Creating Innovations

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The main arguments in favour of continuous processing, according toJanet Woodcock, Director of the FDA’s Center for Drug Evaluation andResearch (CDER), are agility, flexibility, geography, quality, costs, and societal benefits1. Continuous manufacturing will permit increasedproduction volume without the current problems related to scale-upand also helps accelerate clinical development. Additionally, continu -ous manufacturing facilitates regional or in-country manufacture andscalable capacity in case of emergencies. It also improves uniformity ofproducts so that higher-quality drugs can be produced with less waste.Less waste and a better utilisation of resources also reduces theenvironmental impact.

With a view to these opportunities, experts expect that continuousprocesses will grow from 5% of business today to as much as 30% overthe next 10 years. At the same time, continuous manufacturing requiresa shift in mind-set on different levels within the pharmaceuticalindustry. It creates the need for a tighter integration between process,PAT, and control systems.

From proof of concept to production scaleAt the 2013 Continuous Bioprocessing Conference in Barcelona, Spain,an industry consortium initiated by Bayer Technology Servicespresented a proof of concept for a complete continuous bioprocess atlab scale. Since then, the concept has been developed further to cometo a production-scale application, including the matching systems forprocess control and PAT. The findings so far illustrate the significantpayoff of establishing continuous manufacturing in bioprocessing:continuous processes work as a closed production system, so there isno need to enclose equipment units in clean rooms and physicallyseparate the different processing steps from the general productionenvironment. This could result in savings of up to 70%2.

Upgrading processes and systems for continuous processingAs part of a consortium, Siemens provides the process controltechnology (based on the Simatic PCS 7 process control system) and thePAT software (based on SIPAT). Currently, Siemens is working with the partners in the project to create the required standardised

architecture for an integrated process control system for upstream,fermenter, and downstream processing. In continuous processing, theintegration of unit operations requires global coordination of the entireprocess flow. Continuous systems have to be equipped with a second-level software control system that supervises and aligns the operationsof the individual units. Both hardware and software should provide ahigh degree of automation, requiring minimal operator involvement.Another focus is on defining and developing a standard interface foreasy and efficient integration of equipment units from multiplemanufacturers, which is a prerequisite for modular continuous-production processes.

Maybe the biggest challenge is in developing suitable analysers tomonitor critical-to-quality data in process and in real time. To create a working solution while the available technology is developed toprovide adequate options for monitoring biological processes, theintegration of Siemens’ SIPAT software with rapid at-line, on-linesampling and analysis with integrated advanced modelling tools willprovide a basis for continuous quality verification and, ultimately, real-time release capability.

Continuous manufacturing: The next stepAlthough a large amount of research and development is still needed,continuous manufacturing is an essential part of meeting the growingneed for agile, efficient, local and high-quality biological production inthe pharmaceutical industry. It will help the industry achieveoperational excellence through a higher degree of automation,streamline drug development by offering a uniform platform for clinicaldevelopment and commercial production, and significantly reduceproduction footprint and capital expenditures.

MANUFACTURING SOLUTIONS

The pharmaceutical industry is currently dominated by batch processes. However, a continuous process offerssubstantial benefits – so substantial, in fact, that the US Food and Drug Administration (FDA) actively promotes thedevelopment and introduction of continuous process concepts in pharmaceutical manufacturing. Recently,companies have presented the first concepts for continuous production plants for commercial application in OralSolids Dosing Manufacturing. Now, concepts are being developed for Bioprocessing. A key factor for implementingsuch concepts in an actual production environment are integrated automation solutions and process analyticaltechnology (PAT) systems for in-line quality control.

VOLUME 20 ISSUE 2 2015 European Pharmaceutical Review 69

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1. Janet Woodcock, “Modernizing Pharmaceutical Manufacturing – Continuous Manu -

facturing as a Key Enabler” (paper presented at MIT-CMAC International Symposium on

Continuous Manufacturing of Pharmaceuticals, Cambridge, MA, May 20, 2014)

2. Thomas Daszkowski, “Continuous Processing in Biotech Production: An Alternative to a

Modern Single Use, Batch, Facility?” (paper presented at Integrated Continuous

Biomanufacturing Conference, Castelldefels, Spain, October 20–24, 2013)

References

Ivo BackxManager, Business & Project Development for the Pharmaceutical Industry, Siemens

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