Final Record of Decisions December 4, 2018 Meeting: Canadian Generic Pharmaceutical Association (CGPA)
Health Canada - Health Products and Food Branch (HPFB)
Bilateral Meeting Program
1600 Scott Street, Holland Cross, Tower B, 5th Floor, Boardroom 2048, Ottawa, Ontario
December 4, 2018
(1:00 p.m. to 4:30 p.m.)
Duane Terrill, Apotex (Co-chair)
Sandra D’Agostino-Ferlisi, Apotex
Swamy Subramanian, Apotex
Ana Bascom, Frenesius Kabi
Suresh Arvapalli, Marcan Pharmaceuticals Inc.
Alexandra Comlosan-Pop, Mylan
Joanne Manley, Mylan
Marie-Eve Latendresse, Omega Laboratories (by teleconference)
Deirdre Cozier, Pharmascience
Sonia Gallo, Sandoz Canada
Fong Chan, Sterimax
Lul Ogba-Ghebriel, Taro
Mathi Mathivanan, Teva
Anne Wilkie, CGPA
Jim Keon, CGPA
Jody Cox, CGPA
Health Canada Participants
Bruce Randall, Director, Bureau of Pharmaceutical Sciences (BPS), TPD, Co-chair
Marc Berthiaume, Bureau of Medical Sciences (BMS), TPD
Janet Brunette, Office of Planning, Performance and Review Services (OPPRS), TPD
Mandy Collier, OPPRS, TPD
Gary Condran, BPS, TPD
Émile Geoffroy, OPPRS, TPD
Claire Hughes, Policy, Planning and International Affairs Directorate (PPIAD)
Laura Johnson, OPPRS, TPD
Lisa Lange, Marketed Health Products Directorate (MHPD)
Christine Leroux, OPPRS, TPD
Joseph Mikhael, Resource Management and Operations Directorate (RMOD)
Amanda Moir, PPIAD
May Mok, OPPRS, TPD
Lissa Murseli, PPIAD
Irena Pastorekova, RMOD
Andrew Slot, MHPD
Elizabeth Smith-Kawasaki, Bureau of Policy, Science and International Programs (BPSIP), TPD
Kathy Soltys, MHPD
Thanh Vu, MHPD (by teleconference)
Donna Watt, OPPRS, TPD
Bill Wilson, MHPD
Bruce Wozny, MHPD
Veronica Yip, Bureau of Gastroenterology, Infection and Viral Diseases, TPD
Merryl Ndema-Moussa, Food and Drugs Act Liaison Office (FDALO), Communications and Public Affairs Branch
Tazeen Rahman, OPPRS, TPD
Welcome and Introductions
Bruce Randall, Director, Bureau of Pharmaceutical Sciences, Therapeutic Product Directorate (TPD) welcomed everyone to the meeting. He introduced Duane Terrill as the new CGPA co-chair and thanked CGPA members for travelling to the meeting to meet face-to-face.
There have been a few organizational changes within TPD since the last bilateral meeting on June 5, 2018. Celia Lourenco, former Senior Executive Director, TPD, is now Director General of the Biologics and Genetic Therapies Directorate (BGTD); Kelly Lehman has taken on the role of Interim Director and Rita Beregszaszy is the associate Director for the Bureau of Policy, Science and International Programs (BPSIP); Melissa Hunt has been appointed as the Director of the Bureau of Metabolism, Oncology, and Reproductive Sciences (BMORS); Evelyn Soo, who was the Associate to the Director General of BGTD is now Director for the Bureau of Gastroenterology, Infection and Viral Diseases (BGIVD). Also, the Office of Submissions and Intellectual Property (OSIP) under the direction of Anne Bowes transitioned from TPD to the Resource Management and Operations Directorate (RMOD) on October 1, 2018.
It continues to be an active time in TPD with a high number of key ministerial and branch priorities underway, including: the Health Products and Food Branch’s initiative to improve the Regulatory Review of Drugs and Devices (R2D2); the revised Cost Recovery fee implementation is still anticipated for April 1, 2019; the Treasury Board led Regulatory Review to modernize Health Canada’s regulations; the Federal Action Plan on Antimicrobial Resistance and Use; the Federal Action on Opioids; the Cannabis Act which came into force in October; and the Public Release of Clinical information. Suzy McDonald will be leaving the Opioid Response Team and the new A/Assistant Deputy Minister of the Team will be Michelle Boudreau. Bruce Randall thanked CGPA members for the feedback they have provided on these initiatives.
