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 (www.bio-production.com).
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
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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.