GLP and GMP for recombinant virus

I  Toxic lot run in pilot scale for IND/CTA in US/China

Pilot operation engineers are working on class C/D pilot plant to scale up the process, manufacture drug sample for IND/CTA, following GLP quality system.

· Gene sequence construction in plasmid vector.

· Ecoli strain manufacturing, storage and stability test.

· HEK293T cell bank manufacturing, RCB/MCB/WCB validation/characterization/stability study.

· Tech transfer from lab scale to single-use pilot plant.

· Up to 10L Ecoli fermentation in single-use bioreactor.

· Plasmid purification by chromatography and UF/DF.

· Up to 50L HEK293T cell culture in single-use bioreactor, XDR 50.

· Virus purification by chromatography and UF/DF.

· Single use filling/finish system.

· In-process sample test.

· Virus drug substance or product release test.

· Assay method qualification or validation.

· Drug substance and drug product stability study, long-term and other conditions as required for IND.

· Preclinical PK/PD/Tox study in GLP lab.

· IND/CTA document preparation.

· Regulatory on-site audit.

II  GMP manufacturing service for recombinant virus

We are setting up our GMP facility for virus manufacturing, to provide drug product or drug substance for clinical phase stage. The facility is about 5000sqm, with HVAC, clean utility, warehouse, plasmid plant, virus plant, QC labs, filling/finishing plant. The manufacturing process equipments are mainly GE single use Flex FactoryTM, with some additional equipments from Merck Millipore and Pall Life Science. It will be the first single-use technology GMP plant for recombinant virus in China, to provide service for gene therapy and cell therapy industry. The concept design and basic design was completed yet in Sep 2017, and detailed design is finished in Dec 2017. The whole plant will be validated in Nov 2018, and ready to start the GMP run in early 2019. The GMP grade CMO will cover:

· Tech transfer from pilot scale to large scale.

· Raw material test.

· GMP grade material supplier auditing system.

· 100L, 200L, and up to 500L single use bioreactor for virus manufacturing.

· 10L, 50L and up to 100L single use bioreactor for plasmid manufacturing.

· Whole single-use for hybrid purification platform for plasmid and virus.

· GMP grade filling/finish system for virus.

Quality management for CRO and CMO service

I  Virus Quality control platform

We have been developing the assay method for virus to support the whole life cycle of the virus drug, from lab process development to GMP manufacturing.

· Virus Titer: QPCR, protein concentration by Elisa, and virus particle counter.

· Virus purity: HPLC, SDS-Page.

· Impurities: HCP, HCDNA, other additives in the process.

· Potency: West Blot, Transfect target cell.

· Wild-type or other contaminant virus: rcAAV, RCL, HAV, HBV, HCV, HIV, HSV.

· Safety test: endotoxin, sterilization, mycoplasma, apprance, osmolality.

· Virus characterization: protein glycosylation, SEM, gene sequence.

II  Quality management system

The quality team is experience in biopharm, most of the member used to work in MAB companies. We have been developing our quality management system (QMS). Right now, it is following GLP and fully qualified for IND/CTA. There are more than 300 different documents, SOPs, batch records to support the pilot plant daily operation, to ensure that:

· People are well trained and qualified.

· Material quality can meet process requirement.

· Sample in/out are recorded.

· Environment is under control and monitoring.

· Equipments appliance, and instrument are well validated or qualified.

· SOPs are well applied according to QMS.

We guarantee that all the operations and data generated in our platform can meet:

· Trackability,

· Integrity,

· Reality.

The GMP QMS is under setting up. The team will be more than 10 members to support the new GMP plant operation.

III   Equipment and facility

We are well equipped with global standard equipment, to execute the high quality experiment, operation, test in lab, in pilot plant or in GMP plant.

· 900sqm BSL2 lab.

· 900sqm pilot plant with class C and Class D.

· 900sqm SPF animal plant.

· 4500sqm GMP facility.

· 2 Wave 20/50

· 1 Ecoli Fermentation bioreactor

· 2 GE XDR 50 bioreactor

· 1 GE XDR 200 bioreactor

· 2 GE AKTA Process

· 1 GE AKTA Pilot

· 2 GE AKTA Pure

· 2 GE AKTA Flux UF/DF

· 2 Millipore UF/DF system

· 3 SPECTRUM UF/DF sytem

· 4 Membrane integrity test from Millipore and Pall

· 7 Fuser and Sealer from GE

· Nova 400

· Cell counter

· Agilent HPLC

· Roche QPCR

· Biotek microplate reader

· Memert Stability Chamber

· More than 40 XDM, XDUO and RTP Bin for buffer preparation and storage.

· More than 30 LN2 tanks

· More than 20 CO2 shakers

· More than 10 BSCs.

· Environment monitoring system

· Temperature monitoring and recording system.