Duane Terrill, CGPA co-chair, thanked TPD for arranging this meeting and indicated that it is important to meet face-to-face in order to address industry concerns. CGPA appreciated that the Bureau of Pharmaceutical Sciences, TPD has posted the guidance documents on complex products. The association indicated that it is a good start but there is work to be done. CGPA also mentioned the new regulatory proposal on generic drug equivalents.
Review of Agenda
There were no changes to the agenda.
Approval of Meeting Notes / Action Items of the June 5, 2018 Meeting
The Record of Decisions from the June 5, 2018 meeting was approved. There were no action items from the previous meeting.
Opioid Risk Management Plans (RMPs) and Marketing and Advertising of Opioids
a) Opioid Risk Management Plans
As part of the Federal Action on Opioids, Regulations Amending the Food and Drug Regulations (Opioids) were published in Canada Gazette, Part II on May 2, 2018. As these regulations require mandatory risk management plans for all opioids, CGPA requested an update. Andrew Slot, Manager, and Kathy Soltys, Director, Marketed Health Products Directorate (MHPD) addressed this item. Health Canada is committed to openness and transparency with respect to the mandatory Canadian Specific Opioid targeted Risk Management Plans (CSO-tRMP) process. The goal is to publicly post which products have CSO-tRMPs under review and the status of those reviews. The information provided within individual CSO-tRMPs cannot be shared with CGPA or other companies unless MHPD has received authorization to do so from the company which submitted the RMP.
MHPD indicated that all of the CSO-tRMPs for wave one molecules have been received. Once the reviews of the CSO-tRMPs have been completed, MHPD is interested in meeting with the companies to discuss the results. MHPD is expecting to complete the reviews by March 2019. Some gaps noted to date include the need for product specific risks, data on different rates of abuse among products and the need to identify gaps in Canadian data (what are they and how to fill the gaps). Health Canada indicated that they would be making a strong recommendation to use The Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) system for surveillance data and CGPA expressed concern about the cost and overlap if other Market Authorization Holders (MAHs) were also expected to use the same data source. CGPA requested that Health Canada provide a leadership role in having opioid manufacturers join together to purchase one subscription. MHPD responded that it is looking at streamlining the process.
b) Opioid Marketing and Advertising
CGPA also requested an update on the scope and status of Health Canada’s proposed restrictions on the marketing and advertising of opioids. Amanda Moir, Director, and Lissa Murseli, Manager, Strategic Horizontal Policy Division, Policy, Planning and International Affairs Directorate (PPIAD), addressed this item. On June 19, 2018, the Minister of Health announced measures to restrict the marketing and advertising of opioids to health care professionals. Canadians were invited to submit comments on the Notice from June 19 to July 18, 2018. Over 40 submissions were received from a range of stakeholders. Feedback from these consultations is informing how Health Canada proceeds and a summary of responses received will be published.
Additionally, in June 2018, the Minister called on opioid manufacturers and distributors to immediately cease opioid marketing activities to health care practitioners, on a voluntary basis. Health Canada encouraged all companies that manufacture or distribute opioids in Canada who have not yet responded to this request to do so. CGPA has provided the response to Health Canada that the association does not promote products. See a summary of companies that received a letter and the correspondence received by Health Canada.
PPIAD indicated that the goal is to ensure that the information being shared with prescribers is factual. Health Canada has created a dedicated marketing compliance and enforcement team to proactively monitor advertising and to enforce the existing rules around improper advertising. MHPD mentioned that as of October 2018 , all opioid product materials from industry that are intended for health care professionals must be submitted to an advertising preclearance agency recognized by Health Canada for review and preclearance. CGPA questioned whether sell sheets that are provided to pharmacies and not to prescribers would fall within the scope of marketing and advertising materials. CGPA offered to provide an example of a sell sheet to PPIAD. MHPD is also designing a web page targeted to health care professionals in order to open up a dialogue to discuss the type of information being provided. Healthcare practitioners will also have the ability to report materials that they think are questionable.
