Test for sterility

Perform sterility test for the bulk media after hltration and bioburden count before hlteration. 

STERILITY TEST FOR RUBBER STOPPER AND GLASS VIALS... 

The time lag in imposition of a legal requirement for sterility of ointments compared with solutions and suspensions was due to the absence of a reliable sterility test for the petrolatum-based ointments until isopropyl myristate was employed to dissolve these ointments and allow improved recovery of viable microorganisms by membrane filtration. Manufacturers found that, in fact, many of their ointments were sterile, but revised their manufacturing procedures to increase the assurance of sterility. 

The contamination of pasteurized products is usually caused by specific bacteria species that exist in the raw material and environment. The current sterility test for pasteurized products is that the products are incubated and then applied and cultured... 

The ATP bioluminescence method would detect any contaminated bacteria, if the bacteria were growing over its detection limit in the product. When many samples must be checked, it is possible to select whether each product is aseptic or not in a short time. Dubious samples would be tested by the ordinary plate method. The ATP bioluminescence method is one of the most available sterility tests for initiate screening. 

S-Tt>capherol, 3,4-Hihydro-2,8 1 i methyl. 2- 4,8,-12-trimethyUridecyl)-2H-l-benzopyran-6-ol 8-methyltocol. C H O, mol wt 402-64. C 80.54%, H 11.52%, O 7.95%. Appears to be a rather common member of the vitamin E complex. Ingredient of Mixed Toeopherols Concentrate, N.F. It was found to constitute approx 30% of the mixed toeopherols in soybean oil. 5% of those in wheat germ oil. and there is evidence of its occurrence in cottonseed and peanut oils. Claimed to be the most potent antioxidant of the toeopherols. It has only one hundredth of the activity of natural -tocopherol in the Evans resorption sterility test for vitamin E. Lsoln from soybean oil Stern et al., J. Am ... 

Cross contamination of vaccines with other pathogens has also resulted in mortality and morbidity in animals. These incidents have included pseudorabies virus contaminated with pestivirus, Marek s disease virus contaminated with reticuloendotheliosis virus, contamination of cell lines and vaccines with bovine diarrhoea virus, bluetongue in dogs arising from contaminated live canine vaccine and clostridial disease in ruminants of 202 523 animals in affected herds, 41 767 were infected with Clostridium sordellii and 22 189 died, possibly as a result of a failure in a sterility test for detecting contaminants in a clostridial vaccine. 

S. Tellez, R. Casimiro, A. I. Vela, J. F. Fernandez-Garayzabal, R. Ezquerra, M. V. Latre, V. Briones, J. Goyache, R. Bullido, M. Arboix and L. Dominguez, Unexpected inefficiency of the European pharmacopoeia sterility test for detecting contamination in clostridial vaccines. Vaccine, 2006, 24, 1710-1715. 

Dry-heat sterilization is generally conducted at 160—170°C for >2 h. Specific exposures are dictated by the bioburden concentration and the temperature tolerance of the products under sterilization. At considerably higher temperatures, the required exposure times are much shorter. The effectiveness of any cycle type must be tested. For dry-heat sterilization, forced-air-type ovens are usually specified for better temperature distribution. Temperature-recording devices are recommended. 

All preparations of enzymes intended for parenteral use are tested for safety in lower animals under the conditions anticipated in clinical trials ie, their use must be nonpyrogenic in the USP rabbit assay (255), and must be sterile. Such toxicologic studies are usually a prerequisite for approval by the FDA for the sale of such pharmaceuticals. 

Each interferon preparation was ultracentrifuged at 20,000 revolutions per minute for one hour to remove tissue debris and inactivated virus. The supernatant was dialyzed against distilled water (1 400) for 24 hours at4°C. The material was then freeze-dried. The dried product was reconstituted in one-tenth of the original volume in distilled water and dispensed into ampoules. Reconstituted solutions were assayed for interferon activity, examined for toxicity, and tested for sterility. 

These are essentially tests for sterility (Chapter 23) upon bacterial suspensions performed after treatment with the antibacterial agent for a prescribed time and under controlled conditions. They differ in the manner in which the experimental findings are calculated as well as in the details of experimental procedure. 

In-process quality control is the control exercised over starting materials and intermediates. Its importance stems from the opportunities that it provides for the examination of a product at the stages in its manufacture at which testing is most likely to provide the most meaningful information. The WHO Requirements and national authorities stipulate many in-process controls but manufacturers often perform tests in excess of those stipulated, especially sterility tests (Chapter 23) as, by so doing, they obtain assurance that production is proceeding normally and that the final product is likely to be satisfactory. Examples of in-process control abound but three of different types should suffice. 

British Pharmacopoeia (1993) Appendix XVI A Test for Sterility, A180-A184. London HMSO. (3.4) Denyer S. Baird R. (eds) (1990) Guide to Microbiological Control in Pharmaceuticals. Chichester Ellis Horwood. (3)... 

A sterility test is basically a test which assesses whether a sterilized pharmaceutical or medical product is free from contaminating microorganisms, by incubation of either the whole or a part of that product with a nuhient medium. It thus becomes a destructive test and raises the question as to its suitability for testing large, expensive or delicate products or equipment. Furthermore, by its very nature such a test is a statistical process in which part of a batch is randomly sampled and the chance of the batch being passed for use then depends on the sample passing the sterility test. 

Fig. 23.2 Isolators used for sterility testing. The operator works within the hood which is suspended inside the cubicle the hydrogen peroxide generator which is used to sterilize the isolators is shown in the left foreground. (Courtesy of SmithKline Beecham Pharmaceuticals.)...

All the controls may be conducted either before, or in parallel with, the test itself, providing that the same batches of media are used for both. If the controls are carried out in parallel with the tests and one ofthe controls gives an unexpected result, the test for sterility attempt is recorded as invalid, and, when the problem is resolved, the test is recommenced as if for the first time. It is important to recognize that the terms recommenced and retest have different meanings. A retest may, under certain circumstances, be performed when the first (and, exceptionally, even the second) valid test shows signs of product contamination. 

The British Pharmacopoeia makes an allowance for acddenlal contamination which may arise during the execution of a sterility test by aUowing the test to be repeated. Under these circumstances the following rules apply. 

Several enzymes have important therapeutic and other medical or pharmaceutical uses (Table 25.3). In this section, those enzymes used therapeutically will be described, with section 4 discnssing the applications of microbially derived enzymes for antibiotic inactivation in sterility testing and diagnostic assays. 

Sterile pharmaceutical preparations must be tested for the presence of fungal and bacterial contamination before use (see Chapters 18 and 23). If the preparation contains an antibiotic, it must be removed or inactivated. Membrane filtration is the usual recommended method. However, this technique has certain disadvantages. Accidental contamination is a problem, as is the retention of the antibiotic on the filter and its subsequent liberation into the nutrient medium. 

Breeze A.S. Simpson A.M. (1982) An improved method using acetyl-coenzyme A regeneration for the enzymic inactivation of aminoglycosides prior to sterility testing. JApplBacteriol, 53, 277-284. 

Frozen reference materials have been produced by NIST (Wise et al. 1993). These materials do not have the disadvantages of the oils or freeze-dried materials, but are more difficult to transport. Obviously they have to be kept deep-frozen during transport, which makes their use rather expensive. Since the early 1990 s a new approach in this field has been introduced. This concerned the use of wet, sterilized fish and shellfish samples. These samples, packed in glass jars or in tins, were firstly used in the QUASIMEME program as reference materials for inter-laboratory studies (de Boer 1997). Later, when it appeared that the stability was maintained for longer periods, tests for organic contaminants based on this principle were also prepared. 

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