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

GMP-like viral vectors for preclinical studies and GMP-grade plasmid for clinical and commercial use.
  • 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 
ApplicationsBasic research, drug discovery, and preclinical studiesPreclinical studies such as animal testing of drug safety and metabolismPreclinical studies, clinical studies, and commercialization
Production scales5x1010 to 1014 GC per batch5x1013 to 1017 GC per batch1014 to 1017 GC per batch
Turnaround time10-50 days4-5 months6-12 months
Production siteIn parallel production in standard BSL-2 laboratoryProduced in segregated BSL-2 production suitesProduced in certified GMP suites (BSL-2)
Quality systemISO9001ISO9001 while adopting key features of GMP manufacturingICH quality guidelines for GMP manufacturing
Document control and traceabilityNoYesFull traceability
Vector characterizationRE digestion, ITR sequencingSequencingSequencing
Process developmentNoPerformed on a case-by-case basis depending on individual project needsYes
Cell bankingNoAvailable upon requestYes
Antibiotic-freeNoAvailable upon requestYes
Animal component-freeNoAvailable upon request for suspension cultureFor suspension culture
PurificationUltracentrifugationUltracentrifugation, affinity purification, IEX purification, mixed-mode chromatographyUltracentrifugation, affinity purification, IEX purification, mixed-mode chromatography
QC and release testsTiter measurement, SDS-PAGE, endotoxin detection, sterility testing, mycoplasma detection, etc.Performed on a case-by-case basis depending on individual project needsFull panel QC assays, analytical development upon individual project needs
Aseptic fill/finishNoAvailable upon requestYes
Storage of retain sampleAvailable upon requestAvailable upon requestYes
Document deliverableCOA1. 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-likeGMP-grade
ApplicationsBasic research, drug discovery, preclinical studiesPreclinical studies such as animal testing of drug safety and metabolismPreclinical studies, clinical studies, and commercialization
Production scales>2.5x107 TU109 to 1012 TU per batch5x109 to 1012 TU per batch
Turnaround time8-16 days4-5 months6-12 months
Production siteIn parallel production in standard BSL-2 laboratoryProduced in segregated BSL-2 production suitesProduced in certified GMP suites (BSL-2)
Quality systemISO9001ISO9001 while adopting key features of GMP manufacturingICH quality guidelines for GMP manufacturing
Document control and traceabilityNoYesFull traceability
Vector characterizationNoSequencingSequencing
Process developmentNoPerformed on a case-by-case basis depending on individual project needsYes
Cell bankingNoAvailable upon requestYes
Antibiotic-freeNoAvailable upon requestYes
Animal component-freeNoAvailable upon request for suspension cultureFor suspension culture
PurificationUltracentrifugationUltracentrifugation, affinity purification, IEX purification, mixed-mode chromatographyUltracentrifugation, affinity purification, IEX purification, mixed-mode chromatography
QC and release testsTiter measurement, sterility testing, mycoplasma detection, etc.Performed on a case-by-case basis depending on individual project needsFull panel QC assays, analytical development upon individual project needs
Aseptic fill/finishNoAvailable upon requestYes
Storage of retain sampleAvailable upon requestAvailable upon requestYes
Document deliverableCOA1. 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

Vector characterization > Bacteria and mammalian cell banking, process development, and plasmid production > Engineering run > GMP run > QC and release.

 

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/Suspension > Transfection > Harvest and lysis > Clarification and concentration (TFF) > Purification > Formulation > QC.       

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/Suspension > Transfection > Clarification and concentration (TFF) > Purification > Formulation > QC.   
Learn more about our process development services Learn more about our QC and stability study services

Documents

Brochures & Flyers