The document discusses ways to accelerate vaccine development and manufacturing. It proposes adopting a template and platform approach to streamline process development. A template provides a standardized starting point for each vaccine's development process. A platform accumulates expertise across multiple vaccines using common unit operations, parameters, and facilities. This approach can speed development times, lower costs, simplify supply chains, and facilitate technology transfer and manufacturing.

1. Accelerating Vaccine Development and
Manufacturing
Priyabrata Pattnaik, PhD
Director – Worldwide Vaccine Initiative

2. Objective
Vaccine process development and manufacturing tend to
be diverged and highly customized.
In this presentation we will discuss:
 How the divergence in vaccine process can be streamlined
 How simple available tools can help speed up process development
 The benefits of following a vaccine template/ platform

3. Global Vaccine Pipeline is Strong
Source: Medicines in Development, Biologics, America’s Biopharmaceutical Research Companies, 2013 Report by PhRMA
There are several vaccine in early stage of clinical development

4. Vaccines is one of the Strong Growth Driver
Vaccine revenue forecast for non US & EU markets (2007-2016)
Source: GBI Research.
4
3.5 b$ in 2007 >>>> 7.5b$ in 2013
Vaccine market is growing in emerging countries @ >10% CAGR

5. The Journey of a Vaccine to Clinic Often
Follows a Long, Tortuous Path
5
Challenge
Reduce timelines with
current or fewer
resources

6. Accelerating the Journey of a Vaccine to Clinic
6

7. Accelerating Vaccine Process
Development

8. Demands on Process Development
 Pipelines are growing ⇨ demand on PD resources
 Speed to the clinic/market ⇨ faster/more efficient PD
 Cost pressure on vaccines ⇨ PD for process economics
 QbD, PAT initiatives ⇨ PD for process understanding

9. Value of Process Development (PD)
Example: Therapeutic Antibody
Ineffective PD Effective PD
Titer = 200 mg/L 1000 mg/L
Yield = 50% 70%
Capacity Required(CC) = 2,500 m3/yr 360 m3/yr
COGS = 345$/g 91 $/g
Capital = $280 MM $73 MM
Process Development Payback:
$2-4 million investment
< 1 year payback!
Source: Parrish M. Gallahar, Achieving Competitive Advantage Through Process Development, bioLOGIC 2002

10. PD Activities Across Development
Stages of Vaccine
Phase I Phase IIPreclinical Phase III Manufacturing
● Establish
basic
process
scheme
● Sequence
of unit ops
fixed
● Use of
simple
process
templates
● Finalize process
definition & purification
schemes
● Process optimization &
control
● Tech transfer to clinical
manufacturing
● Process
characterization
● Reuse testing &
cleaning validation
● Pilot scale studies
● Tech transfer to
launch site
● Process validation
● PD activities
driven by
manufacturing
changes or
regulatory
● Comparability
studies

11. Company Specific Vaccine PD Strategy
 Use un-optimized processes to generate clinical supplies (Fast-to-Efficacy)
& Develop commercial process, methods, formulations during clinical
development
– Pros: Speed
– Cons: another PD phase is required
 Use more rigorous methods & formulation for all clinical trials (Front-Load)
– Pros: Single development phase
– Cons: Slower to clinic
 Use either method based on product risk profile (Hybrid)
– Low risk → “Front Loading”
– High risk → “Fast-to-Efficacy”
Source: Geoffrey Slaff, Bioprocess International Meeting, Boston, 2005

12. Accelerating Process Development
Some Approaches to ‘Efficient’ Process Development
 Tailoring the scope of PD to the stage of development of the
vaccine
 Company specific strategy
 Size, knowledge-base and experience
 Adopting a template based approach to characteristic vaccine
molecules
 Tapping into vendor expertise

13. Role of Vendors in Accelerating Vaccine PD…
 More than 900 vaccine projects executed by Merck Millipore since 1995
 Know-how on process and regulatory trends
 Advice on optimization
 Minimize risk of scaling
 Perform trials with skilled staff
Merck Millipore has >95 engineers & scientists WW providing such support
29 based in Asia / 9 based in China

14. Let’s review a generic vaccine template……
Most of the unit operations need buffer.
Do you pay attention to buffer filtration ?

