Periodic Reporting for period 3 - Pharma-Factory (Building the product pipeline for commercial demonstration of Plant Molecular Factories)
Okres sprawozdawczy: 2020-11-01 do 2022-08-31
Pharma-Factory was active between November 2017 to August 2022. It was a highly ambitious project to advance commercial development of plant molecular farming (PMF) in Europe.
Plant Molecular Farming is the production of high-value compounds from plants through the use of biotechnology. High-value compounds in this project are biologics as human and animal medicines and high quality recombinant proteins for use as reagents, diagnostics and in biomedical research. The overarching aim of Pharma-Factory was to drive new and innovative recombinant products towards the market. This was achieved through the refinement and demonstration of plant platforms as manufacturing systems that compete with and complement existing and conventional microbial or animal-based systems, as well as a concerted effort to address regulatory issues and understand the wider perception of PMF technologies. To emphasise the key roles of small companies in Pharma-Factory and to ensure translational focus, companies led our efforts on product development.
Acceptability of new products of manufacturing processes is one of the most important contributory factors to success and has historically been ignored in many high profile technology cases. Acceptability can be divided into public acceptability and regulatory acceptability, and both were addressed independently in Pharma-Factory.
Our public engagement and involvement effort was the largest and possibly most innovative programmes of work yet, addressing Plant Molecular Farming. We were able to gather a very broad understanding of public opinions relating to plants, plant biotechnology and the challenges of introducing innovation into the pharmaceutical and medical product markets.
Pharma-Factory’s activities between academic and industrial partners has also brought new scientific and technological insights with broad scientific impact outside of the project, in areas including enhancing protein stability and subcellular targeting to increase productivity, enhance the function of therapeutic modules, developing new libraries of genetic elements and host lines, and a variety of other strategies to broaden the versatility of Plant Molecular Factory platforms.
Plant Molecular Farming is the production of high-value compounds from plants through the use of biotechnology. High-value compounds in this project are biologics as human and animal medicines and high quality recombinant proteins for use as reagents, diagnostics and in biomedical research. The overarching aim of Pharma-Factory was to drive new and innovative recombinant products towards the market. This was achieved through the refinement and demonstration of plant platforms as manufacturing systems that compete with and complement existing and conventional microbial or animal-based systems, as well as a concerted effort to address regulatory issues and understand the wider perception of PMF technologies. To emphasise the key roles of small companies in Pharma-Factory and to ensure translational focus, companies led our efforts on product development.
Acceptability of new products of manufacturing processes is one of the most important contributory factors to success and has historically been ignored in many high profile technology cases. Acceptability can be divided into public acceptability and regulatory acceptability, and both were addressed independently in Pharma-Factory.
Our public engagement and involvement effort was the largest and possibly most innovative programmes of work yet, addressing Plant Molecular Farming. We were able to gather a very broad understanding of public opinions relating to plants, plant biotechnology and the challenges of introducing innovation into the pharmaceutical and medical product markets.
Pharma-Factory’s activities between academic and industrial partners has also brought new scientific and technological insights with broad scientific impact outside of the project, in areas including enhancing protein stability and subcellular targeting to increase productivity, enhance the function of therapeutic modules, developing new libraries of genetic elements and host lines, and a variety of other strategies to broaden the versatility of Plant Molecular Factory platforms.
Our results have furthered the development of our Molecular Pharming products and accelerating their routes to market. In our social science work, we have held scoping discussions with commercial partners and held co-design workshops with our SME and academic partners to establish a value proposition for each of our technologies and products. We have engaged with the public through 'quick-take' interviews and public engagement activities including Plant Designer at the London Design Festival, attended by ~1200 visitors; our public exhibitions in the UK and France (attracting over 1000 interactions) and many other events at schools, and science fairs. In our work related to regulatory issues, we have consulted at national and European levels to establish pathways to assured production from a range of diverse plant manufacturing platforms.
Over the course of the project, we have delivered novel SARS-CoV-2 reagents and particles with diagnostic potential for rheumatoid arthritis to the market and distributed a ‘kit’ demonstrating a Plant Molecular Farming approach. Product development was further supported by patents around specific hairy root production approaches, and scientific publications on the viability of our technologies.
We have extended existing validated plant molecular farming platform technologies into new product areas in work related to targeting new therapeutics for HIV and diagnostics for rheumatoid arthritis and Sjogren’s syndrome and identified manufacturing solutions for “hard to produce” high value proteins such as Albajuna's target HIV-therapeutics. Our Molecular Pharming kit is now publicly available for non-commercial use, and is already drawing new free-thinking new users to PMF technologies.
Over the course of the project, we have delivered novel SARS-CoV-2 reagents and particles with diagnostic potential for rheumatoid arthritis to the market and distributed a ‘kit’ demonstrating a Plant Molecular Farming approach. Product development was further supported by patents around specific hairy root production approaches, and scientific publications on the viability of our technologies.
We have extended existing validated plant molecular farming platform technologies into new product areas in work related to targeting new therapeutics for HIV and diagnostics for rheumatoid arthritis and Sjogren’s syndrome and identified manufacturing solutions for “hard to produce” high value proteins such as Albajuna's target HIV-therapeutics. Our Molecular Pharming kit is now publicly available for non-commercial use, and is already drawing new free-thinking new users to PMF technologies.
