ARCHIVED - Biomanufacturing Vaccine Facility Project overview and status deck

Slide 1

NRC Biomanufacturing Vaccine Facility (BVF) Project: Overview & Status

September 25, 2020
Maria Aubrey, VP and Special Advisor to the President
Working Draft

Slide 2

Context

• Covid-19 pandemic
• Vaccine Task Force
• NRC Covid-19 vaccine mandate

Slide 3

The COVID-19 pandemic

The federal government developed a three-pronged strategy to address the crisis:

Recognizing the urgent need for Canada to be able to guarantee access for all Canadians to a safe and effective COVID-19 vaccine, when one becomes available

• Scale-up domestic manufacturing capacity
• Partner with the most promising global vaccine candidates through advance purchase agreements and in-licensing arrangements
• Invest in a small number of the most promising domestic vaccine candidates

Slide 4

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Slide 5

NRC's COVID-19 vaccine mandate

Clinical Trial Manufacturing Facility (CTMF) (Spring 2020): $44M for producing vaccines for clinical trials

• Ensure that facility complies with good manufacturing practices (GMP) for development, testing, scale-up and production of promising vaccine candidates.
• Enable the preliminary production of 250,000 doses of vaccine per month starting in November 2020.

Biomanufacturing Vaccine Facility (BVF) (Summer 2020): $126M over two years for vaccine biomanufacturing

• Establish a new biomanufacturing facility at the Royalmount site operated through a public-private partnership.
• Enable GMP certified vaccine production capacity to produce approx. two million doses per month by next year.

Slide 6

BVF & CTMF: What they are and are not…

Slide 7

Scope of the BVF & CTMF

What the facilities do

BVF

• A End-to-End GMP Manufacturing facility
• Up to 2500L throughput capacity (1 x 500L, 1 x 2000L) and approx. 4000L production capacity per/mth
• Fill/Finish included
• Pandemic response GMP production - (Phase III) / national/ international public good role – potential co-development with other countries
• Post-pandemic GMP production – Phase II onward/ national/ international projects for rare diseases (public good)
• Training – focused on enhancing GMP expertise in Canada
• De-risk biomanufacturing capacity in Canada; work collaboratively with industry, SMEs and academia
• Public interest funded projects (e.g., rare diseases)

CTMF

• Research and Development facility
• R&D bench scale to Phase I and Phase II
• Non-validated processes/ methods validated to Phase II
• Up to 500L throughput capacity
• Fill/ Finish outsourced
• Pandemic response clinical production – up to Phase II trial
• Post-pandemic clinical production – up to first human trials
• Training – graduate students
• Collaboration with industry, SMEs and academia

What the Facilities do not do

• Bulk commercial production – selling products
• Competing with the private sector
• Outside of pandemic response – producing traditional flu vaccines

Slide 8

Continuum between CTMF, BVF & ecosystem

Long description of slide 8

• The continuum demonstrates the positioning of the CTMF and BVF in the biomanufacturing ecosystem
• In general, the CTMF is involved with proof-of-concept, specifically, with vaccine development and early, clinical trial material (up to 500-litre scale)
• In general, the BVF in involved with proof-of-product, specifically small and large-scale production of vaccines (500-litre and 2000-litre scale) ensuring scalability and process maturation up to distribution, or to technology transfer
• In general, the CDO/CDMO eco-system is involved with product commercialization, specifically biomanufacturing services and bulk commercial production of vaccines and other biologics

Slide 9

BVF project overview & status

• Objectives
• Design & build
• Governance

Slide 10

BVF project objectives

Goals

1. Establish a GMP Biomanufacturing Vaccine Facility with capacity to produce approx. 2M doses^{Footnote *} per month to help mitigate the lack of domestic access and surety of supply for COVID-19 vaccines, including the international community.
2. Support a pipeline of "made in Canada" vaccines and biologics, and help accelerate Canadian innovation.

This Project helps address both the immediate COVID-19 crisis and the enduring need to bolster Canada's biomanufacturing capacity to better position the country now and for the future.

Long description of slide 10

The BVF project will help to de-risk vaccine biomanufacturing in order to address the lack of domestic biomanufacturing capacity.

