This project is a Sanofi-UL project led by Prof. Sarah Hudson Challenge: Many biopharmaceutical products have a frozen intermediate step for drug substance (DS) prior to Fill Finish Manufacturing, often DS is shipped in multiple containers from the DS site to the Dug Product (DP) site and as per the orange guide for parenteral biopharmaceuticals, each container is required to be identified. This usually requires liquid state sampling and testing which can lead to significant product waste over time. Solution: The SSPC team developed a non-destructive method to ID frozen bulk providing the following improvements to the manufacturing process.

This project was co-funded with Sanofi through the SSPC funding programme, a mechanism that supports the sharing of IP for industry led-projects. Sanofi is an active member of SSPC the SFI Research Centre for Pharmaceuticals with staff members from across the organisation regularly contributing to the research discussion within the Centre.

Dr Kumar Khamar, Director of Analytical Science and Technology at the Waterford site, was the primary industry lead and worked in partnership with the SSPC academic lead Prof. Sarah Hudson to develop the scope of this research project. Dr Khamar is also an alumnus of the SSPC and as such is very familiar with the complementary skills and expertise available within the community to support the Sanofi challenge. The overall aim of the project was to develop a new method for the identification of biopharmaceutical drug substances using non-destructive Raman spectroscopy.

This was an effective collaboration from the beginning as the Sanofi team brought the industrial challenge to SSPC, provided the drug substance materials for experimental work, access to testing capabilities and shared data for analysis. The SSPC post-doctoral researcher supporting the project, Dr Mahendra Shukla, was fully inducted in Sanofi and integrated into the team in Waterford. Dr Shukla was able to spend time working on site once Covid restrictions were lifted which added further value to the partnership through skills and knowledge exchange on both sides. Monthly team meetings were attended by both the SSPC and Sanofi team at which results were shared, issues discussed and both teams worked actively to achieve the common objective.

Benefits of this collaboration to both parties
Many biopharmaceutical products have a frozen intermediate step for drug substance (DS) prior to Fill Finish Manufacturing. Often DS is shipped in multiple containers from the DS site to the Dug Product (DP) site and as per the orange guide for parenteral biopharmaceuticals, each container is required to be identified. This usually requires liquid state sampling and testing which can lead to significant product waste over time, require the Frozen Drug Substance (FDS) to be filled ‘at risk’ with heavy Quality Control oversight and Complex immunoassay testing.

For example, for one MAb product at the Sanofi site in Waterford, 40 batches were filled in 2021, using 1,720 containers requiring a labour intensive 1,720 hours of quality control (QC) analysis. The process resulted in 5.2 litres of frozen drug substance waste during sampling, equating to a 1 year supply for 93 patients.

The overall benefit of this project collaboration for Sanofi is the development of a rapid non-destructive method to ID the frozen bulk providing the following improvements to the manufacturing process:

• Improved process compliance through the elimination of the requirement to fill at risk
• Increased Batch Yield, resulting in a savings of 3.6M over 4 years for 2 products at 1 site only to 2026
• Reduction in Quality Control resources, enabling capacity to help with other product volumes

The benefits of the collaboration to the SSPC research team

• Ability to analyse two commercial drug substances
• Improved understanding of the commercial challenges of the drug substance fill finish process
• Post-doctoral researcher experience working in an industrial environment

Impact
The identification method developed as a result of this project has significantly improved a quality control process for biopharmaceutical sector. This method has relevance and can be applied across the sector transferring to many other sites and other products.

This project has the potential to contribute to the manufacturing of faster, better medicines for society through the rapid testing approach developed. The method developed will significantly reduce the amount of product waste on site and increase the volume of drug substance that is available for patients improving the efficiency and volume of medicines being produced.
The project has also led to an improvement in process compliance due to the elimination of the ‘fill at risk’ step in the in process and therefore increasing the safety of the medicines being produced for the patient and less energy being used to have an environmental impact.

This project integrated the Raman spectroscopy and with the expertise of the data science group led by Prof. Norma Bargary of MACSI to reduce the dimentionality of a data set while preserving as much variability (statistical information) as possible. This resulted in an innovative model for implementation by Sanofi.