Sensitivity: CEPI Internal
CEPI 100 day mission
Innovative CMC technologies to enable rapid
response
Ingrid Kromann
Director, Manufacturing & QC development
Vaccine Technology Summit
March 20-21, 2023 #100DaysMission
1

Sensitivity: CEPI Internal
2
The Creation of CEPI
Launched at the World Economic Forum at Davos in 2017 as a global coalition to tackle epidemics

Sensitivity: CEPI Internal
Governments
Philanthropists
Regulators
Pharmaceutical
Industry
Civil society and
health
organisations
Academia
CEPI's unique connecting
role and extensive networks
allow it to pool and deploy
resources in ways that
nation states
often cannot.
A world in which epidemics and
pandemics are no longer a threat
to humanity.
Vision
To accelerate the development of
vaccines and other biologic
countermeasures against
epidemic and pandemic threats
so they can be accessible to all
people in need.
Mission
CEPI: A global partnership
3

Sensitivity: CEPI Internal
4
4
CEPI’s active vaccine portfolio
1 includes broadly protective SAR-CoV-2 and broadly protective betacoronavirus.
2 Finishing Ebola : CEPI is funding 8 Ebola clinical projects for Merck and Janssen vaccines. In addition, CEPI is in dialogue with WHO to potentially support Ebola Sudan ring vaccination.
2 Vaccine
Candidates
MERS
4 Vaccine
Candidates
Lassa
3 Vaccine
Candidates
Nipah
3 Vaccine
Candidates
Chikungunya
Rift Valley
fever
2 vaccine
Candidates
COVID-19 / broadly
protective1
7 COVID-19
Vaccine
Candidates
12 Broadly
Protective1
Vaccine
Candidates
3 Platform
Technologies
Disease X
8 Clinical
Projects for
2 Vaccine
Candidates
Ebola2
Jan 2023

Sensitivity: CEPI Internal
What we achieved in
response to COVID-19
We were able to respond quickly to
COVID-19 due to:
1. Prior research in two closely related
coronaviruses, SARS and MERS, including
early funding from CEPI to support
Oxford’s ChAdOx platform.
2. Decades of development of mRNA
technologies, allowing for fast, adaptable
and highly scalable vaccine development —
a step change from traditional biological
manufacturing.
#100DaysMission

6
During COVID-19, it took 326 days for development
to EUA by stringent regulatory authority
Vaccine development then and now, months
Sample baseline scenario1, (after multiple years of research)
~12-24 ~12-24 ~24 ~36-48 ~12 ~12
Preclinical,
including
toxicity,
technology
development
Phase I:
Safety and
immunology
Phase II:
Proof-of-
concept study
Phase III:
Large-scale
safety and
efficacy trials
Filing Registration
~10
years
1. Timelines can vary widely based on disease and trial designs
2. Patient safety was paramount despite the condensed timeline
Sample accelerated timeline2, (based on previous SARS/MERS research)
Development was simultaneous rather than sequential. Clinical phases were continued after
subsequent steps were initiated
326
days
Authorization
(EUA by
stringent
regulatory
authority)
~2 ~2 ~2 ~4 ~1

Sensitivity: CEPI Internal
Coupled with improved surveillance, and swift use of non-pharmaceutical interventions, a vaccine in 100
days could defuse the threat of a new pathogen with pandemic potential.
#100DaysMission
CEPI’s 100 Days Mission
Definition
‘Vaccines should be ready for initial authorisation and manufacturing at scale
within 100 days of recognition of a pandemic pathogen, when appropriate.’

8
Compressing timelines further will require a fundamental shift towards
preparedness
100
Days

9
Achieving
maximal
response
acceleration will
require a
paradigm shift
Preparedness
Prepare the scientific toolkit,
development infrastructure &
policy
Response
Adapt, create & test the
pathogen-specific vaccine
Roll-out and review
Release vaccine & expand
clinical evidence
Paradigm shift: significant front-loading in preparedness, and breaking
the firewall between development and intervention
Response
acceleration under
different scenarios

