About VectorBuilder
As a global leader in gene delivery technologies, VectorBuilder offers a full spectrum of gene delivery solutions covering
virtually all research and clinical needs from basic research to therapy. We have supported tens of thousands oflaboratories and biotech/pharma companies across the globe along their entire drug-discovery pipelines, going fromresearch-grade vectors for early discovery, to GMP-like vectors for preclinical testing, to full GMP-grade vectors for clinical
trials. Our 4 major business segments include research vectors & viruses, gene delivery CRO services, CDMO services,and IP out-licensing.

VectorBuilder is a full-service CDMO with extensive experience in cGMP vector manufacturing. Operating several state-ofthe-art facilities, we have supported many customers along their entire drug-discovery pipelines with GMP manufacturingof plasmid DNA, IVT mRNA, and viral vectors such as lentivirus, AAV, adenovirus, MMLV, and other viruses. Besides GMP
manufacturing, our CDMO services include process development, analytical development, cell banking, fill/finish, andregulatory support. We have provided IND-enabling vectors to a worldwide client base in the US, Europe, Japan, China,
and South Korea.

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Table of Contents
About VectorBuilder

01

Our CDMO Capabilities

03

CDMO Services Overview…………….....…...…...…...…...…...…...…..........…04
Process Development…………….....…...…...…...…...…...…...…...…..........…05
Analytical Development………….......…...…...…...…....…................…….....…06
Plasmid Manufacturing…………...…...…...…...…...….......……....................…07
Viral Vector Manufacturing……..……….....….....…...…...…...…...….............…09
IVT RNA and LNP Manufacturing……………...…...…...…...….....…...….......11

Off-the-Shelf GMP Products

13

Virus Packaging Plasmids……………....…...…...…...…....…...…...…......…13

Regulatory Support

14

2

Our CDMO Capabilities
Our comprehensive quality system is embedded in every aspect of our GMP manufacturing process that spans facilities, supplies,
production, fill/finish, storage, in-process and release QC, and personnel. Our company culture places great emphasis on quality,
innovation, continuous improvement, and “white-glove” customer service. As such, we can consistently meet and exceed customer
expectations. We also strive to achieve rapid turnaround and affordable prices while maintaining high quality and full regulatorycompliance.

1.2 M+
Custom vectors

VectorBuilder currently has about 100,000 ft² of modern GMP facilities with advanced designs and state-of-the-art equipment.
Our facilities include:
10+ GMP manufacturing suites
Fill/finish suites
QC laboratories and analytical development suites
Process development suites
GMP warehouse3Revolutionize Gene Delivery

CDMO Services Overview
Process & Analytical Development
We develop and optimize GMP manufacturing processes for a varietyof gene therapy vectors. We can develop and validate all the in-process
and release QC assays required for the production of GMP-grade genetherapy vectors.

Plasmid Manufacturing
We can manufacture GMP-grade plasmid DNA at various scales, employing
antibiotic-free and animal component-free production methods.

Viral Vector Manufacturing
We can produce GMP-grade AAV and lentivirus using our platform
technologies. We also have experience producing other types of viral
vectors such as adenovirus, MMLV, HSV, and vesicular stomatitis virus(VSV).

IVT RNA and LNP Manufacturing
We provide optimal in vitro transcription vector designs, large-scale IVTmRNA manufacturing, and LNP encapsulation followed by thoroughquality control tailored to a wide range of research and clinical needs.

Cell Banking
We can generate GMP-grade Master Cell Banks (MCBs) and Working
Cell Banks (WCBs) for E. coli, mammalian cells and insect cells, derived
either from our in-house validated cell lines or customer-provided celllines.

Fill/Finish
We can do manual or automated aseptic filling of the DS/DP into glass
vials (0.25 ml to 2 ml) or cryo bags. We have the capacity to complete>3000 vials per batch.

4

Process Development
VectorBuilder has a dedicated process development team thatis highly experienced in developing optimal manufacturing
processes for GMP-grade gene therapy vectors. We consider
many factors in our process development, including biologicalproperties of the vector, quality and safety requirements,
production quantity and scalability needs, regulatory
requirements in the intended market, and the customer’s cost
and timeline target.

Upstream Process Development
Cell line development
E. coli, mammalian cell lines, insect cell lines

Vector Optimization
Rich collections of fully validated vector
components
Backbones, promoters (constitutive, tissue-specific,

E. coli fermentation scale-up and scale-out

inducible, synthetic), ORFs, linkers, tags, shRNA andFermentation systems range from flasks to up to

CRISPR target site libraries, etc.

