5.1.6. Alternative Methods for Control of Microbiological Quality

1. GENERAL INTRODUCTION The objective of this chapter is to facilitate the implementation and use of alternative microbiological methods where this can lead to cost-effective microbiological control and improved assurance for the quality of pharmaceutical products. These alternative methods may also find a place in environmental monitoring. The microbiological methods described in the European Pharmacopoeia have been used for almost a century and these methods for enumerating and identifying micro-organisms still serve microbiologists well. Over the years, these methods have been invaluable to help control and secure the production of microbiologically-safe pharmaceutical products. Nevertheless conventional microbiological methods are slow, and results are not available before an incubation period of typically up to 14 days. Thus the results from the conventional microbiological methods seldom enable proactive, corrective action to be taken. Alternative methods for control of microbiological quality have been introduced in recent years, and some of these methods have shown potential for real-time or near-real-time results with the possibility of earlier corrective action. These new methods can also offer significant improvements in the quality of testing. In this informational chapter new microbiological methods offering pharmaceutical applications are described. For each method the basic principle is stated and the benefits and disadvantages of the method are then discussed. Potential uses describe applications that may be envisaged in view of the principles on which the method is based : it is not intended to suggest that actual application has been made. Finally, general considerations for the validation of the method are outlined. These are illustrated by specific examples for each type of method. A detailed validation protocol is given for information at the end of this chapter. It is not the intention of this chapter to recommend one method over another, nor is it the intention to provide an exclusive or exhaustive list of alternative methods that can be used for pharmaceutical microbiological control. This informational chapter however may be used in the process of choosing an alternative microbiological method as a supplement or as an alternative to conventional microbiological approaches and to give guidance in the process of validating the chosen method. In this rapidly developing field, further methods are likely to appear. The guidance offered in this chapter may be equally applicable to these methods. There are 3 major types of determinations specific to microbiological tests. These include : — qualitative tests for the presence or absence of micro-organisms; — quantitative tests for enumeration of micro-organisms; — identification tests.