IND grade-Hillgene

Lentivirus, a subtype of retrovirus, can integrate the target gene into the host cell genome, and is commonly used as a viral vector for ex vivo cell engineering. With the emergence of cellular therapy industry, the market demands for lentiviral vectors are also increasing with each passing year. Hillgene is specialized in provision of integrated CDMO solutions for cellular therapy products, has established an advanced GMP grade platform for serum-free suspension culturing of lentiviral vectors, and therefore, can provide high-quality CDMO services for lentiviral vectors to clients with various demands.

Services

IND grade	1	Independently developed four-plasmid system	●　Third generation four-plasmid system ●　Kanamycin-resistance gene ●　Granting the license, if required	●　Following standards for submission in both China and US ●　Full-GMP workshop ●　Separate area for creating cell banks ●　Separate workshops within non-sterile and sterile areas ●　GMP quality management system
	2	Creation of GMP Cell Bank	●　Tailorable number of cell banks to be created ●　Cell bank stability study
	3	Process and Test Method Development	●　Following project requirements (subject to customized changes)
	4	GMP Manufacturing of Lentiviral Vectors	●　Bioreactor process: 5~50 L disposable bioreactor process (subject to customized changes) ●　Production scale: 2~30 L (subject to customized changes)
	5	Testing of Lentiviral Vectors	●　Physical titer ●　Infective titer ●　Functional titer ●　Residual 293T host cell DNA testing ●　Residual 293T host cell protein testing ●　Residual exogenous DNA testing ●　Residual Benzonase testing ●　E1A/SV40 ●　Residual plasmid testing ●　DNA fragment size ●　Exogenous virokines ●　Sterility ●　Mycoplasma ●　Endotoxin
	6	Method Validation	●　Specificity ●　Accuracy ●　Precision ●　Linearity and Range ●　LOD
	7	Stability Study	●　Long-term stability ●　Accelerated stability ●　Stress testing

*Note: We offer relatively flexible and customized changes to above services, including but not limited to above services.

Advantages

Advantages of using our platform for serum-free suspension culturing of lentiviral vectors:

• Free of animal-derived components throughout the process

• Linearly scaled up production of lentiviral vectors

• Using a single container of a 50 L disposable bioreactor

• Cell bank creation in separate workshops

• Dispensing final products using a sterile isolator

• Dedicated lentivirus system for CAR-T cells, with high infection efficiency

• Low production costs and testing costs (no requirements of testing for BSA and residual pancreatic enzymes)

• Several successful IND submissions to NMPA of lentiviral vectors for CAR-T cells

Manufacturing process

Quality control

Product	Test Item	Test Method
Harvest Fluid	Adventitious virus contamination	Method 3302 of ChP 2020
Harvest Fluid	Replication-competent lentiviruses	Indicator cell culture method
Drug substance/finished product	Appearance	Visual inspection
	Sterility	Method 1101 of ChP 2020
	Mycoplasma	Method 3301 of ChP 2020
	pH	Method 0631 of ChP 2020
	Osmolality	Method 0632 of ChP 2020
	Target gene structure identification	Sequencing
	Residual host cell protein	ELISA
	Physical titer (p24)	ELISA
	Functional titer	Flow cytometry
	Endotoxin	Method 1143 of ChP 2020
	Residual Benzonase	ELISA
	Residual host cell DNA	q-PCR
	Residual E1A gene transfer	Co-culture method
	Residual SV40 gene transfer	Co-culture method

*Note: Hillgene established QC methods corresponding to different technology platforms, with QC methods including but not limited to above items.

Project Timeline

Project Management Plan

Hillgene Project Management Team, consisting of chief scientists, project managers, Project QA and GMP experts, will make efforts to ensure the smooth and sound operation of each and every GMP project.

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Integrated CDMO Solutions for CAR-T Cells

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