Viral Vector Manufacturing

VectorBuilder has extensive expertise in producing many different types of viruses. We can provide viruses of different scales and quality attributes to meet the full range of demands along the gene therapy drug development pipeline. We have established and validated platform technologies for large-scale GMP manufacturing of adeno-associated virus (AAV) and lentivirus. We also have experience producing other types of viral vectors such as adenovirus, MMLV, herpes simplex virus (HSV), and vesicular stomatitis virus (VSV). We can produce viruses in several grades that cover different downstream applications including drug discovery research, pre-clinical studies, clinical trials and commercialization.

Grades of Viral Vectors Offered

Research-grade virus

Research-grade virus is suitable for basic research and drug discovery studies. It is produced in conventional cell culture facilities. Stringent QC assays are performed to ensure the quality of the virus meets the standards requested by customers.
Learn more about our research-grade virus
GMP-like virus

GMP-like virus is suitable for pre-clinical studies including drug safety and metabolism testing in animals. The manufacturing of GMP-like virus follows key features of GMP guidelines, such that the production process and quality attributes are comparable to GMP with document control and traceability. GMP-like grade is therefore intended to be a small-scale mimic of the final GMP product, but with significantly lower cost and much faster timeline. Product release is accompanied by a certificate of analysis (COA). TSE/BSE statement can be provided upon request.
GMP-grade virus

GMP-grade virus is produced in our certified GMP cell culture suite following strict GMP guidelines. A comprehensive quality assurance system is embedded throughout the manufacturing process, including an array of in-process and release QC assays to ensure that the virus meets customer specifications and regulatory standards for quality and safety. At product release, a COA and a batch release report fully documenting the production process are provided.

Comparison of different grades of virus

AAV

Lentivirus

	Research-grade	GMP-like	GMP-grade
Applications	Basic research, drug discovery, and preclinical studies	Preclinical studies such as animal testing of drug safety and metabolism	Preclinical studies, clinical studies, and commercialization
Production scales	5x10¹⁰to 10¹⁴ GC per batch	5x10¹³to 10¹⁷ GC per batch	10¹⁴to 10¹⁷ GC per batch
Turnaround time	10-50 days	4-5 months	6-12 months
Production site	In parallel production in standard BSL-2 laboratory	Produced in segregated BSL-2 production suites	Produced in certified GMP suites (BSL-2)
Quality system	ISO9001	ISO9001 while adopting key features of GMP manufacturing	ICH quality guidelines for GMP manufacturing
Document control and traceability	No	Yes	Full traceability
Vector characterization	RE digestion, ITR sequencing	Sequencing	Sequencing
Process development	No	Performed on a case-by-case basis depending on individual project needs	Yes
Cell banking	No	Available upon request	Yes
Antibiotic-free	No	Available upon request	Yes
Animal component-free	No	Available upon request for suspension culture	For suspension culture
Purification	Ultracentrifugation	Ultracentrifugation, affinity purification, IEX purification, mixed-mode chromatography	Ultracentrifugation, affinity purification, IEX purification, mixed-mode chromatography
QC and release tests	Titer measurement, SDS-PAGE, endotoxin detection, sterility testing, mycoplasma detection, etc.	Performed on a case-by-case basis depending on individual project needs	Full panel QC assays, analytical development upon individual project needs
Aseptic fill/finish	No	Available upon request	Yes
Storage of retain sample	Available upon request	Available upon request	Yes
Document deliverable	COA	1. COA 2. Manufacturing summary 3. TSE/BSE statement upon request	1. COA 2. TSE/BSE statement 3. CTD documents 4. Others (BMR etc.) upon request

	Research-grade	GMP-like	GMP-grade
Applications	Basic research, drug discovery, preclinical studies	Preclinical studies such as animal testing of drug safety and metabolism	Preclinical studies, clinical studies, and commercialization
Production scales	>2.5x10⁷ TU	10⁹ to 10¹² TU per batch	5x10⁹ to 10¹² TU per batch
Turnaround time	8-16 days	4-5 months	6-12 months
Production site	In parallel production in standard BSL-2 laboratory	Produced in segregated BSL-2 production suites	Produced in certified GMP suites (BSL-2)
Quality system	ISO9001	ISO9001 while adopting key features of GMP manufacturing	ICH quality guidelines for GMP manufacturing
Document control and traceability	No	Yes	Full traceability
Vector characterization	No	Sequencing	Sequencing
Process development	No	Performed on a case-by-case basis depending on individual project needs	Yes
Cell banking	No	Available upon request	Yes
Antibiotic-free	No	Available upon request	Yes
Animal component-free	No	Available upon request for suspension culture	For suspension culture
Purification	Ultracentrifugation	Ultracentrifugation, affinity purification, IEX purification, mixed-mode chromatography	Ultracentrifugation, affinity purification, IEX purification, mixed-mode chromatography
QC and release tests	Titer measurement, sterility testing, mycoplasma detection, etc.	Performed on a case-by-case basis depending on individual project needs	Full panel QC assays, analytical development upon individual project needs
Aseptic fill/finish	No	Available upon request	Yes
Storage of retain sample	Available upon request	Available upon request	Yes
Document deliverable	COA	1. COA 2. Manufacturing summary 3. TSE/BSE statement upon request	1. COA 2. TSE/BSE statement 3. CTD documents 4. Others (BMR etc.) upon request

Workflow for GMP Production of Viral Vectors

RE digestion
Sequencing

Cell line development
USP/DSP
Analytical development

Segregated suite (GMP-like)
GMP suite (GMP-grade)

General/physical properties
Identity
Purity
Safety

Vector
Charaacterization

Process
Development

Plasmid
Production

QC
and Release

Bacteria and Mammalian
Cell Banking

Engineering
Run

GMP
Run

Fill/Finish

Closed system

Platform Technologies

AAV Platform

Lentivirus Platform

We package AAV in HEK293 cells under either adherent conditions (Cell Factory or fixed-bed bioreactors) or serum-free suspension conditions (up to 200 L single-use bioreactors). We also package AAV in suspension Sf9 insect cells. We can achieve a scale of up to 10¹⁷ GC AAV per batch.

Adherent
(Cell Factory, fixed-bed
bioreactors)

Suspension
(single-use bioreactors)

Transfection
(PEI, calcium phosphate)
/Infection (helper virus)

Harvest and lysis

Clarification and
concentration (TFF)

QC and release

Fill/
finish

Sterile
filtration

Concentration and
buffer exchange (TFF)

Purification
(chromatography)

Formulation

We package lentivirus (2nd and 3rd generation, pseudotyped with VSV-G or other viral surface proteins) in HEK293, under either adherent growth conditions (Cell Factory or fixed-bed bioreactors) or serum-free suspension conditions (up to 200 L single-use bioreactors). We can achieve a scale of up to 10¹² TU per batch.

Adherent
(Cell Factory, fixed-bed
bioreactors)

Suspension
(single-use bioreactors)

Transfection
(PEI, calcium phosphate)