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24 Pharmaceutical Technology ® Trends in Manufacturing eBook May 2023 PharmTech.com continuous manufacturing Applications of the digital twin The applications of the digital twin have been demon- strated for scenario analysis, digital optimization, a nd design a nd development of suitable cont rol architecture for a continuous APIs manufacturing process. Dynamic optimization provides the opti- mum operating conditions for the manufacturing process that improves the critical quality attributes (CQAs). A suitable control architect ure t hen has been developed using the digital twin to track the optimum set points for the key control variables. The developed control architecture is also modular in na- ture and can be easily adapted for different manu- facturing processes of APIs that may have different material and information f lows, dead time varia- tions, and tuning parameters. The proposed digital t win can save t he time and resources needed for continuous APIs manufacturing and improve the product quality significantly. Results and discussion The feeding system model has been considered here for demonstration purposes. For successful contin- ! !"#$%&'()'!"#$%&'()"*+,*$"$-(./0(1&*$2&)+$',*3(4'")5--( !"#$%&'()'*'+,&-".,&'/"01&20"2#34&56"2#37"-"2#'78/$,&'5.,&'68'7"-'698' %&5:65260'"2'52;'/&0"%&/'1%818%6"82'52/'/&,"<&%'64&7'50'5'4878#&2&8$0' 06%&57'4&56&/'68'5'/&0"%&/'6&71&%56$%&=' !"#$%&' (( !"#$%&' )( !"#$%&'()'!"#$%&'()"*+,*$"$-(./0(1&*$2&)+$',*3(4'")5--( !"#$%&'()'*'+,&-".,&'/"01&20"2#34&56"2#37"-"2#'78/$,&'5.,&'68'7"-'698' %&5:65260'"2'52;'/&0"%&/'1%818%6"82'52/'/&,"<&%'64&7'50'5'4878#&2&8$0' 06%&57'4&56&/'68'5'/&0"%&/'6&71&%56$%&=' !"#$%&' (( !"#$%&' )( schematic representation of chromatographic separation module ! "#$% ' ( ( Schematic representation of the PFR reactor the monitoring of conversion and Figure 4: schematic representation of the chromatographic separation module ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ( !"#$%&'))(6225)+-("2(+,-(+7'"$374$+(+.-'1&+5',&%(4'"45'+,5-("*('52,%%(-+'&+5389! ! ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ( !"#$%&'))(6225)+-("2(+,-(+7'"$374$+(+.-'1&+5',&%(4'"45'+,5-("*('52,%%(-+'&+5389! ! ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ( !"#$%&'))(6225)+-("2(+,-(+7'"$374$+(+.-'1&+5',&%(4'"45'+,5-("*('52,%%(-+'&+5389! ! ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ( !"#$%&'))(6225)+-("2(+,-(+7'"$374$+(+.-'1&+5',&%(4'"45'+,5-("*('52,%%(-+'&+5389! ! ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ( !"#$%&'))(6225)+-("2(+,-(+7'"$374$+(+.-'1&+5',&%(4'"45'+,5-("*('52,%%(-+'&+5389! ! FIGURE 5. Refill model response. Figure 4: schematic representation of the chromatographic separation module ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( FIGURE 4. Schematic representation of the chromatographic separation module. Figure 4: schematic representation of the chromatographic separation module ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ( !"#$%&'))(6225)+-("2(+,-(+7'"$374$+(+.-'1&+5',&%(4'"45'+,5-("*('52,%%(-+'&+5389! ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ( !"#$%&'))(6225)+-("2(+,-(+7'"$374$+(+.-'1&+5',&%(4'"45'+,5-("*('52,%%(-+'&+5389! ! ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ( !"#$%&'))(6225)+-("2(+,-(+7'"$374$+(+.-'1&+5',&%(4'"45'+,5-("*('52,%%(-+'&+5389! ! ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ( !"#$%&'))(6225)+-("2(+,-(+7'"$374$+(+.-'1&+5',&%(4'"45'+,5-("*('52,%%(-+'&+5389! ! ! !"#$%&'*(!"#$%&&!'()#&!*#+,(-+#( ( !"#$%&'))(6225)+-("2(+,-(+7'"$374$+(+.-'1&+5',&%(4'"45'+,5-("*('52,%%(-+'&+5389! ! FIGURE 6. Effects of (a) throughput (b) material properties on refill strategy.