Final Record of Decisions - November 30, 2017, Meeting with Canadian Generic Pharmaceutical Association (CGPA)

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

1600 Scott Street, Holland Cross, Tower B, 5^th Floor, Boardroom 2048, Ottawa, Ontario

November 30, 2017
(1:00 p.m. to 3:40 p.m.)

CGPA Participants

• Len Arsenault, Sandoz (Co-Chair)
• Duane Terrill, Apotex
• Sandra D'Agostino-Ferlisi, Apotex
• Swamy Subramanian, Apotex
• Ana Bascom, Fresenius-Kabi
• Sudheer Paladugu, Marcan
• Joanne Manley, Mylan
• Fong Chan, SteriMax Inc.
• Ritesh Acharya, SteriMax Inc.
• Lul Ogba-Ghebriel, Taro
• Anne Wilkie, CGPA
• Jim Keon, CGPA
• Jody Cox, CGPA

Health Canada Participants

• John Patrick Stewart, Director General, Therapeutic Products Directorate (TPD), Co-chair
• Marilena Bassi, Bureau of Policy, Science and International Programs (BPSIP), TPD
• Ariel Arias, Biologics and Genetic Therapies Directorate (BGTD)
• Rita Beregszaszy, Bureau of Cardiology, Allergy and Viral Diseases (BCANS), TPD
• Janet Brunette, Office of Planning, Performance and Review Services (OPPRS), TPD
• Michèle Chadwick, BGTD
• Mandy Collier, OPPRS, TPD
• Gary Condran, Bureau of Pharmaceutical Sciences (BPS), TPD
• Jiazhen Minnie Dai, Marketed Health Products Directorate (MHPD)
• Deborah Dinakaran, Office of Risk Management, TPD
• Émile Geoffroy, Regulatory Project Management Division (RPMD), TPD
• Debra Haltrecht, Office of Legislative and Regulatory Modernization (OLRM), Policy, Planning and International Affairs Directorate (PPIAD)
• Laura Johnson, OPPRS, TPD
• Tanja Kalajdzic, MHPD
• Christine Leroux, OPPRS, TPD
• Kelly McClellan, Director General's Office (DGO), TPD
• Nick Orphanos, BGTD
• Bruce Randall, BPS, TPD
• Craig Simon, BPS, TPD
• Sarah Topham, BPSIP, TPD
• Donna Watt, OPPRS, TPD
• Bruce Wozny, MHPD

Observers

• Heather Cherry, RPMD, TPD
• May Mok, RPMD, TPD

1. Welcome and introductions

John Patrick Stewart, the new Director General of the Therapeutic Products Directorate (TPD), welcomed everyone to the meeting.  Dr. Stewart thanked the representatives of CGPA companies who travel to attend these meetings and indicated that the effort to participate face to face is appreciated.

There have been a few organizational and senior management changes within TPD.   Celia Lourenco, former Director of the Bureau of Gastroenterology, Infection and Viral Diseases (BGIVD) is Interim Senior Executive Director of TPD; Lucye Galand replaces Celia Lourenco as Interim Director of BGIVD; Léo Bouthillier is now Director of the Bureau of Cardiology, Allergy and Neurological Sciences; and Mandy Collier is now Director of the Office of Planning, Performance and Review Services.

Internally, a high number of key ministerial and branch priorities are underway, including Regulatory Review for Drugs and Devices, and Cost Recovery.  There are a number of specific initiatives related to generic drug submissions.   Litigation also continues to occupy much of TPD's time.

Len Arsenault, CGPA Co-chair, welcomed John Patrick Stewart and indicated that CGPA appreciates the opportunity to dialogue.  The association noted that while there has been a lot of progress on some files, there remain several other important files where significant progress is required.

2. Review of agenda

There were no changes to the agenda.

3. Approval of meeting notes / action items of the June 21, 2017 meeting

The Record of Decisions from the June 21, 2017 meeting was approved.  All action items were completed.

4. Introduction of the Caribbean Regulatory System (CRS)

Ariel Arias, Senior Advisor, Biologics and Genetic Therapies Directorate presented this item. As a member of the group of National Regulatory Authorities of Regional Reference (NRAr) in the Pan American region, Health Canada has been working with the Pan American Health Organization (PAHO) and the United States Food and Drug Administration on the development and establishment of the Caribbean Regulatory System (CRS).  The System aims at helping states perform key drug regulatory functions.  It does this by using efficiencies, such as reliance on reference authorities and a focus on essential medicines, to enable a sustainable enterprise in the resource-constrained environment of small states.  PAHO has asked Health Canada to communicate to the Canadian generic companies the existence and opportunities of this common portal for licensure to Caribbean countries.

The Caribbean Regulatory System /Caribbean Public Health Agency Website.

