SSPC are working with Pfizer, Eli Lilly, Johnson & Johnson, BMS and MSD to address the global protein A resin shortage, under the direction of SSPC Principal Investigator Professor Sarah Hudson, University of Limerick. Many of the challenges include the rising need for early diagnosis of chronic diseases, the growing demand for drugs in development of vaccines and therapeutics (specifically proteins called antibodies), and an increase in R&D investments in pharmaceutical companies.
Challenge
The rising need for early diagnosis of chronic diseases, coupled with growing demand for drugs which work better and have fewer side effects, is largely responsible for the growth of the protein A resin market. At the moment, protein A resin cannot be reused. If BioPharma companies use it with one antibody, they can’t use it with a different antibody. The resins are expensive and in short supply. A current global shortage of protein A resin, is slowing product analysis across the sector, thus increasing the cost and slowing the rate at which new antibody medicines can reach the patient.
Chromatography resins used for purifying biopharmaceuticals are generally dedicated to a single product. This practice can result in the resin being used for a fraction of its useful life. This partnership investigates the feasibility of extending resin reuse to a second product which would significantly support biopharmaceutical manufacturing sector.
Resin plays a vital role in the production of various medical products, including antibodies, vaccines, and therapeutics. However, traditional manufacturing processes often result in significant waste generation and resource depletion. This not only puts strain on our planet’s limited resources but also contributes to rising healthcare costs.
Solution
By harnessing the power of recycled resins, we can not only mitigate environmental impact but also enable greater access to life-saving medicines. This project explores the possibility and feasibility of reusing these resins, making the production of antibody medicines, faster, cheaper and more sustainable. The project team will inform regulatory opinion by disseminating results at conferences with a regulatory audience. Product carryover and cleaning effectiveness are being assessed, as well as mass spectroscopic analytical methods and in-depth characterisation of the resin, including binding efficiencies.
By using several techniques such as high-performance liquid chromatography (HPLC) and capillary electrophoresis with sodium dodecyl-sulfate buffer (CE-SDS), this project has developed a new and easily transferable methodology to monitor the presence or absence of antibody carryover in a multiproduct resin reuse context. Moreover, through this research engagement we have developed an innovative method using liquid chromatography coupled to mass spectrometry (LC-MS) for monitoring the presence or absence of product carryover more precisely and directly inside the purified product.
Impact
The project, now in it’s second phase, has the potential to revolutionize the way we think about antibody-based products and their applications. Many antibody based drugs are used for cancer, arthritis and chronic diseases. Biopharmaceutical industries are currently reluctant to adopt resin reuse procedures, despite the enormous cost saving it could introduce. This research could massively support industry partners and their endeavours to bring down their costs and the cost of medicines.
This collaborative project is using state of the art research instrumentation to explore the possibility and feasibility of reusing resins, making the production of antibody medicines, more cost effective and environmentally friendly. It is also intended that the research outputs from this project will contribute to building confidence, and challenge current regulatory thinking around the multi-product reuse of resins in specific circumstances with the potential to reduce waste, maintain standards, and minimise costs in pharmaceutical processes.
Without clear regulation on the practice of reusing protein A resins with different antibody products and without the option to reuse this substance, this process is expensive and produces a lot of waste.
The first publication is now live In Process Biochemistry:
Carryover analysis by liquid chromatography mass spectrometry in a multiproduct resin reuse context.
Authors:
Stanislas Helle, SSPC, University of Limerick
Francisco Vitor Santos da Silva, SSPC, University of Limerick
Jodie McAvinue, SSPC, University of Limerick
Laura Coffey, SSPC, University of Limerick
Aisling Arthur, SSPC, University of Limerick
Jonathan Cawley, Pfizer Ireland Pharmaceuticals, Grange Castle
Mark Brophy, Pfizer Ireland Pharmaceuticals, Grange Castle
Amie O’Neill, Pfizer Ireland Pharmaceuticals, Grange Castle
Mary Sheehy, Pfizer Ireland Pharmaceuticals, Grange Castle
Ronan M. Kelly, Eli Lilly, Manufacturing Science and Technology, Cork, Ireland
Theresa Ahern, Eli Lilly, Manufacturing Science and Technology, Cork, Ireland
Matthew D. Osborne, Eli Lilly, Manufacturing Science and Technology, Cork, Ireland
Conor P. Horgan, Eli Lilly, Manufacturing Science and Technology, Cork, Ireland
Derek Foley, Johnson and Johnson, Manufacturing Science and Technology team (MSAT), Janssen Sciences UC, Cork, Ireland
Ronan Hayes, Johnson and Johnson, Manufacturing Science and Technology team (MSAT), Janssen Sciences UC, Cork, Ireland
Donal Monaghan, Bristol Myers Squibb (BMS), Cruiserath, Ireland
Pamela O’Brien, Bristol Myers Squibb (BMS), Cruiserath, Ireland
James Mahon, Merck Sharp & Dohme (MSD), Dublin, Ireland
Sarah P. Hudson, SSPC, University of Limerick
The findings suggest that the acceptance of chromatographic resin reuse for multiple products will be dependent on the development of analytical/bioinformatics tools such as those proposed in this work.
Technical: This project is a concrete application of a proposed technique in a white paper of a small-scale study prior application to a large-scale application to monitor the presence of carryover in a multi-product situation. It is to our knowledge the first time liquid chromatography coupled to mass spectrometry (LC-MS) is being used in this context. This project simplifies the process of identifying carryover mass spectra by creating a dedicated algorithm for it using Python.
Societal: Research into protein A resin multi-use has the potential to revolutionize the way we think about antibody-based products and their applications. This research could have a significant impact on society, providing numerous benefits, such as health and environmental sustainability. In terms of human capacity building, this project is upskilling researchers and facilitating knowledge transfer to industry in the technical, quality assurance and economical aspects of downstream biopharma processing.
Commercial: The project has the potential to reduce the cost of downstream production by reusing the same resin to purify multiple products. With the application of such procedures, monitoring the quality of the purification is essential to ensure that the carryover level of the previous product is below the safety margins. Biopharmaceutical industries are currently reluctant to adopt resin reuse procedures, despite the enormous cost saving it could introduce (estimated at annualized savings of $2,100,000 if moved to 48 cycles based on Sharnez et al. 2018), because of the deemed high safety risks due to cross contamination.
Environmental: The reuse of protein A resin, will limit and reduce unnecessary waste of material during production cycles and improve the resource efficiency of the manufacturing process contributing to the European Green Deal.
In addition to the five industry partners leading the collaboration, this partnership also includes a memorandum of understanding with the BioPhorum Group, a global collaboration of industry
Testimonials
“This innovative project has brought multiple industry and research partners together to take on the industry relevant challenge. This has been a very beneficial collaboration, driving the feasibility of extending resin reuse to a second product which would significantly support our biopharmaceutical manufacturing industry. We have agreed to extend the project into a second phase of activity demonstrating the value and success of the partnership”. Pamela O’Brien, Director, Manufacturing Science and Technology
“The significance of the contribution of this project in implementing multi-product Protein A re-use for clinical manufacture cannot be underestimated. Whilst the regulatory authorities understand the problem faced by the bioprocessing industry in the under-utilisation of resins, it takes a comprehensive process and analytical data package to make a compelling technical case for the re-use of resin. The successful delivery of the data package through this industry and SSPC project collaboration, coupled with the integration with the larger BioPhorum group means that a risk-based, data-driven industry guideline will be published for the implementation of multi- product Protein A re-use”. Theresa Ahern, Senior Advisor, Manufacturing Science and Technology
“BioPhorum partners with organizations and academia to enable it to deliver its mission to provide an environment where the global biopharmaceutical and medical device industries can collaborate to accelerate their rate of progress, for the benefit of all. Working with the University of Limerick (UoL), this collaboration is focused on harnessing the use of experimental data to save resources and ultimately money, through the reuse of Protein A resin across multiple products within a clinical manufacturing environment.
BioPhorum’s Protein A Resin Reuse team, in partnership with UL, aims to use its data to support a proposition paper that will shape the current industry and provide a justification for Protein A resin reuse, which could ultimately lead to an estimated annual saving of $8 million per site”. Donna Hamilton, Global change Facilitator, BioPhorum
