MICROBIOLOGICAL SPO1LAGE IN 'PHARMACEUTICALS AND COSMETICS 735 limits which are meaningful and yet can be applied generally to pharma- ceutical and cosmetic products is extremely difficult, if not impossible, in view of the multiplicity of organisms and products involved. In practice, regular monitoring during development and manufacture establishes the type and minimum number of organisms which are achiev- able for each specific product. Providing, of course, that this level is compatible with microbiological stability it forms the best approximate guide-line for a product. (Received: 13th June 1971) REFERENCES (1) (2) (3) (4) (5) (6) (7) (8) (9) (1o) (11) (12) (13) (14) (15) (16) (17) (•8) (19) (20) (21) Butler, N.J. The microbiological deterioration of cosmetics and pharmaceutical products. In Biodeterioration of Materials 269 (1968) (Elsevier Publishing Co., Amsterdam, London and New York). Sykes, G. Microbial contamination in pharmaceutical preparations for oral and topical use. Indian J. Pharmacy 31 No. 2 33 (1969). Barnes, J. M. Aflatoxin as a health hazard. J. Appl. Bacteriol. 33 285 (1970). Perlman, D. and Peruzzotti, G. P. Microbiological metabolites as potentially useful pharmacologically active agents. In Advances in Applied Microbiology 12 277 (1970) (Academic Press, New York and London). Smith, G. N. and Worrel, Celia S. Studies on the action of chloramphenicol on enzymatic systems. Archives Blochem. 23 No. 1 341 (1949). Hugo, W. B. The degradation of preservatives by micro-organisms. Sci. Tech. Symp. 122 112th Ann. Mtg Am. Pharm. Assoc. C411, 1 (1965). Kedzia, W., Lewon, J. and Wisnienski, T. The breakdown of attopine by bacteria. J. Pharm. Pharmacol. 13 614 (1961). Grant, D. J. W., de Szors, J. and Wilson, J. V. Utilization of acetylsalicylic acid as sole carbon source and the induction of its enzymatic hydrolysis by an isolated strain of Acinetobacter lwoffi. J. Pharm. Pharmacol. 22 No. 6 461 (1970). Omelianski, V. C. Aroma-producing micro-organisms. J. Bacteriol. 8 No. 4 393 (1923). Gerber, N. N. and Lechevalier, H. A. Geosmin, an earth-smelling substance isolated from actinomycetes. Appl. Microbiol. 13 935 (1965). Margalith, P. and Schwartz, Y. Flavor and micro-organisms. In Advances in Applied Microbiology 12 35 (1970) (Academic Press, New York and London). Shooter, R. A., Cooke, Mary E., Gaya, H., Kumar, P. and Patel, N. Food and medica- ments as possible sources of hospital strains of Pseudomonas aeruginosa. Lancet i 1227 (1969). Guyne, C. J. and Bennet, E. O. Bacterial deterioration of emulsion oils. Appl. Microbiol. 7 117 No. 2 (1959). Bean, H. S. The microbiology of topical preparations in pharmaceutical practice. 2. Pharmaceutical aspects. Pharm. J. 199 No. 5 421,289 (1967). Bart, M. and Tice, L. F. The preservation of aqueous preparations containing non-ionic surfactants I. J. Am. Pharm. Assoc. Sci. Ed. 46 No. 7 442 (1957). Tice, L. F. and Barr, M. Factors to be considered in the preservation of cosmetic emulsions. J. Soc. Cosmet. Chem. 9 171 (1958). Wedderburn, D. L. Preservation of emulsions against microbial attack. In Advances in Pharmaceutical Sciences 195 (1966) (Academic Press, London). Rivers, S. M. and Waiters, V. The effect of benzoic acid, phenol and hydroxybenzoates on the oxygen uptake and growth of some lipolytic fungi. J. Pharm. Pharmacol. 18 supp. 45S (1966). Eggins, H. O. W. and Walters, V. The decomposition of pharmaceutical emulsions by fungi. W. African J. Biol. Appl. Chem. 7 No. 1 2 (1963). Bryce, D. M. and Smart, R. The preservation of shampoos. J. Soc. Cosmet. Chem. 16 187 (1965). Walker, H. W. and Ayres, J. C. Yeasts as spoilage organisms. In The Yeasts 3 463 (1969) (Academic Press, London and New York).

736 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS (22) English, M.P. The fermentation of malt extract by an osmophilic yeast. J. Gen. Microbiol. 9 No. 1 15 (1953). (23) Wills, B. A. Fungal growth in Syrup of Tolu. J. lPharm. Pharmacol. 10 302 (1958). (24) Payne, M. and Smart, R. Unpublished. (25) Kallings, L. O., Ringertz, O., Silverstolpe, L. and Ernerfeldt, F. Microbiological con- tamination of medical preparations. Acta lPharm. Suecica. 3 No. 3 249 (1966). (26) Elliot, R. P. and Michenar, H. D. Microbiological standards and handling codes for chilled and frozen foods. A review. Appl. Microbiol. 9 No. 5 452 (1961). DISCUSSION D•.. H. S. BE^N: We have been talking about the levels of contamination and many people have been talking in terms of not more than 100 micro-organisms g-• product. Connected with this standard there should be a time factor. When must the product meet this requirement? Immediately after manufacture or when somebody has been around the country and bought some off pharmacists' shelves 2 months, 2 years later? My colleagues and I have examined perhaps many thousands of different types of systems in our laboratory and we have found that the count never remains constant for very long. If the product has some antimicrobial action itself the count goes down but it may go up. The product may pass the test today and fail next week, next month, or next year. The third possibility is that the count will initially go down, and then we shall suffer quite considerable subsequent multiplication. If the product is liable to contamination and good manufacturing practice will not, or cannot, keep the number down below the limit we must include a preservative. When we are talking in terms of standards for pharmacopoeias or some other compendia we have to be quite sure about the type of product to which we are applying these standards. If the product is capable of support- ing growth then it is not sufficient to merely state that the product should contain not more than 100 micro-organisms g-• because inevitably sooner or later it will. If the pro- duct is capable of supporting growth then we have to state some measure of the activity of the product against the invading micro-organisms. DR. J. R. GWILT: YOU referred to the need to train production people in micro- biological techniques and a participant from Italy also referred, en passant, to the need to check production people, at least to ensure that the products were not contaminated where they had infections. One thing that concerns me very much is that there seems to be more stress upon the environment and particularly upon the raw materials, than upon the people concerned. It seems that there are two ways in which the people who are in production, hospitals, and so on are involved. The first one I would call a negative way-- the people who are the shedders and the carriers in production some of these we can pick up through high plate counts in the area when they are actually working with, for instance, sterile products, or we can find some of the carriers by throat and nose swabs. The second instance is where the people are positive, i.e. they definitely contribute. There is a tendency, certainly in the U.S.A., to dub quality controllers as second class, and bacteriologists, I fear, sometimes as third class. They are the people who should be involved in plant hygiene and also consulted where there are any changes in process, procedure or in packaging because all these can have such an enormous influence upon the survival, and the persistence, of bacteria in the products. DR. SPOONER: I agree and would like to applaud you when you say that people are important because I think that obviously they are the major factor in manufacturing.