DNA manufacture

R&D grade plasmid 

The Clinical Biotechnology Centre can offer R&D grade plasmid at scales between 10mg up to 500mg.

High Quality grade plasmid 

HQ plasmid coming soon to CBC. To find out more about our HQ grade offering, please contact us. 

GMP-grade plasmid 

We have considerable expertise in the manufacture of small batches of bespoke GMP-grade plasmids in our MHRA-licensed facilities.  

Our typical production ranges from 0.2g to 2.5g, but this is tailored to individual customer requirements.  

Plasmids may be used for direct vaccination of patients, for cell therapies (such as induced pluripotential stem cells) or as the starting material for viral vector production (e.g. adeno-associated virus or lentiviral vectors).  

We can manufacture plasmids for a variety of research, pre-clinical and clinical campaigns. We have the capacity to scale up your processes and offer a flexible, high quality, and competitive service. 

Innovation Hub for Gene Therapies at NHS Blood and Transplant manufactures GMP-grade Lentiviral Vectors and recombinant Adeno-associated Viral Vectors at different scales to enable early-stage clinical studies.

We offer our platform technology for producing and purifying vectors and welcome technology transfer alternative methods based on clients' requirements.

We manufacture 10L and 40L vector batches using the HEK293 suspension cells grown in stirred tank bioreactors. Other scales and cell culture formats are supported. We offer high-quality non-GMP vector manufacturing to support developers at pre-clinical stages to translate more therapies to clinical stages. 

A range of downstream purification methods are available including; filtration, affinity chromatography, ion-exchange chromatography and ultrafiltration. Vector formulation and vialing are also a part of our services. We offer viral characterisation and quality control testing along with the QP release.

Our products are filled using a grade A positive-pressure isolator in a grade C background. The isolator is decontaminated before each batch using an integrated vapour phase hydrogen peroxide generator. An Aseptic Technologies Crystal^TM M1 closed vial filling system, with a laser sealing device and disposable needle assembly is used for bottling. Our aseptic fill technology can fill up to 500 bottles per batch in a single session at various fill volumes from less than 1mL to 50mL.

Our services also include the capacity for producing sterile products utilising our fully disposable systems, which meet strict sterility and GMP requirements.

We develop, optimise and validate product-specific assays, enabling us to offer a complete range of analytical testing services. Using our quality control assays, we are able to establish identity, potency, purity and safety of your products.

Our services include:

• Microbial cell bank characterisation testing
• Plasmid DNA concentration, identity, residuals, and quality testing
• Viral vector concentration, identity, residuals, and quality testing
• Bioburden and endotoxin testing
• Physio-chemical testing – pH, conductivity, osmolality
• DNA sequencing including Sanger and Next Generation Sequencing
  
• Stability testing in accordance with ICH guidelines

There are many challenges in the transfer of advanced therapy medicinal products (ATMPs) from the laboratory environment into GMP manufacturing. Process development is a critical aspect in de-risking the smooth transition of such products into GMP.

Our dedicated process development team has over 15 years’ experience in the work up of new production processes & QC assays or for the transfer of existing platforms for a range of products. Activities are conducted in well-equipped dedicated laboratories with “state of the art” technologies.

The CBC has successfully developed, optimised and transferred processes for the delivery of GMP-grade products for clinical trials.

Clinical Trial submission

In the United Kingdom, a Clinical Trial Authorisation (CTA) from the Medicine and Healthcare products Regulatory Agency (MHRA) is necessary for a clinical trial of an Investigational Medicinal Product (IMP). IMPs are substances used for clinical trials, and include placebos and controls, as well as active drugs.

They are characteristically products that are to be used to prevent or treat disease, make a diagnosis or modify a particular physiological function.

• We offer expert advice to help you identify whether your product classifies as an IMP, and to support you through the CTA process.
• We can advise on relevant legislation, liaise with relevant regulatory bodies on your behalf, support the completion of CTA documentation including the Application Form, Investigators Brochure (IB) and the IMP Dossier (IMPD).

Before starting the extensive CTA process, it is useful to identify whether your product is indeed an IMP. We can assist with this classification, and support your team in understanding applicable EU legislation.

Every CTA application will contain standard documents, including:

• Clinical trial application forms in PDF and XML
• Protocol documents
• Investigators brochure (IB)
• Investigational medicinal product dossier (IMPD)

For more detailed information on how to prepare and submit documentation for clinical trials approvals, visit the MHRA website, or contact a member of our team.

We operate an industry standard cell banking system, where a microbial master cell bank (MCB) is used to produce a working cell bank (WCB). Cell banking systems are created to ensure that a uniform population of cells are preserved, integrity is maintained and sufficient material is accessible for the lifetime of the product. Clones that have been established are cryopreserved to minimise contamination, degradation and genetic variation; passaging is kept to a minimum.

All of our cell banking is performed in a dedicated GMP cell banking area. We can work with a bacterial line of your choice, or can provide recommendations on a suitable strain for your project.

The Clinical Biotechnology Centre has extensive experience of manufacturing GMP recombinant proteins for therapeutic use at a scale suitable for phase I/II clinical trial.