SSPC are working with Pfizer, Eli Lilly, Janssen, BMS and MSD to address the global protein A resin shortage on a project led by Prof. Sarah Hudson, University of Limerick. Prof. Hudson and her team will investigate the multi-product use of a resin in downstream biopharmaceutical production.

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 is expected to build confidence that will challenge current regulatory thinking around the multi-product reuse of resins in specific circumstances and the implications for global health are significant. Embracing resin reuse represents a transformative step towards a more sustainable future in biopharmaceutical manufacturing. The project has the potential to revolutionise 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.

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