15. A Generic Buffer Filter Sizer
an attempt to accelerate Process Development (PD)

16. A Generic Buffer Filter Sizer
an attempt to accelerate Process Development (PD)
 “Estimate sizing” for a buffer filtration operation based on simple inputs
such as volume, time, pressure, etc.
 Output will be unit operation size & conditions (filter type/area, loading, flux, etc.)
 Offers a high level overview of process sizing, configuration and, therefore, filter
requirements for a given step
 Carry out ‘paper-studies’ to estimate facility fit, analyze different
production scenarios as well as system size for a given duty
Note:
Use as a complementary tool
Not a substitute for Process Development

17. Case Study: Buffer Filter Sizing
Source: Mok et al., Sterilizing-grade filter sizing based on permeability , Bioprocess International, 2012, 10(6): 58 - 63.
6000L of buffer would require 4 units of 10” filter
device to filter at 10psi in 1hr time

18. Guidance on use of permeate controlled TFF
for vaccine applications

19. Guidance on use of permeate controlled TFF
for vaccine applications
 Detailed approach to process development of TFF-MF using
permeate control method that enables….
– Improved process performance
– Better process control
– Better product recovery
– Longer life of TFF device

20. Case Study: Permeate controlled TFF-MF
Source: Raghunath et al., Best Practices for Optimization and Scale-Up of Microfiltration TFF Processes, Bioprocessing Journal, 2012, 11(1): 30-40.

21. Process Templates to Expedite Vaccine
Process Development and Manufacturing

22. Current approach to vaccine development is
too diverged
What’s wrong with tailored approach ?
 Knowledge is not accumulative
 Longer developmental time
 Supply chain security adds risk

23. Template and Platform Approach for Vaccines
 A template is a preset format, used as a starting point for a particular
process, so that the format does not have to be recreated each time it is used.
 A platform is an accumulation of know how and experience which can be
incorporated in the template
 A common set of systems that can be used for more than one Vaccine molecule
 Facility Platform
 A single facility has the capability to produce multiple Vaccines without modification
 Unit Operation Platform
 A common series of unit operations (e.g. Centrifugation, Benzonase Treatment, Anion IEX, TFF)
 Process Parameter Platform
 For each unit operation the same process parameters (flow rate, pH, conductivity, load) are used

24. Essential Points – Platform Processes
 The platform includes processes from cell line/ strain selection to supply
chain practices
 The platform is implemented from process development through
manufacturing
 The platform provides benefits to Vaccine producers in terms of speed to
clinic, risk mitigation and resource optimization
 The platform provides a streamlined approach to CMC activities in
product commercialization

25. Platform Options
Centrifuge
Harvest
UF/DFSecondary
Clarification
DNA
Removal
Chrom Filtration
Centrifuge
Harvest
Pellicon 2Polysep II Benzonase
Treatment
Fractogel
TMAE
Durapore
Centrifuge
Harvest
Pellicon 2Polysep II Benzonase
Treatment
28oC
pH 7.6
4mM MgCl2
4 hrs
Fractogel
TMAE
100 cm/hr
pH 7.4
7.5mS
20cm
Durapore

26. A Generic Viral Vaccine Process Template

27. Value of template approach for vaccine
Process Development
Additive effect of experience
Better understanding of product/process interaction
Enables quick process development (Lower development costs)
Harmonizes multi-centric PD activity

28. Value of template approach for vaccine
Manufacturing
Easy implementation in multi-product facility (Enables faster
plant changeover)
Lean inventory management (Raw material supply chain
simplification)
Enable quick technology transfer
Better adaptation by CMO for clinical/commercial production
Lower capital costs
Speed to clinical trials and market
Facilitates modular validation approach
Minimizes process specific training

29. Summary
 There are ways to increase productivity of PD and manufacturing
by following simple measures
 Adopting a template and platform approach for vaccine
development has significant benefits
 Accelerate vaccine process development by best utilizing vendor/
supplier’s product/ process knowledge and technical support
capability