726 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS hazard of photo-sensitization should be taken into account. Other diffi- culties include instability on storage, odour deterioration, loss by volatiliz- ation and spoilage due to corrosion. 2.28 Association with biologically-active product constituents could result in unexpected changes in the antimicrobial properties of the product itself or in its toxicity towards the skin or mucous membranes. 2.29 The packaging should be designed to avoid (a) access of contaminants, (b) inactivation of preservative by the container or the closure, and (c) diffusion of preservative through the container or closure. As indicated above, a preservative agent should be selected for its broad spectrum of antimicrobial activity. The contamination problem can be exacerbated by using a narrow spectrum preservative which is itself susceptible to contamination by insensitive micro-organisms. This hazard must be precluded by appropriate testing. Since "self-sterilizing" capacity is a desirable target, the preservative system should preferably exhibit bactericidal and fungicidal rather than bacteriostatic and fungistatic activity. In practice, the objective is to achieve rapid destruction of a reasonable number of contaminants, the "inoculum" being kept within bounds by sound hygienic manufacturing arrangements. To insist on "self-sterilizing" capacity against all possible degrees of contamination would call for unduly high concentrations of powerful antimicrobial compounds the consequent hazard of eliciting adverse skin reactions would almost certainly exceed the risk of transmitting infection with a non-sterile product. Whilst the suggestions given in this section have been mainly directed towards safety aspects, the same considerations naturally apply to the avoidance of product spoilage (e.g. unsightly mould growth, development of "off"-odour) from an aesthetic or economical standpoint. The techniques required to deal with the problem of preservative selection are described in Appendix B. 2.3 Bacterial contamination of cosmetics subsequent to purchase Products supplied in containers allowing for the intermittent with- drawal of material are exposed to contamination each time the closure is removed in particular, they often acquire contaminants from the user's fingers. The health hazard to an individual user is probably limited but cross-infection could well occur owing to use by different members of a family unless the product has a relatively high level of "self-sterilizing"

HYGIENIC MANUFACTURE AND PRESERVATION 727 activity. Particular attention should be paid to this problem in the case of products for use on newborn infants, on broken skin, or in the vicinity of the eyes. 3. REQUIREMENTS FOR HYGIENIC MANUFACTURE 3.1 General principles Hygienic requirements differ according to the objective sought if the final product needs to be sterile, the manufacturing process obviously differs from that required to attain a less rigorous standard. To achieve sterility, production must either (a) employ sterile ingredients which are handled in such a way as to exclude all risks of contamination, along with the employment of sterilized plant and packaging materials, or (b) utilize normal, clean manufacturing procedures, ending at the final stage (i.e. after applying the closure to the filled unit packs) with a reliable sterilizing procedure, such as an autoclaving process. The first alternative, generally described as "aseptic technique", demands an exceedingly high standard of specialized knowledge and ex- perience, along with complementary plant design to facilitate its successful achievement. It also calls for the most exacting sampling and control pro- cedure so that any failure to achieve sterility is rapidly identified. Such an expensive and skilled method of operation is sometimes unavoidable in the preparation of, for example, certain injectable pharmaceutical formulations but would not normally be feasible in the cosmetic industry. The more practicable approach to sterile manufacture for cosmetics will almost invariably be the conduct of operations in a clean manner, followed by a terminal sterilization process. Guidance on hygiene and sterilizing technique are given in this document and the principles discussed here can be adapted to a wide range of different types of product. Sterility is, how- ever, a criterion of an absolute nature and, if the product is one that calls for such a standard, proof of its achievement will be an essential feature that is, adequate sterility testing must be carried out by the control labor- atory and the product should be isolated and only released for sale when the tests have been completed. As previously indicated, cosmetic manufacture does not, and need not, usually aim at yielding a sterile product. The more limited target of "self- sterilizing" capacity or adequate preservation, calls for less demanding manufacturing requirements and control procedures appropriate to the