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CTSG April 2019 Update

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CTSG April 2019 Update - We had our bi-annual Cell Therapy Stakeholder Group (CTSG) meeting with Health Canada on April 30, 2019.

9 Agenda items were presented and discussed at this meeting. Approved meeting minutes are available here.  

1) The first agenda item included a welcome, roundtable and announcements of retirements and new appointments. Cathy Parker co-chair of the CTSG group and Director General of BGTD had retired in December 2018. Dr. Celia Lourenco took up this role as new DG of BGTD. Marianne Tang was introduced as the new director for the Office of Regulatory Affairs (ORA), with Georgette Roy’s retirement in December 2018. With Lindsay Elmgren’s departure in September 2018, Michael Rosu-Myles became the new director of the Centre for Biologics Evaluation (CBE). Beth Beaulieu was introduced as BGTD’s new Bilateral Meeting Program Coordinator, taking over from Ashley Baer.

2) The second agenda item led by Deborah Ashby from HECSB was an Update on the Draft Supplementary Guidance Document for the Notification and Testing of New Substances: Organisms – Comments were received on the supplementary guidance document and a new version of the guidance document is expected to be available in Summer 2019. This guidance document will be helpful to sponsors submitting for gene therapy, cell therapy or immunotherapy trials. The review time has been shortened from 120-days to 30-days. Sponsors are encouraged to schedule a pre-notification consultation meeting with the NS program before or at the same time as the pre-CTA meetings. Environmental submission packages can be submitted before CTA packages.

There were discussions about developing a test case on NSN submissions for cell and gene therapy substances, and there was considerable enthusiasm for this from the CTSG stakeholders.

BGTD clarified that HECSB is another Health Canada Branch outside of BGTD and that BGTD has implemented a notice in our response to stakeholders in the meeting confirmation notice, where they are made aware of the need for the environmental assessment. There was questions around who assumes liability around the NSN submission, and HECSB clarified that this would be the importer or Canadian manufacturer, which may or may not be the same sponsor.

3) The third agenda item was a follow up on previous agenda items and this included an update on ROEB communication plan, which was being rolled out to the stem cell clinics from Mimi Lin/Manager from Health Product Compliance and Enforcement, ROEB. Over 30 clinics were contacted to gather information, and three clinics engaged in allogenic stem cell activity were asked to immediately stop importation and sale of the products. All three clinics complied with Health Canada’s request.

Health Canada also provided contact information should any concerns on safety or quality of a health product:

1-800-267-9675, or complete an online complaint form: http://healthycanadians.gc.ca/apps/radar/MD-IM-0005.08.html.

Media outlets requiring comment or statement from Health Canada and the Public Health Agency of Canada are urged to contact
T: 613-957-2983; x: 613-952-7747;
Email: hc.media.sc@canada.ca.

Another follow-up item metrics that BGTD collected on out-of-specifications on traditional vs. investigational cell therapy products. CTSG stakeholders wondered if there was significant increase in OOS for investigational cell therapy products, it could lay the ground for future policy considerations around OOS for cell/gene therapy products, especially fresh autologous products with limited shelf-lives. BGTD responded that it does not systematically collect this information. However, there are mechanism in place, especially during investigational clinical trials, which require Fax-Back form for lot releases. OOS can be checked off on this form, and approved, provided sufficient rationale where benefits outweigh the risk are properly provided. This turnaround is rapid for autologous fresh products. Additional safeguards such as informed consent to infuse patients with OOS products are typically required. Sponsors are urged to collect this data and help refine specifications through the clinical trial process.

4) The fourth agenda item on the list was an Update on Understanding and differentiating the R2D2 and Budget 2019 Implementation Strategies and Timelines from BGTD. BGTD clarified that the The Regulatory Review of Drugs and Devices (R2D2) initiative began with Budget 2017 and was focused on:

  • streamlining HC processes and policies
  • creating new review pathways
  • enhancing use of real word evidence
  • working with health technology assessment organizations to reduce time between Health Canada approval and reimbursement recommendations
  • working with international regulators on joint reviews or to make use of foreign decisions to support product access in Canada

Consultations on this regulatory review are ongoing and implementation of regulatory initiatives is expected by 2021. Please see this link for more information - https://www.canada.ca/en/health-canada/corporate/transparency/regulatory-transparency-and-openness/improving-review-drugs-devices.html#a2

BGTD also provided a clarification on The Budget 2019 Implementation is a separate initiative. These led by the Treasury Board Secretariat and Policy, Planning and International Affairs Directorate (PPIAD) PPIAD and focused on improvements to clinical trials and creating regulatory approval pathways for advanced therapies. The Regulatory Reform initiative started after the Federal Budget 2018 and led to a horizon scan by HPFB which identified three key elements for regulatory modernization:

  1. the need to remove outdated requirements,
  2. increase regulatory flexibility and
  3. support access to the most advanced therapeutic products. A “Regulatory Roadmap” was developed for each of the Reviews, and Budget 2019 contains the necessary funding and legislative revisions to move forward on these Roadmaps.

