with respect to expanding Health Canada’s current role as an Observer.

The ADM did want Rx&D to be made aware of these discussions in order that they would be prepared with a position on this if required.

Mike Ward indicated this was a ‘heads up’ notice to Rx&D. Any views that could be put together quickly would be greatly appreciated.

Barbara Sabourin, TPD was thankful to Rx&D for their support and indicated that Health Canada would get back to them after the meeting in Japan to debrief on developments and obtain their views.

ACTION: Health Canada to advise Rx&D on outcome of ICH meeting in Japan and if any further input is required on their part.

14. Adjournment:

Meeting adjourned at 4:20 p.m.

15. Next Meeting

Wednesday, October 24th, 2012 at 1:30 p.m.

Original signed by
Barbara J Sabourin
Director General
Therapeutic Products Directorate