Mandatory Reporting of Serious Adverse Drug Reactions (ADRs) and Medical Device Incidents (MDIs) by Hospitals
Bill Wilson, Acting Manager, and Thanh Vu, Regional Coordinator, Marketed Health Products Directorate (MHPD) presented this item. The proposed mandatory reporting regulations would amend the Food and Drug Regulations and the Medical Devices Regulations to require hospitals to provide reports of serious adverse drug reactions (ADRs) and medical device incidents (MDIs) directly to Health Canada. This is to ensure that Health Canada receives enough information to detect safety problems. Improving Health Canada’s knowledge about product safety will help Canadians to make better, more informed decisions about their medical treatment and support overall patient safety. The draft regulations were published in Canada Gazette, Part I, and stakeholders had until August 29, 2018 to provide their feedback on the proposal. After analyzing the feedback, Health Canada will consider if any changes are necessary before publishing the final regulations in Canada Gazette, Part II. Currently, for ADRs, all domestic post-market reports are posted to the Health Canada website via the Canada Vigilance Adverse Reaction Online Database. For MDIs, Health Canada is currently exploring the possibility of releasing data in line with the methods used for ADR reports.
CGPA requested information on how this initiative will be monitored. MHPD responded that promotion is the key and that Health Canada will not be going into hospitals to do inspections. MHPD indicated that it will help institutions that are not reporting and will look into why they are not reporting. CGPA requested that market authorization holders be kept informed. MHPD indicated that it is upgrading its database in order to provide information to the public and stakeholders. CGPA expressed the opinion that hospitals will not be interested in double reporting to industry as well as to Health Canada and is concerned about underreporting. MHPD indicated that the challenge is that hospitals are not reporting all adverse reactions to industry or to Health Canada. The proposed regulations apply to all hospitals (not healthcare professionals) regulated through provincial or territorial legislation, as well as to those operated by the federal government and that provide health services to persons who are in-patients.
TPD Review Performance
Christine Leroux, Office of Planning, Performance and Review Services and Bruce Randall, Director, Bureau of Pharmaceutical Sciences, TPD addressed this item. A Cost Recovery Performance Summary for fiscal year to date (FYTD) 2018-19; TPD on-time performance for FYTD 2018-19; TPD Workload for FYTD 2018-19 (as of September 30, 2018); Performance on Time Action Plan Updates; received vs. forecasted submissions; CGPA versus non-CGPA member submission filing numbers, and a pipeline data summary was presented. All 34 fee lines with decisions to report were within their cost recovery performance standard for FYTD 2018-19. On-time review performance for Abbreviated New Drug Submissions (ANDS) was 96% and for Supplemental Abbreviated New Drug Submissions (SANDS) was 100% for fiscal year to date 2018-19. The on-time target is 90% for all decisions.
CGPA indicated that industry appreciates that TPD is on target. CGPA asked if it would be possible to receive information for products that are going off of patent hold in the early afternoon rather than late in the day. Companies also requested that they receive Notices of Compliance (NOCs) earlier in the day so as not to miss the monthly provincial formulary deadline. CGPA indicated that it is also a challenge for change controls if the NOC comes in at the end of the day. TPD responded that it would look into the matter.
At the Bureau of Pharmaceutical Sciences bilateral meeting with CGPA, changes to the management of submission documents were discussed. A separate meeting is to be held in the future to discuss the topic. CGPA indicated that it has some proposals for improvements related to the administrative guidance. TPD responded that the administrative guidance is currently in the process of being revised and that it is anticipated to be published on the Health Canada website by March 2019. CGPA indicated that currently the licencee needs to follow the licensor and asked if TPD can look at whether a subset of licensors market authorization can go through an administrative pathway instead of labelling pathway. TPD responded that it will evaluate the issue.
TPD Pipeline Data Response Rate
Emile Geoffroy, Manager, Planning, Performance and Stakeholder Engagement Division, Office of Planning, Performance and Review Services (OPPRS), TPD presented this item. TPD has been collecting and collating CGPA pipeline data twice a year since 2012. This data allows TPD to resource plan and more effectively adjust to anticipated workload spikes. Participation in this initiative by CGPA members has been low with only a few companies consistently providing data. In response to TPD’s last pipeline call out in June 2017, only four of nine member companies responded. TPD continues to find value in generic pipeline data for resource planning and to inform revenue forecasting.
