DNA Platform Process Development & Scale Up
Since 1998 our expert DNA platform process, under continual process improvement and now RNase free, has allowed for rapid process scale up, reducing timelines and costs for customers’ advanced therapy programs.
We offer a standard platform process that includes plasmid transformation, high density fermentation, alkaline cell lysis, chromatographic purification and formulation.
DNA Analytical Development & Qualification
We provide full analytical support for our customers, including the development of specific assays, assay transfer services, expert product characterisation and DNA sequencing. Support is also available for IND (Investigational New Drug) applications and BLAs (Biological License Applications).
Cleaning validation and raw materials testing is undertaken internally to ensure the highest standards are maintained for all of our customers’ programmes.
Our Quality Assurance (QA) team provide Quality Control (QC) release testing of Drug Substance & Drug Product.
Shipping studies to determine stability for product transportation including variations in temperature, humidity, light and oxygen levels can be undertaken as required.
A typical GMP analytical package would be:
- DNA concentration by absorbance spectroscopy (DNA purity by OD 260/280)
- Purity (Total plasmid) by agarose gel electrophoresis
- Identity by Restriction Digest
- Purity (Supercoiled DNA) by Capillary Electrophoresis
- Residual protein by SDS-PAGE
- Host Cell protein by ELISA
- Residual host cell DNA by QPCR
- Residual host cell RNA by HPLC
- Residual Kanamycin
- Plasmid sequence GMP grade (four-fold coverage)
Our High Quality (HQ) offering adopts features of Cobra’s GMP manufacture, including RNase free, with a 6 week delivery time. HQ plasmid can be used as an ancillary or starting material for the clinical manufacture of immuno-oncology therapies, for example in AAV and lentiviral vectors, plasmid templates for mRNA therapies, and CRISPR products.
Current standard offerings for HQ supply are from 50mg to 500mg of purified plasmid; this can be tailored to meet specific customer requirements.
HQ production is performed in a Class 2 segregated laboratory using HQ production cell banks as starting material. The HQ grade plasmids are released with a Certificate of Testing and QA TSE BSE Certification.
A typical HQ analytical package would be:
- DNA concentration by Absorbance Spectroscopy (DNA purity by OD260/280)
- Purity (Total Plasmid) by Agarose Gel Electrophoresis
- Identity by Restriction Digest
- Purity (% Supercoiled DNA) by Capillary Electrophoresis
- Host Cell Protein by ELISA
- Residual Host Cell DNA by QPCR
- Residual Host Cell RNA by HPLC
- Plasmid sequence
- Detection of Mycoplasma by Real-Time PCR (outsourced)
GMP Manufacturing & Cell Banking
Cobra manufactures non-GMP plasmid DNA plus High Quality (HQ) and fully GMP plasmid DNA which follows Good Manufacturing Practices of production and testing including DNA sequencing to ensure the release of quality products for our customers’ preclinical and clinical trials through to commercial supply.
All manufacturing processes are defined and controlled to ensure compliance. Clear records are made and any deviations are investigated and documented.
Operating efficiently and consistently through our platform DNA process, Cobra’s DNA programs meet manufacturing standards worldwide, with full regulatory support from our Quality Assurance (QA) team. We are able to provide a certificate of GMP compliance and GMP campaign summary report with QA review of completed documentation.
Since 1998 Cobra has also been providing cell banking and full GMP certification to support customers’ projects. Working within GMP manufacturing regulations, we can supply both Master & Working Cell Banks (MCB & WCB).
We utilise a specific proprietary antibiotic-free maintenance technology, ORT® (Operator-Repressor Titration), which provides highly stable, antibiotic-free high copy-number plasmids.
Our comprehensive service offerings include the capacity to produce sterile drug products, utilising fully disposable systems and meeting rigorous sterility requirements in accordance with aseptic manufacturing procedures.
With batch sizes from 1 to 100 litres, we manufacture for clinical through to commercial scale supply with products filled in single-use syringes (0.5 - 10.0ml) or vials (2.0 - 100.0ml), with the option of freeze drying / lyophilisation, if required.
All batch records are fully traceable under QA observation with QP review and issue of GMP Certificate of Compliance, and regulatory documents are reviewed as required to support product release to clinic. Primary labelling of drug product vials for human clinical centres, secondary packaging and labelling of vials for dispatch to clinical centres, and tertiary and transport labelling and packaging can also be arranged according to regulatory requirements.
As part of the Quality Assurance process, DNA plasmid stability is tested according to ICH guidelines for Drug Substance and Drug Product. These studies help to determine the effect of external factors on the active component within a customer’s product and are critical for regulators.
The effects of different levels of light, heat, humidity and oxygen levels, as well as a broad range of pH levels, are examined.
Forced degradation studies, to accelerate the natural degradation process, are also undertaken to determine the effect on the product.
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