AAV cGMP Manufacturing
As the gene and cell therapy landscape has expanded there has been a subsequent expansion in the need large-scale production of GMP-grade AAVs that meet regulatory filing standards. PackGene aims to meet this need across phases of the gene and cell therapy lifecycle including PI initiated clinical trials (IIT), to Investigational New Drug (IND) filings, to Phase I-III clinical trials, and large-scale commercial production of GMP-grade AAV.
Using our proprietary platforms and technologies PackGene provides mass-production services of GMP-compliant AAV, as well as GMP production line set-up, virus processing and assays, and IND pharmacological documentation for services ranging from the upstream rAAV generation to the downstream isolation and purification. We also ensure AAV manufacturing services comply with GMPs and all applicable regulatory and required standards for IIT and IND applications.
AAV Manufacturing Process
PackGene GMP-compliant services include AAV upstream production and downstream development, purification, large-scale fermentation, material segregation, traceability record keeping, document control, and a comprehensive range of quality control assays.
PackGene has developed core processing technology that multiplies the single-batch AAV output/yield and reduce the input cost, giving our customers a leading edge.
AAV Quality control (or customized based on specific process)
|Identity||GOI Sequence||Sanger Sequence|
|AAV Capsid||SDS PAGE/MS|
|%Empty capsids||AEX HPLC|
|Potency & Content||Capsid Titer||ELISA|
|Protein Expression||In Vitro assay|
|Impurity||Residual Host Cell DNA||qPCR|
|Safety||Mycoplasma||qPCR/Mycoplasma culture /DNA staining|
|Sterility||Direct Inoculation Method/Membrane filtration|
|Adventitious agent||Cell Culture|
|Abnormal toxicity||Animal test|
|General Characterization||Appearance||Visual Inspection|
|Particulate matter||Light Obscuration Particle Count test|
AAV Manufacturing Facilities
Our GMP manufacturing site fully adopts “disposable technology” and advanced design concepts. Our facility is equipped with a clean environment in line with quality by design (QbD) concepts. This includes physical isolation and full-exclusion systems to segregate different functional workshops. The GMP workshop is only used for pilot testing or large-scale production of AAV carriers, and this completely avoids multi-species sharing or cross-contamination issues commonly found in traditional CDMO platforms.
The upstream production line of the GMP site is equipped with the leading iCellis 500 disposable bioreactor system (up to 500m2 wall area), STR200T 200L disposable reactor, Xpansion disposable reactor, XDR 50 MO 50L disposable reactor, and several wave-shaped bioreactors to meet the needs of large-scale wall and suspension culture production of AAV. The downstream line is equipped with ÄKTA chromatographic purification and ultrafiltration systems. Based on years of experience in large-scale production, single batch AAV yields of 1E+15-17GC or vg can be achieved, allowing for a shortened pilot production cycle of AAV under GMP standards to be completed within 1-2 months. PackGene’s core process technology route can help partners to significantly increase single batch yields and reduce input costs. This results in valuable speed advantages for customers and ultimately leads to accelerated registration filings and clinical level production of gene therapy services.
The purpose of final generation cell assays is to confirm cell suitability and to determine if cells have mutated or produce carcinogenic substances. Cells are resuscitated and passaged from the working cell bank according to the production process route, transferred to the bioreactor for passaged digestion, cultured according to the proposed process, and then digested for lyophilization or sent for testing at the end of bioreactor production. The generation of cell resuscitation and passaging methods are carried out according to your custom production process SOP.
PackGene facility includes iCellis500 (~500m2 adhesion area), STR50/200/500T with the single-use technology that can flexibly conduct both GMP AAV upstream production by adherent and suspension culture.
- Designed with QbD concept and optimization
- Clean environment in accordance with C+A standards
- Reaching the maximum AAV yield up to 1E+15GC-1E+17 GC/batch
- Isolated vector producing line to completely avoid cross-contamination between different vectors
- GMP-compliant pilot production cycle can be shortened to 1-2 months
- Single-use technology and water supply to ensure batch cleaning verification