TPD requested CGPA’s input on the reasons for the low response rates (eg. lack of resources, burdensome, confidentiality). TPD indicated that even if companies are not able to provide the complexity questionnaire, it is still open to receiving any information. CGPA members agreed that January and June would be best to provide pipeline information to Health Canada. The association added that the number of submissions can be difficult to predict and that supplements are even harder to predict. TPD asked CGPA if it would be possible for members to provide information on Abbreviated New Drug Submissions (ANDS) over the next two years. CGPA responded that one year is better, and even that is difficult. TPD requested that CGPA provide its best estimates. CGPA requested that Anne Wilkie, CGPA, be copied when TPD sends out the call to CGPA members for pipeline data.
Action: CGPA requested information as to whether pipeline data can be disclosed under Access to Information (ATI). TPD responded that it has a reasonable belief that the pipeline data will remain confidential but Emile Geoffroy, TPD, will look into the matter.
Regulatory Enrolment Process (REP) and Electronic Common Technical Documents (eCTD) Updates
Joseph Mikhael and Irena Pastorekova, Office of Submissions and Intellectual Property (OSIP), Resource Management and Operations Directorate (RMOD) presented this item. REP consists of a set of web-based templates that capture sponsor provided information in Extensible Markup Language (XML) format. REP facilitates the filing and processing of information related to a company, dossier, regulatory activity and regulatory transaction. Once fully implemented, the REP templates will replace existing Health Canada forms such as the HC 3011 form and Fee forms. Furthermore, this process enables a move towards a common submission intake process across product lines and allows Health Canada to receive non-eCTD regulatory transactions via the Common Electronic Submission Gateway (CESG) and to automate the import of regulatory transactions into its repositories. Health Canada has currently expanded piloting the REP templates and process with pharmaceutical and biologic human drugs (Divisions 1 & 8) filed in eCTD and non-eCTD formats, and a Notice was published to solicit pilot participants on December 29, 2017. All sponsors are encouraged to take advantage of this opportunity. See the REP eCTD Pilot Notice.
A consultation notice was published on May 7, 2018 to inform stakeholders that Health Canada was considering January 1, 2019 as the date for mandatory filing of all New Master Files in eCTD format. As not enough feedback was received, the date has been moved to September 1, 2019.
The United States Food and Drug Administration (FDA) is expected to finish the development of the two-way functionality for sending and receiving documents through the CESG gateway towards the end of 2019.
Update: This date has been moved to sometime in 2020 due to various delays, including the government shutdown. CGPA members were encouraged to send any feedback on any of the initiatives above to: email@example.com
Policy and Guidance Update
a) Possible Changes to the Food and Drug Regulations: Generic Drug Equivalence and Related Terminology - Gary Condran, Associate Director, Bureau of Pharmaceutical Sciences, TPD addressed this item. The development of the regulatory proposal remains on track. The comments received from the Notice of Intent and subsequent in-person meetings with stakeholders are being considered. A draft companion Guidance document: Generic Drug Equivalence of Subsequent-Entry Products with Different Forms of the Medicinal Ingredient is being developed and is anticipated to be posted for stakeholder comments soon after the publication of the proposed amendments to the Regulations in Canada Gazette in January 2019.
b) Use of a Foreign-sourced Reference Product as a Canadian Reference Product
Bruce Randall, Director, Bureau of Pharmaceutical Sciences, TPD addressed this item. The final Guidance Document - Use of Foreign-sourced Reference Product as a Canadian Reference Product (CRP) was posted in July 2018. Revisions including administrative changes were made based on comments received during the consultation.
