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Special Report Special Report

result in higher product throughput and nitric acid – something not feasible  Further case studies illustrate con- Challenges and future directions continually expanding the scope of support from both industry and regula-

better compliance with environmental or safe in standard open batch reac- tinuous pyrazole rearrangement Despite the compelling advantages applicable reactions. tory bodies, point towards a promising
standards. These long-term benefi ts tors. Real-time PAT controls were with enhanced heat removal and of fl ow technology and continuous trajectory. The future of chemical pro-
underscore why many leading fi rms crucial in maintaining safe opera- safety, the continuous synthesis of manufacturing, several challenges Looking ahead, the future of chemi- duction will likely be characterised by
across pharmaceuticals, fi ne chemi- ting boundaries. The industrial a tetrazole Valsartan intermediate remain for their widespread adoption: cal manufacturing is likely to be char- the pervasive integration of these inten-
cals, and specialty materials have impact was substantial decrease with in-situ azide generation and  Scalability beyond numbering-up: acterised by the increasing integration sifi ed and inherently safer technologies,
embraced fl ow-based methodologies. in acid usage and safer waste han- quenching, microwave-assisted Ensuring uniform performance of fl ow technology and continuous paving the way for a more sustainable
dling signifi cantly cut disposal fl ow chemistry for faster reactions across a large number of parallel manufacturing with digitalisation and and responsible chemical industry that
Real-world case studies demon- costs. Also, continuous manufac- and improved safety, and ultra- reactors can be complex. Research smart manufacturing initiatives. The meets the evolving demands of society
strating process intensifi cation and turing aligned well with the FDA’s sound-assisted fl ow for biodiesel into alternative scale-up strategies convergence of modular, intensifi ed while minimising its environmental
enhanced safety emerging guidance on innovative production with reduced reagent and improved manifold designs is processes with advanced data analytics, footprint and ensuring the safety of
The tangible success of continuous manufacturing approaches, facili- consumption and milder condi- ongoing. artifi cial intelligence, and digital twins its operations and the communities it
fl ow chemistry and manufacturing is tating compliance. tions. These processes demon-  Initial capital investment: The up- will enable real-time process optimisa- serves. The pursuit of operational excel-
clearly demonstrated through nume- strated to regulatory bodies (e.g., front costs associated with specia- tion and predictive maintenance, fur- lence, environmental stewardship, and
rous industrial case studies:  Lonza’s continuous hydrogena- FDA, EMA) as a safer, more robust lised fl ow chemistry and continu- ther enhancing effi ciency, safety, and robust risk management will continue
 DSM’s transformation of batch tion approach for agrochemicals method for producing an API inter- ous manufacturing equipment can sustainability. Collaborative efforts to drive the chemical sector towards a
nitration into a continuous process improved productivity and mini- mediate. Also, decreased waste be higher than traditional batch across academia, industry, and regu- continuous future, where innovation in
is a prime example of eliminating mised hydrogen gas buildup risks disposal and improved raw mate- reactors. However, long-term latory bodies will be crucial in over- fl ow technology and continuous manu-
thermal runaway incidents and in- by cleverly employing tube-in-tube rial effi ciency led to lower OPEX operational savings often justify coming the remaining challenges and facturing plays a pivotal role in achieving
creasing yield due to precise tem- reactors. This addressed both mass cost. this investment. accelerating the widespread adoption these critical goals.
perature control. This shift also transfer limitations and safety con-  Need for multidisciplinary exper- of these transformative technologies.
resulted in a signifi cant reduc- cerns. In numbers, 20-30% yield These examples collectively illu- tise: Designing, operating, and It must be remembered that these
tion in acidic waste generation. improvement was attributed to the strate how fl ow chemistry and contin- maintaining continuous fl ow sys- Conclusion: Towards a future of sunny uplands cannot be reached with-
Rather than exposing large vol- tight control of residence time and uous manufacturing revolutionise tems requires a specialised un- safer, greener, and more effi cient out a massive multidisciplinary effort.
umes to reactive nitrating agents, temperature. Also, production scal- the chemical industry’s operational derstanding of not only chemistry chemical manufacturing No longer can expertise operate in
