Development and optimisation of downstream processing for next generation biotherapeutics
Lead Research Organisation:
University College London
Department Name: Biochemical Engineering
Abstract
In recent years there has been rapid development of a "Next Generation" of protein-based therapeutics, yet the need remains for new manufacturing processes that can deliver these at a price healthcare providers can afford. For the first time these new therapies can safely modify a patient's DNA, or harness the body's own immune system, to treat inherited diseases, neurological conditions, and cancer. However, to achieve this clinical functionality the complexity and size of the therapeutic protein has increased. This has meant that existing purification technologies have been unable to be applied effectively in this new application. This project aims to build on existing collaborations and feasibility data to develop new purification tools and strategies that can be applied across a range of next generation biotherapeutics to enable their cost effective manufacture delivering novel therapies to patients at an aceeptable price for healthcare payers.
Publications
Ruscic J
(2019)
Lentiviral Vector Purification Using Nanofiber Ion-Exchange Chromatography.
in Molecular therapy. Methods & clinical development
Turnbull J
(2019)
Adenovirus 5 recovery using nanofiber ion-exchange adsorbents.
in Biotechnology and bioengineering
Turnbull J
(2019)
Cover Image, Volume 116, Number 7, July 2019
in Biotechnology and Bioengineering
| Description | Biopharmaceuticals are an increasingly important sector of the pharmaceutical industry, over one third of all drugs now in development are biopharmaceuticals and they make up half of the top 10 revenue blockbusters. It typically takes over 10 years and $800 million to develop a new drug. Global demand for cheaper biotherapeutics, which represent many of the new tools in the fight against diseases such as cancer and neurodegenerative conditions, drives the need for a reduction in manufacturing costs. A significant proportion of current costs arise from the purification technologies now used to ensure the safety and efficacy of these treatments. This project aims to build on existing collaborations between Puridify, an SME with a novel nanofibre purification technology, and University College London (UCL), a world leading research organisation for the development of industrial bioprocessing technologies. The successful award of this project lead by Puridify and supported by shadow industrial partners will see the development and commercialisation of innovative bioprocessing platform technologies allowing the cost effective manufacture of a wide range of existing and new products. The project will accelerate development of Puridify's novel platform downstream bioprocessing technologies towards commercial activity. The technologies increased productivity will provide an efficient manufacturing route to both new and existing products benefiting society and the sector as a whole by reducing costs and enabling the economic manufacture of next generation biotherapeutics. A particularly focus is the application of the technology to viral vector manufacture for use in gene therapy and T-cell therapy. Using new processing technologies, theory and modelling, this integrated Industrial Research and Development project will accelerate the commercialisation of this technology by bringing together key academic and business components of the UK Industrial Biotechnology community. |
| Exploitation Route | Global demand for cheaper biotherapeutics, which represent many of the new tools in the fight against diseases such as cancer and neurodegenerative conditions, drives the need for a reduction in manufacturing costs. A significant proportion of current costs arise from the purification technologies now used to ensure the safety and efficacy of these treatments. This project aims to build on existing collaborations between Puridify, an SME with a novel nanofibre purification technology, and University College London (UCL), a world leading research organisation for the development of industrial bioprocessing technologies. The successful award of this project lead by Puridify and supported by shadow industrial partners will see the development and commercialisation of innovative bioprocessing platform technologies allowing the cost effective manufacture of a wide range of existing and new products. |
| Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| URL | https://www.uclb.com/2017/11/30/ucl-spinout-company-puridify-limited-has-been-acquired-by-ge-healthcare/ |
| Description | SUMMARY: A new purification technology using nanofibre materials, developed through research at UCL, has improved separation processes during the manufacture of therapeutic antibodies. The patented Fibro technology is used by pharmaceutical companies including AstraZeneca, accelerating drug-discovery, which led to the spin-out company Puridify being acquired by tech giant GE Healthcare. TEXT Antibodies are used as therapeutics to treat conditions from cancer to cardiovascular disease and can now be manufactured in the lab, but the process can be inefficient. Nanofibres are being used in medical settings including in the manufacture of implants, as tissue replacement, and in wound dressing. Professor Daniel Bracewell at UCL in collaboration with Professor Bob Stevens at STFC Rutherford Appleton laboratories developed novel nanofibres that could be used to enhance the purification of therapeutic antibodies. The manufacture of antibodies for therapeutic use requires their separation from the crude production mixture. Commonly, chromatography is used, and the antibodies separated by attaching to a beaded resin through a process called adsorption. The UCL/Rutherford Appleton team set about designing a new chromatography process that would intensify the separation