Product sterility test

An anaerobic condition exists if there is need for sterile inert gas to break the vacuum on the chamber and remain in the container after sealing. The use of anaerobic medium (e.g., alternative fluid thioglycolate medium) would be appropriate where the presence of anaerobic organisms has been confirmed in either environmental monitoring or, more likely, during end product sterility testing. 

The incubation period should be not less than 14 days per procedure. An incubation temperature in the range of 20 to 35°C may be used depending upon information gained from the environmental monitoring (during routine production, sterility testing, and media filling). 

Increased incidence of product sterility test failures... 

The integrity of the product container/closure is assessed by physical tests or microbiological challenge tests and long-term product sterility tests. These tests are specific for container size, fill volume, and closure type. All integrity tests are performed after sterilization and are defined in manufacturing site SOPs. 

All media should be preincubated for 14 days at appropriate test temperatures to demonstrate sterility prior to use. Alternatively, this control test may be conducted concurrently with the product sterility test. Media sterility testing may involve a representative portion or 100% of the batch. 

Additional tests in response to adverse trends or failures in the ongoing monitoring of the facilities or process, such as (1) continued critical area environmental monitoring results above the action levels or (2) an increased incidence of product sterility tests failures or to evaluate changes to procedures and practices, such as... 

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. 

These major limitations demonstrate that reliance on end-product sterility testing alone in ascertaining the sterility of a parenteral product may lead to erroneous results. One purpose of validation in the manufacture of sterile products is to minimize this reliance on end-product testing. Three principles are involved in the validation process for sterile product. 

To provide greater assurance and support of the results of the end-product sterility test... 

Institute a documented monitoring system primarily relying on biological indicators, with lesser reliance on end-product sterility testing. 

Mascoli, C. C. Should end-product sterility testing continue Med Dev Diag bid 3 8-9 (1981). 

The end-product sterility test suffers from at least... 

The contaminated bottles were not detected by end-product sterility testing. The batch was released to a wholesaler and distributed to the Devonport Section of Plymouth General Hospital in March 1972. The high concentrations of microorganisms found in the infusion fluid can be attributed to the period of time betweeit sterilization, distribution, and final administration to the patients. 

The prime purpose of sterile filtration is to produce a sterile effluent that has not been altered as a result of the process of sterilization. Within these considerations. validation must address the performance of both the filler media and the whole filtration unit including housings, seals, connections, etc., versus its practical application. As with any other sterilization process, the continued effectiveness of sterile filmuion cannot be assumed without confirmation from routine monitoring end-product sterility testing (or testing for nonsteriiity) is unsuited for this purpose. 

The price of parametric release is in process control. The requirement to control processes is critical. There is no defence to the legal barrier discussed above if the sterility test is dropped in favor of process controls that are inadequate. Processes should not only be controlled but monitored, and there must be predetermined standards for process characteristics, and these standards must be met, or product must be rejected. Parametric release is an all-or-nothing condition—there is no way that a batch of product can be tested and released by an end-product sterility test if satisfactory process criteria are not met. 

By and large it is in the control of bioburden that opinions differ. Batch-by-batch sampling and monitoring of product bioburden prior to sterilization is one route. Much of the commercial advantage of parametric release is lost if this expedient is adopted. Without due attention to process control criteria, product bioburden control prior to sterilization is as statistically and technically flawed as end-product sterility testing. 

Where authorization for parametric release has been issued pursuant to paragraph C.0l.065(b)(ii), end product sterility testing is not required. 

Microbial ChaUenge/Product Sterility Test Methods. There are really two types of microbial barrier test those performed on materials and those performed on whole packages. Microbial barrier... 

Aerosol Challenge. At the risk of oversimplifying the procedural demands of microbial testing, here is a summary of how a microbial challenge/product sterility test is performed. There are two types of whole-package microbial barrier tests currently in use. 

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