100 L stirred fermenters.

Mammalian and insect cell culture scale-up
and scale-out
Adherent systems: flasks, Cell Factory, fixed-bed

Large-scale screening platforms
Tissue-specific promoter/enhancer screening, capsid
evolution, shRNA screening, CRISPR screening, Rep/Cap
promoter optimization, CAR antibody screening, etc.

bioreactors (up to 600 m2)
Suspension systems: flasks, wave bioreactor (up to50 L), single-use bioreactors (up to 200 L)

Viral genome engineering
De novo construction of novel viral vectors, including
utilizing BAC and YAC recombineering to build vectors

Media screening and optimization

containing large viral genomes such as coronavirus andAntibiotic-free, serum-free, animal-free, chemicallyherpes simplex virus (HSV).

definedHigh-density cell culture optimization
E. coli, mammalian cells, insect cells

Transfection/infection optimization
Rep/Cap and helper plasmid optimization, plasmid
DNA ratio, transfection reagent, infection MOI, celldensity, etc.

Downstream Process Development
Harvest and lysis optimization
Harvest time, cell lysis method, nuclease treatment, etc.

Purification optimization
Chromatography: size exclusion, ion exchange, affinity,
mixed mode
Gradient centrifugation: sucrose, CsCl, iodixanol

Clarification, concentration and buffer exchange
UF/DF (tangential flow, hollow fiber, depth filtration)5

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Analytical Development

VectorBuilder can provide the full range of analyticaldevelopment services capable of developing, optimizing,
qualifying and validating in-process and release QC
assays tailored to individual gene therapy vectors.
We can also provide drug stability studies to ascertain
vector shelf life under various storage and transportconditions.

QC Attribute

QC Assay

General/physical properties

Appearance, concentration, pH, extractable volume, osmolality, aggregation

Identity

Restriction enzyme digestion, sequencing, agarose gel electrophoresis,
SDS-PAGE, immunoassay

Strength/potency

Physical titer: qPCR, ddPCR, immunoassay, OD260/280
Infectious titer: plaque assay, TCID50
Expression of the transgene: transduction test, Western blot, RT-qPCR, flow cytometry

PurityProduct related• Full/empty viral particle ratio: TEM• Supercoiled plasmid ratio: agarose gel electrophoresis, HPLC
Host cell related• Host cell protein: immunoassay, SDS-PAGE, silver stain, Micro BCA, BCA, HPLC
• Host cell DNA: qPCR, agarose gel electrophoresis• Host cell RNA: agarose gel electrophoresis, RT-qPCR, fluorometric quantification
Process related• Residual plasmid DNA: qPCR
• Residual benzonase: immunoassay• Residual BSA: immunoassay• Residual PEI: HPLC
• Residual antibiotic: immunoassay

SafetySterility: direct inoculation, membrane filtration sterility test
Endotoxin: kinetic chromogenic assay (KCA)
Mycoplasma: qPCR, culture method, indicator cell culture method
Replication competent virus: qPCR, immunoassay, Southern blotting
Adventitious virus: qPCR, in vitro cell culture
Presence of viral oncogenes such as E1A and SV40: qPCR

6

Plasmid Manufacturing

We can provide optimal vector designs tailored to awide range of research and clinical needs. For plasmid
DNA manufacturing, we offer several grades thatcover different downstream needs including drug
discovery research, pre-clinical studies, clinical trials, andcommercialization.

