The cell and gene therapy market is growing rapidly and is projected to reach $10 billion in 5 years. There are three main segments: gene therapy, stem cell therapy, and cell immunotherapy. Gene therapy uses viral vectors like lentivirus or adenovirus to deliver nucleic acids. The production of viral vectors like AAV involves growing HEK 293 cells in bioreactors, transfecting them with plasmids, harvesting and purifying the virus through clarification, filtration, and chromatography. CAR-T cell therapy is also discussed as an example of cell immunotherapy, which uses lentivirus to modify patient T-cells that are then reintroduced to the patient.
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Production and purification of Viral vectors for gene and cell therapy applications
1. Priyabrata Pattnaik, PhD
Director & Head of Biologics Operations
Asia Pacific
Production and
purification of
Viral vectors for
gene and cell
therapy
applications
2. The cell & gene therapy market is poised for rapid growth
with projections reaching ~$10B in 5 years
Source: Seed Planning; METI; Kuick Research; Med Market Diligence;Transparency market research
Global market
size & CAGR
USD B
Products in
the pipeline
74
74
34
54
75
Stem cell
therapy
106
17
14
Cellular
therapy,
other
123
15
Gene
therapy
144
16
Phase I
Phase II
Phase III
10
9
1
12
8
3
2020
+36% p.a.
20182012
Kuick research (India)
See Planning/
METI (Japan)
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 20162
3. The cell & gene therapy market can be split into 3 broad segments...
Description and
examples Major players
Cell & gene
therapy
Non-geneti-
cally modified
cell therapies
• Purified populations of
allogeneic cells are
expanded and injected
topically
• E.g., mesenchymal stem
cells
Viral gene
therapies
• Drug product is virus
particle, injected into
patient topically (or
systemically)
• E.g., Spark’s night-
blindness therapy
• Autologous patient cells are
extracted, genetically
modified using viral
transduction, then reinfused
into the patient
• E.g., CAR T-cell therapy
Genetically
modified cell
therapies
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 20163
4. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
3 broad segments
Gene Therapy Stem-cell Therapy Cell Immunotherapy
Gene Therapy
Stem-cell Therapy
Cell Immunotherapy
Nucleic acid
Lenti/Adeno virus-based delivery
Somatic or germline
Stem cells banking
Replace or regenerate organs and tissue
Broad use of bone marrow in ALL
Autogenetic CAR-T
1. Most common
2. Immune cells separation
3. Lentivirus-based delivery
4. Chimeric Antigen Receptors (CARs)
Allogeneic modified T cells
1. Industrialized trend
2. Genetic modification of immune cells
3. Allogeneic T cell generation
4. Lentivirus-based delivery or genome edit (CRISPR)
CAR-TVirus
Stem cells
T-cells
Virus
CAR-T
4
5. Methods for producing genetically modified T-cells for
immunotherapy
Source: Bure et al. (2016) Automation of CAR-T Cell Adoptive Immunotherapy Bioprocessing. Bioprocess International, 14(4)s: 22-31.
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 20165
6. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Overall Process Map of CAR-T
T-cell separation
Virus generation
GMP-grade lentivirus
Recovery rate= 70%
2.5*109 virus per trial
5*106 titer/ml
500ml bulk
T-cell modification
MOI=5
1.7*109 virus per trial
Car-T Cell Amplification
Reintroduction
5*106 CAR-T/kg
E.g.: 70 kg weighting
3.5*108 CAR-T per trial
6
7. 7 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Viral Vectors For Gene Therapy
Introduction
Gene Therapy – Main Applications:
• Treat Heridatery Single-Gene Defects.
• Cancer
• Cardiovascular Diseases
• Ocular Diseases
• Infectious Diseases
• Other Diseases Where Gene Transfer Will Have an Impact
Main Features for Virus-Based Vectors:
• Lacks Viral Genes Involved in Replication.
• Expression Cassette is Cloned into the Vector.
• Helper Function is Provided in trans
• Co-Transfection of Vector Genome and Packaging Construct Produce Recombinant Vecotor
8. 8
~60% of the vaccines undergoing clinical trials are viral based.
~ 640 viral vaccines
~ 200 viral vectors
~ 60 virus like particles
Another ~240 gene therapy products in development that utilize
the same technology.
