What Are the Challenges for Clinical Biomanufacturing and Supply Chains of the COVID-19 Pandemic? - Steven Chamow, Ph.D - Alira Health
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Steven Chamow, Ph.D. What Are the Challenges for Clinical Biomanufacturing and Supply Chains of the COVID-19 Pandemic? San Mateo, CA USA | +1 650-345-1878 | info@chamowassociates.com
Overview
HOW ARE VACCINES MADE?
1 Four types of vaccines
WHAT ARE THE RISKS TO VACCINE
2 SUPPLY?
How do the Pfizer and Moderna supply chains differ?
3 LONG-TERM IMPACTS 2
Pre-Reads
Steve Banker, “It Isn’t Just About a COVID Vaccine, There Are
01 Significant Supply Chain Hurdles”, Forbes, 9 Nov 2020
Brooke Sutherland, “Vaccine Supply Chains Bend But Don’t
02 Break”, Bloomberg Opinion, 4 Dec 2020
Jonathan Gardner, Ned Pagliarulo and Ben Fidler, “The First
03 Coronavirus Vaccines Have Arrived. Here’s Where the Rest Stand.”
BiopharmaDive, 14 Jan 2021
3Key take-aways
We face the biggest medical manufacturing challenge in history, and it is
driven by
§ The sheer number of doses and the compressed time in which they are
needed
§ The number of vaccine candidates in play
§ The fact that this is a global pandemic
These factors are placing tremendous stress on biomanufacturing capacity
and on its supply chain
4How are Vaccines Made?
Four types of vaccines
Number of leading
Vaccine type Immunogen type Examples programs for COVID-
19
Smallpox, rabies, polio,
Whole virus vaccine Inactivated virus measles, mumps, rubella, 2
yellow fever
Subunit vaccine Protein subunit Hepatitis C, shingles 3
First approved in 2019 for
Viral vector vaccine against Ebola (rVSV- 4
ZEBOV)
Genetic vaccine
Technology developed in the
DNA or RNA-based 4
2010s.
6
6Producing vaccines
Whole Virus Protein Subunit Viral Vector DNA RNA
Synthesis cDNA Synthesis cDNA Synthesis DNA Synthesis RNA
Construct Construct Construct Encapsulate in
recombinant plasmid recombinant recombinant lipid
containing cDNA adenovirus plasmid nanoparticle
Cells containing vaccine
element to be manufactured
713 leading vaccine candidates
Sponsor Country Target supply
Moderna* USA 600-1,000M doses in 2021
Planned Pfizer/BioNTech* USA/Germany 2,000M doses in 2021
production of Clover China 100M doses annually
doses for CureVac Germany 300M doses in 2021
COVID-19 Gamaleya Research Institute* Russia 200M doses in 2021
vaccines Inovio USA 100M doses in 2021
Johnson & Johnson USA 1,000M doses
Merck USA Undisclosed
Novavax USA 2,000M beginning in 2021
Oxford University/AstraZeneca* UK 2,000M doses
Sanofi/GSK USA 1,000M doses by mid-2021
Sinopharm* China Undisclosed
Sinovac China 100M doses annually
8
*Authorized for use by regulatory authorityHow much is needed and by when?
Anticipated US demand* US supply targets
Date US Govt. Goal Vaccinations Moderna Pfizer
Dec 2020 20M 2.1M 20M 25M
Apr 2021 100M 75M
Jun 2021 180M 70M
Jul 2021 120M 30M
Total 240M 200M 200M
*First doses only, so x 2 = 480M
Supply targets fall short of
anticipated demand
9
9What Are the Risks to the Vaccine Supply? “Sometimes people confuse capacity and supply…” Stephane Bancel, CEO Moderna at 39th JPM Conference, Jan 2021
Risks
Raw Material Sourcing Defense Production Act
§ Adhering to this production schedule § Pfizer’s supply targets include a
depends on the companies’ ability to stipulation that the government use the
source raw materials and vaccination kit Defense Production Act to increase
supplies (e.g., syringes) availability of key vaccine ingredients.
§ Initially in 2020, Pfizer’s goal was to
deliver 75M doses by the end of the
year. It delivered far fewer—25M
doses---due to supply chain issues.
Scheduling Complex Logistics
§ Rapid and successful scale up and § Both supply chains require complex
scheduling to supply all required distribution logistics
elements is needed § Cold storage creates substantial
§ Any shortfall of raw materials will cause challenges
a delay in production and potential § Highlight's importance of
stock-out formulation/stability studies
11Impressions from CDMOs doing COVID work
§ Trend at CDMOs toward rapid process development and scale up. The ability to leverage platform
processes is a major factor in achieving these compressed timelines.
§ CDMOs are using raw materials at a faster pace than ever before
§ Bags, vials and stoppers are critical raw materials that have been most impacted
§ Formularies are expanded to include alternate suppliers for key items
§ Currently COVID projects are dominant
§ Infectious disease is now 50% of total business vs. 25% in 2019
§ COVID has brought more stakeholders together
§ Sponsors, government, key raw materials suppliers, manufacturer
§ Additional people in conversations, additional opinions
§ But everyone is committed, and decisions are being made quickly
§ Government is acting in support, removing roadblocks
Interview Insights
12The Pfizer supply chain…
§ Retains significant in-house manufacturing assets
§ It plans to make raw materials, mRNA API, lipid encapsulated DS and
finished doses at its own plants
§ Linearized DNA template made in St. Louis, MO
§ mRNA made in Andover, MA
§ Lipid encapsulated mRNA DS and DP in vials in Kalamazoo, MI
§ Ex-US production
§ Pfizer is producing at Purrs, Belguim, and a new site in Marburg, Germany
§ BioNTech will also produce the vaccine at two sites in Germany
§ Lipids will be supplied by Croda
13…Is different from the Moderna supply chain
§ Initial commercial supplies were produced internally (Potential for 100M
doses annually from Norwood, MA)
§ Established commercial supply agreements with Lonza (Apr 2020) and
Catalent (Jun 2020)
§ mRNA API, lipid-encapsulated DS and finished doses are outsourced
§ Dose = 100 ug
§ Scale of production is relatively small (DS production vessel 100’s of L)
§ Lipid encapsulated mRNA DS is made by Lonza
§ Lonza is building out capacity for 400M doses annually using 4 x 100M dose-
manufacturing lines (1 line at Portsmouth, NH (began in Jul 2020) and 3 lines at Visp,
Switzerland (beginning Dec 2020))
§ DP is filled and packaged by Catalent (Bloomington, IN and Philadelphia, PA)
§ Lipids made by CordenPharmaLong-Term Impacts on Biomanufacturing
New investment and increased regulatory flexibility
Investment
§ Significant new investment and expansion of biomanufacturing and supply
chains
§ Pall $114M investment to increase supply of components for single use
manufacturing
§ ThermoFisher $700M investment to add global capacity to meet COVID-
related demand
§ Fujifilm $928M investment in biomanufacturing site in Hillerod, Denmark
and $40M for new site to manufacture viral vectors in Watertown, MA
§ Expansion at Emergent is being fast-tracked—a new DP viral line will be built
in 18 mo rather than the standard 36 mo
§ Lonza $2B capital investment in biomanufacturing capacity worldwide
Regulations
§ We--innovators and FDA--have learned that we can move faster to evaluate
clinical products
16Questions
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