c) Foreign Reviews and Decisions - Elizabeth Smith-Kawasaki, Bureau of Policy, Science and International Programs (BPSIP), TPD addressed this item. The Use of Foreign Reviews (UFR) project is focused on developing processes for standardizing the use of foreign reviews, when appropriate, with clear definition on how they can be used more efficiently for the review of submissions. Under the Use of Foreign Decisions (UFD) project, Health Canada is seeking to introduce a new regulatory pathway that would allow submissions for prescription products that meet specific criteria to rely on a foreign decision to issue a Health Canada authorization. These products would be those with adequate post-market experience, that address an unmet medical need, and that would not have otherwise been marketed in Canada. Regulatory amendments will be required in order to implement the proposed UFD pathway. It is anticipated that draft guidance documents for both the UFR and UFD initiatives will be posted for comment in the Fall/Winter of 2018 and finalized in 2019. CGPA asked if these foreign decisions could be used to complement Abbreviated New Drug Submission (ANDS) filings. TPD responded that we would take this comment into consideration.
d) Amendments to the Food & Drug Regulations / Vanessa’s Law - Foreign Risk Communications - Bruce Wozny, Marketed Health Products Directorate (MHPD) addressed this item. The document Notifying Health Canada of Foreign Actions - Guidance Document for Industry was posted on November 20, 2018 with an on-line reporting form. These documents are to assist Market Authorization Holders in complying with the regulatory requirement to report actions taken in foreign jurisdictions in response to serious safety issues. MHPD thanked CGPA members who participated in the consultation and indicated that most comments received have been integrated. A webinar will be provided in the future. CGPA indicated that it appreciates the revisions of the guidance document and requested information about the level of pharmacovigilance that is required. MHPD noted that a mixture of good vigilance practices and common sense is needed. CGPA members should determine what is relevant to their companies and their products in order to plan for environmental scanning. Any suggestions related to refining the language in the guidance can be sent to Bruce Wozny, MHPD. A CGPA member indicated that its pharmacovigilance group has raised the concern about how the guideline is interpreted. The pharmacovigilance group does monitoring in markets where the company has a licence to sell and CGPA noted that any further requirements would be burdensome.
An update to the colorants list for oral products is anticipated to be published on December 22, 2018. There will be an addition of a new colorant for titianium oxide.
The Bureau of Pharmaceutical Sciences, TPD has engaged their Policy Group on options regarding Schedule B challenges.
Regulatory Pathways for Complex Products
CGPA requested an open discussion of Health Canada’s plans for the development of regulatory pathways for complex generic products. Bruce Randall, Director, Bureau of Pharmaceutical Sciences, TPD addressed this item. The Health Canada guidance document on Data Requirements for Safety and Effectiveness of Subsequent Entry Inhaled Corticosteroid Products Used for the Treatment of Asthma was published on October 31, 2018 and effective as of November 1, 2018. At a meeting on November 2, 2018, Health Canada’s Scientific Advisory Committee on Respiratory and Allergy Therapies (SAC-RAT) voted in favour of a proposal that would see the approval of subsequent-entry orally inhaled products, and changes to or line extensions of innovator products, on the basis of in vitro (including device sameness) and pharmacokinetic data, without the need for pharmacodynamic studies. The Record of Decisions for the meeting is expected to be published in January 2019. This is an opportunity to introduce products to the untapped Canadian market where there has been little generic penetration. The goal is to improve access for Canadians while still maintaining safety and efficacy. CGPA member companies may wish to reach out to TPD in the near future. CGPA indicated that receiving the endorsement of the SAC-RAT is a big step forward. CGPA suggested a government-industry working group would help move this file forward.
International Regulatory Collaboration and Convergence
CGPA indicated that its member companies are supportive of Health Canada’s participation in international regulatory convergence activities that are of relevance to the generics industry and requested an update on the topic. Gary Condran, Associate Director, Bureau of Pharmaceutical Sciences, TPD addressed this item. Working collaboratively and effectively with international partners have been long-standing priorities for the Branch. TPD indicated that it is interested in hearing CGPA’s views on the United States FDA Reflection Paper on Generics. CGPA responded that it is particularly interested in the section of the paper that discusses establishing a generic drug submission group. The association noted that the Reflection Paper focuses on having one bioequivalence standard. CGPA added that doing an additional bridging study is not helping to leverage Health Canada acceptance of non-Canadian reference products. CGPA noted that in non-Canadian biostudies, tablets and capsules are not interchangeable, whereas this is allowed in Canada. The association added that in the United States, a biostudy is not required.
