Final Record of Decisions - November 16, 2017, Meeting with Groupement provincial de l'industrie du médicament (GPIM)

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

Holland Cross, 1600 Scott Street, Tower B Room 2048, Ottawa, Ontario

November 16, 2017
(1:00 p.m. to 3:20 p.m.)

GPIM Participants

• Pierre Morin, GPIM
• Stéphane Lévesque, GPIM
• Barry Poole (Biomed / Pharmapar)
• Elsa Reyes (Biomed / Pharmapar)
• Viken Afarian (Lernapharm)
• Esther Tremblay (Erfa)
• Vassilios Christodoulopoulos (Euro-Pharm)
• Régine Angers (April Pharma)
• Yuka Fukushima (Omega)
• Marie Eve Latendresse (Omega)
• Meera Tomar (Omega)
• Marie-Christine Régis (Pharmalab)
• Pranav Pandya (Accord)
• Olivier St-Denis (Riva)
• Obayda Debs (MantraPharma)

Health Canada Participants

• John Patrick Stewart, Director General, Therapeutic Products Directorate (TPD)
• Andrei Baume, Regulatory Operations and Regions Branch (RORB)
• Janet Brunette, Office of Planning, Performance and Review Services (OPPRS), TPD
• Vianney Caron, Office of Submissions and Intellectual Property, TPD
• Mandy Collier, OPPRS, TPD
• Émile Geoffroy, OPPRS, TPD
• Laura Johnson, OPPRS, TPD
• Christine Leroux, OPPRS, TPD
• Kelly McClellan, Director General's Office, TPD
• Gita Nayeri, RORB
• Étienne Ouimette, Resource Management and Operations Directorate (RMOD)
• Bruce Randall, Bureau of Pharmaceutical Sciences (BPS), TPD
• Sarah Topham, Bureau of Policy, Science and International Programs (BPSIP), TPD
• Lorraine Van Loon, RORB
• Donna Watt, OPPRS, TPD

1. Welcome and introductions

John Patrick Stewart, Director General, Therapeutic Products Directorate, welcomed participants and indicated that these bilateral meetings are a good way to exchange information and discuss questions of interest. Dr. Stewart is the former Director General of the Marketed Health Products Directorate and he became Director General of TPD on July 17, 2017.

Organizational changes that have taken place since the last bilateral meeting was held in May 2017 were highlighted. In June, Marion Law, former Director General of TPD, accepted a two-year assignment with the World Health Organization (WHO) in Geneva. Celia Lourenco, formerly Director of the Bureau of Gastroenterology, Infection and Viral Diseases, is now the Interim Senior Executive Director; Lucye Galand is Acting Director of the Bureau of Gastroenterology, Infection and Viral Diseases; Léo Bouthillier is Director of the Bureau of Cardiology Allergy and Neurological Sciences; and Mandy Collier is Director of the Office of Planning, Performance and Review Services.

Pierre Morin, GPIM, provided the update that while the last two years have been challenging in Quebec in regard to the legislation for drugs, the legislation has been passed. As a result, the market is opening up for the smaller GPIM member companies.

A roundtable of introductions followed.

2. Review of agenda

There were no changes to the agenda.

3. Approval of meeting notes of May 18, 2017 / action items

The May 18, 2017 meeting notes were approved.

4. Implementation of the revised Quality Guidance Document (Chemistry and Manufacturing)

Bruce Randall, Director, Bureau of Pharmaceutical Sciences, TPD addressed this item. The revised Quality Guidance Document (Chemistry & Manufacturing) on New Drug Submissions (NDSs) and Abbreviated New Drug Submissions (ANDSs) was published in October 2017. The majority of the guidance will be effective in January 2018, and the complete implementation for all aspects will be October 2019.

While on the subject of Guidance Documents, Pierre Morin raises an issue related to changes to the Guidance Document on Notifiable Changes in 2011 that removed mention of sterile injectables without addressing new requirements. A GPIM company modernized its manufacturing facilities, approached RORB for an inspection in June 2016 and was told to approach TPD for filing requirements which were felt to be burdensome and a challenge for company growth and development.

5. Proposal regarding costs for medication and medical instruments

Health Canada's Fee Proposal for Drugs and Medical Devices (Fee Proposal) has been published on the Health Canada Website, with consultations closing on January 4, 2018

Étienne Ouimette, A/Director General, Resource Management and Operations Directorate (RMOD), addressed this item. GPIM participated in a Cost Recovery Information Clarification Session that Health Canada hosted on the morning of November 16, 2017 and sector specific meetings will take place on November 21, 2017. It is anticipated that the new fees will be implemented by April 2019.