process and increase productivity. They created cellulose nanofibre materials with high surface area to provide high binding capacity and that allowed directed transfer of the antibodies from the mixture to the fibres. After patenting the materials, Oliver Hardwick, a doctoral student at UCL at the time, established a spin-out company Puridify, to develop the product further. By 2016, the company had 14 scientists at their site at Stevenage and 4 postdoctoral researchers working with Professor Bracewell at UCL via Innovate UK funding. Puridify has won six Innovate UK Awards and in 2015, Bracewell and Hardick were finalists in the BBSRC Innovator of the year competition. The company has since been acquired by GE Healthcare and the nanofibre product marketed as 'FibroPrismA'. Puridify's Fibro technology platform (commercially available as Fibro PrismA) improves efficiency, by speeding up the separation process. These faster work rates, means small disposable units can replace much larger cumbersome beaded resin chromatography. Additionally, the technology allows a manufacturer to switch more easily between different biopharmaceutical products. This cost effective solution means that manufacture of advanced treatments in low- and middle-income countries is more feasible. UCL has already applied the nanofibre separation technology to other therapeutic products such as the viral vectors used in gene therapy and vaccine technologies, improving the yield of active viral vector product over other methods. QUOTE: "The economic impact of the research extends further than Puridify, as the company's Fibro technology for purification is now being used by clients including AstraZeneca, resulting in a 6- fold increase in efficiency of biopharmaceutical manufacture and an acceleration of the drug- discovery process." This exploitation is supported by the original patent application (PCT/GB2012/052768) and a new patent application filed during this project (PCT/GB2013/052626). An on-going IP strategy to build and further protect future commercialisation opportunities is structured and continually evolving based on the development work that is being carried out. The spin-out Puridify was acquired by GE Healthcare (now Cytiva) in November 2017. https://www.uclb.com/2017/11/30/ucl-spinout-company-puridify-limited-has-been-acquired-by-ge-healthcare/ https://www.gov.uk/government/news/uk-bioprocessing-firm-acquired-by-ge-healthcare |
| Sector | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal,Economic |
| Description | Centre of Excellence |
| Amount | £1,393,742 (GBP) |
| Organisation | PALL Europe |
| Sector | Private |
| Country | United Kingdom |
| Start | 01/2018 |
| End | 12/2024 |
| Description | The Future Vaccine Manufacturing Research Hub (Vax-Hub) |
| Amount | £6,968,180 (GBP) |
| Funding ID | EP/R013756/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2018 |
| End | 03/2021 |
| Description | Ultra Low-cost Transferable Automated (ULTRA) Platform for Vaccine Manufacturing |
| Amount | $17,670,648 (USD) |
| Funding ID | OPP1154682 |
| Organisation | Bill and Melinda Gates Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 11/2016 |
| End | 11/2021 |
| Title | CHROMATOGRAPHY MEDIUM |
| Description | The present invention provides a chromatography medium comprising one or more electrospun polymer nanofibres which in use form a stationary phase comprising a plurality of pores through which a mobile phase can permeate and use of the same. |
| IP Reference | US2018094022 |
| Protection | Patent granted |
| Year Protection Granted | 2018 |
| Licensed | Yes |
| Impact | The patent is now owned by the spin-out company Puridify and forms part of company's patent portfolio. The company was bought by GE Healthcare in November 2017. http://www.pressreleasepoint.com/ge-healthcare-acquires-bioprocessing-start-puridify |
| Title | Chromatography medium |
| Description | The present invention provides a process for preparing a functionalised polymeric chromatography medium, which process comprises (I) providing two or more non- woven sheets stacked one on top of the other, each said sheet comprising one or more polymer nanofibres, (II) simultaneously heating and pressing the stack of sheets to fuse points of contact between the nanofibres of adjacent sheets, and (III) contacting the pressed and heated product with a reagent which functionalises the product of step (II) as a chromatography medium. |
| IP Reference | CN105636686 |
| Protection | Patent application published |
| Year Protection Granted | 2016 |
| Licensed | Yes |
| Impact | The patent is now owned by the spin-out company Puridify and forms part of company's patent portfolio. The company was bought by GE Healthcare in November 2017. http://www.pressreleasepoint.com/ge-healthcare-acquires-bioprocessing-start-puridify |
| Description | BioProNet Bioprocess Intensification Symposium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | BioProNET Bioprocess Intensification Symposium 4th July 2018 The continued growth of the biopharmaceutical industry is being challenged by a greater number and variety of products than in the past. The industry is also increasingly concerned with the affordability of these products. These key factors means process intensification has become a critical objective. The goal is higher productivity processes to enable small process trains, resulting in cost-effective, lean, and agile manufacturing facilities. The symposium assembles 8 leaders from the biopharmaceutical industry and academia who will present their latest findings and opinions on the subject. By bringing together scientists and engineers from academia and industry who are actively engaged in bioprocess intensification the event will provide forum for lively debate. |
| Year(s) Of Engagement Activity | 2018 |
| URL | http://biopronetuk.org/biopronet-funded-collaboration-building-workshops/ |