Association bilateral meeting - BIOTECanada - Meeting Minutes - 2012-04-18

Bilateral meeting between BIOTECanada and Health Canada

Wednesday, April 18, 2012
1:00 pm to 4:00 pm
200 Tunney's Pasture Driveway, Room 0105, Tunney's Pasture, Ottawa, ON

Attendance

Health Canada Participants

Robert Cushman, Director General, BGTD (Co-Chair)
Catherine Parker, OPIC, BGTD
Agnes Klein, CERB, BGTD
Georgette Roy, ORA, BGTD
Lindsay Elmgren, CVE, BGTD
Monica Dhir, OLRM, HPFB
Ariel Arias, CBTE, BGTD
Martin Nemec, CERB, BGTD
Julie Wallace, OPIC, BGTD
Kwasi Nyarko, OPIC, BGTD
Greg Monsour, OPIC, BGTD
Scott McCash, OPIC, BGTD

BIOTECanada Participants

John Cockhill, Biologics Regulatory Advisory Group (Co-Chair)
Ron Boch, BIOTECanada
Peter Brenders, BIOTECanada
Karen Burke, Amgen
Anita Hammer, Amgen
Jennifer Chan, Merck
Laurel Christmann, Biogen Idec
Lawrence Colero, Novo Nordisk
Roceyln DelCarmen, Astra Zeneca
Loretta Del Bosco, Abbott
Sue Drohan, Genzyme
Cathy Lau, Janssen
Lise Lotter, Sanofi-Pasteur
Maria Perrotta, Novartis
Sandra Usik, Eli Lilly
Vratislav Hadrava, Pfizer

Teleconference

Sheila Critchlow, Nycomed

1.0 Welcome and Introductions

Following round table introductions, co-chair Dr. Robert Cushman introduced himself as the new Director General of BGTD and expressed his commitment to maintaining the longstanding and productive bilateral relationship with BIOTECanada. Co-chair John Cockhill thanked R. Cushman for his remarks and noted that BIOTECanada members look forward to hearing Dr. Cushman's vision for BGTD at future bilateral meetings.

2.0 Review of Agenda

The agenda for the meeting was approved.

3.0 Standing Items

A. Regulatory Performance

G. Roy informed BIOTECanada that the latest BGTD Quarterly report is currently in draft form and will be posted shortly. Between November 2011 and April 2012, a total of 535 regulatory decisions were made. All decisions met the performance target.

B. Legislative and Regulatory Modernization

M. Dhir provided an update on regulatory modernization, noting that the process is planned to unfold in three separate phases. The first phase, which is currently underway, includes regulatory frameworks for orphan drugs for rare diseases, food additives and plain language labelling. Although a firm timeline for implementation has not been established, M. Dhir noted that regulatory modernization is a top priority for the Branch.

4.0 Analysis of Clarifaxes

Following up on a commitment made at the last bilateral meeting to provide a more detailed analysis of recently issued clarifaxes, G. Roy provided a summary of the clarifaxes issued for all New Drug Submissions received by BGTD in 2011, including the number of clarifaxes issued for each submission, the proximity of their issuance to the target date and a breakdown of the sorts of questions being asked of sponsors.

In general, the majority of clarifaxes issued were for clinical questions and many were for recurring issues. Fewer clarifaxes were issued for Chemistry and Manufacturing (C&M).

5.0 Yearly Biologics Product Report (YBPR) Template

J. Chan requested an update on the status of the YBPR template project, wondering if the template had been re-drafted based on previous BIOTECanada comments and whether a face-to-face meeting of subject matter experts from BGTD and BIOTECanada member companies to finalise the template is expected.

M. Nemec provided hard copies of the latest draft of the template, which was updated to reflect BIOTECanada's comments and stated that the YBPR Working Group agreed with the idea of holding a meeting with BIOTECanada representatives to finalise the document.

It was decided that the latest draft of the template would be circulated electronically and serve as the basis for the face-to-face meeting, to be scheduled between the two parties.

