ISI is part of a consortium that has won funding to develop in-situ process analytical technologies (PAT) for freeze-drying, a key element in the manufacturing and distribution of vaccines and treatments such as biological drug therapies. Widely adopted, the novel PAT will deliver substantial cost-savings and environmental benefits and shorten development times. It will also help align the pharma-manufacturing sector to the UK Clean Growth Strategy. This project, named Digital_Lyo, is part of the UK government’s Digitalisation and Automation of Medicines R&D and manufacture competition funded through Innovate UK.
The number of biopharmaceutical injectable products is increasing. Currently, for 40% of biopharmaceuticals (EurPharmRev2018), including those re-purposed for COVID-19, freeze-drying (lyophilization) is the only method for enabling an acceptable shelf life without relying on refrigeration and cold-chain infrastructure. However, freeze-drying is a wasteful, expensive, energy-consuming batch process with long process times, and cold chain distribution is essential to maintain product viability. Manufacture and distribution, therefore, represent a significant contribution to global carbon emissions.
Freeze-drying removes water from sensitive or high-value products such as vaccines. It requires long process times, between 24 and 96 hours, and the quality of the product can only be assessed at the end of the cycle. This results in increased energy consumption, CO2 emissions, loss of valuable product, and increased environmental bioburden. Furthermore, freeze-drying uses environmentally dangerous refrigerants (classified as high-global warming potential or GWP, banned from 2030) or liquid nitrogen (high energy use in manufacture) for cooling.
Through the Digital _Lyo project, the consortium is developing a unique, first-of-its-kind multi-PAT freeze-dryer suitable for laboratory-scale freeze-dryers, with the potential to be retrofitted to existing systems.
- Reduce freeze-drying cycle time, leading to increased use of freeze-drying equipment, typically located in high-energy-consuming good manufacturing process (GMP) facilities,
- Reduce losses and batch failures, thereby reducing wastage/bioburden,
- Shorten development times through increased reliability of data in clinical trials,
- Increase process robustness, leading to improved product quality and consistency,
- Significantly enhance drying economies by facilitating the development and adoption of new, continuous processes,
- Enable more sustainable pharmaceutical-product supply chains, key to the treatment and prevention of multiple diseases,
- Bring the pharma-manufacturing sector into line with the UK Clean Growth Strategy.
Digital_Lyo will use real-time, multiplexed Process Analytical Technology (multi-PAT-lyo) to integrate and exploit process signatures from inline impedance spectroscopy, Raman spectroscopy, and accurate vapour-sensing technology to generate large rapidly, information-rich data sets, suitable for modelling and process feedback.
The Digital_Lyo project team consists of:
Micron Design Ltd (Lead) is a complete engineering service from design concepts to manufactured prototypes and production. They are developing a precision broadband impedance spectrometer for fast measurements of the freeze-drying process and will oversee the whole project.
IS-Instruments is responsible for determining the optimum Raman excitation wavelength, developing the Digital_Lyo Raman System, and overseeing the system integration.
Siemens Process Systems Engineering Ltd – Digital Process Twin technology supplier to the process industries. SPSE is providing and enhancing its digital-twin models to enable novel PAT methods and the development of robust lyophilization processes.
DMU is responsible for developing the analytical routines to map impedance data to freeze-drying process parameters.
AstraZeneca Plc – a global, science-led biopharmaceutical business with comprehensive experience in freeze-drying complex pharmaceutical products. They provide leadership to ensure the industrial direction of the project, access to their assets with support from experienced scientists to test new PAT tools and produce quality data to populate and develop modelling tools.
Qrometric Ltd – UK metrology company specialising in measuring and calibrating temperature and humidity. They are optimising the required humidity/vapour-pressure metrology to develop the Digital_Lyo model in secondary drying.
Medicines and Healthcare Products Regulatory Agency – regulates medicines, medical devices and blood components for transfusion in the UK. They are assisting with lyophilisation development through experience in formulation/standards development, and the validation of Digital_Lyo approaches to formulation and process design.
Successful development of multi-PAT-Lyo will give biopharma innovators more reliable methods for formulating, scaling up and manufacturing new drugs, including fusion proteins, gene therapy, and mAbs. Patients with debilitating and life-limiting diseases such as Alzheimer’s, rheumatoid arthritis, and Crohn’s will benefit as a result of faster drug manufacturing and access to new treatments.
Our end user evaluators, who will derive direct and immediate benefits from the application of Digital_lyo technologies, are AstraZeneca (manufacturers of innovator products and new modalities) and the Biological Standards Laboratory at the MHRA, South Mimms.
This project builds on our work with DMU on the AtlasBio project (Ref 102610) – through-vial impedance spectroscopy and Raman spectroscopy for data synergy across multiple scale lengths.