ABSTRACT
Quality by Design principles such as design space can also be applied to cleaning validation. As discussed in the recently
published PDA Technical Report No. 49: Points to Consider for Biotechnology Cleaning Validation, well–designed laboratory-scale studies can be performed using design of experiments, and the data analyzed to understand
the cleaning process. With the knowledge of large-scale equipment, one can create an approach that results in a successful
cleaning validation.
Anurag S. Rathore
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Cleaning validation plays an important role in reducing the possibility of product contamination from biopharmaceutical manufacturing
equipment. It demonstrates that the cleaning process adequately and consistently removes product residue, process residue,
and environmental contaminants from the cleaned equipment or system, so that this equipment or system can be safely used to
manufacture subsequent products, which may be the same or a different product.
Table 1
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PDA recently issued the Technical Report No. 49: Points to Consider for Biotechnology Cleaning Validation (1). This report, more than 70 pages long, was created by a team of European and North American professionals from biotechnology
manufacturers, cleaning-chemical suppliers, regulatory agencies, and consulting companies. The report provides a single-source
overview for biotechnology manufacturers and complements existing guidance and reference documents. It builds on and updates
previous PDA publications, including the 1998 Technical Report No. 29: Points to Consider for Cleaning Validation (2) and the 1996 Technical Monograph, Cleaning and Cleaning Validation: A Biotechnology Perspective (3). The report uses a life-cycle approach to biotechnology cleaning validation that encompasses design and development,
process qualification, and ongoing control of effectiveness. It also considers the risks of the process. In particular, this
technical report addresses unique features of biotechnology cleaning validation, including the way in which limits are established
for bulk biotechnology manufacture. The report also considers the effect of degradation of the active on cleaning-validation
practices and the widespread use of nonspecific methods, such as total organic carbon (TOC) and total protein, for measuring
residues of actives. Table I provides a list of the major topics covered in Technical Report No. 49.
This article is the twenty-second in the "Elements of Biopharmaceutical Production" series and will discuss the various issues
to consider when designing a cleaning-validation program.