Example of vectors:
Adenovirus (70-100 nm)
Lentivirus (80-100 nm)
HSV (300 nm)
Viral Vectors – Introduction
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
9. 9 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Features AAV Lentivirus
Genome ssDNA ssRNA(+)
Virus Coat Non-Enveloped Enveloped
Diameter 18 – 26nm 80 – 130nm
Packaging size 4.5 kb 8 kb
Infection Range Dividing & Non-Dividing Cells Mostly Dividing
Post Infection Mostly Non-Integrating* Integrates into Host Genome
Gene Expression Long lasting (?) Prolonged
Main Advantage Non-pathogenic; Non-inflamatory Persistent Gene Transfer
Main Disadvantage Small packaging capacity Oncogenesis may occur
Characteristics of AAV & Lentivirus
^ AAV (mainly serotype 2) may integrate into Chromosome 19
10. 10 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
AAV Serotype Tissue Tropism
AAV1 Muscle, Heart, Ocular, CNS
AAV2 CNS, Kidney, Muscle, Testes
Various in vitro applications
AAV4 Lung,
AAV5 Lung, CNS, Ocular, Pancreas
AAV6 Lung, Heart
AAV7 Muscle, Liver
AAV8 Liver, Muscle, Ocular, CNS, Heart
AAV9 Lung, Liver, Muscle, Heart, CNS, Kidney, Testes
AAVrh10 Pleura, CNS
Other Various
AAV Serotypes and Tissue Tropism
11. 11 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Transient Transfection Mediated by PEI or Calcium Phosphate. Co-transfection of AAV
production cells with 3 plasmids:
• Plasmid with AAV ITR and the gene of interest
• Plasmid with AAV rep/cap
• Plasmid providing the helper genes isolated from adenovirus.
Wild Type Adenovirus Infection Into Cell Lines with AAV rep/cap Genes and AAV Vector.
Infection using two HSV viruses harboring the gene of interest and the rep/cap genes to
produce AAV.
Infecting sf9 cells with two baculoviruses harboring the gene of interest and the rep/cap
genes to produce AAV.
Production Modes for Recombinant AAV
12. Sufficient Production of
virus vector copies
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201612
Adenovirus vectors manufacturing
Key requirements and needs
Antigens attributes
have to meet pre-set
Critical Quality
Attributes
Reproducibility &
consistency
Biosafety
Sufficient recovery to
achieve acceptable
economics
Ex: nucleic acid
content, product
identity & safety, etc.
Titer
Regulatory
Recovery
Purity &
Quality
13. Process Schematics of AAV vector production and Purification
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201613
UF/DF Benzonase
Treatment
Primary
Purification
Chromatography
Media and Inoculums
Preparation
Cell growth in Bioreactor
HEK 293 Cells
Virus Inoculation
Transfection
Virus
Harvest
(Lysis)
Primary
Clarification
UF/DF
Sterile
Filtration
Secondary
Clarification
Secondary
Purification
ChromatographyFill & Finish
Thaw and
Expand
Cells and
Seeds
Optional Benzonase
Treatment
14. Process Schematics of AAV vector production and Purification
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201614
UF/DF Benzonase
Treatment
Primary
Purification
Chromatography
Media and Inoculums
Preparation
Cell growth in Bioreactor
HEK 293 Cells
Virus Inoculation
Transfection
Virus
Harvest
Primary
Clarification
UF/DF
Sterile
Filtration
Secondary
Clarification
Secondary
Purification
ChromatographyFill & Finish
Thaw and
Expand
Cells and
Seeds
Optional Benzonase
Treatment
15. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201615
Amplification & culture of HEK-293
Bioreactors
T-Flasks*
*Source: Wang and Rivière (2015) Manufacture of tumor-
and virus-specific T lymphocytes for adoptive cell therapies,
Cancer Gene Therapy (2015) 22, 85–94.
Segura et al., Biotechnology & Bioengineering, 2005,
90 : 391-404
Virus Total Protein DNA
MCB
Innoculation
Shake/spin
16. Sf-9
HEK 293
EB66® Cells
BHK21
Sf-9
HEK 293
EB66® Cells
16
Minimize Your Process Development Efforts
Leverage Merck’s Experience with Various Cell Lines in Mobius® Bioreactors
CHO
Hybridoma
SP 2/0
Vero
h-MSC
T cells
HepaRG®
Adherent
Suspension
Public references at the bench (2 L) … and production scale (50 to 2000 L)
Vero
Power/Volume
Agitation speed
MDCK
S2
Drosophilia
mAb / Rec-
protein
Virus
Production
(Suspension)
Cell
Therapy
Virus
production
(Adherent)
h-MSC
HepaRG®
CHO
Hybridoma
*application data available
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
17. 17 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
• Standard media: EX-CELLTM 293 Serum-Free
Medium for HEK 293 Cells in suspension
• Custom media on demand
• Supplements
Cell culture Media preparation
Durapore® or
Express® 0.22 or
0.1 µm
Sterilizing
Or Viresolve®
Barrier (available
soon)
Lynx sterile
connectors
18. 18 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Bioreactor Biosafety: Preventing contamination
Control
Protect
Maximum control of animal derived materials
In-coming test of critical materials
Move to animal free raw materials processes.
Recombinant versions of Trypsin, insulin, albumin etc
(Cellprime® range).
• As a minimum: sterile filtration of cell culture
media (Express SHC for example)
• Implementation of a Mycoplasma or a Virus
barrier: filtration of cell culture media for
example using Viresolve® barrier
• Sterile Sampling with NovaSeptum
• Aervent filters for the aeration (0.22µ)
• Sterile connectors (Lynx)
19. Process Schematics of AAV vector production and Purification
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201619
UF/DF Benzonase
Treatment
Primary
Purification
Chromatography
Media and Inoculums
Preparation
Cell growth in Bioreactor
HEK 293 Cells
Virus Inoculation
Transfection
Virus
Harvest
(Lysis
AAV)
Primary
Clarification
UF/DF
Sterile
Filtration
Secondary
Clarification
Secondary
Purification
ChromatographyFill & Finish
Thaw and
Expand
Cells and
Seeds
Optional Benzonase
Treatment
20. 20 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Adherent cells may be lysed in situ or
detached from the growth substrates
Lysis can happen by freeze-thaw lysis,
mechanical homogenization or
chemically via the use of surfactants.
Large volume suspension cultures may
be treated with surfactants, e.g. Triton
X-100, or homogenized with a
mechanical device.
Nuclease treatment is incorporated
following lysis to reduce viscosity and
facilitate subsequent filtration and
chromatography steps.
Cell lysis to release virus particles
Purification
21. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201621
Clarification
Centrifugation
Centrifugation allows effective removal of microcarriers, but not so much for
cell/debris separation; the viral yield recovery is typically low (≤30-50%)
Post-centrifugation clarification using double layer PES filter offer low throughput
due to insufficient clarity of the post-centrifuge viral supernatant and cause
additional losses of viral yield
22. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201622
Clarification strategies
Cell density & size matters
Low
Concentration
High
Concentration
Small particles
Colloids
Charged
Depth Filters
TFF Filters
Surface Filters
Non-charged
Depth Filters
Filter capacities
depend on cell
density and degree
of lysis and particle
size distribution
Large/hard
particles
Milligard, Polysep,
Polygard CN
Polygard CR, Clarisolve 60HX
Prostak, Pellicon 2
Millistak+
Clarisolve 20/40 MS
23. 23 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Case study: Clarification of AAV8
• Adeno-associated virus harvest clarification. Previous process
using a competitive depth filter.
• Clarisolve 20 MS was selected for primary clarification
• No pre-treatment required
• Adeno-associated virus harvest clarification. Previous process
using a competitive depth filter.
• Clarisolve 60 HX was tested for primary clarification.
Increase of 4 x throughput vs previous depth filtration
filter = reduction of footprint
• No pre-treatment required
Depth filtration based clarification – primary
AAV case studies
20MS: Polypropylene &
Millistak® media
60HX: Polypropylene
media construction with
no (+)-charged resin
binder and no DE offer
inert surface, hence no
virus binding issues
24. 24 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Millistak+ D0HC can be also used for the clarification
of virus lysates despite of (+) charges (cellulose
fibers with Diatomaceous earths).
Can be an option to test side by side with Clarisolve
(similar format, same holder for large scale) & NFF
filters
Example: Capacity range from 30 – 300 L/m2 for
Adenovirus from Per.C6 cell harvest
Depth filtration based clarification
Millistak+ for primary clarification
25. 25 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
NFF based clarification of AAV
Filtration train example
Cell/Virus
Harvest
Polysep II
1.2/0.5 µm
Durapore
0.45µm
Pellicon 2
Biomax 100-300kDPolygard CR
5µm
OR
Clarigard
3 µm
Clarification
Bioburden
reduction
Concentration
26. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201626
Clarification systems with Single Use flow paths
Semi-automated systems
For POD formats (Millistak+
& Clarisolve®
For NFF filter capsules
27. Process Schematics of AAV vector production and Purification
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201627
UF/DF Benzonase
Treatment
Primary
Purification
Chromatography
Media and Inoculums
Preparation
Cell growth in Bioreactor
HEK 293 Cells
Virus Inoculation
Transfection
Virus
Harvest
Primary
Clarification
UF/DF
Sterile
Filtration
Secondary
Clarification
Secondary
Purification
ChromatographyFill & Finish
Thaw and
Expand
Cells and
Seeds
Optional Benzonase
Treatment
28. Solution: Genetically engineered endonuclease that cleaves all forms of
DNA and RNA.
