CDMO SERVICES

A dedicated solution provider of cellular therapy products

CAR-T
CDMO Services for Plasmids-IND grade

Manufacturing of plasmids, a critical step of manufacturing CAR-NK cell therapy products, involve a series of complicated processes of manufacturing, purification, and analysis. As essential tools for genetic engineering, bacterial plasmids can not only be used as final products for gene and cellular therapy, but also as intermediate vectors for the manufacturing of gene and cell therapy products, and are inevitably used in manufacturing steps for most gene and cellular therapy products. With the emergence of cellular therapy industry, the market demands for plasmids are also increasing with each passing year. Hillgene is specialized in provision of integrated CDMO solutions for cellular therapy products, has established a GMP manufacturing platform for nucleic acid products, and therefore, can provide high-quality CDMO services for plasmids to clients with various demands.

Services

CDMO Services for Plasmids
TypesServices
IND grade1Independently 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

2GMP Creation of Bacterial Cell Bank

● Selection of monoclonal antibodies

● Tailorable number of cell banks to be created

● Cell bank stability study

3Process and Test Method Development

● Following project requirements (subject to customized changes)

4GMP Manufacturing of Plasmids

● Production output: 10 mg~1 g (subject to customized changes)

● Fermentation volume: 3~30 L (subject to customized changes)

● Purification method: three-step approach/two-step approach

5Plasmid Testing

● Purity (HPLC)  

● Residual E.coli DNA testing 

● Residual E.coli HCP testing 

● Residual E.coli RNA testing 

● Residual antibiotics testing  

● Sterility 

● Mycoplasma 

● Endotoxin

6Method Validation

● Specificity  

● Accuracy 

● Precision  

● Linearity and Range 

● LOD

7Stability 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 our plasmid system:

• An independently developed four-plasmid system with kanamycin-resistance gene 

• A system with the capability of sustained optimization 

• Plasmid sequences are traceable, compliant with requirements, and efficient  

• Extensive experience in successful IND submissions 

• CAR-NK cell samples for clinical use are currently manufacturing and in use 

• 2-5 folds higher titers after using our plasmid system from the comparison in several projects

Advantages of our plasmid manufacturing:

• Free of antibiotics throughout the manufacturing process 

• Plasmid production and bank creation in separate workshops 

• Complete isolation between non-sterile and sterile areas 

• Dispensing final products using an isolator  

• Completed CTD dossiers for packaging plasmid (for lentiviral vector), reducing the submission preparation time by 3-4 months, with INDs of a few products granted preliminary approval and currently in phase I of clinical study




Manufacturing process


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Quality control


Test ItemTest Method
AppearanceVisual inspection
IdentificationIdentification 1Restriction mapping
Identification 2Sanger sequencing
TestpHMethod 0631 of ChP 2020
PurityHigh performance liquid chromatography (HPLC)
Residual E.coli host cell proteinELISA
Residual E.coli DNAq-PCR
Residual E.coli RNAq-PCR

Residual antibiotics

ELISA
EndotoxinMethod 1143 of ChP 2020
SterilityMethod 1101 of ChP 2020
Concentration determinationDNA concentrationMethod 0401 of ChP 2020

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



Project Timeline

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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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