13TSB_TIBio: Technology Inspired Innovation Bioscience - Puridify

Lead Research Organisation: University College London
Department Name: Biochemical Engineering

Abstract

This collaborative project between our leading academic group at UCL and SME Puridify gives the opportunity for a highly focused project with high level expertise to carry out the technologically innovative work described below aiming to address the established purification challenges during industrial manufacture of biopharmaceuticals. UCL and Puridify are supported in this activity by three industrial partners selected to provide support to the analytical and manufacturing aspects (being leading companies in their respective areas) as well as to provide a route to transfer the findings of the research to practice.

The research collaboration described here is focused on the study of the performance of the core purification method used for the manufacture of biopharmaceuticals - chromatography. Specifically we seek understand the methods of immobilisation for this novel matrix material thereby allowing for optimised fabrication of functional adsorbent materials. This is an essential part of establishing a robust purification platform with a novel technology that offers significant operations advantages in terms of productivity, lifetime, feedstream complexity and indeed opportunity to facilitate continuous downstream operations.

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 takes over 10 years and $800 million to develop a new drug. The attrition rate for biopharmaceuticals is severe, only 9% at Phase 1 clinical trials reach the market and only 3 out of 10 drugs launched actually generate enough revenues to recoup development costs. Given the high attrition rate during development, companies are resistant to committing manufacturing resources at the early stages. The potentially significant manufacturing cost reduction that this technology is capable of reduces this early burden with significant external 'spill over' benefits.
The new bioprocess purification technologies created here would continue to allow UCL to play their part in advancing manufacturing routes to the UK bioindustry while maintaining research at the forefront of industrial development. The UK bioprocessing sector is economically important, currently over 480 companies, employing 26,000 people and generating annual revenues of £4bn.
The deliverables of this CRD project are a key step towards developing this technology for industrial implementation. The industry has to reduce costs to make biotherapeutics more widely available and to increase the amount of research in the area.

Key objectives relating to UCL's involvement in this CRD project are listed below:
- Expand knowledge and research activity in the area of purification within the department and UCL.
- Disseminate this work by publishing papers with the aim of generating further research opportunities and increased collaborations.
- Contribute to industrially focused developments of a new technologies and screening platforms.
- Share knowledge through events such as MBI training courses, conferences and teaching.
- Introduce new analytical techniques and develop leading technologies.

Technical Summary

Key objectives relating to UCL's involvement in this CRD project are listed below:
- Expand knowledge and research activity in the area of purification within the department and UCL.
- Disseminate this work by publishing papers with the aim of generating further research opportunities and increased collaborations.
- Contribute to industrially focused developments of a new technologies and screening platforms.
- Share knowledge through events such as MBI training courses, conferences and teaching.
- Introduce new analytical techniques and develop leading technologies.

Planned Impact

The focus of this project, biotherapeutic purification technologies, has an identifiable technological risk combined with the highly lucrative market. Technological development here would provide advanced manufacturing routes across the UK bioindustry, such as industrial biocatalysis. The UK bioprocessing sector is economically important, currently over 480 companies, employing 26,000 people and generating annual revenues of £4bn. The Bioscience 2015 Report to the UK Government by the Bioscience Innovation Growth Team highlighted "the inevitable increase in the importance of bioprocessing". This CRD project involves close collaboration between industrial and academic partners in the UK. The ultimate goal is to generate new, cutting edge materials and tools for purification operations while gaining a better understanding of the processes involved.

Economic impacts are core to this technology with biotherapeutic manufacturers (both in this consortium and beyond) having the potential to benefit from reduced operating costs and increased process flexibility allowing for wider reaching research to take place. The industry must reduce costs to make biotherapeutics more widely available and to increase the amount of research in the area.
Social impact will result from widening patient access to biotherapeutics as this technology could further open up the biosimilars market, particularly relevant in developing countries and for potential savings by the NHS leading to spill over social benefit to the UK public. UCL Biochemical Engineering has a long standing relationship with many other academic and industrial groups, both in the UK and internationally. These collaborations allow UCL to remain at the forefront of industrial technology and this is recognised by the continued support from a wide range of on-going collaborations.
Environmental benefits include reduced WFI water and energy consumption for operations thanks for the fixed solid structure and reduced use of ceaning agents due to the increased resistance to fouling. As development in this technology continues other exploratory routes have the potential to yield attractive 'spill over' applications given the desirable properties of this material. One potentially key area is its use in immobilised enzyme catalysis for the chemical, food or energy source production; thus providing green/low carbon routes to products currently produced from fossil fuels. This CRD project will allow us to build the primary skills base for this technology in the UK which will allow expertise to develop and remain in UK industry and academia.