GPIM expressed concern about the impact of additional fees on smaller generic companies. The association noted that smaller companies may decide not to market in Canada as it is a small market. RMOD responded that it is holding the consultation on the proposal in order to understand the impact on industry, including small companies. After the consultation, a final version of the fee proposal will be developed and will be subject to a complaint process, if applicable.

GPIM requested information about the possibility of fee mitigation. RMOD noted that there is a mitigation measure in the fee proposal, related to the first submission of a small company, if the fee to be paid is greater than $10K. RMOD invited GPIM to provide as much information as possible as part of their response to the consultation, especially on the financial impact, and to propose measures for mitigating such impacts.

GPIM highlighted the importance of working together to find a solution for this issue. The association indicated that for a New Drug Submission (NDS), small companies are paying the same rate as the large ones.

Health Canada last updated its fees for human drugs and medical devices in 2011. With the new authorities to set fees under the Food and Drugs Act, Health Canada will have the ability to adjust fees more quickly. The Department will review its fees annually so that they better reflect actual costs. Stop the Clock provisions will have to be developed and implemented to enable greater predictability and efficiency in review times.

6. Atypical Active Pharmaceutical Ingredients (APIs)

GPIM requested an update on the consultation on active pharmaceutical ingredients that was held from December 2, 2016 to January 15, 2017. Andrei Baume, Senior Corporate Regulatory Advisor, and Gita Nayeri, Manager, GMP Inspections, both of the Health Products Inspection Licensing Division of the Regulatory Operations and Regions Branch (RORB) addressed this item. The objective of the consultation was to provide stakeholders the opportunity to propose specific ingredients for inclusion on, or exclusion from the List of Atypical APIs, with adequate rationale. As a result of the feedback received, Health Canada has made changes to the list of atypical APIs, standardized ingredient names and clarified the scope of the interim approach.

In terms of next steps, Health Canada plans to maintain the interim approach outlined in the Consultation Notice until the final Notice and List are published. It is anticipated that a final Notice to Stakeholders and Atypical API list will be published on the Health Canada website the week of November 20, 2017, along with a comprehensive summary of the changes made as a result of the consultation. RORB in collaboration with HPFB will continue to assess and review new incoming requests with respect to atypical APIs received and provide guidance and responses. After publication, the list will be kept open for the proposal of inclusions and exclusions that have been justified by stakeholders.

GPIM requested information on a situation where a product is sold as an excipient but is used as an active ingredient. RORB responded that as part of the Active Pharmaceutical Ingredient Framework, it is important that vendors understand the final use of a product in order to comply with Regulations. GPIM indicated that it has found workarounds such as importing directly from the manufacturer, however, sometimes manufacturers do not want to sell directly to a company if it does not meet the minimum volume. The association occasionally has challenges even if a member company tells the vendor that the product is being used as an API.

RORB indicated that GPIM should send any questions about atypical active pharmaceutical ingredients to: API_questions_IPA@hc-sc.gc.ca

Post-meeting note: The final Notice to Stakeholder, the Atypical API List and the Consultation Summary have been published on the Health Canada website on November 23, 2017.

7. Consultation on proposals to increase pre-market transparency related to human prescription drugs

GPIM expressed concern that the proposals for prescription drug transparency would involve disclosure of confidential business information. Laura Johnson, Office of Planning, Performance and Review Services, TPD addressed this item. An online consultation was held from September 28 to October 28, 2017. Feedback received from the consultation will be included in the analysis and decision making process related to the proposed initiatives.

The five proposals outlined in the consultation are the following:

1. publishing a summary explaining our decision on certain prescription generic drug submissions
2. publishing a list of prescription generic drug submissions sent to Health Canada for review
3. expanding the scope of the current Regulatory Decision Summary initiative to include more drug submissions
4. adding company (sponsor) names to entries on the Submissions Under Review (SUR) List
5. adding the submission 'class' to entries on the SUR List

Only the first two proposals apply to generic submissions (Abbreviated New Drug Submissions [ANDSs]) at this time. The other three proposals involve changes to the current Regulatory Decision Summary and Submissions Under Review List initiatives, and therefore they are not proposed to apply to ANDSs at this time. If Health Canada was to consider adding company names to entries on the SUR list, it would hold a consultation first.

GPIM indicated that it had submitted feedback for the consultation. TPD provided a preliminary update to GPIM on the feedback that was received from the consultation proposals, and conveyed next steps.

TPD highlighted that expanding transparency for generics does not necessarily mean having the exact same measures as the ones developed for innovator products. GPIM noted that generics and innovator products are two different worlds; major innovator companies are public and generally publish the results of their clinical studies, and the fact that they are making a submission to Health Canada may already be in the public domain.

