Cleaning validation refers to establishing documented evidence providing a high degree of assurance that a specific cleaning process will produce consistent and reproducible cleaning results that meet a predetermined level. A cleaning program can be divided into three phases: cleaning process and cycle development, cleaning validation, and maintenance. The program should begin with equipment design evaluation and cycle and process development that includes, but is not limited to, the following: sanitary equipment design, selection of final rinse water, approved equipment specifications that address an evaluation of the compatibility of construction materials with product and cleaning solutions, sprayball design optimization, cleaning process design studies, cleaning sample assay validation, suitability of sampling, and recovery studies for assay and sampling methods. Without these design and development activities, validation could potentially lead to unnecessary troubleshooting and cleaning verification exercises.
The cleaning process should remove materials such as media, buffers, storage solutions, cell culture fluids, cell debris, non-active pharmaceutical ingredients containing placebos, and formulations and concentrations of drugs or active pharmaceutical ingredients (API). Selection of appropriate sampling to demonstrate that residues have been removed to an acceptable level is vital for the success of cleaning validation.At Genentech, Inc., design and cleaning-cycle development is considered a prerequisite for cleaning validation. The purpose of cleaning validation at Genentech for biopharmaceuticals is to:
Cleaning validation is driven by regulatory expectations to ensure that residues from one product will not carry over and cross-contaminate the next product. An effective cleaning program starts with appropriately designed equipment and cleaning processes, followed by validation and maintenance. The following are some good manufacturing practice (GMP) cleaning validation requirements for the biopharmaceutical industry.
US Food and Drug Administration 21 CFR Part 211: Current GMP for Finished Pharmaceuticals
§ 211.63 Equipment design, size, and location:
§ 211.67 Equipment cleaning and maintenance:
§ 211.182 Equipment cleaning and use log: