Continuous or intensified bioprocessing? The gold standard for improved productivity

by Nick Hutchinson

Process intensification and continuous biomanufacturing continue to attract a lot of interest within the biopharmaceutical industry as method that can increase productivity and make the most efficient use of production assets.

I interviewed Dr Gerben Zijlstra, formerly of DSM Biologics and the first named inventor on the patent for the XD® (Concentrated Fed-Batch) Technology. He now designs and implements continuous process platforms for biomanufacturers around the world for Sartorius Stedim Biotech.

What is the difference between intensified and continuous bioprocessing?

GZ: A fully continuous biomanufacturing process consists of interconnected continuous unit operations, without intermediate holding tanks, through which the product travels into the containers for Drug Substance in a seemingly constant flow.

Continuous unit operations represent an extremely intensified form of processing and have short downtimes relative to the amount of time they are used for production. A fully continuous biomanufacturing process might have a perfusion bioreactor coupled to a multi-column chromatography capture step, followed by flow-through virus inactivation, multi-column intermediate purification, a flow-through membrane adsorber polishing step, continuous virus filtration and a final ultrafiltration step operated in continuous mode. K.B. Konstantinov and C. Cooney have written an excellent review on this subject.

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Under the Microscope: Latest Trends

With such a fast paced industry, it is sometimes hard to keep up with the most current trends in the industry. We asked a selection of the speakers here at the conference what they saw as the emerging trends in the industry; here is what they had to say.


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Bringing it all Together for Commercialisation Pt.2

Brian Caine, co-founder and publisher of Bioprocess International Magazine sets out the topic of discussion for the fireside chat, “Bringing it all Together for Commercialisation – perspectives from every stage” and introduces the panel of experts, with conservatively over 100 years of experience between them,

Opening the discussion, Brian explores the problem of cost and time inefficiencies currently causing the industry pain.

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Be in or be out: Continuous Processing of Biopharmaceutical Proteins with Günter Jagschies

At BioProcess International Conference & Exposition West in Oakland, CA, we sat down with Günter Jagschies, Senior Director of Strategic Customer Relations in the BioProcess Division at GE Healthcare Life Sciences, to discuss continuous processing.

Dr. Jagschies explains the benefits of continuous and what technologies are making companies more receptive to the process. For him, the scale of operation is a clear advantage; you can essentially produce the same quantity of product in a bioreactor 1/5 of the size, which reduces not only the capital expenditure, but also the footprint.

Dr. Jagschies adds that having the living organism in a steady state environment that is less artificial than a fed batch operation also improves the quality of the product.

Watch the full interview with Dr. Jagschies above, where we also delve into the difficulties of implementation and the technologies that would facilitate change.

Join 1,700+ bioprocessing professionals at Biotech Week Boston on October 4 -7 2016 – find out more here

Read More:

– Margit Holzer, Consultant at Ypso-Facto, on the Benefits & Issues Surrounding Continuous Processing

Exclusive: Margit Holzer, Consultant at Ypso-Facto, on the Benefits & Issues Surrounding Continuous Processing

For many, continuous processing is the future of the biopharma industry, and yet there are still numerous concerns over its implementation. For Margit Holzer, Scientific Director at Ulysse-Consult and consultant at Ypso-Facto, the reasons to pursue it are numerous: “We want to shrink process lines and make them portable. We also expect improved quality attributes due to reduced product hold times and more controlled processing”.

EXPLORE: Find out more and register for the
Continuous Processing workshop

Continue reading “Exclusive: Margit Holzer, Consultant at Ypso-Facto, on the Benefits & Issues Surrounding Continuous Processing”

Continuous Manufacturing within the Biopharmaceutical Industry

Continuous manufacturing is a key topic within the biopharmaceutical industry at the moment. The topic will be the focus of one of the five tracks at BioProduction 2015 which will be held in Dublin in October (

Why then is continuous biomanufacturing attracting such a lot of attention at the moment? Despite much analysis the answer to this question is in fact not that simple.

Continuous Upstream Bioprocessing

Performing cell culture in a continuous fashion has always made sense when the biopharmaceutical being expressed was vulnerable to degradation within the environment of the bioreactor. Monoclonal antibodies which have historically been key drivers for growth within the industry and are usually relatively stable, but biopharmaceutical companies these days can have diverse pipelines which include other recombinant human proteins including enzymes which can have their quality reduced by prolong exposure to bioreactor conditions.

