Sterility tests

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. 

They may also be required in industrial applications where they become part of venting systems on fermenters, centrifuges, autoclaves and freeze-dryers. Certain types of filter (membrane filters) also have an important role in sterility testing, where they can be employed to trap and concentrate contaminating organisms from solutions under... 

Sterility testing Methods Antimicrobial agents 8 Further reading... 

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. 

There are three alternative methods available when conducting sterility tests. 

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.)...

Specific details of the sterility testing of parenteral products, ophthalmic and other non-injectable preparations, catgut, surgical dressings and dusting powders will be found in the British and European pharmacopoeias. 

A sterility test attempts to infer the state (sterile or non-sterile) of a batch from the results of an examination of part of a batch, and is thus a stahstical operation. 

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. 

It can be seen from the above that a sterility test can only show that a proportion of the products in a batch is sterile. Thus, the correct conclusion to be drawn from a satisfactory test result is that the batch has passed the sterility test not that the batch is sterile. 

The techniques discussed in this chapter comprise an attempt to achieve, as far as possible, the continuous monitoring of a particular sterilization process. The sterility test on its own provides no guarantee as to the sterility of a batch however, it is an additional check, and continued compliance with the test does give confidence as to the efficacy of a sterilization or aseptic process. Failure to carry out a sterility test, despite the major criticism of its inability to detect other than gross contamination, may have important legal and moral consequences. 

Absence of microorganisms Sterility test (see also Chapter 23)... 

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. 

Lactamases Bacillus cereus (or other bacteria, as appropriate) Sterility testing, treatment of penicillin-induced allergic reaction 2.4.4, 4.5... 

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. 

The purpose of a sterility test is to determine the probable sterility of a specific batch. The USP lists the procedural details for sterility testing and the sample sizes required [1], The USP official tests are the direct (or culture tube inoculation) method and the membrane filtration method. 

Sterility testing is conducted on each lot of ophthalmic product by suitable procedures, as set forth in the appropriate pharmacopeia and validated in each manufacturer s laboratory. While the majority of ophthalmic preparations contain preservatives for multiple-dose use, sterile preparations in special containers for individual use on a single patient must be made available. This availability is especially critical for every hospital, office, or other installation where accidentally or surgically traumatized eyes are treated, as well as for patients intolerant to preservatives. 

Currently the main application of interest for parametric release is to replace the sterility test as a control method in appropriate cases (given the limited value of that test to predict sterility assurance due to statistical considerations, although it is also pointed out that a sterility test provides a final opportunity to identify a major failure, although other means should provide a more reliable way of detecting such failures). The concept is applicable to well-founded methods of sterilization where the product stability is known and development data have identified the critical process parameters. The measured parameters should be such as to ensure that correct processing of the batch provides sufficient assurance that the sterility assurance level intended has been achieved. 

Even where it is possible to omit routine or even any sterility testing of finished product, the sterility requirement should be retained in the finished product specification. 

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