Participate in the full, interactive on-demand webinar here: https://bit.ly/ProcessValWebinar
Process validation is a complex step in the transition to commercial scale manufacturing. While Quality By Design (QBD) is the standard option for a risk-mitigating process validation strategy, there are other options for more flexibility and speed. Join our webinar to learn how outsourcing to a CDMO, able to take an adaptive, risk-based validation approach, will accelerate your time to market.
In this webinar, you will discover more about:
• How outsourcing to a CDMO partner in late-stage will increase flexibility and speed
• How a risk-based approach can help you optimize your process validation strategy
• How we have implemented a risk-based approach for our clients via case studies
Vip sexy Call Girls Service In Sector 137,9999965857 Young Female Escorts Ser...
Optimize Your Process Validation Package
1. The life science business of Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma in the U.S. and Canada.
Christian Cattaruzza
Corinne Lavie-Cambot
David Delvaille
BioReliance® End-to-End Solutions
Optimize your
Process validation
Package!
2. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada
3. Agenda
Process validation key considerations and critical success
factors, Christian Cattaruzza
Process validation for biotechnological products, Corinne Lavie-
Cambot
Case study: efficient discrimination of critical process,
David Delvaille
1
2
3
5. process validation IS…
A series of activities taking place over the
lifecycle of the product and process
process Validation IS NOT…
A one-time event or an activity performed
just prior to commercial launch
Objective:
• Demonstrate that the manufacturing process is capable of consistently producing acceptable quality
products within the commercial manufacturing conditions
• Build confidence to regulatory authorities that a process is consistently under control and can remain in
control
Critical steps towards successful registration and commercial
manufacturing
Process Validation Definition and Purpose
Optimize your process validation package
5
6. 6
- The process must be frozen prior to starting
process validation activities
• Limited information and data available
from clinical stage
- Process knowledge should be developed and
documented along clinical development
- Single-use technologies simplify and speed
up process validation and technical transfer
• Standardization of process equipment
• Simplified process validation (Cleaning
validation)
• Simplified technical transfers
- Regulatory agencies expectations will
depend on the nature of the project and the
biologic drug
• Process validation strategy to be adapted
Critical steps towards successful registration and commercial
manufacturing
Process Validation Scope and Activities
Optimize your process validation package
7. Documented risk-based approach - Estimate residual risk for the patient considering:
Product knowledge (existing accumulated experience)
Process knowledge and understanding (existing accumulated experience)
Appropriateness of the Control Strategy
What is the appropriate quantity and type of data to demonstrate that the process
delivers reproducibly a product that meets pre-determined quality attributes?
What is the expected time to market? Is there any regulatory designation such as a
breakthrough therapy or fast track approval?
Process Validation Scope and Activities
Process Validation Strategy Speed to Market Risk
Take time to characterize process and gain knowledge Slow Low
Take shortcuts to save time at cost of building process knowledge and data Fast High
Risk-based approach based on experience of molecule, processes and equipment Fast Medium
How to determine validation needs?
Optimize your process validation package
7
8. Phase I
Pre-clinical Phase II Phase III Commercial
Cell line development
(any mammalian cells)
Cell banking
USP/ DSP process development
Templated or customized
Analytical development
GMP clinical manufacturing
Single-use 50 to 2.000L scale
Product characterization testing
PPQ campaign, GMP commercial manufacturing
Single-use 200 to 2.000L scale
Process optimization/ scale up/ fitting
Process characterization
Process & analytical validation
We are your full-service biologics CDMO with late-stage
capabilities that get you ready for to commercial success
8
9. Optimize your process validation package
9
Global resources Locally delivered
Biodevelopment
and production
Product characterization,
Biosafety testing
Cell line development
Boston, US
Shanghai, China GMP
Bordeaux, France GMP
Wisconsin
St Louis
Glasgow, UK
Rockville
Singapore
Validation Services
Molsheim, France
Bangalore,
India
Yokohama, Japan
10. 1987
Converted into a
fully Single-Use GMP
facility in Martillac,
France
1995
Production of the
first GMP batch
2015
Creation of the first
CDMO site in
Martillac, France
2011
Scaled up to
2,000 L
bioreactor
2017
• Opening of non-
GMP facilities in
Shanghai, China &
Burlington, USA
2018
Opening of GMP
facility in Shanghai,
Pudong, China
2020
China facility
delivers first full-
scope project
• Opening of GMP
commercial
facility in
Martillac,
France
• Expansion of
our
development
center in
Burlington, MA
2022
• Built within one
year
A History of 34+ Years of Global Contract Development and
Manufacturing Success
Optimize your process validation package
10
11. Our BioReliance®
End-to-End facilities are GMP certified
1 5 8
33
57
76
91
98 99 103 107 109
116
122
129 129 131 133 136 139 141 142 145 148 150 154
163
176
191
204
219
234
251
267
272
1st production
in
batch without
FBS
1st batch in
250L
1st perfusion
process
1st clinical batch
produced
in proteins free
media
1st cell bank without
FBS
Last process
developed
with FBS
2 x 1250L capacity
increase
Single Use
100% successful scale up
Revamping with
full single Use
process
1st PPQ run campaign
for an FDA Fast Track
designation
GMP certified
Major milestones: 1987-2021
molecules
2011-2021
>100 molecules developed
to GMP manufacturing
Optimize your process validation package
11
We abide to our global Group Quality Systems
13. Optimize your process validation package
13
What is Process Validation?
