724 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS copoeia, 18th Revision: British Pharmacopoeia 1968 and in the British Pharmaceutical Codex 1968. For most cosmetic products a criterion of sterility is not appropriate and suitable testing procedures are described in various sections of this monograph. Generally, the microbiologist will not seek to identify every contaminant found but it is advisable to undertake detailed identification if there is any reason to suspect the presence of pathogenic micro-organisms. If the presence of potentially harmful micro-organisms is confirmed, the product should either be rejected as unfit for sale or treated in such a way that such micro-organisms are no longer detectable on further testing. Test methods for verifying sterility and for enumerating viable micro- organisms should ideally be fully reproducible in different laboratories and should preferably be simple and quickly carried out. Unfortunately there are no available techniques capable of satisfying all these criteria. For example, the microbial count is liable to vary according to factors such as (i) the size of sample and frequency of sampling, (ii) the specified counting technique, (iii) whether inactivation of any antimicrobial preservative is carried out, (iv) the diluent and recovery medium used and the methods employed in mixing with the prcd]ct, and (v) the temperature and duration of incubation. Appendix B gives a selection of recommended procedures from which an appropriate scheme for testing a range of cosmetic products may be chosen. As indicated above, the sampling procedure in particular manu- facturing conditions can only be properly determined on the spot and deciding on the most suitable tests to apply similarly demands consideration of formulae and manufacturing techniques actually in use. For example, the criterion of excluding known pathogens might suggest the need for an elaborate programme of microbial identity tests on every batch of product. For a suitable testing programme in a given set of circumstances, however, it will probably suffice to devise a scheme capable of monitoring the overall product quality over the course of time this is preferable to a prohibitively expensive and elaborate check on every batch, providing that a compre- hensive study of product preservation has been undertaken at the research stage. If good provisions for hygienic manufacture are made and the preserv- ative system is shown to be capable of dealing with likely levels of con- tamination, routine control can safely be restricted to a limited range of testing.

HYGIENIC MANUFACTURE AND PRESERVATION * 725 2.2 The selection of a preservative system There is no satisfactory way of choosing preservative agents for a particular formulation on a theoretical basis or from a list of available compounds. Experimental determination of the efficiency of a preservative system is essential for satisfactory results. Furthermore, the choice and testing of preservatives should be regarded as an integral feature of pro- duct development it should not be left until formulation work is thought to be complete. The formulation chemist, packaging technologist, physical chemist, and microbiologist will need to reach a compromise, because the ideal product, the ideal preservative, and the ideal pack may well prove to be incompatible with each other. In the course of product development, the following aspects of preserv- ation will be important:-- 2.21 The preservative system should preferably act bactericidally and fungicidally in the actual product formulation concerned against a broad spectrum of possible contaminants. This activity should be achieved at all likely storage temperatures and in low concentration. 2.22 The preservative system should have adequate efficiency at a pH corresponding to that of the product formulation. 2.23 The preservative should have solubility and partition characteristics such that it is available in the aqueous phase of a biphasic system. Complete solubilization in an oily phase or in surfactant micelies can result in loss of bactericidal or fungicidal activity. 2.24 The selection of product ingredients providing carbon, nitrogen or sulphur sources which may be utilized as nutrients by contaminating micro- organisms, will increase the difficulty of achieving preservation. 2.25 Blends of more than one preservative often ensure synergistic or complementary activity certain blends in which only one compound has antimicrobial activity may also be of value, e.g. the saturation of micelies with a non-inhibitory compound having a partition coefficient higher than that of the inhibitor may limit the level of preservative needed. 2.26 Product ingredients tending to carry a significant level of contamin- ation should be avoided unless they are easily sterilized by heating or by a gaseous inhibitor such as ethylene oxide. 2.27 The physical, chemical and biological compatibility of preservatives with the other product constituents must be examined. For example, toxic or irritant effects on skin or mucous membranes might be encountered the