6.0 TSE Guidance

The draft Guidance Document: Regulatory Requirements to Minimize the Risk of Transmission of Transmissible Spongiform Encephalopathies (TSEs) via Animal-Sourced Materials used in the Manufacture of Schedule D (Biologic) Drugs was introduced by C. Parker, who explained that in 2004 BGTD developed a policy document to address the risk of TSEs. The policy was based on information communicated by the World Health Organization (WHO) but it was never finalized for external release, used only for guiding reviewers in conducting risk assessments. Recent WHO updates to its categories of TSE infectivity have been incorporated into a revised version of the Guidance Document.

In keeping with efforts to increase transparency of its internal processes, C. Parker announced BGTD's intention to release the guidance externally for a 90-day comment period.

7.0 Foreign Collaboration

R. DelCarmen requested comment from BGTD on two issues related to foreign regulatory collaboration. First was the question of having BGTD reviewers sit in on United States Food and Drug Administration (FDA) meetings as observers, including "clusters" of foreign reviewers coming together in the interest of providing harmonized advice. Second was a request for an update on the Use of Foreign Reviews Project.

A. Klein noted that BGTD is collaborating with foreign regulators on a number of fronts, including an oncology cluster currently led by TPD but whose lead will transfer to BGTD under Dr. Jian Wang at the end of April 2012 and two regular paediatric teleconferences. BGTD has also recently received invitations from the FDA to participate directly in the meeting of two advisory committees.

C. Parker added that BGTD also recently received an invitation from the FDA and European Medicines Agency (EMA) to participate in a cluster related to blood products.

G. Roy explained that while BGTD has yet to use any of the methods outlined in the Draft Guidance Document: The Use of Foreign Reviews by Health Canada, the directorate routinely uses the foreign regulatory information from that sponsors provide.

8.0 Monoclonal Antibody Production Capacity

G. Monsour shared the background on the Canadian HIV Vaccine Initiative (CHVI) between the Government of Canada and the Bill and Melinda Gates Foundation (BMGF) regarding global efforts to develop a safe, effective, affordable and globally accessible HIV vaccine. The BMGF would like to have a better understanding of Canada's production capacity for broadly neutralizing monoclonal antibodies and have the following questions:

1. Approximately how many companies have any direct experience with cGMP manufacturing of human monoclonal antibodies?
2. How many companies have the capacity for commercial scale? (defined as >10,000 litre bioreactor with a batch rate of approximately 100/year); and to what extent is capacity currently underutilized?
3. What is the range of companies that would engage in small-scale manufacturing of multiple antibodies, using transient transfection or incompletely optimized cell lines? Manufacturing for clinical trials?

Action Item:

BIOTECanada will survey member companies and provide a response to BGTD, if requested.

9.0 ORA Process Efficiencies

G. Roy requested discussion about and, if possible, decisions on two proposals that would enable the Office of Regulatory Affairs (ORA) to reduce processing costs and improve efficiencies.

First was the proposal to begin sending review reports to sponsors by email rather than by mail courier. The second was to send screening acceptance letters by email rather than by fax and mail. Both proposals were met with unanimous approval from BIOTECanada members and the new processes will be implemented in ORA.

10.0 On-Site Evaluations

C. Parker introduced proposed changes to on-site evaluations (OSE) conducted by BGTD. It was noted that the OSE plays an integral role in the pre-market evaluation process at manufacturing facilities for biologics in Canada. The main purpose of the OSE is to confirm that the review team has verified the integrity of the manufacturing process, to ensure that the facilities, processes, and testing regime are appropriate for the product(s) under review, and that this information is adequately captured in the submission documentation.

Currently, the need to perform an OSE is rationalized based on risk. For most biologic drug submissions, the decision to perform an OSE is complex and balances the potential benefits of performing the OSE against the risks associated with not performing it and the human and financial resources available. A set of Standard Operating Procedures has been developed by the BGTD to standardize the OSE program across the directorate. The final decision on whether or not to perform an OSE rests with the product-line centre directors and the rationale is documented in the review report and the executive summary.

