Sterility testing random sampling

For parenteral use, the antibiotic is packed in sterile vials as a powder (reconstituted before use) or suspension. For oral use it is prepared in any of the standard presentations, such as film-coated tablets. Searching tests are carried out on an appreciable number of random samples of the finished product to ensure that it satisfies the stringent quahty control requirements for potency, purity, freedom horn pyrogens and sterility. 

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. 

Wearing sterile gloves and a clean lab coat, collect 20 random samples of the vials to be tested. Place in a sterile container for transport to the microbiology lab. 

Unlike many dosage form specifications, the sterility specification is an absolute value. A product is either sterile or nonsterile. Historically, judgment of sterility has relied on an official compendial sterility test however, end-product sterility testing suffers from a myriad of limitations [1-4], The most obvious limitation is the nature of the sterility test. It is a destructive test thus, it depends on the statistical selection of a random sample of the whole lot. Uncertainty will always exist as to whether or not the sample unequivocally represents the whole. If it were known that one unit out of 1000 units was contaminated (i.e., contamination rate = 0.1%) and 20 units were randomly sampled out of those 1000 units, the probability of that one contaminated unit being included in those 20 samples is 0.02 [5], In other words, the chances are only 2% that the contaminated unit would be selected as part of the 20 representative samples of the whole 1000-unit lot. 

The number of units sampled for the test varies according to the following factors (1) the number of units per batch, (2) the fill volume of the container, and (3) the method of product sterilization. Generally, 10-20 units are randomly sampled from the lot. If the lot size is between 20 and 200 units, then n = 10. 

However, the results show that if two tins are taken at random for testing there is a probability of 99.6% that the contamination would not be detected, whilst if the number of samples rises to four the probability of non-detection is still over 99%. The results also show that if varying sample sizes are used (for a given level of contamination), then as the sample size increases, the probability of the batch being passed as sterile falls. It is therefore important to point out that, as sterility testing only tests samples from a batch, the conclusion is not that the batch is sterile, but that the batch has passed the sterility test. There is obviously an important difference between the two. 

The difficulty in demonstrating quality is that the tests carried out are designed to detect its absence. For example, the test for sterility (Chapter 20) involves taking samples at random and testing for microorganisms. The absence of microorganisms only allows an estimate of the statistical probability that the batch is sterile. Therefore it is important that a product be manufactured in a suitable environment by a procedure that minimizes the possibility of contamination occurring. At the end of this process the tests can be performed as an additional measure. 

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