The BVF project will collaborate and help our collaborators get products approved for emergency and general use in Canada.

Slide 11

Results/benefits to be realized

Increase

• The number of vaccine candidates that are brought to clinical trial and market
• The number of health innovation companies in Canada
• The amount of manufacturing undertaken by these companies
• The number of professional, science and technology-related jobs
• Firm expenditure on research and development

Strengthen

• Strengthen Canada's domestic capacity to manufacture, fill and disseminate a COVID-19 vaccine
• Improve Canadians' access to a COVID-19 vaccine and potentially reduce the cost of accessing vaccine(s)
• Strengthen Canada's ability to respond to the current global pandemic and other future public health crises

Slide 12

BVF Design & Build

• Location
• Design
• GMP process
• Critical milestones

Slide 13

Project location at Royalmount

Long description of slide 13

The project is located next to the NRC's Human Health Therapeutics (HHT) Research Centre on Royalmount Avenue in Montreal. HHT already exists at the Royalmount site. As shown in the aerial photo, the BVF is being constructed adjacent to HHT. Additional parking will be available next to the existing NRC building.

Slide 14

Facility design

• Facility production capacity 4000L/month
• Dosage dependant on vaccine (current est. 2M/month)
• ~ 4,900 m2 (on 2 floors)
• Biomanufacturing:
  • USP (500L +2000L lines)
  • DSP (2 dedicated lines)
  • Fill & Finish (10ml multi-doses & 2ml single doses)
  • Prefab panels, Grade C and D
  • Multi-products capabilities (airlocks)
  • BSL2 rooms (virus sees, subculture, USP, DSp, Fill)
• Support:
  • Decontamination
  • Cleaning & Sterilization
  • Secondary packaging
  • Warehouse
  • Visitor center
• QC labs + Mechanical Area + Offices on the second floor

[REDACTED]

Slide 15

Process overview

(Aug 8, 2020)

Long description of slide 15

• This is an overview of the process to produce vaccines from cells.
• The upper right quadrant depicts the process of making the buffer and growth media in which the cells will grow by reproducing. Essentially the growth media protect and feed the cells, so they can multiply and the buffers are utilized to clarify the product to the final form.
• The growth process for the cells starts at the top of the upper left quadrant. The cells arrive frozen, then are thawed and placed in liquid (represented by the red boxes).
• Beneath them in the graphic is the contained virus (represented by purple boxes), which will enter the vaccine production process at a later point.
• In the lower left quadrant are the bioreactors in which the cells are placed to multiply (represented by orange boxes). The bioreactors are fed by growth media (represented by the small light-blue boxes). There are two sizes of bioreactors – 500L and 2000L.
  • The top row (with more small light-blue boxes representing buffer and growth media) shows the 2000L process, where the cells are first placed in 20L containers, then transferred to 200L ones as they grow and multiply, until transferred to the largest container of 2000L.
  • The row below shows the 500L bioreactor process (with fewer small light-blue boxes) in which the cells are transferred only from 50L to 500L.
• Cell growth is about a 2-week process. When the cells have fully expanded to fit their containers, they are "infected" with the virus.
• These cells are then transferred to the chromatography area in the lower right quadrant. The cells are in liquid in containers (represented by dark-blue boxes) and are still fed with buffer media (represented by the small light-blue boxes).
• The cells undergo two chromatography processes and move to a tangential filtration concentrate. Chromatography is about a 1-day process.
• The cells are diluted with solution to make the right concentration, which becomes the vaccine.
• In the final steps, at the very bottom of the graphic, from left to right, the vaccine is moved to a fill-and-finish area where it is put in vials, and inspected. The vials are then closed and labelled, packaged, put into cartons on pallets, then shipped.

Slide 16

Facility design and build: Mission critical milestones

• Design and build launched (August 2020)
• Procurement of long-lead equipment (September 2020)
• Interior design complete (November 2020)
• Shell construction complete (December 2020)
• Interior fit-up (March 2020)
• QA and QC for facility commissioning (starts May 2021)
• Facility commissioned & qualified (July 2021)

Slide 17

Construction is underway

Long description of slide 17

Photos show early construction of the foundation for the external shell of the biomanufacturing facility.

