바이러스 벡터 제조

VectorBuilder는 세포 및 유전자 치료 개발을 위한 다양한 유형의 바이러스 벡터 생산에 대한 풍부한 전문성을 보유하고 있습니다. 유전자 치료제 개발 파이프라인의 모든 수요를 충족하기 위해 다양한 스케일과 품질 특성을 갖춘 벡터를 제공합니다. VectorBuilder 팀은 AAV (adeno-associated virus)와 렌티바이러스의 대량 GMP 생산을 위한 플랫폼 기술을 확립하고 검증했으며, 아데노바이러스, MMLV, HSV (herpes simplex virus), VSV (vesicular stomatitis virus) 등 다른 유형의 바이러스 벡터 생산에도 전문성과 역량을 보유하고 있습니다.

주요 특징 

Experts in Virus Packaging 바이러스 패키징 전문가 어떤 스케일에서도 최고의 역가와 효능을 달성할 수 있게 최적화된 독자 기술.
Scalable Solutions 확장 가능한 솔루션 연구용부터 상업적 목적까지, 고객의 생산 요구사항을 지원하는 다목적 플랫폼.
Highest Quality and Consistency 최고의 품질과 일관성 최첨단 GMP 시설 및 장비로 최고의 순도와 일관성을 제공.

제공되는 바이러스 벡터의 등급

VectorBuilder는 신약 개발 연구, 전임상 연구, 임상 시험 및 상용화를 포함한 다양한 다운스트림 응용 분야에 활용할 수 있도록 다양한 등급의 바이러스를 생산합니다.

     R&D
     Preclinical
     Clinical
     Commercial
Research-grade
GMP-like
GMP-grade
  • 유전자 기능 및 조절 연구, 신약 개발 연구 등 기초 연구에 적합
  • 일반 세포 배양 시설에서 엄격한 QC로 생산
  • 전임상 연구 (예: 약물 안전성 및 대사에 대한 동물 실험)에 적합
  • PAS 또는 GMP 시설에서 GMP 가이드라인의 주요 특징을 채택하는 방식으로 생산
  • Antibiotic-free 및 animal component-free 조건에서 생산 가능
  • 전임상 연구, 임상 연구 및 상용화에 적합
  • GMP 가이드라인을 엄격히 준수하는 인증된 GMP 스위트에서 생산
  • 종합적인 QC 분석 및 배치 릴리즈 리포트 포함

다양한 등급의 바이러스 비교

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 5x1010 to 1014 GC per batch 5x1013 to 1017 GC per batch 1014 to 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, insert sequencing RE digestion, full-length sequencing RE digestion, full-length 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 RE digestion, insert sequencing RE digestion, full-length sequencing RE digestion, full-length 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

바이러스 벡터 GMP 생산 워크플로우

VectorBuilder는 최고 품질의 제품을 적시에 제공하기 위해 최선을 다합니다. 바이러스 벡터의 일반적인 GMP 생산 워크플로우는 다음과 같습니다.

Vector characterization > Process development and cell banking > Plasmid production > Quality control and release.
Vector
Characterization
Process
Development
&
Cell
Banking
&
Plasmid
Production
Engineering
Run
GMP Run
QC & Release
1 week
2.5 months
1 month
1 month
1 month
  • RE digestion
  • Sequencing
  • Cell line
    development
  • USP/DSP
  • Analytical
    development
  • RCB
  • MCB
  • WCB
  • Segregated
    suite
    (GMP-like)
  • GMP suite
    (GMP-grade)
  • Closed system
  • Fill/finish
  • General/physical
    properties
  • Identity
  • Purity
  • Safety

플랫폼 기술

AAV 플랫폼
Lentivirus 플랫폼

AAV는 HEK293 세포에 adherent 조건 (multi-layer flasks 또는 fixed-bed bioreactors) 또는 serum-free suspension조건 (up to 200 L single-use bioreactors)으로 패키징됩니다. 별도 요청 시, suspension Sf9 곤충 세포로 AAV를 패키징할 수 있습니다. VectorBuilder는 배치당 최대 1017 GC AAV까지 생산 스케일을 확장할 수 있습니다.

Cell Bank recovery and culture > Fermentation > Harvest and lysis > Centrifugation > Chromatography > TFF > Sterile filtration > QC
Adherent
(Multi-layer flasks,
fixed-bed bioreactors)
Suspension
(Single-use bioreactors)
Transfection
(PEI, calcium
phosphate
Harvest and
lysis
Clarification and
concentration
(TFF)
Purification
(Chromatography)
Formulation
(TFF, sterile
filtration, fill/finish)
QC and release

렌티바이러스 (2nd or 3rd generation, pseudotyped with VSV-G or other viral surface proteins)는 HEK293 세포에 adherent 조건 (multi-layer flasks or fixed-bed bioreactors) 또는 serum-free suspension조건 (up to 200 L single-use bioreactors)으로 패키징됩니다. VectorBuilder는 배치당 최대 1012 TU까지 생산 스케일을 확장할 수 있습니다.

Cell Bank recovery and culture > Fermentation > Harvest and alkaline lysis > Centrifugation > Chromatography > TFF > Sterile filtration > QC
Adherent
(Multi-layer flasks,
fixed-bed bioreactors)
Suspension
(Single-use bioreactors)
Transfection
(PEI, calcium
phosphate
Clarification and
concentration
(TFF)
Purification
(Chromatography)
Formulation
(TFF, sterile
filtration, fill/finish)
QC and release

VectorBuilder의 제조 플랫폼 및/또는 GMP 역량에 대한 자세한 내용은 VectorBuilder 서비스팀에 문의해 주시기 바랍니다.

Talk to Our Experts

분석 방법

QC 분석

아래 표는 GMP-like 및 GMP-grade 바이러스 벡터 릴리즈를 위한 기본 QC 분석 (✓ 표시)을 요약한 것입니다. 개별 프로젝트 요구사항에 따라 추가 옵션 QC 분석이 수행됩니다.

AAV 플랫폼
Lentivirus 플랫폼
Attribute QC Assay GMP-Like GMP-Grade
General/Physical Properties Osmolality Freezing point depression Optional ✓
pH pH meter ✓ ✓
Particulate matter Light obscuration particle count test Optional ✓
Appearance Visual inspection Optional ✓
Extractable volume Direct measurement Optional ✓
Physical titer qPCR ✓ ✓
ddPCR Optional ✓
ELISA ✓ ✓
Infectious titer TCID50 Optional Optional
Potency mRNA transcription RT-qPCR Optional ✓
RT-ddPCR Optional Optional
Protein expression Flow cytometry (FCM) Optional Optional
Identity Full-length plasmid sequence Sanger sequencing ✓ ✓
NGS Optional Optional
Third-generation sequencing Optional Optional
Purity Capsid protein purity SDS-PAGE with silver staining ✓ ✓
Empty capsid ratio Transmission electron microscopy (TEM) Optional Optional
Mass photometry (MP) ✓ ✓
Analytical ultracentrifugation (AUC) Optional ✓
Charge detection mass spectrometry (CDMS) Optional Optional
Aggregation Dynamic light scattering (DLS) Optional Optional
Size exclusion chromatography (SEC) Optional ✓
Genome integrity Alkaline gel electrophoresis ✓ ✓
Process-Related Impurity Residual plasmid DNA qPCR ✓ ✓
ddPCR Optional Optional
Residual host cell DNA qPCR ✓ ✓
Residual E1A sequence qPCR ✓ ✓
Residual host cell DNA fragment  size Capillary electrophoresis (CE) Optional ✓
Residual host cell proteins ELISA ✓ ✓
Residual Benzonase ELISA ✓ ✓
Residual affinity ligand HPLC Optional Optional
Residual transfection reagent HPLC Optional Optional
Residual ultracentrifugation agent HPLC Optional ✓
Residual detergent HPLC Optional Optional
Product-Related Impurity Replication competent AAV qPCR Optional ✓
Safety Sterility Direct inoculation Optional Optional
Membrane filtration sterility test ✓ ✓
Endotoxin Kinetic chromogenic assay (KCA) ✓ ✓
Mycoplasma DNA staining ✓ Optional
qPCR ✓ Optional
Direct culture and indicator cell culture Optional ✓
Adventitious virus testing Cell culture (using MRC-5, VERO, and HEK293 cells) Optional ✓
Documentation - -
1. COA
2. Manufacturing summary
3. TSE/BSE certificate upon request
1. COA
2. TSE/BSE certificate
3. CTD documents
4. Others (BMR, etc.) upon request
Attribute QC Assay GMP-Like GMP-Grade
General/Physical Properties Osmolality Freezing point depression Optional ✓
pH pH meter ✓ ✓
Particulate matter Light obscuration particle count test Optional ✓
Appearance Visual inspection Optional ✓
Extractable volume Direct measurement Optional ✓
Physical titer RT-qPCR Optional ✓
ELISA ✓ ✓
Functional titer qPCR ✓ ✓
Flow cytometry (FCM) Optional ✓
Infectious titer TCID50 Optional Optional
Potency mRNA transcription RT-ddPCR Optional Optional
Protein expression Flow cytometry (FCM) Optional Optional
Identity Full-length plasmid sequence Sanger sequencing ✓ ✓
NGS Optional Optional
Third-generation sequencing Optional Optional
Purity Aggregation Dynamic light scattering (DLS) Optional Optional
Process-Related Impurity Residual plasmid DNA qPCR ✓ ✓
ddPCR Optional Optional
Residual host cell DNA qPCR ✓ ✓
Residual E1A sequence qPCR ✓ ✓
Residual SV40 LTA sequence qPCR ✓ ✓
Residual host cell DNA fragment  size Capillary electrophoresis (CE) Optional ✓
Residual host cell proteins ELISA ✓ ✓
Residual Benzonase ELISA ✓ ✓
Residual affinity ligand HPLC Optional Optional
Residual transfection reagent HPLC Optional Optional
Residual detergent HPLC Optional Optional
Product-Related Impurity Replication competent lentivirus Cell culture Optional ✓
Safety Sterility Direct inoculation Optional Optional
Membrane filtration sterility test ✓ ✓
Endotoxin Kinetic chromogenic assay (KCA) ✓ ✓
Mycoplasma DNA staining ✓ Optional
qPCR ✓ Optional
Direct culture and indicator cell culture Optional ✓
Adventitious virus testing Cell culture (using MRC-5, VERO, and HEK293 cells) Optional ✓
Documentation - -
1. COA
2.Manufacturing summary
3.TSE/BSE certificate upon request
1. COA
2. TSE/BSE certificate
3. CTD documents
4. Others (BMR, etc.) upon request