Another reason for implementing continuous upstream bioprocessing is that it allows higher cell concentrations and product titres to be achieved. In this way, the same amount of product can be manufactured in smaller bioreactors. Utilizing smaller bioreactors reduces the capital cost of the vessel itself but also enables the use of single-use bioreactor technology thereby saving money, time and complexity in the set-up of utilities required to run a stainless steel system. The burden of battling the laws of physics in scaling up to 15,000L or even 20,000L bioreactors becomes diminished although it can be argued it is replaced with the burden of battling the danger of microbial ingress leading to contaminations. Increasing production output of perfusion systems is typically achieved by increasing the number of bioreactors rather than increasing the size. This can allow operational flexibility, not only, as to when product is produced but where. In this way biomanufacturers can choose to produce biologics allow over the world and close to emerging markets as part of global supply chain networks.

Continuous Downstream Bioprocessing

A key driver for the operation of downstream processes in a continuous manner has been the significant increase in upstream product titres that have occurred over the past 15 years. This has created purification bottlenecks that must be addressed to ensure all the product synthesised can be purified. Continuous chromatography technology has come of age in recent years and is being promoted as a viable alternative to traditional batch methods. In industries in which continuous chromatography is more common it increases resin utilization, reduces down time and optimizes consumable costs including buffer components.

Integration of Upstream and Downstream Continuous Steps

Genzyme, in particular, have stressed that for the full potential of continuous bioprocessing to be realised continuous upstream and downstream operations must be effectively integrated. They achieved this by using hollow fibre filtration and the alternating tangential flow system to give a highly clarified filtrate that can feed a continuous operated capture chromatography step. This philosophy of coupling upstream and downstream steps will be the subject of a Knowledge Exchange Roundtable Discussion featuring Neha Shah of Genzyme and Massimo Morbidelli at the BioProduction 2015 event.

If you are simply considering whether continuous bioprocessing will suite your product, you are planning your approach or you are seeking to overcome challenges in the implementation, this is an event you must attend this autumn.

Dr Nick Hutchinson

Dr Nick Hutchinson

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Dr Nick Hutchinson has a Masters and Doctorate in Biochemical Engineering from University College London, UK where he focused on laboratory tools for rapid bioprocess development and characterization. He then worked at Lonza Biologics in an R&D function investigating novel methods for large-scale antibody purification before moving to an operational role scaling-up and transferring manufacturing processes between Lonza sites in the UK, Spain and USA. Nick now works in Market Development at Parker domnick hunter where his focus is in bringing Parker’s strengths in Motion & Control to Bioprocessing. This will enable customers to improve the quality and deliverability of existing and future biopharmaceuticals.

BioProduction 2015 – 4 Conferences, 1 Forum, 1 Exhibition


14-15 October 2015

Citywest Conference & Event Centre, Dublin, Ireland

Benchmark technological developments and explore best practices in biomanufacturing

The Bio Pharmaceutical industry is making a capital investment of approximately $8 billion in new facilities in Ireland, most of which has come in the last 10 years, representing close to the biggest wave of investment in new BioTech facilities anywhere in the world.

Join us at BioProduction 2015 in Dublin this October to see why so much is being invested in this area and to network with leading players within this growing industry!

BioProduction 2015: Europe’s leading and largest event for a comprehensive update on all aspects of large scale biological manufacturing. Providing insights on the latest technologies, upstream/downstream processing, process analytics, the implementation of continuous manufacturing, facility design, flexibility facilities and single use systems to reduce inefficiencies during the bio manufacturing process.

4 Conferences – 1 Exhibition – 1 Congress

  • Conference 1: Continuous Manufacturing
  • Conference 2: Upstream Processing- Production, Development & Analytics
  • Conference 3: Manufacturing Strategy & Technology
  • Conference 4: Downstream Processing

250+ Industry Experts – 130+ Companies Represented – 10 Interactive Discussions

Global panel of senior level industry professionals companies including:

  • Sean McEwen, Vice President, Biologics Manufacturing, AbbVie, Ireland
  • Guy McDonnell, Director of Engineering & EHS, Pfizer, Ireland
  • Trent Carrier, Vice President, Vaccine Technology & Engineering, Takeda Vaccines, USA
  • Roman Necina, Vice President Process Science & Technical Operations, Baxalta, Austria
  • Thilo Henckel, Vice President Manufacturing, Roche Diagnostics GmbH, Germany
  • Lada Laenen, Senior Director; Allston Landing Manufacturing Science and Technologies Head, Genzyme Corporation, USA
  • Lars Dreesmann, Executive Director, Head of Clinical Supply & Transfer, Biopharma Bioprocess & Pharmaceutical Development, Boehringer Ingelheim, Germany
  • Ciaran Brady, Director, Biotech Technical Services/ Manufacturing Sciences, Eli Lilly and Company, Ireland
  • Joe Runner, Manufacturing Technical Specialist, Genentech, USA
  • Weibing Ding, Principal Scientist, Process Development, Amgen Inc., USA

For more information on the 2015 event please visit the event website at