Slide 18

BVF Governance & Risks

Slide 19

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Slide 20

Key risks to manage

Construction delay

• There is a risk that facility's physical build will be delayed.
• Mitigation: This strategy leverages existing buildings and infrastructure in order to minimize the risk of new builds.

Operational readiness delays

• There is a risk that we won't be able to acquire the resources needed to get the facility operationally ready.
• Mitigation: Expedite purchase of long lead equipment and on boarding of experts/qualified personnel immediately.

Regulatory and commissioning delays

• There is a risk that the time it takes to validate the new facility and receive regulatory approval/testing will cause delays.
• Mitigation: Involve Health Canada regulators in each step to provide them transparency and shorten turnaround.

Delay in COVID-19 vaccine candidate

• There is a risk that the vaccine candidate to respond to the COVID-19 pandemic may be delayed, impacting the facility's readiness due to the time required for technology transfer and regulatory approval prior to GMP vaccine production.
• Mitigation: Get the facility operationally ready based on generic GMP vaccine process, and adjust once vaccine is received.

Long-term sustainability

• There is a risk that we create short-term capacity to respond to COVID-19 that lies dormant in the future.
• Mitigation: Develop BVF sustainability business case based on market assessment and financial modelling scenarios (opex costs & pricing).

Slide 21

Project governance & structure

Long description of slide 21

• The VP & Special Advisor to the President, is leading the Biologics Manufacturing Project and reports directly to the NRC President
• The VP and Special Advisor to the President are informed by External Advisors and an Independent Third Party Review
• Direct Reports to the VP & Special Advisor to the President include:
  • Senior Project Manager, responsible for the design, construction and qualification of the facility, including procurement of equipment and other items for the facility.
  • Director General, BVF Operations, responsible for operationalizing the biomanufacturing facility.
  • Director General, BVF Project, responsible for project management and administration, policy analysis and business strategy, as well as the guidance and oversight functions of the project.

Slide 22

Annex A: Other Biomanufacturing Facilities Abroad

Slide 23

[REDACTED]

Slide 24

VMIC: Operational governance

Board composition:

• [REDACTED]
• 3 academic institutions; University of Oxford, Imperial College and the London School of Hygiene and Tropical Medicine
• 3 industrial partners; Janssen, MSD and Cytiva, formerly GE Life Sciences who contribute in-kind industry funding

Slide 25

VMIC: Management governance

[REDACTED]

UK Government present as an observer only and level of involvement is establish in the partnership agreement:

• VMIC will serve as an emergency response capability for the UK government in order to produce vaccines against emerging infectious diseases and deliberate/accidental release of biological agents

Slide 26

CIADMs (USA): Overview

• U.S. Department of Health and Human Services (HHS) issued RFPs for CIADMs as public‐private partnerships
• Centers for Innovation and Advanced Development Manufacturing's (CIADM) formed part of a national strategy to increase domestic vaccine and other biologicals manufacturing capabilities in an emergency
• CIADMs run by a consortium led by an organization experienced in developing or manufacturing medical countermeasures
• HHS awarded 3 contracts;
  • Emergent Manufacturing Operations Baltimore LLC, Baltimore, Md
  • Seqirus, Holly Springs, NC (originally operated by Novartis )
  • Texas A&M University System of College Station, Texas
• HHS supports cost of operation and maintenance in subsequent years

Slide 27

CIADMs: Operational governance

• CIADM's formed part of a national strategy to;
  • Addressing capacity to respond to pandemics and bioterrorism threats, and increase domestic vaccine and other biologicals manufacturing capabilities in an emergency
  • Support development and manufacturing of chemical, biological, radiological and nuclear medical countermeasures
  • Advance and promote the biotech workforce by providing workforce development programs
• CIADMs run by a consortium led by an organization experienced in developing or manufacturing medical countermeasures
• Overseen by BARDA (Biomedical Advanced Research and Development Authority) within the HHS office
• Contracts can be renewed for up to 25 yrs representing long-term commitment to partnership with industry and national security
• HHS supports cost of operation and maintenance in subsequent years

Slide 28

Thank You

Maria Aubrey, VP and Special Advisor to the President