10
10
1950 2021
97% reduction
in elapsed time
1
min
2
sec

“Valleys of Death”
Sensitivity: Privileged and confidential
Figure from: Witek Jr, T J, How the Global COVID-19 Pandemic Brought Drug and Vaccine Development into
the Public Mainstream, J. Pharmaceutical Medicine (2021) 35:287–295
“For CEPI 2.0 and the
100 day mission to be
successful we need to
bridge both valleys.
,

Sensitivity: CEPI Internal
Critical path towards vaccine availability
Based on the 100 Days Working Group:
• Analysis of COVID-19 vaccine development timelines shows that
manufacturing is on the critical path to get to first-in-human
• Manufacturing scale-up and technology transfer is critical to make
doses available and equitably accessible
Alert trigger Vaccine available
for use
100 days
BNs of doses
manufactured
Post 100 days
Preparedness
(speed) (Scale, access)
(Speed, scale, access)
Candidate
development and
preclinical testing
Early and any
required clinical
trials; Emergency
authorization
Large-scale
clinical trial
Real-world
evidence
Process
development and
PhI manufacturing
Scale-up and PhIII
manufacturing
Process validation
Scale-up and -out,
technology
transfer
Preclinical, clinical,
regulatory process
dev, scale-up, scale-
out experience with
platform
Epi monitoring
12

Sensitivity: CEPI Internal
CMC framework
▪ Manufacturable at different scales with
maintained quality attributes
▪ Ensuring safety and efficacy
▪ Meeting Regulatory Agency Expectations
▪ Targeting the 100 Days Mission
Drug Substance & Drug Product Process
# Status Comments # # #
1.1 Pre-clinical 1.2 Phase I 1.3 Phase II 1.4 In
High level
definition
Process description & unit operations
defined
Process transferred to manufacturing site
Process fixed suitable for Ph II and
stockpile
Pr
Must Have
Deliverables
A Lorem ipsum dolor sit amet g A Lorem ipsum dolor sit amet A Lorem ipsum dolor sit amet A Lo
B consectetur adipiscing elit g B consectetur adipiscing elit B consectetur adipiscing elit B co
C Morbi congue quis ex vitae dapibus a xxxx C Morbi congue quis ex vitae dapibus C Morbi congue quis ex vitae dapibus C M
D Donec ac convallis enim r yyyy D Donec ac convallis enim D Donec ac convallis enim D Do
E
Integer et diam eu erat commodo finibus non
bibendum augue
E
Integer et diam eu erat commodo finibus non
bibendum augue
E
Integer et diam eu erat commodo finibus non
bibendum augue
E
In
bi
F
Curabitur vel porttitor nisl, vitae commodo
augue
b F
Curabitur vel porttitor nisl, vitae commodo
augue
F
Curabitur vel porttitor nisl, vitae commodo
augue
F
Cu
au
G
Suspendisse elementum erat non justo
convallis accumsan
G
Suspendisse elementum erat non justo
convallis accumsan
H Quisque egestas ullamcorper posuere H Quisque egestas ullamcorper posuere
I Fusce ac congue orci I Fusce ac congue orci
J Sed blandit elit a sagittis laoreet J Sed blandit elit a sagittis laoreet
K
Donec porta ex sapien, vitae condimentum
ligula accumsan egestas
Additional
considerations
A
Integer velit nulla, faucibus vitae ex vel, finibus
scelerisque velit
a zzzz A
Integer velit nulla, faucibus vitae ex vel, finibus
scelerisque velit
A
Integer velit nulla, faucibus vitae ex vel, finibus
scelerisque velit
A
In
sc
B Nulla facilisi a xyxyxy B Nulla facilisi (where applicable)
C Cras in odio eu metus ullamcorper tempor a xzxzxz C Cras in odio eu metus ullamcorper tempor
D In suscipit ultrices mauris id pretium a zyzyz D In suscipit ultrices mauris id pretium
E Vivamus luctus ut arcu eget mattis
F
In nisi dolor, fermentum in tristique eu,
vestibulum eu purus
G
Pre-clinical Phase I Phase II
SG
I
SG
DD SG
13

Sensitivity: CEPI Internal
14
14
Scaling to meet the post 100 day need
Platform - manufacturing process and assays developed
• Standardised Technology Transfer of process and assays
Facility equipped, validated and trained staff
Vaccine manufacturing and delivery Supply Chain established
Regulatory preapproval of CMC and clinical dossier
Vaccine delivery prepared