Up until now BGTD has exclusively borne the expenses and costs associated with the performance of an OSE, which include travel and accommodation costs as well as personnel time. Given the fiscal constraints BGTD is facing in the upcoming years as part of the Deficit Reduction Initiative, alternate ways of funding the OSE program must be examined. BGTD would like to move forward in 2012/2013 with a new process whereby the travel related expenses of performing an OSE are paid by the manufacturer. This process is already in place within the Health Products and Food Branch Inspectorate, which is reimbursed for such expenses when performing certain GMP inspections. A draft service agreement for the conduct of OSEs under this new process was provided for comment.

BIOTECanada acknowledged the value of OSEs, but recommended that any additional costs should be planned for launch in 2013 so that companies can budget accordingly in advance. It was also noted that the draft service agreement for the conduct of OSEs under this new process (as provided for comment) would need to be reviewed by the legal department of most sponsors before use, and that a certain amount of customization might be expected.

It is anticipated that OSEs will be discussed on a more standard basis at pre-submission meetings.

Action Item:

BIOTECanada agreed to have the proposed contract language and statements regarding liabilities examined by the BIOTECanada legal group and respective legal counterparts and report back to BGTD with comments.

11.0 Subsequent Entry Biologics

C. Lau expressed an appreciation for BGTD's thorough review of the Subsequent Entry Biologics (SEB) International Nonproprietary Naming (INN) position paper provided by BIOTECanada in advance of the meeting. The paper noted that the concern is traceability from a pharmacovigilance point of view regarding the issue of immunogenicity - if we have several biosimilars and reference products we need to be able to identify to which drug the immunogenicity pertains.

K. Nyarko responded on behalf of BGTD and made the following points in a slide presentation:

1. A case could be made for the development of a globally harmonized naming system for tracking and attributing suspected adverse reactions to SEBs but the INN system may not be the most appropriate system as it was developed for small molecule pharmaceutical drugs.
2. If SEBs are new drugs, why should they have a distinct (different) naming system?
3. Why not promote the use of brand names rather than INNs for reporting of ARs?

Health Canada supports a global harmonized naming system for SEBs for traceability of AEs but INN may not be the most appropriate system. As SEBs are new drugs and not generic biologics, a distinct naming system is not required and AE should be traced by reporting on brand name of the SEB. The INN was not developed for tracking purposes and the INN is not regularly used on ADR forms.

As BGTD also believes that the field will continue to evolve and global consensus among regulators is required (this is the most active area for international collaboration and under the work plan with the WHO), BIOTECanada would like to request SEB and its naming system to be standing agenda items for future bilateral meetings especially if SEBs are included in future Phases of the LRM process.

12.0 Update on Personalised Medicine

M. Perrotta inquired about the status of the Steering Committee that was to be formed to assess the role of the federal government in the uptake of personalized medicines. 

A. Klein informed the group that the establishment of an external working group has been deferred from the initial timeline but that this is still a priority for BGTD. C. Parker noted that OPIC will likely take the lead on moving the project forward, while coordinating efforts with the Strategic Policy Branch.

A follow-up workshop regarding Personalized Medicines has been scheduled for May 15-16 in Montreal. Industry will be present at this workshop. BGTD will follow-up with Hans Yu to determine participation and A. Klein will send a note to Dr. Morag Park regarding this CIHR Workshop.

A guidance document on stem cell therapies is under internal review. Following internal review external consultations will take place possibly by the end of 2012.

There are a number of stem cell initiatives where BGTD is involved.

Action Item:

BGTD proposes to provide an update on activities pertaining to cellular therapies at the next bilateral meeting.

13.0 Roundtable

Meetings will continue to take place twice annually. The next meeting is tentatively scheduled for October or November 2012. A date will be agreed upon following the meeting.

Meeting adjourned at 3:30 PM.