As part of the recently tabled Budget Implementation Act, a number of amendments have been propose including:

  1. classification of products that blur the current category lines of drug, device, food or cosmetic;
  2. oversight for conduct of clinical trials for drugs, devices and foods for special dietary purposes throughout the whole lifecycle of the trial; and
  3. create a market pathway for novel advanced therapeutic products through the use of regulatory “sandboxes”.

Health Canada is seeking ongoing consultation on the Regulatory Review Roadmaps.

There was much discussion on what would fit under the new market pathways, and Health Canada clarified that it was really new technologies that challenge current pathways that would enter the market through this novel pathway, which would require the product to the placed on “Schedule G.” Health Canada offered Artificial Intelligence (AI) that are currently challenging current regulatory framework that would go through this new pathway, which is currently a pathway for market authorization, not for initiating investigational clinical trials. It was clarified that “Schedule G” was not an accelerated pathway, but rather a customized pathway for product that do not currently fit in Health Canada’s current regulatory framework.

5) Agenda Item 5 was on Advanced Cell and Gene Therapies Action Plan and Working Group. This update was provided by BGTD policy initiatives with focus on three main areas: i) ongoing policy work and guidance to support safe and effective Advanced Cell Therapy development in Canada; ii) international engagement to support harmonization at an early stage of product development, and iii) stakeholder engagement to promote regulatory capacity of this largely academic community. BGTD will launch an a cross-branch internal working group to prioritize and address challenges across the lifecycle of advanced therapies, keeping an eye on new guidelines from the US FDA around products starting in academia, and will work through both the pre-and post-market space. The idea is to develop a new advanced therapies action plan. Consultation through public roadshows or with this stakeholder group will occur as needed.

6) Agenda Item 6 was on Regulatory Sandbox Proposal for GMP Audits. CTSG wanted to engage with Regulatory, Operations, and Enforcement Branch (ROEB) of Health Canada on a pilot site visit to have the ROEB Inspectors and BGTD reviewers visit with a Canadian manufacturing facility to i) help train and educate the Canadian manufacturers on processes for GMP audits and Establishment License (EL) requirements, and ii) for ROEB Inspectors and Reviewers to understand the unique challenges and gaps in the highly specialized area of manufacturing for advanced cell and gene therapies. This was deemed an excellent learning opportunity for the stakeholders and ROEB, as currently inspection does not take place at the clinical trial stage, and challenges on source material variability, different manufacturing models, specialized equipment used in gene and cell therapy field, unique manufacturing requirements and difficulties in distribution and comparability between manufacturing sites often arise. Potential dates for two site visits will be discussed with ROEB and will be open to stakeholder group, CTA reviewers, ROEB inspectors, and the learning from this visit will be shared and disseminated to help other interested stakeholders.

7) Agenda Item 7 was on inclusion of examples of minimally manipulated autologous cells for homologous use in current guidelines, in response to a letter from the International Society for Stem Cell Research (ISSCR) and as follow up to previous agenda items on a policy statement on this issue. Health Canada clarified that other than allogeneic minimally manipulated cell therapies intended for homologous use in patients, which falls under the scope of the Safety of Human Cells, Tissues and Organs for Transplantation Regulations (CTO Regulations), most of cell therapies are regulated under the Food and Drug Regulations. Health Canada clarified that it would be putting out a position paper, and this in fact has been issued as of May 15, 2019. Please see this link: Position Paper. Health Canada shared that if there are concerns about potential non-compliant sales or advertising of health products, CTSG members should contact HC online by submitting the Health Product Complaint Form (FRM-0317).

8) Agenda Item 8 was on BGTD Pipeline Initiative to compile data to enhance planning and forecasting, as part of an ongoing initiative since 2011. BGTD is looking to collect information on New Drug Submissions on an annual basis, similar to the Therapeutics Products Directorate for this initiative. A template would be circulated to the CTSG group and would involve collection of traditional information along with some additional input on whether the indication is a rare disease, pediatric, based on real world evidence, approved in other jurisdictions, or for
a biosimilar.

9) Agenda Item 9 was a roundtable discussion and focused on getting the Terms of Reference for the CTSG group approved. Amendments had been sent in 2017/2018 but not formally approved by Health Canada. BGTD said that they had some concerns with the ToR and wanted to ensure that it was be open, transparent and fair to all groups working in this field. CTSG was concerned that their group was being seen as being restrictive as this was not the intention, and wanted to get BGTD comments on the ToR in advance of the next meeting to be able to address them through internal discussions.

Details
  • 17/09/2019

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