林旭-清洁验证培训稿.ppt

Cleaning Validation for Biopharmaceutical Manufacturing at Genentech, Inc. Part 2 Mar 1, 2008By: A. Hamid Mollah, PhDBioPharm InternationalVolume 21, Issue 3  ? Previous 1234 Next ? VALIDATION SAMPLING Sampling depends on the characteristics of soiling and cleaning agents. At Genentech, swabbing and visual inspection are used to inspect product-contact surfaces directly for assessment of surface cleanliness. Visual inspection and surface Fourier transform infrared spectroscopy (FTIR) are sometimes called real direct surface sampling. Rinsate sample testing for pH, conductivity, total organic carbon (TOC), bioburden, and endotoxin are indirect testing methods. Both direct and indirect sampling methods should be used to measure residues in cleaning validation. Establishing limits for final rinse water based solely on compendial water specification (such as final rinse meeting conductivity specification for water for injection) is not acceptable; however, a risk-based method can be applied to determine appropriate sampling type.1 Both rinse and swab samplings are considered acceptable methods of sampling in cleaning validation guidance documents.2,3 In the early 1990s, there was an inclination toward swab sampling for cleaning validation. This was possibly because at that time, equipment was designed to be disassembled for effective cleaning, and this made swab sampling very convenient. More recently, as more large equipment has been designed for CIP cleaning and therefore designed not to be disassembled, it makes less sense to require tank entry to perform swabbing. Opening up the system for entry—as opposed to depending on rinse sampling alone for cleaning validation purposes—leads to concerns about operator safety, as well as concerns about equipment cleanliness and resulting product quality. The use of a remote camera to inspect the interior of a large tank (e.g., a 20,000-liter bioreactor) is being introduced at Genentech. In biotech manufacturing, protein a