Plasmid DNA OfferedResearch-grade

GMP-like

Applications

Basic research,drug discovery,
preclinical studies

Preclinical studies

Preclinical studies,clinical studies, andcommercialization

Production scales

10 ug to several 100 mg

10 mg to 1 g per batch

10 mg to 5 g per batch

Turnaround

1-8 days

1-3 months

A few months to half a year

Quality system

ISO9001

ISO9001 while adopting key
features of GMP system

ICH quality guidelines for
GMP manufacturing

COA upon request

1. COA
2. Manufacturing summary
3. TSE/BSE statement uponrequest

1. COA
2. TSE/BSE statement
3. CTD documents
4. Others upon request

Document deliverable

Workflow for GMP Production of Plasmid DNA

7

GMP-gradeRevolutionize Gene Delivery

Technology Platform

QC and Release Criteria
QC Item

MethodGMP-like

GMP-grade

Plasmid concentration

UV spectrophotometry≥500 ug/ml≥500 ug/ml

pH

pH meter

Report result

Report result

Restriction digest

Agarose gel electrophoresis

Identical to expected
restriction pattern

Identical to expected
restriction pattern

Sanger sequencing

Sanger sequencing of the entire
plasmid

Identical to reference
sequence

Identical to reference
sequence

A260/A280

UV spectrophotometry

1.80-2.00

1.80-2.00

ccc plasmid DNA ratio

EtBr stained agarose gelelectrophoresis

≥80%

≥80%

Residual protein

BCA or equivalent≤2.00%≤2.00%

Residual RNA

Fluorescence analysis orequivalent≤5.00%≤5.00%

Residual host cell DNA

Quantitative PCR or equivalent

Report result≤5.00%

Endotoxin

Kinetic chromogenic assay≤50 EU/ml≤10 EU/ml

Sterility

Direct innoculation

No growth

No growth8Viral Vector Manufacturing

We can provide viruses of different scales and quality
attributes to meet the full range of demands along thegene therapy drug development pipeline. We haveestablished and validated platform technologies for largescale GMP manufacturing of adeno-associated virus (AAV)
and lentivirus.

Viral Vectors OfferedResearch-grade

GMP-like

GMP-grade

Basic research,drug discovery,
preclinical studies

Preclinical studies

Preclinical studies,clinical studies,and commercialization

AAV

5x1010 to 1014 GC

5x1013 to 1017 GC per batch

1014 to 1017 GC per batch

Lentivirus>2.5x107 TU

109 to 1012 TU per batch

5x109 to 1012 TU per batch

AAV

10-50 days

4-5 months

6-12 months

Lentivirus

8-16 days

4-5 months

6-12 months

Quality system

ISO9001

ISO9001 while adopting key
features of GMP system

ICH quality guidelines for
GMP manufacturing

QC and release tests

Titer measurement,
SDS-PAGE,
endotoxin testing,
mycoplasma detectection,etc.

Depending on individual
project needs

Full panel QC assays,
analytical development upon
individual project needs

Applications

Production
scalesTurnaround9

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Workflow for GMP Production of Viral Vectors

Technology Platforms
AAV

LV

10

IVT RNA and LNP Manufacturing
VectorBuilder offers a full range of CRO and CDMO services for in vitro transcription (IVT) mRNA manufacturing and lipid
nanoparticle (LNP) therapeutic development. Relying on our revolutionary vector design platform and extensive experience,
we can provide optimal in vitro transcription vector designs, large-scale IVT mRNA manufacturing, and LNP encapsulation
followed by thorough quality control tailored to a wide range of research and clinical needs. We offer several grades thatcover different downstream needs including drug discovery research and pre-clinical studies.

Workflow for Production of IVT mRNA

IVT mRNA and LNP Offered11

Research-grade

GMP-like

Applications

Basic research, drug discovery, and preclinicalstudies

Preclinical studies such as animal testing of drug
safety and metabolism

Production scalesmRNA: 0.1-10 mg
LNP: 0.1-3 mg

mRNA: 0.01-20 g
LNP: 3-20 mg

Turnaround49-71 days
• Vector design & cloning: 26-36 days
• Plasmid production & linearization: 14-21 days
• IVT mRNA production: 14-21 days
• LNP encapsulation: 9-14 days

59-90 days
• Vector design & cloning: 31-41 days
• Plasmid production & linearization: 14-28 days
• IVT mRNA production: 14-28 days
• LNP encapsulation: 14-21 days

Quality system

ISO9001

ISO9001 while adopting key features of GMP
manufacturing

Revolutionize Gene Delivery

Quality Control Assays
Product

IVT DNA template

mRNA

LNP

Attribute

QC AssayConcentration

Spectrometry

Identity

Gel electrophoresis, Sanger sequencing

Linearization

Capillary gel electrophoresis

Residual host E. coli DNA

qPCR

Concentration

UV-Vis spectrometry

Identity

Capillary gel electrophoresis, reverse transcription
followed by Sanger sequencing

Capping efficiency

LC-MS, Capillary gel electrophoresis

PolyA tail integrity

LC-MS, Capillary gel electrophoresis

Residual protein

NanoOrange assay

Residual plasmid

qPCR

dsRNA

Dot blot

Endotoxin

Kinetic chromogenic assay (KCA)

Encapsulation efficiency

RiboGreen assay

Diameter, PDI, and Zeta potential

Zetasizer

Lipid Nanoparticle Encapsulation
Our production suite can accommodate custom lipid formulations and perform microfluidic mixing, dilution, buffer exchange,
sterile filtration, and fill/finish using state-of-the-art equipment.