In summary the successful execution of the proposed work will have substantial impact on the biotechnology industry. Firstly, the economic driver is clear, resins dominate current cost of goods and cost of therapeutics much be reduced. Secondly, this kind of success will help to demonstrate that innovation within universities is readily important for the industrial arena. Thirdly, this collaboration widens the on-going relationship with UK industry. All of these are important factors to continuing efforts of driving down the cost of new and existing therapeutics of global demand.
Beneficiaries summarised:
UCL
- Expose research students to the latest bioprocessing purification technologies
- UCL to remain at the forefront of industrial technology UK & International Industry
- Reduction in COGs
- Faster process development resulting in faster route to market
- Additional tools for new complex biotherapeutic production
UK & International Academia
- New development tools for improved research
- A better understanding of immobilisation techniques with novel materials
Wider beneficiaries
- Increased patient access to expensive biotherapeutics
- Increased rate of drug development

Publications

10 25 50
 
Description Key Deliverables:
1) Develop ligand immobilisation routes to fabricate chosen Ion-exchange (IEX), Hydrophobic Interaction (HIC) & Affinity reagent materials is proved and optimised through performance evaluation using true process media.
Ligand immobilisation has been achieved to the original set goals in terms of purification performance and reproducibility of manufacture. This work package has been extended due to a variety of methodologies that have been developed by the consortium members which have shown promise to deliver purification performance well beyond the initial expectations of the material. This has been an unexpected advantage of the work carried out in this project and has resulted in the commitment of further resources in the form of 2 FTEs with safeguarded positions of employment to continue exploring the material development beyond this project.
2) Develop high-throughput screening platform prototype device and fabricated to house different functional reagent materials for high-throughput chromatographic operations.
This device has been developed prototyped and refined over the course of this project and has delivered a device that has met the original criteria. This is uniquely allowing the operation of our adsorbent materials in both positive and negative flow regimes to be most universally applicable. This is already proving to be a powerful tool for both our internal purposes and for our industrial collaborators, GSK & Lonza Biologics.
3) Puridify will have validated the scaled performance characteristics with end users, a key requirement providing robustness of performance data for adoption.
Data has been generated with important industrial collaborators which is providing the first steps of driving towards our commercial adoptions. The project has yielded a vital tool for enabling the high throughput screening utilisation of Puridify's technology. This has both proved to be a useful tool for demonstrating the power of the technology, and for demonstrating the scalability of the technology which will aid the robustness argument and subsequent adoption into the conservative pharmaceutical industry. In addition we hope to exploit this tool as an internal process and material development opportunity along with potential future commercial applications into the analytical research market space.
Exploitation Route 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.
Sectors Manufacturing, including Industrial Biotechology

 
Description 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.
First Year Of Impact 2015
Sector Healthcare,Manufacturing, including Industrial Biotechology
Impact Types Economic

 
Company Name Puridify 
Description Puridify's technology, FibroSelect - a novel chromatography reagent, offers significant advantages across key performance attributes that not only allow chromatography associated costs to be reduced by up to 90% but are also well aligned to meet the industry demands today and as the market evolves. 
Year Established 2013 
Impact Puridify have proven at research scale (0.2mL reagent) that their technology can operate at 50x throughput due to better permeability and fast mass transfer. This improves process economics by increasing productivity and is also beneficial when processing labile products. The reagent has shown better resistance than our competitors to impurity fouling and cleaning steps, a common cause of performance degradation over multiple cycles. The technology allows cheap and rapid bioprocess development due to uniform performance at all scales, promoting its adoption in industry.
Website http://puridify.com/