A regulatory requirement
FDA guideline [1]
Process Validation is “the collection and evaluation of data, from the
process design stage through commercial production, which establishes
scientific evidence that a process is capable of CONSISTENTLY delivering
quality product”.
EMA guideline [2, 3]
“Process validation is the documented evidence that the process, operated
within established parameters, can perform EFFECTIVELY and REPRODUCIBLY
to produce an active substance or intermediate, meeting its predetermined
specifications and quality attributes”.
[1] « Guidance for Industry : Process validation : general principles and practices », FDA, 2015
[2] « Guideline on process validation for the manufacture of biotechnology-derived active substances and data to be provided in the regulatory submission », EMA, 2016
[3] « ICH Q7A Godd manufacturing practice guide for active pharmaceutical ingredients », ICH, 2010
14. Optimize your process validation package
14
What is Process Validation consisting in?
Three stages – A Lifecycle Drug Substance/Product approach
Regulatory Submission
Process Design Process Development
and Evaluation
Process Qualification
Facility & Equipment Qualification
Process Performance Qualification (PPQ)
& validation studies
Process Verification
Continued Process
Verification (CPV)
Ongoing Process
Verification (OPV)
U.S. Food & Drug
Administration (FDA)
European Medicines
Agency (EMA)
Stage
1
Stage
2
Stage
3
15. Optimize your process validation package
15
What are the critical paths to go to BLA submission?
VMP cQA pCPP/CMA
Process
Characterization
pCPP/PAR
pPCS
PPQ
campaign
Viral clearance
PPQ reports
Final PCS
CPV protocol
Qualified Scale
Down Model
Locked commercial
process
Validated analytical
methods
BLA SUBMISSION
STAGE 1
STAGE 2
PROCESS VALIDATION STUDIES
Others Asmt
16. Optimize your process validation package
16
What are the validation studies to perform?
MIXING/HOMOGENEITY STUDIES
Shipment
studies
Studies from
assessments
Resin /
Membranes
Studies
Freeze-
Thaw
Studies
Stability /
Holding
times
Studies
Mixing /
Homogeneity
Studies
Viral
Clearance
Studies
Shipment studies
DS
QC Sample
Freeze - Thaw studies
DS
QC Sample
Resin / Membranes studies
Recycling
Cleaning
Viral Clearance studies
New resins
Aged resins
Stability / Holding
time studies
Media/Buffer
Solutions
Process
Intermediates
Drug Substance
QC samples
Resins/membranes
Mixing /
Homogeneity
studies
Media/Buffer
Solutions
Process
Intermediates
Drug Substance
17. Optimize your process validation package
17
When is it convenient to validate a process?
Discovery
Development
Preclinial
research
Phase
I
Phase
II
Phase
III
Phase
IV
Commercial
Clinical Phases
Stage
1
Stage
2
Stage
3
Regulatory Submission
Process Validation Exercice In Theory
Commercial
Strategy
Product
Designation
Evaluation
based on risk
assessment
18. To see the rest of the
presentation and get real-
life examples from our
speakers, participate in the
full, interactive on-demand
webinar.
Watch Now