Figure 1. (A) Particle size was determined by dynamic light scattering (DLS) which measures the intensity differences offluctuated light due to motion of particles. The polydispersity index (PDI) reflects the heterogeneity of a sample on particle
size. (B) Zeta potential reflects the stability of LNP. The Zeta potential of the sample is between -1.872 mV and +1.872 mV. (C)TEM of LNPs produced at VectorBuilder.

12

Off-the-Shelf GMP Products
Virus Packaging Plasmids
VectorBuilder offers GMP-like and GMP-grade lentivirus and AAV packaging plasmids for the manufacturing of pre-clinicaland clinical viral vectors for gene and cell therapies. Produced in our state-of-the-art facilities, each plasmid has been
optimized to produce high titers of virus and has undergone thorough quality control.

Highlight
Optimized and validated for high virus yield
Off-the-shelf plasmids available for immediate use
Plasmids produced under animal-free and antibiotic-free conditions
Royalty free
Drug Master Files available facilitating FDA IND application
Kanamycin resistance

QC and Release Criteria
QC Item

13

MethodGMP-like

GMP-grade

Plasmid concentration

UV spectrophotometry≥500 ug/ml≥500 ug/ml

pH

pH meter

Report result

Report result

Restriction digest

Agarose gel electrophoresis

Identical to expected
restriction pattern

Identical to expected
restriction pattern

Sanger sequencing

Sanger sequencing of the entire
plasmid

Identical to reference
sequence

Identical to reference
sequence

A260/A280

UV spectrophotometry

1.80-2.00

1.80-2.00

ccc plasmid DNA ratio

EtBr stained agarose gelelectrophoresis

≥80%

≥80%

Residual protein

BCA or equivalent≤2.00%≤2.00%

Residual RNA

Fluorescence analysis orequivalent≤5.00%≤5.00%

Residual host cell DNA

Quantitative PCR or equivalent

Report result≤5.00%

Endotoxin

Kinetic chromogenic assay≤50 EU/ml≤10 EU/ml

Sterility

Direct innoculation

No growth

No growthRevolutionize Gene Delivery

Regulatory Support
We work closely with our customers to provide regulatory support at each critical milestone of their drug development
process. These include:

Technology transfer
We can provide technology transfer with bestpractices including detailed bill of materials,
well-documented production process, andfully qualified analytical methods used in the
manufacturing of the gene therapy vector.

14

US Headquarters
VectorBuilder Inc.
1010 W 35th Street, Suite 515
Chicago, IL 60609, USA
Tel: 800-517-2189+1 773-475-7751
Fax: 408-649-5280
Email: service-us@vectorbuilder.com
cdmo@vectorbuilder.com

EuropeVectorBuilder GmbH
Martin-Behaim-Str. 15
63263 Neu-Isenburg, Germany
Tel: +49 (0) 6102-2486890
Fax: +49 (0) 6102-2486891
Email: service@vectorbuilder.com
cdmo@vectorbuilder.com

Japan
VectorBuilder Japan, Inc.
2-12-16, Shin-Yokohama, Kouhoku-ku,
Yokohama, Kanagawa, 222-0033, Japan
Tel: +81-45-628-9207
Email: service-jp@vectorbuilder.com
cdmo-jp@vectorbuilder.com
Kobe Biomedical Innovation Cluster Office
Kobe KIMEC Center Bldg. Rm 9H
1-5-2 Minatojima-Minami-machi, Chuo-ku,
Kobe, Hyogo, 650-0047, Japan
Tel: +81(0)78-945-9155

China (Mainland)
VectorBuilder China
Building D, 3rd Floor, 3 Juquan Road, Science City
Guangzhou, 510663, China
Tel: +86 20-28069042
Email: service@vectorbuilder.cn
cdmo@vectorbuilder.com

UK
VectorBuilder Ltd.
Suite F1 Bush House, Edinburgh Technopole
Penicuik, EH26 0PH, United Kindom
Tel: +44 (0) 7448341295
Email: service@vectorbuilder.com
cdmo@vectorbuilder.com

Korea
Tel: +82-2-833-9631
Email: service-kr@vectorbuilder.com
cdmo@vectorbuilder.com

IsraelTel: + 34631 821 941
Email: service@vectorbuilder.com
cdmo@vectorbuilder.com

Australia
VectorBuilder Australia
Unit 11/42 Stud Road, Bayswater VIC 3153
Tel: 1800-719-779 (9:00 am - 5:30 pm AEDT)Email: service@vectorbuilder.com (for general inquiry)
cdmo@vectorbuilder.com (for CDMO inquiry)

June 2024 (EN)