posted on 2021-12-01, 21:13authored byYuma Miyai, Anna Formosa, Cameron Armstrong, Brian Marquardt, Luke Rogers, Thomas Roper
The
strategies and experimental methods for implementation of process
analytical technology (PAT) on the mobile pharmaceutical manufacturing
system, Pharmacy on Demand (PoD), are discussed. With multiple processes
to be monitored on the PoD end-to-end continuous manufacturing process,
PAT and its real-time process monitoring capability play a significant
role in ensuring final product quality. Here, we discuss PAT implementation
for real-time monitoring of an intermediate and API concentrations
with in-line Fourier-transformed infrared and Raman spectroscopy for
the five-step continuous synthesis of ciprofloxacin on the PoD synthesis
unit. Two partial least squares regression models were built and verified
with flow chemistry experiments to obtain a root-mean-square error
of prediction (RMSEP) of 2.2 mg/mL with a relative error of 2.8% for
the step 2 FlowIR model and a RMSEP of 0.9 mg/mL with a relative error
of 2.8% for the step 5 Raman model. These models were deployed during
an 11 h step 1–3 and a 5 h step 4–5 continuous ciprofloxacin
synthesis run performed on the PoD system. In these runs, the real-time
prediction of intermediate and product concentration was achieved
with an online model processing software (Solo_Predictor) and a PAT
data collection and management software (synTQ).