Cleaning and Sanitization in Downstream Processing

Downstream processing of biopharmaceuticals typically includes chromatography and filtration unit operations. Downstream processing enables the production of highly purified biological therapeutic products for preclinical testing, clinical and commercial use. The design and implementation of suitable cleaning protocols are part of regulatory commitments ensuring the consistent production and control of manufacturing conditions for biotherapeutics. In current modern biomanufacturing, cleaning and validation remain critical concerns for industrial biotechnology products and processes. In this article, the review focuses on cleaning and sanitization of chromatography media, membranes, and equipment for the production of biotherapeutics and in vivo diagnostics. The Cleaning and Cleaning Validation principles described in this review apply to the production of a range of biotechnology products including biotherapeutics such as vaccines [nucleic acid (DNA, RNA) viruses, antigens, and polysaccharides], MAbs, recombinant proteins (rProteins), and peptides. Keywords: downstream processing; residual DNA; cleaning validation; endotoxins; hollow fiber filtration; cleaning; sanitization; downstream processing; chromatography; validation; bioprocessing; biotherapeutics