5. Opioid action plan - Health Products and Food Branch (HPFB) activities update

Rita Beregszaszy, Associate Director of the Bureau of Cardiology, Allergy and Neurological Sciences and Tanja Kaladzic, A/Manager, Post Market Surveillance of Prescription Opioids, Marketed Health Products Directorate provided an update on the activities that the Health Products and Food Branch is undertaking as part of the Federal Action Plan on Opioids.  These activities include but are not limited to:

1. better informing Canadians about opioid risks by requiring a mandatory warning sticker be applied on containers and an information handout be provided to patients, for all dispensed (prescription) opioids
2. reducing access to unnecessary opioids by further updating information in Product Monographs (such as contraindications/warning and precautions) for approved opioids, and requiring mandatory risk management plans for all opioids.

TPD indicated that a Guidance Document for Tamper-resistance Formulations of Opioid Drug Products has been developed and that Health Canada would welcome any applications for these types of products, however it is not mandatory at his time.  CGPA can contact Léo Bouthillier (Leo.Bouthillier@canada.ca) on this topic.

TPD noted that the deadline for the first wave of class labelling for innovator products was November 24, 2017.  The letter for the first wave of generics is expected to go out in March 2018.  Sponsors will have 45 days to respond once they receive the letters.  TPD added that companies do not need to wait to receive the letter to file.
Action:  CGPA requested an update on Tramadol.
Complete:  Tanja Kalajdzic of the Marketed Health Products Directorate provided CGPA with information as requested.

6. International regulatory collaboration and convergence

Gary Condran, Associate Director, Bureau of Pharmaceutical Sciences, TPD and Nick Orphanos, Biologics and Genetic Therapies Directorate addressed this item.  An update was provided to CGPA on the Australia, Canada, Singapore, Switzerland (ACSS) Consortium.  Health Canada requested information as to whether CGPA believes that ACSS is a valuable pathway for getting access to other markets.  CGPA responded that one challenge would be data protection and how filing dates line up.  The association noted that each member company would need to look into its own portfolio for products that would meet the existing criteria.  CGPA also indicated that filing in two regions at the same time may be a challenge in terms of available resources and differences in data protection provisions in various jurisdictions.

An update was provided on the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) meeting in Geneva on November 11-16, 2017.  As announced in the International Generic Drug Regulators Programme (IGDRP) and International Pharmaceutical Regulators Forum (IPRF) public statements following the June 2017 meetings, these two initiatives will be consolidated.
Action: Health Canada to provide CGPA with a copy of their Return on Investment (ROI) analysis of international regulatory activities and their presentation given at the DIA conference.
Complete:  CGPA was provided with a copy of the ROI presentation.

With respect to the Regulatory Cooperation Council Initiative on regulatory convergence Health Canada indicated that there was not a formal working relationship in place, but that they were monitoring United States Food and Drug Administration (FDA) activities.  Health Canada is working on a medical device policy with the FDA.

7. Transparency initiatives

CGPA requested an update on the status and future direction of transparency initiatives as they relate to generic medicines.  Laura Johnson, Office of Planning, Performance and Review Services, TPD addressed this item.  TPD held an external consultation on proposals specific to the generic drug industry from September 28 to October 28, 2017 on the following five proposals:

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

A teleconference was held on October 16, 2017 to answer questions of clarification and discuss the proposals.  TPD provided CGPA with an overview of feedback received from the consultation proposals to increase transparency for generics, and an update on the analysis being conducted internally.  TPD highlighted that expanding transparency for generics does not necessarily mean having the exact same measures as the ones developed for innovator products.  TPD will release a statement on next steps for each of the proposals if the decision is made to move forward.

8. Regulatory review of drugs and devices

Michèle Chadwick, Manager, Regulatory Review of Drugs and Devices addressed this item.  An update of the 15 projects under the Regulatory Review of Drugs and Devices initiative was provided, along with their benefits, allocation of extra review and policy capacity and consideration of the potential impact on generic reviews.

CGPA expressed concern that the cost recovery renewal initiative was being undertaken in parallel with the regulatory reform initiative rather than streamlining review processes and then calculating appropriate fees for services. The industry is also involved in discussions with the Pan Canadian Pharmaceutical Alliance with the potential that drug prices may drop significantly over the upcoming years.

CGPA expressed the need to look at a more reasonable fee approach, particularly with respect to the Right to Sell Fee that is proposed to increase more than 400% and apply to dormant Drug Identification Numbers (DINs) as well.  As a result of the proposed fee increases and ever-increasing cost-intensive compliance measures, its member companies are looking at sustainability of maintaining some existing generic products in the Canadian market, and the feasibility of undertaking the costly development activities to introduce new generic products.