Presence of Mg2+ (1-2 mM) is required for enzyme activity.
One unit of Benzonase® degrades approximately 37µg DNA in 30 min to as
low as 3-8 base pairs (<6 kDa).
Benzonase® can be detected with dedicated ELISA kit. Sensitivity 0.2 ng/ml
Nucleic Acid Digestion
Benzonase® Endonuclease
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201628
Regulatory:
<10 ng nucleic
acid/dose
Characteristics
Origin Serratia marcescens
Expression E. Coli K-12 mutant
Molecular mass ~ 30 KD
Isoelectric point 6.85
Functional in pH range 6-10
Temperature 0-42°C
Bioprocess International, February 2014
29. Parameters Biomax 300kD
Feed flow (l/min/m²) 6
TMP (bar) <0.3
Initial flux (LMH) 30
Final flux (LMH) 30
Average flux (LMH) 30
Volumetric Concentration
Factor
10
Diafiltration volume 2
Purification: First Step
Target: 25-fold conc + DF, vector recovery of 90%
Success Criteria
Good yield & Retention
Higher purity and
Contaminant Removal
- hcDNA
- HCP
- Spent Benzonase
Solution
Permeate control
Pellicon 2 Biomax 300 kD, V Screen for Lentivirus
100 kD for AAV
Lentivirus & AAV: Typical TFF process parameters
29
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201629
30. TFF-MF (0.1-0.65 µm) and Open UF (300-1000 kDa)
optimization
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201630
31. Process Schematics of AAV vector production and Purification
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201631
UF/DF Benzonase
Treatment
Primary
Purification
Chromatography
Media and Inoculums
Preparation
Cell growth in Bioreactor
HEK 293 Cells
Virus Inoculation
Transfection
Virus
Harvest
Primary
Clarification
UF/DF
Sterile
Filtration
Secondary
Clarification
Secondary
Purification
ChromatographyFill & Finish
Thaw and
Expand
Cells and
Seeds
Optional Benzonase
Treatment
32. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201632
Purification of AAV Using cation exchange Fractogel EMD SO3- as
primary step
“The recovery from the Fractogel SO3 − column was almost
100% based on the infective viral particle recovery. In our
laboratory the Fractogel SO3 − has consistently shown a
recovery between 80 and 100%, which is dependent upon
the extraction procedures and the variability in the infective
viral particle assay”
+ Benzonase®
Fractogel® EMD
33. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201633
Purification of AAV
Ion exchange schemes
(A) Two-step purification protocol involving a strong cation exchange chromatography
resin (Fractogel SO3-) followed by a strong anion exchange resin (Fractogel TMAE)
(B) Capture of the AAV vector by anion exchange chromatography using a strong anion
exchange resin (Fractogel TMAE) with subsequent polishing by gel filtration
chromatography.
34. 34 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Best method of separation is ultra centrifugation, but has challenges of scalabaility.
Ion exchange chromatography with dual shallow gradient (pH & conductivity) can be used.
pI of empty particles could be higher than that of packaged virions.
AAV empty capsid separation
SOURCE: Okada et al., (Sep. 2009) Scalable Purification of Adeno-Associated Virus Serotype 1 (AAV1) and AAV8 Vectors, Using Dual Ion-Exchange Adsorptive Membranes. Human Gene Therapy, 20:1013–1021
35. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201635
TFF & chrom systems with Single Use flow paths
Fully automated, recipe driven
Chromatography TFF (UF/DF)
Controls Automated with recipe control CCP6
Operating
pressure
Up to 60 psi
Operable fluid
temp
4o
C-30o
C 4o
C-45o
C
Area
Column diameter: 60 – 350
mm
System 1: 0.5-2.5 m2
System 2: 2.5-5 m2
Sensors
Pre & post column
pH, conductivity, UV,
temperature, pressure
Added sensors for
conductivity, UV
Flow Rate
System 1: 0.1 – 2.2 L/min
System 2: 1.6 - 8L/min
System 1: up to 18 L/min
System 2: up to 28 L/min
Other
Linear & step gradient
mix: Mixing range 10-90%
Accuracy :+/-2 %
Mixing tank 50L to 100/200L
Optional jacketed
36. Process Schematics of AAV vector production and Purification
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201636
UF/DF Benzonase
Treatment
Primary
Purification
Chromatography
Media and Inoculums
Preparation
Cell growth in Bioreactor
HEK 293 Cells
Virus Inoculation
Transfection
Virus
Harvest
Primary
Clarification
UF/DF
Sterile
Filtration
Secondary
Clarification
Secondary
Purification
ChromatographyFill & Finish
Thaw and
Expand
Cells and
Seeds
Optional Benzonase
Treatment
37. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201637
Screening for excipients that prevent AAV2 vector aggregation
SOURCE: Wright et al., 2005. Identification of Factors that Contribute to Recombinant AAV2 Particle Aggregation and Methods to Prevent Its Occurrence during Vector Purification and Formulation.
