Assessing PAT for process monitoring and modification of viral vector manufacture processing

This project is aligned with the scope of the "Mechanising and Improving Advanced Therapy Manufacture" competition. Specifically, the project will address challenges in the manufacture of AAV gene therapies and will establish Allergan's UK-based 200-strong workforce as a key player within the AAV industry improving the competitiveness and productivity of their therapeutic products.

The project will introduce novel technologies early within Allergan's product development to allow for improved reproducibility and control in manufacture. Allergan has a portfolio of AAV therapies in pre-clinical and Phase I development primarily targeting ophthalmic indications with large, global patient populations. However, industry-standard manufacturing strategies for AAV vectors lack the ability to be efficiently scaled to allow Allergan to meet their commercial ambition. One such challenge facing AAV manufacturers is the incorporation of new analytical technologies to perform rapid measurements of critical quality attributes allowing implementation of a real-time control strategy.

The partners will:

*Utilise the consortiums unique analytical and measurement expertise to identify critical process parameters and critical quality attributes specific to AAV production, using multi-site analysis of surrogate and clinically-relevant AAV products to determine transgene impact on monitoring and characterisation.

*Empirical data-driven models will be developed linking traditional off-line analysis to data collected from disruptive in-line process analytical technologies (PATs) during both upstream and downstream manufacturing processes.

*A control strategy will be determined using the product CPPs and CQAs to determine the sensitivity of in-line detection.

* Next-generation PATs, Raman spectroscopy and multi-angled dynamic light scattering detectors, will be developed using multiple AAV products to assess product CQA variability. The PATs will be used to demonstrate the impact of full end-to-end in-line monitoring and product characterisation during a full manufacturing process of Allergan's exemplar clinical AAV product.

*A final prototype, proof-of-concept, in-line set up will be integrated within Allergan's production process to demonstrate the disruptive approach to PAT in AAV manufacture.

NPL are providing substantial measurement expertise to this consortium to aid in the development of these technologies, overcoming challenges and limitations, and informing future considerations. NPL will also benefit from this project through involvement in viral vector processing identifying novel challenges for future focus.

Supporting Allergan in the investigation of novel PATs for in-line AAV manufacture will enable the UK-based organisation to implement refined control strategies to improve reproducibility, product quality and manufacturing costs allowing increased adoption of their novel advanced therapy portfolio by the patient population.