CONFIDENTIAL
Sensitivity: CEPI Internal
15
• Focused on mRNA, protein and viral vector
manufacturing platforms:
• Mapping from antigen sequence availability to
CTM supply for emergency use
• Common themes identified:
• Analytical methods, release testing
• Cell-based steps
• Adjuvant availability for proteins
• Platform optimization
• Critical path analysis presented at several meetings
and conferences – not formally ‘validated’ yet
Critical path analysis for key vaccine
manufacturing platforms
mRNA platform
Viral vector platform
Protein production platform

CONFIDENTIAL
Sensitivity: CEPI Internal
16
The critical path analysis of different vaccine manufacturing platforms identified the following
areas for innovation:
Platform optimization; can make multiple vaccine platforms rapidly adaptable to new pathogen
• Synthetic biology approaches for cell-free manufacturing of DNA template, proteins and viruses
• Or: transient transfection of cell lines at scale for proteins
Rapid testing of drug substance/product can reduce hold times between manufacture and product release using
• Accelerated release testing, especially sterility, adventitious agents, potency
• Process analytical technology and real-time release
• Rapid testing methods exist - require implementation
CMC is on the critical path

CONFIDENTIAL
Sensitivity: CEPI Internal
CfP launch April/May 2023
Focus areas
• Focus Area 1: Platform process development, optimization, standardization and acceleration
• mRNA, viral vectors, proteins or other novel platforms in batch or continuous processing
modes to be considered
• Focus Area 2: Analytical technologies to accelerate drug substance/product batch release and
availability of master cell bank (MCB) / master viral stock (MVS)
• Deployment of existing rapid technologies, and new technologies (e.g., ID and potency tests or
reagents) - both types require implementation as partner
• Focus Area 3: Innovations to accelerate cell-based manufacturing steps, including synthetic
approaches
• Implementation of cell-free manufacturing innovations to improve vaccine production
• Focus Area 4: Any other manufacturing-related innovations that can accelerate clinical trial
material availability

CONFIDENTIAL
Sensitivity: CEPI Internal
Manufacturing innovations are also required to meet
100-day mission’s speed, scale and access goals
Alert trigger Vaccine available
for use
100 days
BNs of doses
manufactured
Enable equitable
access
Speed
• Platform optimization
• Synthetic biology approaches
• Accelerated release testing
• Adjuvant libraries and stockpiles
Scale
• Flexible, modular, scalable
manufacturing solutions
• High-expression cell lines
• Characterization methods to
support tech transfer
• Improved access to adjuvants
Access
• Thermostability – current Call for
Proposals
• Lower COGS
• Novel formulations that are easy to
distribute and administer

Sensitivity: CEPI Internal
CEPI‘s 100-Days Mission: Regulatory Initiatives
It is about accelerating all aspects of product development
and identifying opportunities for early deployment
Prepare, Develop, Deploy are essential for future outbreaks
Partnering with regulatory authorities worldwide and other key stakeholders to capitalise on lessons learnt and embed regulatory innovation
Enable maximal use of
platform data and
pre-approved
documentation Evaluate product
development pathways for
any acceleration /
streamlining
Identify circumstances to
accelerate development
and deployment based on
anticipated benefit risk
Harmonise outbreak ready
pathways and maximize
speed of review and
regulatory reliance to
enable rapid regional and
global roll-out
Prepare
Develop
Deploy
19

Sensitivity: CEPI Internal
CMC Regulatory Templates
• During the pandemic, there were an
unprecedented number of technology
transfers and non-linear CMC activities.
• For readiness, CEPI, industry and academics
collaborate and develop CMC protocol
templates for comparability exercise and
process validation.
• Consultation with global health authorities
will occur to gain feedback and endorsement
on the template approaches.
20

Sensitivity: CEPI Internal
• Vaccine Library
for Disease X
• Platform
Development
• Innovate and
Fine-tune
processes
100 Days Mission
ACESS
SPEED
Quality
&
Regulatory
• Geo-diversified
manufacturing
network
• Thermostability
• Quality-by-Design
• Quality Management
System
• Strategy to
accelerate regulatory
path
21

Sensitivity: CEPI Internal
What if we had
lifesaving vaccines
in 100 Days?
#100DaysMission
22