reaction took place in seconds or ability was observed with multiple landscape. Enhanced heat and mass and chemical engineering, but also The adoption of fl ow technology silos with one department throwing
minutes, reducing formation of identical fl ow units (“numbering-up”) transfer, tighter reaction control, inte- inputs from mechanical engineers, and continuous manufacturing repre- specifi cations “over the wall” to the
byproducts. The Inline temperature which were deployed in parallel to grated processing pathways, and real- electronic and instrumentation and sents a fundamental shift towards a “downstream” department. Everyone
and pressure monitoring allowed meet commercial demand without time monitoring converge to provide process control expertise, and ex- future of safer, greener, and more effi - must sit at the same table – educating
rapid intervention if any para- revalidating entirely new reactor inherently safer, more effi cient, and perience from skilled fabricators. cient chemical manufacturing. The each other. This is the only way the
meter deviated from the set point. designs. more profi table modes of production. This is in contrast to the operation inherent advantages in heat and mass industry can not only meet the tremen-
The Industrial Impact was product As environmental and regulatory pres- of traditional batch stirred tanks transfer, precise process control, signi- dous challenges coming our way, but
consistency w.r.t improved repro-  Bayer’s continuous polymerization sures intensify, these technologies which are often run by operators fi cantly reduced reaction volumes, and thrive in the midst of them.
ducibility and less batch-to-batch achieved consistent polymer pro- stand as pillars of sustainable develop- who learn on the job with mini- the seamless integration of reaction and
variability. DSM reportedly scaled perties while curtailing energy con- ment. They also drive profi t as plants mal formal training in engineering, separation steps offer compelling solu- REFERENCES
this lab concept to commercial pro- sumption and spatial requirements. modernise to handle complex reac- chemistry or control. tions for achieving both process inten- 1. Gutmann, B., et al. (2015). An-
duction within a year, demonstrating The use of inline viscosity sensors tion schemes while cutting waste and  Regulatory considerations: The sifi cation and enhanced process safety. gewandte Chemie International
the agility of continuous fl ow tech- ensured product consistency. energy demands. pharmaceutical industry, in parti- The numerous industrial case studies, from Edition, 54(23), 6688-6720. DOI:
nology. cular, faces stringent regulatory large chemical companies to pharma- 10.1002/anie.201409318
 Merck’s integration of microre- In embracing continuous fl ow, hurdles for adopting new manufac- ceutical innovators, provide compel- 2. Roberge, D. M., et al. (2016).
 Novartis’s transition to fl ow-driven actors to perform diazotization companies can effectively streamline turing processes. However, regu- ling evidence of the tangible benefi ts, Organic Process Research & Deve-
API synthesis involving highly re- drastically lowered the probability of operations, minimise the potential for latory agencies are increasingly including improved yields, reduced lopment, 20(8), 1401-1409. DOI:
active intermediates such as azides diazonium salt decomposition and catastrophic failures, meet evolving supportive of continuous manu- waste, lower energy consumption, and 10.1021/acs.oprd.6b00151
led to reduced classifi cations for improved yields by mitigating side regulatory requirements, and reinforce facturing due to its potential for a signifi cantly reduced risk of hazardous 3. Kockmann, N., et al. (2017).
hazardous operations, saving on reactions. Generating and imme- a market edge by delivering higher- enhanced quality and safety. incidents. Industrial & Engineering Chemis-
safety overheads while retaining diately consuming diazonium quality products. These outcomes cap-  Handling complex multiphase try Research, 56(16), 4869-4881.
exceptional product quality. intermediates in sub-millilitre ture the essence of process intensifi ca- reactions: Effi ciently processing While challenges related to scalabi- DOI: 10.1021/acs.iecr.7b00345
Novartis used a pressurized tubular volumes eliminated storage risks. tion and underscore its importance to slurries and highly viscous mate- lity, cost, expertise, and regulatory land- 4. Mascia, S., et al. (2013). Ange-
reactor to run the nitration at ele- The adapted fl ow process met ICH the future of green, safe, and economi- rials in the small channels of fl ow scapes remain, the ongoing advance- wandte Chemie International
vated temperatures (~120-130°C) Q11 guidelines for continuous cally benefi cial chemical manufactur- reactors can still present challen- ments in fl ow chemistry and continuous Edition, 52(47), 12359-12363.
above the normal boiling point of manufacturing. ing. ges. Advances in reactor design are manufacturing, coupled with increasing DOI: 10.1002/anie.201305429

190 Chemical Weekly April 22, 2025 Chemical Weekly April 22, 2025 191

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