J. Soc. Cosmet. Chem. 23 721-737 (1972) ¸ 1972 Society of Cosmetic Chemists of Great Britain Microbiological spoilage in pharmaceuticals and cosmetics R. SMART and D. F. SPOONER* Presented on 29th September 1971 in London, at the Symposium on 'Microbial control', organized by the Pharmaceutical Society of Great Britain and the Society of Cosmetic Citemists of Great Britain. Synopsis--Manifestations of SPOILAGE by bacteria, yeasts and fungi are described. TOXIC visible, olfactory and audible effects and changes in texture and taste may be found and susceptible products are reviewed. LIQUIDS, including aqueous solutions and suspensions, syrups, emulsions and creams are particularly at risk. Spoilage of ointments and oils, solid raw materials, powders, tablets and solid COSMETICS also occurs. The involvement of PACKAGING materials and the CONTROL of MICROBIOLOGICAL spoilage is briefly discussed. INTRODUCTION A spoiled product may be described as one that has been rendered unfit for use. As pharmaceuticals and cosmetics are consumed by, or applied to, the user, manifestations of spoilage are essentially subjective, spoiled products becoming objectionable or perhaps even therapeutically inactive. Microbial spoilage can be caused by bacteria, yeasts or fungi which are all extremely versatile in their metabolic activities. This capacity for variation, whether due to mutation in genetic composition followed by selection or to changes in behaviour unaccompanied by genetic change, allows adaptation to a very broad range of environmental conditions. As a result, all classes of natural organic compounds are susceptible to * Quality Control--Microbiology, The Boots Company Ltd, Nottingham, NG2 3AA. 721

722 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISIS degradation and synthetic compounds are also attacked, although often less readily. In spite of this, relatively few accounts of the microbial degradation of pharmaceuticals or cosmetics have been published (1). This is partly due, no doubt, to the careful control measures exercised by responsible manu- facturers. It is also due to the difficulties of elucidating the mechanisms involved in a spoilage event. Each tends to be a unique encounter between a specific organism and substrate and often there is only time to record the happening and remedy the situation. In contrast, much has been written on the contamination of pharmaceuticals and cosmetics by micro-organisms (2). If the contaminants are potential pathogens then the products are obviously rendered unfit for use and are therefore spoiled. However, in this paper we are mainly concerned with degradation caused by contaminating micro-organisms. Their clinical significance is dealt with in detail elsewhere in the Symposium. MANIFESTATIONS AND MECHANISMS OF MICROBIAL SPOILAGE Before spoilage can occur organisms which are capable of altering the components of a product in situ must first be introduced via raw materials, the processing plant, packaging materials, operatives or elsewhere in the environment. Although spoilage does not necessarily depend upon the growth of these contaminants it is generally facilitated if the formulation and the ambient conditions of temperature and humidity encourage their multiplication. When these criteria are satisfied changes in the product will occur and may ultimately manifest themselves to the user in one or more of the following ways: Toxic effects Microbial toxins Several species of micro-organisms produce toxic molecules and may render a product dangerous if they grow in it under conditions supporting toxin production. Endotoxins, produced by Gram-negative bacteria such as Escherichia coli, are intimately bound to the cell, lipopolysaccharide in nature and are not necessarily inactivated by sterilization as they are heat stable. Toxins of this type are poorly absorbed by the oral route but are very important in connection with injectable products, particularly per- fusion fluids. Exotoxins are much more highly lethal and are bound less rigidly to the cell so that they are readily liberated into the growth medium. The outstanding example, of course, is that produced by Clostridium