위에 기재되지 않은 추가 QC 서비스는 별도 요청 시 제공될 수 있습니다. 자세한 내용은 VectorBuilder 서비스팀에 문의해 주시기 바랍니다.

Talk to Our Experts
안정성 시험

약물 안정성 시험은 ICH 가이드라인에 따라 수행됩니다. 강제 분해 시험은 빛, 온도, pH 등이 바이러스 벡터의 품질 특성에 미치는 영향을 평가하기 위해 수행됩니다.

시설

VectorBuilder는 현재 미국, EU, 일본, 중국 및 PIC/S의 GMP 규정을 충족하는 첨단 설계와 장비를 갖춘 약 100,000 ft² 규모의 최신 GMP 준수 시설을 보유하고 있습니다. VectorBuilder의 시설은 ICH 가이드라인을 준수하며, 임상 1/2/3상 시험을 위한 GMP 생산에 적합합니다.

  1. Process & Analytical
    Development Suites
  2. GMP Manufacturing
    Suites
  3. Fill/finish Suites
  4. QC Laboratories
  5. GMP Warehouse

We have multiple GMP suites totaling 8,400 ft2 for PD/pilot runs. All BSL-2 certified areas are set up with Grade A BSC in Grade C environment.

Our suites are designed for manufacturing plasmid, viral vector, and cell line production at various scales. Each suite is equipped with independent airflow. Our suites contain GrOur suites are designed for manufacturing plasmid, viral vector, and cell line production at various scalesade A BSC in Grade B/C environment and are BSL-2 certified.

Our automated filling system is installed within a Grade A isolator in a Grade C environment.

Our independent QC laboratories consist of multiple lab suites totaling 9,500 ft2 for a wide range of QC assays.

We have 6,500 ft2 of ICH-compliant warehouse space for product storage and monitoring.

정보 자료

문서
브로셔 & 리플렛
관련 서비스
MiniVec™ 
CliniVec™ 
Plasmid manufacturing 
IVT RNA and LNP manufacturing