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4 BioPharm International ® Manufacturing and Facilities eBook November 2024 www.biopharminternational.com JOSEF - STOCK.ADOBE.COM Sarah Le Merdy, senior strategic marketing manager mAb and ADC, Merck KGaA, Darmstadt, Germany; Christophe Dufossé, senior strategic marketing manager Next- Gen Bioprocessing, Merck KGaA, Darmstadt, Germany W ithin the biopharmaceutical industry, the term "closed processing" refers to manufacturing performed using sys- tems operating in a contained, segregat- ed way. The reduction of interactions between biolog- ical products and sources of contamination opens up substantial possibilities for facility designs. This article provides a brief history of closed process- ing, highlighting the progress made, future develop- ments, benefits, challenges, and anticipated gains. It reviews regulatory context and emerging guidance, concluding with innovations in facility design using closed process components, shaping the "Facility of the Future" in biopharmaceutical manufacturing. Vocabulary and definitions Below are definitions of the terms related to closed processing as generally spelled out. More than a decade ago, the International Soci- ety for Pharmaceutical Engineering (ISPE) defined "closed processing" as, "A process condition when the product, materials, critical components, or container/ closure surfaces are contained and separated from the immediate process environment within closed/ sealed process equipment. A process step (or system) in which the product and product contact surfaces are not exposed to the immediate room environment" (1). BioPhorum defines closed process as, "a scheme in which all manufacturing systems used in process are closed" (2). This is complemented by the definition of a "closed system" as, "A system that isolates the process zone from its manufacturing environment and prevents ingress of environmental contaminants during product contact. The process zone is limited by equipment […]" (2). The following three criteria were identified by ISPE to define a closed system (3): • bioburden: quantity of viable microorganisms present and able to grow • initial cleanliness of materials: level of chemical res- idues or nonviable particles in the product pathway A Step Closer to Closure in Bioprocessing As biopharma anticipates the "Facility of the Future," a definition of what closed processing is, and quantification of its value, can be helpful information.