F.25 Whyte pp 55-61

Analytical methods for hazard and risk analysis are being considered for controlling contamination in pharmaceutical cleanrooms. The most suitable method appears to be the HACCP system that has been developed for the food industry, but this requires some reinterpretation for use in pharmaceutical manufacturing. This paper suggests a possible system. To control contamination effectively, it is necessary to have a good appreciation of the routes and sources of contamination, and the means of controlling them. An overview of these is given. Introduction Cleanrooms must be operated so that the contamination of the manufactured product is controlled. Standards of particle and microbial contamination, such as found in the European Union guide to good manufacturing practice 1 are set, and controlled, so that they are not exceeded. Unfortunately, such standards do not take account of different degrees of risk, the varying routes and sources of contamination in different processes, and whether the product supports the growth of micro-organisms. To ensure that the correct control measures are taken, a scientifically based contamination control system is needed to analyse the degree of risk posed by the varying hazards. This approach has been advocated by ISO 14698-1 2 . Hazard and risk analytical systems A contamination control system should assess the degree of risk of potential hazards found in a cleanroom. 1. Conduct a hazard analysis 2. Determine the critical control points (CCPs) 3. Establish critical limit(s) 4. Establish a system to monitor control of the CCPs 5. Establish the corrective action to be taken when monitoring indicates that a particular CCP is not under control 6. Establish procedures for verification to confirm that the HACCP system is working effectively 7. Establish documentation concerning all procedures and records appropriate to these principles and their application It is also suggested in some HACCP documents that personnel associated with the HACCP system need to be trained. The HACCP system is explained in various documents A cleanroom contamination control system As indicated in the previous paragraph, the HACCP system requires some reinterpretation if it is to be used in the manufacture of non-food items in cleanrooms. A reinterpretation of the first three principles of HACCP is particularly needed. To achieve this, a cleanroom contamination control system (CCCS), based on HACCP, is suggested. This contains the following steps