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bp8 01How “Closed” is a Functionally Closed System?

Open. Closed. Functionally Closed. What do these terms mean in bioprocessing? Learn about the purpose of functionally closed systems in bioprocessing below.

Clear definitions were published in a classic BioPharm International article[1] here, in part:

 

Open system: A process system that exposes the product to the room environment. In these systems, the room environment is controlled to minimize the risk of product contamination. For nonsterile, bioburden-controlled processing, open operations are expected to be performed in a classified environment, such as grade C. The process fluid is often filtered for bioburden control within a controlled amount of time after completion of any open process step.

Closed system: A process system with equipment designed and operated such that the product is not exposed to the room environment. Materials may be introduced to a closed system, but the addition must be done in such a way to avoid exposure of the product to the room environment (e.g., by 0.2 µm filtration).

Functionally closed: A process system that may be routinely opened (e.g., to install a filter or make a connection), but is returned to a closed state through a sanitization or sterilization step prior to process use. It is the owner’s responsibility to define and validate the sanitization or sterilization process required to return an opened system to a functionally closed system.

Risk aversion in biopharmaceutical manufacturing has reduced the initial appeal of functionally closed systems. Personnel need to be especially vigilant in carrying out sanitization or sterilization processes at every breach point or all of the risks in an uncontrolled space are brought to bear on the interior. Could a functionally closed system adequately protect the product without all the expense and hassle of a classified space?

A terrific blogpost from TheCellCultureDish here and another BioPharm International article here explore the trade-offs between risky room-air processing and the high costs that accompany the maintenance of cleanrooms.

Is there a third option?

Enclosing a “functionally closed” cell processing system within a barrier isolator can relieve the environmental maintenance issues of a cleanroom, but provide all the protection the cells need from uncontrolled room air. This turns a functionally closed system into a closed system.

By simply excluding people from environment of a functionally closed system, the single largest source of contamination risk is removed. This represents a tremendous reduction in risk to critical cell cultures.

One of the most exciting prospects of closed systems for cellular therapies is the possibility of bringing cell processing steps to the patients’ room, the doctors’ office, or other non-classified spaces. In these cases, it is appropriate to enclose the cell preparation equipment, even if it is functionally closed, within a barrier isolator to further reduce risks related to cell culture contamination.

1. Gil, P., Rogalewicz, J. Chalk, S., Probst S., Palberg, T., Kennedy, M. Johnson, J., Green K. Challenging the Cleanroom Paradigm for Biopharmaceutical Manufacturing of Bulk Drug Substances. BioPharm International. Aug. 01, 2011.

 


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About The Author

Alicia D Henn, PhD, MBA

Alicia D Henn, PhD, MBA

Chief Scientific Officer of BioSpherix, Ltd

 

 

Alicia Henn has been the Chief Scientific Officer of BioSpherix, Ltd since 2013. Previously, she was a researcher at the Center for Biodefense Immune Modeling in Rochester, NY. Alicia obtained her PhD in molecular pharmacology and cancer therapeutics from Roswell Park Cancer Institute in Buffalo, NY and her MBA from the Simon School at University of Rochester in Rochester, NY.

ahenn@biospherix.com

 

 

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