Industrialisation of Spherical Agglomeration: Pilot-Plant Case Study at AstraZeneca
Background
CMAC is at the forefront of advancing particle engineering technologies to address challenges in active pharmaceutical ingredients (APIs). Among these, spherical agglomeration stands out as a promising route to improve particle properties and manufacturability. Recent collaborations have strengthened both the centre’s scientific understanding and its ability to translate this technology toward industrial implementation.
This case study highlights CMAC’s recent success in translation to industry streams with Tier One partners: AstraZeneca, Chiesi, Lilly, Pfizer, Roche, Sanofi, Shionogi, Takeda and UCB. Through its CORE-funded research programme, CMAC has demonstrated the scale-up of spherical agglomeration from laboratory to pilot-plant operations. This marks a significant milestone in the centre’s mission to simplify pharmaceutical manufacturing.
The technical opportunity and scale-up challenge
Pharmaceutical companies are increasingly adopting continuous direct compression, a streamlined process that blends APIs with excipients and compresses them into tablets. However, many APIs often exhibit poor flowability and compressibility, leading to processing challenges when forming into tablets and limiting manufacturing efficiency and scalability.
Spherical agglomeration offers a solution by enhancing particle properties at source. Improved particle properties enhance filtration and drying performance while improving powder stability during storage, helping to reduce overall processing cycle times. These benefits may be applicable across multiple solid‑forming stages in chemical manufacturing.
Increased bulk density and flowability in the final crystallisation step can also support reliable feeding in loss‑in‑weight powder feeders and may enable direct compression.
Despite its potential, a critical unknown was identified: Can spherical agglomeration be reliably scaled to an industrial environment, particularly with respect to mixing, bridging liquid addition, and downstream isolation?
Our approach
Building on CMAC’s earlier research, a Tier One CORE-funded programme was launched, with AstraZeneca hosting plant trials at its Macclesfield site. Uniquely, this project brought together the partners in a pre-competitive space to collaborate, co-create, share learning, and ultimately support the wider adoption of spherical agglomeration.
A structured scale-up framework was applied, combining laboratory experimentation with modelling-led decision-making to de-risk translation to the pilot plant. This included assessment of mixing behaviour, evaluation of bridging liquid delivery strategies, and assessment of process robustness to changes in raw material attributes.
Three pilot-scale batches (40 kg each) were executed at the 1000 L scale to evaluate operational feasibility under representative manufacturing conditions.
Key achievements
The technology moved beyond lab-scale for the first time amongst CMAC and industry partners, demonstrating viability at relevant manufacturing scales.
Trials confirmed that spherical agglomeration could be incorporated into existing crystallisation–wet-milling–isolation workflows using standard plant infrastructure.
In terms of operational success, the targeted agglomerate size range was achieved in suspension, showing the process behaved as expected during scale-up. Filtration was rapid and although attrition was seen during drying, the spherical agglomeration material demonstrated an improvement in bulk properties. From a collaboration standpoint, CMAC and AstraZeneca’s integrated approach to working enabled joint planning, alignment in analytical strategies and shared insights. This allowed for efficient progression of the project - underscoring CMAC’s ability to understand and operate within real-world industrial frameworks.
Impact
For CMAC partners, the study has provided confidence that spherical agglomeration is a viable particle engineering option beyond lab scale. The results reduce technical risk associated with the use of the technology and support informed decision-making for future development programmes.
For CMAC, the collaboration has demonstrated the centre’s ability to translate mechanistically understood processes into compliant, industrially relevant environments, strengthening its role as a trusted partner in pharmaceutical process innovation.
Project team onsite at AstraZeneca, Macclesfield
“The opportunity to demonstrate novel processing techniques like spherical agglomeration on a manufacturing scale is an important step in their adoption.
The collaboration with experts at CMAC has provided valuable guidance for methods to investigate spherical agglomeration in the laboratory and an insightful way to probe the scale-up approach.
The scale-up trials at AstraZeneca’s Macclesfield Pilot Plant have been a fantastic experience to collaborate with the team at CMAC and the results have given us plenty to think about and confidence to start adopting spherical agglomeration on development projects within AstraZeneca’s portfolio. ”
Next steps
Ongoing work will focus on quantifying agglomerate strength and robustness, improving isolation techniques, refining process analytical strategies, and tailoring agglomerates for continuous direct compression applications. Knowledge generated through this study has been shared with CMAC Tier One partners to support wider industrial uptake of spherical agglomeration technology.