Another major concern expressed by CGPA is the change in the criteria for fee mitigation from a product's annual sales assessment to an evaluation based on overall company size.  This change will likely further result in more generic product rationalization.  TPD responded that CGPA's concerns are being heard and that there will be more discussions on the topic in the future.

Michèle Chadwick indicated that there will be a landing page for the Drugs and Devices initiative on the Health Canada Website.   This Web page will include a section for consultations.  Any questions about the Regulatory Review of Drugs and Devices initiative can be sent to Michèle Chadwick (Michele.Chadwick@canada.ca).

Policies and guidance update

a) Notice of Intent:  Possible Changes to the Food and Drug Regulations:  Generic Drug Equivalence and Related Terminology

Bruce Randall, Director, Bureau of Pharmaceutical Sciences (BPS), TPD addressed this item. The consultation on possible changes to the Food and Drug Regulations: Generic Drug Equivalence and Related Terminology closed on October 27, 2017.  Health Canada received thirteen responses from nine interested parties (some parties responded more than once) and is in the process of reviewing these comments.  There were differing opinions but all comments will be taken into consideration during the development of the regulatory proposal.  The intent is to develop a Guidance Document and a Working Group will be established to lead this.

CGPA indicated that one concern that it expressed in its letter to Health Canada is that the timing of assessment of identicality/equivalence is key and should be based on the active therapeutic moiety at the input/compounding stage as indicated in the Updated Notice: Interim Policy on Health Canada's Interpretation of Medicinal Ingredient and Assessment of Identical Medicinal Ingredient dated October 5, 2017. The association will be watching how the Justice Kane decision moves forward.  If the timeline for determination of equivalence is changed to an assessment based on in-situ equivalence, the evaluation will become extremely complex and will result in fewer generic drug developments.  TPD noted that a big driver for this project is creating international alignment.  CGPA stated that it would not want Health Canada standing alone where a global product could not be introduced into Canada.  The association added that it is pleased that progress is being made on policies.

b) Canadian Reference Product Policy

Craig Simon, Associate Director, Bureau of Pharmaceutical sciences, TPD, addressed this item. The updated guidance entitled Use of Foreign-sourced Reference Product as a Canadian Reference Product has been developed to inform sponsors of Health Canada's current position with respect to the use of a foreign-sourced reference product.  Health Canada is also publishing a Notice to open a 60 day consultation to on potential changes to these proposals that is expected to be posted on December 8, 2017.  TPD is interested in receiving substantive proposals that it can work with and would appreciate any input from CGPA.

On a related note, CGPA indicated that it made a thorough submission to the Competition Bureau of Industry, Science and Economic Development which is actively investigating the issue of lack of availability of the Canadian innovator product for use in the development of generic drug products.  The association noted that the generic system in Canada currently requires comparison to a reference product purchased in Canada and that if there is no access, the whole system falls apart.  Ultimately, CGPA would want to see a change in regulations which would require a Notice of Compliance (NOC) holder to provide access, or Health Canada to provide an exception in instances where the Canadian Reference Product cannot be obtained.

c) Proposed Modification to Bioequivalence Standards for Multiphasic Modified-Release Drug Products

Craig Simon, Associate Director, Bureau of Pharmaceutical Sciences, TPD addressed this item. The Notice on Proposed Modification to Bioequivalence Standards for Multiphasic Modified Release Drug Products was posted on July 27, 2017.  Consultations were held until September 25, 2017.  Comments received are currently being reviewed and will be used to update Health Canada's guidance document, entitled Comparative Bioavailability Standards: Formulations Used for Systemic Effects.  These revisions are anticipated for Spring 2018.  Scott Appleton stated that the generic modified-release products would be subject to the proposed Bioequivalence Standards provided that the corresponding innovator product demonstrated that the multiphasic release profile is clinically meaningful, in which case, it would be reflected as such in one or more sources, including (but not limited to) the product monograph of the innovator product or peer-reviewed scientific literature.

CGPA indicated that the Bioequivalence of Proportional Formulations was not on the list of policies/guidances being updated.  TPD responded that perhaps that could be discussed at the next Bureau of Pharmaceutical Science/CGPA bilateral meeting.

d) Special Access Programme (SAP)

Marilena Bassi, Director, Bureau of Policy, Science and International Programs (BPSIP), TPD addressed this item.

Targeted consultations on a renewed Special Access Programme (SAP) with users and health care system providers are scheduled for December 2017.  Documents will be shared with CGPA ahead of time.  TPD is looking at modernizing the program by using a database that practitioners can use.  In this way, repeat requests and established drugs on the program could be expedited.  Feedback received will serve to confirm the relevance and usefulness of the proposed enhancements for SAP renewal.  The renewal of the SAP is taking place under the Departmental initiative to improve the regulatory review of drugs and devices.