Pharma-Factory has undoubtedly advanced Plant Molecular Farming beyond the state of the art, and we have ambitious expectations that this will happen on several levels.
1. Public and governmental acceptance and acceptability
Whilst the public may appear to hold strong views on GM technologies in plants, when it comes to Plant Molecular Farming, they are generally unfamiliar or at worst agnostic about the technology, but inclined to be favourable towards GM applications that offer true medical benefits. Whilst this may appear to be a good position, a pro-active approach is the most likely to result in the most favourable outcomes. Drawing together industry and academic stakeholders, we introduced and explained Plant Molecular Farming to a range of end users across European regions, identifying barriers to acceptance and developing new novel approaches to lowering these barriers.
2. Scientific and technical advance
The ambitious scientific and technical advances in the Pharma-Factory project are all focused on advancing products. This project was primarily designed to identify approaches that will result in higher yields, better quality and greater product diversity. We have optimised the yield of commercial product targets in multiple Plant Molecular Farming manufacturing platforms, including plant cell cultures, hairy root culture, algae and intact plants. Where yields could not be improved, we have found novel solutions, such as the identification of an alternative viral display platform for our rheumatoid arthritis diagnostic. We have delivered sophisticated gene editing tools for two manufacturing platforms - Brassica species and transgenic algae, and used advanced molecular biology techniques to simplify and accelerate the processes of early development for future products.
3. Product pipeline development
SMEs developing platform technologies are usually only able to develop a handful of products in their early years. Given the development timeline for new biologics and the high failure rate, successful commercialisation, even with a strong product and a viable manufacturing process is a rare event. The ambition of Pharma-Factory has been to help establish the pipeline for products, by addressing early risks in product selection and development. All of the SMEs involved in Pharma-Factory have dedicated part of their effort to the exploration of new products (or new product classes, such as glycoproteins or monoclonal antibodies).
4. Industry engagement
The pharmaceutical industry tends to take more note when technologies become validated and target products approach the market. A criticism that is often levelled at Plant Molecular Farming is the lack of engagement from major pharmaceutical companies. So, the ambition of Pharma-Factory is to elevate the developmental status of multiple European SMEs and to help establish a wave of Plant Molecular Farming products alongside transparent regulatory pathways and positive public opinion. Together, this will make a forceful statement about the viability and future of Plant Molecular Farming, which major industrial players will not be able to ignore. In recent years, major investments by Pfizer, Mitsubishi Tanabe Pharma Corporation, Denka Seiken Co. Ltd, the Osvaldo Cruz Foundation, Glaxo SmithKline and others have helped in this endeavour.
1. Public and governmental acceptance and acceptability
Whilst the public may appear to hold strong views on GM technologies in plants, when it comes to Plant Molecular Farming, they are generally unfamiliar or at worst agnostic about the technology, but inclined to be favourable towards GM applications that offer true medical benefits. Whilst this may appear to be a good position, a pro-active approach is the most likely to result in the most favourable outcomes. Drawing together industry and academic stakeholders, we introduced and explained Plant Molecular Farming to a range of end users across European regions, identifying barriers to acceptance and developing new novel approaches to lowering these barriers.
2. Scientific and technical advance
The ambitious scientific and technical advances in the Pharma-Factory project are all focused on advancing products. This project was primarily designed to identify approaches that will result in higher yields, better quality and greater product diversity. We have optimised the yield of commercial product targets in multiple Plant Molecular Farming manufacturing platforms, including plant cell cultures, hairy root culture, algae and intact plants. Where yields could not be improved, we have found novel solutions, such as the identification of an alternative viral display platform for our rheumatoid arthritis diagnostic. We have delivered sophisticated gene editing tools for two manufacturing platforms - Brassica species and transgenic algae, and used advanced molecular biology techniques to simplify and accelerate the processes of early development for future products.
3. Product pipeline development
SMEs developing platform technologies are usually only able to develop a handful of products in their early years. Given the development timeline for new biologics and the high failure rate, successful commercialisation, even with a strong product and a viable manufacturing process is a rare event. The ambition of Pharma-Factory has been to help establish the pipeline for products, by addressing early risks in product selection and development. All of the SMEs involved in Pharma-Factory have dedicated part of their effort to the exploration of new products (or new product classes, such as glycoproteins or monoclonal antibodies).
4. Industry engagement
The pharmaceutical industry tends to take more note when technologies become validated and target products approach the market. A criticism that is often levelled at Plant Molecular Farming is the lack of engagement from major pharmaceutical companies. So, the ambition of Pharma-Factory is to elevate the developmental status of multiple European SMEs and to help establish a wave of Plant Molecular Farming products alongside transparent regulatory pathways and positive public opinion. Together, this will make a forceful statement about the viability and future of Plant Molecular Farming, which major industrial players will not be able to ignore. In recent years, major investments by Pfizer, Mitsubishi Tanabe Pharma Corporation, Denka Seiken Co. Ltd, the Osvaldo Cruz Foundation, Glaxo SmithKline and others have helped in this endeavour.