We present a methodology to evaluate the robustness of pharmaceutical batch processes on scaling up. The Scale Up Risk Evaluation (SURE) is applied on new processes that are part way through their development. During a SURE study one first collates current process understanding and then extrapolates this understanding to evaluate scenarios at larger scale. The output of the SURE study is a ranked list of scenarios that development teams use to prioritise further development.
Keywords: Batch Process, Process Development,
Scale up, Risk Assessment, Robustness & Reliability.
The pharmaceutical industry is currently expanding the role of process engineers from their
traditional roles in chemical manufacturing and capital projects. Significant process
engineering populations can now be found in process development, which has typically been
the domain of the synthetic and development chemists. Some drivers for this trend are the
regulatory push for increased process understanding, and the frequency at which scale up
issues occur in processes moving to commercial scale (Sherlock & Brewis 2006).
From a process development point of view, the life cycle of an active pharmaceutical
ingredient (API) consists of a series of campaigns executed at scales starting at 10’s of grams
for discovery, then kg scale for early clinical work then 10-1000 kg for late stage clinical
work culminating in commercial manufacture. Although engineers do contribute to kg scale
campaigns, typically, significant engineering contribution is made to campaigns for 10’s Kg
onwards when development teams are formed, drawing on chemistry, analytical, pilot plant
The aim of a development team is to invent and scale up a synthesis in order to generate an
API for use in clinical trials. The pilot manufacture typically takes place in multi-purpose
batch reactors. As outlined by J Double et al. (2005), batch reactors have a degree of
flexibility unsurpassed when executing partially developed often multiphase (typically S-L)
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