cGMP Plasmid DNA Manufacturing Services

Overview

Plasmids are small double-stranded units of DNA, usually in circular or linear form. They are found separately from the bacterial chromosome and can multiply on one’s own.

Their ease of manipulation, ability to make identical copies of themselves, as well as their long-term stability, have made them essential tools in genetic engineering and biotechnology applications. One of their vital roles is as a delivery vehicle to introduce new genetic material into bacteria.

Esco Aster offers CDMO services to process develop and manufacture various grades of plasmid DNA used for early-stage research to preclinical, clinical phase trials. Our process development services support the product development regardless of its current development status, whether the product is in early-stage development or ready to launch. We maintain GMP standards from the starting material to the final drug products in our Plasmid DNA production facility.

The advantage of choosing a GMP-grade plasmid from the start lies in the smooth regulatory transition to the next steps. You can count on our advanced, end-to-end single-use technology, state-of-the-art facility and most importantly, skilled and passionate personnel to find the most suitable path and guide you through your journey from gene to the final vialed product.

Main Applications

Our Plasmid DNA Manufacturing Services are employed in the following areas:

Viral Vector Production

Gene Editing

mRNA Production

DNA Vaccines

Cell and Gene Therapy

Our Production Process

Esco Aster’s state-of-art facility has an end-to-end, single-use bioprocessing capacity to manufacture plasmid of the highest grade of purity following the GMP guidelines FDA 21 CRF Part 820. This facility includes ISO standards cleanrooms, bioprocessing equipment of cutting edge technology coupled with our experts, and in-house product release testing capabilities. Moreover, the use of single-use technology eliminates the possibility of cross-contamination between products and batches. We maintain highest standard of cleanliness of the facility by following EU GMP annex 1 guideline for environmental monitoring.

Esco Aster has a facility to perform microbial fermentation, cell harvesting by continuous centrifugation, cell lysis by alkalization, clarification in tangential flow filtration, purification and polishing in liquid chromatography. All the equipment and core technologies are selected and validated for single-use operation. Esco Aster has branded isolator system for bulk filling of the final product into sterile packaging.

Laboratory Testing Regulations

Esco Aster provides three (3) different grades of plasmids following the intended applications to fit the requirement from clients. The variety of plasmid comes with different level of preparation and documentation as follows:

Grade	Description	Capacity	Lot Size (g)
GLP Grade	Plasmid is produced in GLP laboratory Single-use bioreactor to eliminate possibility of contamination. CoA will be issued as per quality checks Documentation as per GLP lab regulation Batch documentation are reviewed and signed	5-30L	< 5
GMP (HQ) Grade (FDA 820/ISO 13485)	Plasmid is manufactured in a cGMP qualified area E. coli master and working cell bank generation Process equipment are validated Quality assays are performed in controlled environment Manufacturing summary report Plasmids are released with a CoA Batch documentation are reviewed and Signed by QA (critical steps only)	30-100L	5-10
cGMP Grade	Plasmid is manufactured following all GMP manufacturing guidelines Same process as GMP grade and performed with GMP compliance Expected QA oversight of equipment, facilities, personnel and pDNA process	30-100L	5-10

project managed by Esco Aster outsourced to qualified vendor

Quality Control Assay

Esco Aster offers following quality checks on plasmid of different grades based on your applications and requirements

Assay	Method	AQL	cGMP Grade
Appearance	Visual Inspection	Clear, Particle-free
Concentration	UV Spectrophotometry	Product Specific
Purity	UV Spectrophotometry (Abs₂₆₀/Abs₂₈₀)	1.8-2.0
Plasmid Identity	Gel Electrophoresis	Confirm
DNA Homogeneity	Gel Electrophoresis and Gel Densitometry	> 90% supercoiled
Restriction Analysis	Restriction Digest and Gel Electrophoresis	Coherent fragments with the plasmid restriction map
Plasmid Sequence	Gene Sequencing	Confirm
Residual Host Cell Protein	ELISA	<1.0%	Optional
Residual Host Cell Protein	Micro BCA	<1.0%
Residual Host Genomic DNA	Quantitative PCR	<0.1%
Residual Host RNA	HPLC	< 0.1% by HPLC	Optional
Residual Host RNA	SYBR Gold Stained Agarose Gel Electrophoresis	Undetectable (Gel)
Endotoxin	Kinetic Chromogenic LAL	< 10 EU/mg
Mycoplasma Contamination	Quantitative PCR	Negative
Bioburden	Testing for Total Aerobes, Anaerobes, Spore Formers and Fungi	Not Detected
Residual Kanamycin	ELISA	Product Specific
pH	pH meter	Product Specific
Conductivity	Conductivity meter	Product Specific

Project Management

An approximate project management timeline in producing plasmid DNA of different grades in Esco Aster furnished with state of the art, end-to-end, single-use equipment.

Major Project Milestones	GLP Grade	GMP Grade (FDA 820/ISO 13485)	cGMP Grade
Kick-off Project (upon receipt of order)	< 2 weeks	< 3 weeks	< 3 weeks
Manufacturing Production Period (starting from strain transformation) Seed train Fermentation Cell lysis Purification Quality control	2 - 3 weeks	3 - 4 weeks	5 - 6 weeks
Progress Update	Weekly	Weekly	Weekly
Dedicated Project Manager	Yes	Yes	Yes
Certificated of Analysis (CoA)
Manufacturing Summary Report
Manufacturing Batch Records
cGMP Compliance Statement

Disclaimer

Some services are still being built up and ready only by Y2024. Please inquire for further information and updates through [email protected]