Laura Johnson, Office of Planning, Performance and Review Services, TPD indicated that GPIM can send any questions about these initiatives to OPPRS_enquiries@hc-sc.gc.ca.

8. Training on the use of the electronic Common Technical Document (eCTD) format

GPIM requested that Health Canada provide training on the use of the eCTD format that is to be used for submissions. The association also requested that Health Canada recommend one of the technologies.

Vianney Caron, Manager, Office of Submissions and Intellectual Property (OSIP), TPD addressed this item. TPD provided GPIM with of links on how to file submissions in eCTD format:

1. Creation on the Canadian Module 1 Backbone
2. Validation Rules for Regulatory Transactions submitted to Health Canada in the eCTD format

There are a number of eCTD applications available. Health Canada indicated that it is not important which eCTD software is used as long as the submission is in eCTD format. The important aspect is that the standards, which are posted on the Health Canada website, are respected. Health Canada uses docuBridge but the sponsor may choose which application it wishes to use. It is therefore up to the sponsor to gather the information relevant to the specific eCTD application that it has chosen.

While Health Canada does not provide general training sessions for submissions in eCTD format, GPIM member companies are welcome to request an individual training meeting. It would be difficult to create a generic training program as most companies prefer to use their own personalized data.

Health Canada is currently working on a slide presentation containing basic information regarding eCTD format which also includes details on common errors encountered when filling submissions in eCTD format. Once completed, this presentation will be shared with the GPIM.

Furthermore, if the Guidance Documents and the presentation are not sufficient, Health Canada is willing to attend a WebEx that is hosted by the industry/association in order to provide more information/clarity on eCTD format.

Health Canada indicated that while it is not able to recommend a specific eCTD application, it would look into any information it could provide.
Action: Vianney Caron, Office of Submissions and Property (OSIP), TPD will look into the possibility of providing GPIM with further information on the various eCTD applications.

TPD indicated that any questions about submissions in the eCTD format should be sent to eReview@hc-sc.gc.ca .

9. Decision cycles for Abbreviated New Drug Submissions (ANDSs)

GPIM requested information on how to reduce the number of ANDS submissions that require more than one review before approval. Christine Leroux, Office of Planning, Performance and Review Services, and Bruce Randall, Director, Bureau of Pharmaceutical Sciences, TPD addressed this item. Christine Leroux presented performance data for TPD and non-prescription drug and disinfectant submission review performance for the Natural and Non-prescription Health Products Directorate for fiscal year 2017-18 (April to September).

TPD indicated that some of the challenges with ANDS submissions include: data integrity, an increase in complex dosage forms, and a higher level of parenterals. Sometimes it is the studies that were done or the lack of studies that lead to a Notice of Non-Compliance (NON) or a Notice of Deficiency (NOD).

GPIM requested that Health Canada provide a webinar to discuss the topic so that association members can prepare for the future. TPD indicated that it is willing to consider a webinar and posting FAQs.

10. Roundtable

Pre-submission meeting process improvement

Mandy Collier, Director, Office of Planning, Performance and Review Services, TPD, indicated that TPD is looking at ways to improve the pre-submission meeting process. A pre-submission framework is to be developed and a pilot is planned for Spring 2018. GPIM will be receiving an invitation to participate in a teleconference on the topic in the coming weeks.

GPIM indicated that complex generics will be coming in the near future and that Health Canada does not yet have a regulatory pathway for them. GPIM noted that it would be helpful if pre-submission meetings could be held for Abbreviated New Drug Submissions (ANDSs) which are currently not included in the process. TPD indicated that if GPIM members have products with complexities, it is open to having a discussion about them. GPIM is welcome to submit any comments about challenges that its members have with the pre-submission meeting process.

GPIM added that an example of where Health Canada can work with industry to improve process is regarding Active Pharmaceutical Ingredients (APIs). GPIM noted that it received a notice of non-compliance for an API. Within one month, the company regained compliance but the GPIM member company was told that it would have to wait 250 days because it is considered to be a foreign site addition.
Action: John Patrick Stewart, TPD, indicated that TPD would share that information with the Regulatory Operations and Regions Branch (RORB) as it is responsible for that area.

11. Closing remarks and meeting adjournment

John Patrick Stewart, TPD thanked everyone for participating. Pierre Morin, GPIM indicated that the association believes the bilateral meetings are useful.

The meeting was adjourned at 3:20 PM.

12. Next meeting - April 26, 2018

Original signed by:

Celia Lourenco
Interim Senior Executive Director
Therapeutic Products Directorate