Continuous Manufacturing Modular API Manufacturing Plant

Continuous Manufacturing Modular API Plant

Corden Pharma Chenove SAS has commissioned a continuously operating modular API and intermediates synthesis plant that they recently put into operation to realize the benefits of process intensification. It consists of two feed modules with two dosing lines each, and four dosing lines altogether. Two of those dosing lines are made of Hastelloy, one is made of stainless steel and the other dosing line is free of metal. Each dosing line is designed for a flow between 15 and 250 ml per minute at 20 bar.

Furthermore, there is one reaction module and a quench module, both of which can supply a maximum of 500 ml per minute at 20 bar. The four thermostats enable the use of different temperature levels in different stages of the process. The plant can operate with liquids, gasses, and suspensions as feed streams, and it can be used with various continuous reactor technologies while operating automatically.

Our modular design provides smart process flexibility enabled by a standardized and uniform exchange of functionalities for multi-purpose processes and mobile installation in a smart manufacturing environment based on walk-in fume hoods. Achieving full customer satisfaction, Microinnova’s engineers are delighted to have been able to once again provide more flexibility and increased capacity to a valued customer.

Modular Multi-Purpose Production System

A continuously operated plant with four functional modules was delivered to one of Microinnova’s customers in Germany. The plant incorporates advances in process performance and modular plug & play chemical production technology.

Key features of the system are gas/liquid, liquid/liquid processing, multipurpose applications and modular automation systems. The plant system is designed for a small-scale production handling gas/liquid and liquid/liquid processes. To meet customer specifications the plant was made mainly from Hastelloy. The particular design of the gas-feed module allows an extremely wide flow range for a large number of different gases. A broad operation window is achieved by a fully integrated heat/cool tracing system.

The modular design provides smart process flexibility enabled by a standardized and uniform exchange of functionalities for multipurpose processes and operates fully automatically. A plug & play concept was realized with industry standard hardware and sophisticated software programmed to responsively react to any exchange of modules. Meeting the customer’s full satisfaction, the completed plant system was commissioned at the client site. 

Continuous Manufacturing of Formulations in Minutes Instead of Hours 

Modular Plant Skids & Bespoke Skid Plant Modules - API Manufacturing

Microinnova has successfully commissioned two continuous formulation production plants for a European client. The design of the fully automated plant is very compact, which makes it possible to easily transport & install it at a different manufacturing site.  It possesses an integrated plug & play concept with the ability to instantly change the recipe and was designed with a throughput of 14 tons/day. All streams are controlled with precise mass flow meters avoiding the labour intensive pre-weighing of substances. This provides an easy capacity increase for the client and enables the production of new products. 

“This plant replaces several batch vessels, reduces processing time from hours to minutes, minimizes work hours and waste, enables constant product quality, increases safety and can be upgraded for different products”

Mitja Ogrizek, Project Manager

Eight different liquid feeds with varying viscosities are dosed into three static mixers to deliver the end product mixture, which is then used in the downstream production process. The plant can produce different polymer concentration mixtures and the amount can be regulated based on the requirements of the customer. The continuous mixing system is fully automated and can easily be connected to the local site IT systems, such as SAP. 

Continuous Modular Crystallization Plants

Flow Plants - API Manufacturing

Microinnova delivered two modular continuous crystallization plants to the research centre CMAC in Scotland and one continuous crystallization plant with an integrated filter-dryer unit to the University of Sheffield.  Continuous crystallization, filtration and drying, as an integrated system during continuous manufacturing, is one of the most challenging topics in downstream processing.

  • Highly automatic development system on pilot scale 
  • Quick reconfiguration 
  • Process and development data are brought together on one platform 
  • Highly resistant material to enable a broad applicability 
  • Online analytics and PAT 
  • Model Predictive Control 

The delivered plant systems are thoroughly used at the research institutions to develop efficient crystallization processes for API’s and intermediates in pharmaceutical production. The delivered continuous crystallization plants were specifically designed for research purposes. With a capacity of 1-8 L/h, the modules are fully automated and were prepared for PAT integration such as FBRM and RT microscopy allowing for model predictive control (MPC). 

Continuous Manufacturing for Gas-Catalytic Reactions

API Manufacturing

Gas-catalytic projects of Microinnova focus mainly on making fuels and solvents. Input materials for these projects were syngas or synthetic gas mixtures as well as products generated from biomass. Typical reactions are water-gas-shift, methanol synthesis and Fischer-Tropsch including unit operations like gas compression, condensation and evaporation.

Commercial catalysts and proprietary catalysts were used, which have to be prepared in a wash-coat procedure in micro-channels of reactor plates. Microinnova has worked with processes in the fields of process development, engineering and plant construction, using its core competences in continuous manufacturing and process intensification. Skid-based reaction modules were built and installed in a container environment. This enables the usage of the container-based pilot plant on-site for testing with original raw materials.

The modular design allowed for a quick adaptation of the plant setup to different testing scenarios. These plants can be designed with modular automation tools like MTP. Smart manufacturing tools like process analytical technology (PAT) can be integrated into the plants according to the technical requirements of the client.

Advanced control strategies like model predictive control are available on request.

Continuous Cryogenic API plant for a Liquid Solid Reaction

A pharmaceutical client based in the Middle East requested a safe and cost-effective solution for a difficult API synthesis step. Thus, our aim was to improve the economics of the process as well as the safety level by employing continuous processing technology.

  • Reaction: Continuous solid dosing into high corrosive liquid cryogenic conditions 
  • Improved residence time from 7 hours to less than 15 minutes 
  • Increased process safety 
  • Lossless scale-up with the same selectivity as at lab scale 
  • API plant capacity: tons/year scale 
  • The plant consisted of two feed modules and one complex reaction unit 

cGMP Compliant Plant for Lek d.d. (a Sandoz company)

This API producer had problems with an extremely difficult step in a batch process, which reduced the overall yield below which was financially viable. Since the upstream and downstream processes were efficient enough (with yields of about 80%), the problem was solved with a partial renewal of the process. The mixing-sensitive step, almost unmanageable in batch mode, was replaced with a continuously operating mixing and reaction module by Microinnova. 

  • Productivity of 200 l/h 
  • cGMP compliant plant 
  • Doubled yield compared to batch mode 
  • Mixing sensitive reaction that isn’t scalable in batch 
  • Yield difference from lab trials to final production plant lower than 0.1% 
  • From lab development to factory acceptance test to a running plant in 7 months 

Modular Small-Scale Production System

Dosing of alcohol to maintain the reaction control of a highly safety-critical propoxylation reaction is a time-consuming effort, within which our Flow Mini Plant easily increased process safety and dramatically reduced the reaction times. 

  • Reducing reaction times from 12 h to 1 min 
  • Productivity of 20 kg/h 
  • Fits inside a fume hood 
  • Inherently safe 
  • Robust process

Debottlenecking of Chemical Processes

Optimizing production by replacing batch processes with continuous steps.

Process Development & Plant Concept

Learn how we developed and improved chemical processes using flow chemistry technology.

Continuous Manufacturing for 2nd Gen API

Continuous manufacturing offers an interesting toolbox for the process intensification of API manufacturing processes.