posted on 2024-02-13, 13:34authored byDaniel J. Griffin, Hsiao-Wu Hsieh, Nadide Hazal Avci, Nandini Sarkar, James D. Fostinis, Nicholas Klitzing, James I. Murray, Rasangi Wimalasinghe, Simone Spada, Alicia Zeng, Matthew G. Beaver
This is Part II of a series on the development and characterization
of an integrated continuous manufacturing (CM) process developed for
the penultimate step in the synthesis of the drug substance Apremilast
(Otezla). Part I gives the development history and highlights the
achieved process intensification. Here, we describe the process characterization
(PC) undertaken. In doing so, we point out aspects of characterization
that are unique to an integrated CM process and give our strategy
for navigating PC in this scenario. Moreover, we provide data that
support a robust control strategy which relies on parametric control
only (i.e., no in-process controls) followed by batch release of the
produced Apremilast drug substance intermediate. Such a control strategy
is advantageous as it minimizes divert-to-waste loss and operational
costs.