Mol. Ther., 12(1): 171-178.
38. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201638
Formulation
Storage & Transport
Range of formulation buffers and excipients to ensure long-term stability
• Buffers (ex: Tris, HEPES, PBS)
• Salts (freeze-dry)
• Stabilizers (ex: Polysorbate)
• Polyols: Manitol, sorbitol, PEG
• Sucrose, Trehalose (coming soon)
Emprove® dossier
Single Use Mixing & transport technologies
39. 39 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Bioburden monitoring is essential (<10 cfu/ml)
Durapore 0.22µm filter can be used as final filter
and had to undergo retrospective validation
Process need to operate at low pressure to avoid
product loss during filtration
Lot release will depend on sterility testing of final
dosage form & filter IT test
Sterile filtration and storage
40. 40 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Wide range of buffers in solid or liquid forms
• Biological buffers (organic, ex amino-acids)
• Purfication & formulation buffers (ex: NaOH, NaCl, PBS, etc..)
• Cleaning in place (ex: NaOH, HCl)
• Emprove® dossier c
Buffers
Liquid buffers: dual sourcing strategy
• Berlin, Germany (batch size: up to 2000 L)
• Irvine, Scotland (batch size: up to 10000 L)
41. 41 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Final Filling
Component choice
Criteria
Gamma compatibility
>40kGy
Statement of animal origin
USP<88> Class VI
post-gamma >40kGy
USP<85> Endotoxin,
post-gamma >40kGy
USP<788> Particulates,
post-gamma >40kGy
USP<661> Physicochemical,
post-gamma >40kGy
Shelf life >2.5 years,
post-gamma>40kGy
Total Bioburden
pre gamma
Bacteriastatis/Fungistasis,
Post-gamma >40kGy
Configurable
Assembly
Component Library
All available
Components
42. Solutions from Merck for AAV vector production and Purification
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201642
Pellicon 2
Biomax 100 kD
Benzonase
ELISA Kit II
Mobius Mix
Fractogel TMAE
Express HPF > SHR Mobius Bioreactor
NovAseptum Sampling
Aervent (vent filter)
Mobius
Mix
Polygard CR 5µm
Clarisolve 60HX
Pellicon 2
Biomax 300 kD
Durapore
0.22µm
Polysep II
2.0/1.2
Fractogel DMAE
Mobius
Integrated
Fill Finish
Solutions
Thaw and
Expand
Cells and
Seeds
Optional Benzonase
Treatment
43. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201643
Benzonase® Treatment Clarification Intermediate TFF
Tangential Flow
Filtration
Last Step
Drug
Substance
First step
Cell thawing
Cell culture (perfusion) – 5 weeks Virus infection – 2 days
3-6weeks
USP
week 1 to 5
DSP
week 5
DSP
week 6
Final
Filtration
2 stage Ion Exchange Chromatography
Virus vector– Single Use Process manufacturing overview
44. Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201644
Quality-control assays for clinical-grade AAV vectors
SOURCE: Arie van Oorschot (UniQure) Setting up a market scale manufacturing platform from scratch. Cell Culture World Conference. 23 February 2016
45. 45 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Schematic of the manufacturing steps associated testing regimes for
a cell therapy production process
Source: Alison Armstrong (2016) Advances in Assay Technologies for CAR T-Cell Therapies. BioPahrm International, 28(2): 32-37.
Quality, Science and Services You Can Trust
46. Merck Life Science (SAFC and BioReliance) provide the greatest array of process
development, manufacturing and testing support services for our clients.
Viral Based Gene Therapy products (Adenovirus, AAV, Retrovirus, Lentivirus, others)
Cell Banking
Viral Banking
Bulk Drug Substance
Bulk Drug Product
Custom Assay Development
BioSafety Testing
Viral Vector Production at SAFC Carlsbad Facility
Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 201646
47. 47 Production and Purification of Virus Vectors | Priyabrata Pattnaik | October 2016
Merck offers wide range of technology, tools
and services for Production and purification of
Viral vectors for gene and cell therapy
48. Thank You
Priyabrata Pattnaik, PhD
priyabrata.pattnaik@merckgroup.com
@pattnaik_p
https://sg.linkedin.com/in/priyabratapattnaik
https://plus.google.com/109816383630328905377