There are a number of products that have been accessed via SAP for a long time and TPD would like to see them move towards market authorization.  A number of products have been coming off of SAP.  CGPA requested information on whether there is any consideration for lowering fees for products moving off of SAP.  TPD indicated yes, including waiving of the fee.  TPD is interested in hearing what would give companies the incentive to bring products from SAP to market.

e) Amendments to the Food and Drug Regulations / Vanessa's Law - foreign risk communications

Debra Haltrecht, Office of Legislation and Regulatory Modernization (OLRM), Policy, Planning and International Affairs Directorate (PPIAD) and Bruce Wozny, Marketed Health Products Directorate (MHPD) addressed this item.
The consultation period for Regulations Amending the Food and Drug Regulations (Vanessa's Law) ended on July 6, 2017 and comments on the accompanying guidance document were received until September 10, 2017.  Health Canada is continuing its work to analyze all the comments received on the proposal.  It is anticipated that it will go to Canada Gazette, Part II in Spring 2018.

CGPA expressed concern that the 48 hour turnaround for notifications of safety events is too short and that 72 hours is more in-line globally.  Health Canada indicated that other stakeholders have identified this challenge.  CGPA indicated that it could provide certain information within 48 hours but requested that three business days be permitted for other information.  TPD responded that three business days could mean five calendar days and that this length of time could be a risk to the safety of Canadians.

f) Importation of products for urgent health needs - Office of Risk Management

Deborah Dinakaran, Office of Risk Management, TPD addressed this item.
Details of drugs eligible for importation and sale under the Urgent Public Health Need (UPHN) regulatory pathway appear on the List of Drugs for an Urgent Public Health Need. To date, these UPHNs include the opioid crisis treatments and therapies for improved management of latent tuberculosis infections in high-risk populations around the country.  Currently the drugs added to the List include: Diaphin, Probuphine, Vivitrol, Suboxone and Priftin.

The goal is also to encourage sponsors to consider submitting an application for authorization of their drug via the New Drug Submission/Notice of Compliance (NDS/NOC) route if there is enough demand for the drug in Canada.

Any questions about generic drugs and urgent public health need should be sent to Deborah Dinakaran (Deborah.Dinakaran@canada.ca).

g) Updates on other policy and guidance documents

Marilena Bassi, Director, Bureau of Policy, Science and International Programs, TPD addressed this item.  A number of guidance documents are expected to be posted shortly:

• Update to the Guidance Document: Classification of Health Products at the Device-Drug Interface
• Final Notice regarding the classification of Dental Plaque-Disclosing Products.
• Revised guidance document: Post-NOC Changes: Safety and Efficacy Guidance and accompanying Notice.
• Update to the Management of Drug Submissions Guidance Document - a revised guidance for consultation is anticipated for late Fall/Winter 2018.
• Development of Guidance on Antimicrobial Therapeutics of Public Health Need. Posting of the guidance document for web consultation is anticipated for Winter 2018.

10. TPD review performance

CGPA requested an update on TPD's review performance over the last two quarters.  The association indicated that it noticed an increase in median time from submission to Notice of Compliance.  Bruce Randall, Director, Bureau of Pharmaceutical Sciences, TPD addressed this item.  A performance summary for User Fee average days performance; TPD on-time performance for fiscal year to date 2017-18 (to September 30, 2017); and TPD workload for fiscal year to date 2017-18 (to September 30, 2017) was provided to CGPA.  All 31 lines with decisions to report met their Cost Recovery performance targets for FYTD 2017-18 at September 30, 2017.  TPD indicated that the overall numbers are positive and that progress is being made.  There have been some files that have been more complex which affects the overall time.  TPD added that for Review 2, more generous time is provided for responses to Clarifaxes.

TPD indicated that while meeting cost recovery targets is a priority, the focus is expected to be on client service.  TPD added that it is working towards performance targets of 90% on time for non-cost recoverable submissions.

11. Roundtable

Upcoming Health Canada web consultations

TPD indicated that CGPA should check the Health Canada web site as a number of consultations are planned for the next six months.

Pre-submission meeting process improvements consultation

Mandy Collier, Director, Office of Planning, Performance and Review Services, TPD reminded CGPA of its sector-specific consultation on Tuesday, December 5, 2017 to discuss pre-submission meetings for generics.

12. Closing remarks and adjournment

John Patrick Stewart thanked everyone for participating in the meeting.   Len Arsenault indicated that CGPA is looking forward to the next TPD bilat meeting and for the upcoming meeting with the Bureau of Pharmaceutical Sciences, TPD.

Meeting adjourned at 3:40 p.m.

13. Next Meeting - June 5, 2018

Original Signed by:

John Patrick Stewart
Director General
Therapeutic Products Directorate