Bioburden Control: Concerns in Continuous Bioprocessing
December 5, 2019
Bioburden control within continuous manufacturing is a key area of concern in the biotech industry. In this short video, I outline how existing technologies can help mitigate potential risks linked to bioburden control among new technologies, and answer important questions around regulatory compliance concerns for continuous technologies.
Continuous bioprocessing is gaining momentum in the market of biopharmaceuticals. As the industry and manufacturers are moving towards the implementation of novel processing technologies, regulatory questions arise.
Pall Biotech has reached out to different regulatory authorities to engage in discussions about regulatory questions. These include topics such as virus safety, quality by design, bioburden control or batch definition. Bioburden is one of the most interesting topics and therefore I'd like to share some strategies with you today.
Even though most downstream processing (DSP) unit operations are not processed under sterile conditions, bioburden management is still critical for operation consistency. In general, DSP units are in the process for a longer period of time and therefore biological contamination could accumulate or propagate between unit operations.
On the other hand, continuous processing also shortens the residence time of fluid in the unit operation. Additionally, the hold time in break tanks is significantly reduced. Nonetheless, bioburden is a critical aspect and it’s important to know how to best mitigate the remaining risks.
Bioburden mitigation of continuous processing platforms depends on the same principles as in batch processing. It essentially comes down to prevention of bioburden. This includes the use of gamma irradiated single-use assemblies to ensure zero initial bioburden at start of the campaign.
Continuous bioprocessing technologies are typically more efficient with resources thanks to the higher specific productivity. This enables or allows a valuable single-use format for most of the DSP unit operations. These unit operations can then be connected aseptically or welded where needed.
A system suitability test before use can be considered, to ensure that the system is functionally closed and can stay at such conditions throughout the manufacturing campaign. In addition, bioburden control filters can be integrated at strategic points in the downstream process in order to segregate certain parts of the process and avoid potential propagation of contaminants.
To address the concern of filter growth through the filters, they can be exchanged periodically. This can be made at strategic points in time. For example, to match with transition between lots.
Rapid microbiological testing methods can be considered especially for the future. They allow detection of bioburden at an early stage in the process thanks to their fast turnover times.
From discussions with end users and regulatory authorities, different strategies have been created to address regulatory aspects and that allows a common approach forward. Regulatory aspects do not represent a road block against implementing novel processing technologies and we are proud to support our end users on their journey towards process intensification.
To learn more about virus safety in continuous processing, view the poster Virus Filtration in Continuous Bioprocessing – Considerations for Filter Design Space and Validation Strategies
Find out more about Pall’s advanced solutions for upstream, downstream, and formulation & filing applications, view our continuous processing section of the website.
Britta Manser – European Manager for Continuous Bioprocessing
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