The recent Australia, Canada, Singapore, and Switzerland (ACSS) Consortium meetings in Canberra Australia in September 2018 were followed by International Pharmaceutical Regulators Forum (IPRP) working groups. The meetings were hosted by the Therapeutic Goods Administration (TGA) of Australia. At ACSS, regular updates were shared and technical issues of interest (eg. salts) were discussed. The Quality working group examined issues such as valsartan, Drug Master Files, a database of administrative information and papers that could inform biowavers. Generics week in Australia focused on bioequivalence. CGPA indicated that it is pleased to see the harmonization efforts but added that there will be challenges. The association noted that the focus should be on what is critical to ensure safety.
a) Generic Company Name Consultation
Emile Geoffroy, Manager, Office of Planning, Performance and Review Services, TPD presented this item. Phase 3 of the Submissions Under Review list was launched October 1, 2018. For the first time, it will include a list of generics under review. The list of Supplement to a New Drug Submission (SNDS) list is being expanded to include company names. TPD will be doing a consultation on how publishing company names in the generic list would affect sponsors. A notice with a 30-day consultation period is anticipated to be published in January 2019. CGPA is strongly encouraged to provide feedback.
Emile Geoffroy, Manager, Office of Planning, Performance and Review Services, TPD presented this item. As Health Canada will be publishing company names for innovators on the Submissions Under Review List, the department has received a lot of feedback as to why company names for generics are not being published. For example, it might be valuable for a patient group to know if a certain product will be marketed. CGPA indicated that there are specific negative factors in publishing the names of generic companies that might negatively affect the generics industry that would not affect innovators. For example, formulary pricing is decided according to whether the product is single source or multi source. CGPA expressed concern that the formulary may not give the single source price to the first company and may delay until the product becomes multi source if that knowledge is available. TPD indicated that there would be an official consultation and that it would send CGPA an e-mail heads up a week before the notice is sent out.
c) Environmental Assessment Regulations Update
Amanda Moir, Director, Strategic Horizontal Planning Division, Policy, Planning and International Affairs Directorate (PPIAD) presented this item. PPIAD distributed a cost benefit survey in the summer and are currently working on analyzing the responses with the goal of moving towards publication of draft regulations in the Canada Gazette in Spring 2019 and a supporting guidance document. The development of a list is being explored that will prevent the need to resubmit substances that have already undergone a complete environmental risk assessment for a specific indication. There is a need to balance between aligning internationally and being deemed Canadian Environmental Protection Act (CEPA) equivalent. CGPA stated that in the United States generics do not have to submit environmental data. PPIAD indicated that Abbreviated New Drug Submissions (ANDS) cannot be de-linked because of the basic dataset need for CEPA equivalency.
Action: A follow-up discussion between PPIAD and CGPA will be held on this topic.
Update: On January 8, 2019, Amanda Moir, PPIAD, sent CGPA a summary of the changes made to the regulatory proposal since the launch of the Cost Benefit survey and indicated that PPIAD would be open to holding a meeting with CGPA to review the proposal.
d) Angiotensin II Receptor Blockers (ARBs)
Bruce Randall, Director, Bureau of Pharmaceutical Sciences, TPD presented this item. ARBs continue to be an issue globally. Market Authorization Holders (MAHs) were sent a letter September 25, 2018. In follow up, a second letter is expected to be sent out in December 2018 requesting testing of the product and/or Active Pharmaceutical Ingredients (APIs) for two nitrosamines. The letter will include some potential analytical methods to conduct the testing. Health Canada is expecting to receive the summary of the Active Pharmaceutical Ingredient (API) testing results by the end of January 2019. TPD asked CGPA what the level of company readiness is for doing these tests. CGPA responded that companies originally relied on suppliers to do quality testing. TPD does not anticipate that there will be a large number of recalls as a result of this request.
Closing Remarks and Adjournment
Co-chairs Bruce Randall, TPD, and Duane Terrill, CGPA thanked everyone for participating in the meeting.
Meeting adjourned at 4:30 p.m.
Original signed by:
Director, Bureau of Pharmaceutical Sciences
Therapeutic Products Directorate
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