Sterilization sterility assurance

Steam Sterilisation and Sterility Assurance Association for Advancement of Medical Instmmentation, Arlington, Va., ANSI/AAMI ST46,1993. 

While the minimum irradiation dose (MID) to achieve a 10" probability of sterility assurance may be calculated by Eq. (2) ... 

Fig. 20.3 Sterility assurance. At Y, there is (literally) 10" bacterium in one bottle, i.e. in 10 loads of single containers, there would be one chance in 10 that one load would be positive. Likewise, at Z, there is (literally) 10 bacterium in one bottle, i.e. in 1 million (10 ) loads of single containers, there is one chance in 1 million that one load would be positive.

For terminal heat processes at 121°C/15 minutes (steam) or 160°C/120 minutes (dry heat), the information required includes time, temperature, and acceptance limits for in-process controls. Validation data are not normally required, but may be requested. For other process conditions, additional information will be required, such as in-process controls and acceptance limits, presterilization bioburden data, and sterility assurance level validation data. 

For sterile products, particular attention should be paid to the choice of an appropriate method of sterilization. Wherever possible a terminal sterilization process should be applied to the product in its final container-closure system, as suggested in the Ph Eur. The preferred options include steam sterilization, dry heat sterilization, and irradiation using the Ph Eur listed conditions (saturated steam at 121°C for 15 minutes dry heat at 160°C for 120 minutes irradiation with an absorbed dose of not less than 25 kGy). Where these cannot be used, the application must include justification for the alternative procedure adopted on the understanding that the highest achievable sterility assurance level should be achieved in conjunction with the lowest practicable level of presterilization bioburden. There is guidance in the form of decision trees as to the preferred options for sterilization method to be applied ... 

Aqueous products moist heat at 121°C/15 minutes then moist heat to achieve a F0 value of not less than 8 minutes to achieve a sterility assurance level of 10 6 then aseptic filtration and aseptic processing then the use of presterilized components and aseptic compounding and assembly... 

Justifications for the use of nonstandard (i.e., nonpreferred or nonpharmacopeial) methods of sterilization may include the heat instability of the active ingredient or an essential excipient. The choice of a method based on filtration through a microbial retentive filter and/or aseptic assembly should be justified, and the appropriate in process controls (including bioburden controls on active ingredients, excipients, bulk solutions, process time constraints etc) discussed in detail in the application. Commercial considerations should not form part of the argument for the application of a nonstandard sterilization process. The highest possible sterility assurance level should be achieved. 

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. 

It provides a high degree of sterility assurance without the intervention of specially qualified personnel. 

Extensive process simulation (broth fill) results for BFS effectively demonstrate that high levels of sterility confidence can be obtained with a properly configured and validated machine. However, in order to maintain high levels of sterility assurance, it is important that levels of microbial contamination are controlled within the filling environment. 

There is no appropriate defined sterility confidence level which can be translated directly into acceptance criteria for broth fill contamination for BFS processes. The most commonly recognized acceptance criterion is a sterility assurance level (SAL) of 10 although modem aseptic filling techniques such as BFS can achieve a higher SAL. This should be reflected by broth fill results and acceptance criteria for this advanced technology. 

This procedure provides the information required to support the sterility assurance of the drug product (product name), USP, manufactured by ABC Pharmaceutical Industries. It references the FDA Guidance titled Guidance for Industry for the Submission of Documentation for Sterilization Process Validation in Applications for Human and Veterinary Dmg Products prepared by the Sterility Technical Committee of the Chemistry Manufacturing Controls Coordinating Committee of the Center for Dmg Evaluation and Research (CDER) and the Center for Veterinary Medicine (CVM) in November of 1994. 

The references used in the development of abbreviated new drug application (ANDA) file should be cited at the end of the sterility assurance report. 

In the second edition, 64 new validation SOPs are added to describe documentation required for sterility assurance, qualification and requalification template reports of major sterile equipments, critical applicable procedures, templates for certification guidelines, media fill procedures, environmental control guidelines, training, and critical environmental performance evaluation procedures. 

The second volume provides 139 template procedures, protocols, and reports that can be downloaded and, after minor changes, adopted. The ready-to-use protocols allow end users to record all raw hard data, further enabling them to prepare final reports. The additional chapters included in this edition provide details on how to ensure sterility and prepare sterility assurance reports. 

Section Val. 1400 provides a unique template on how to prepare and submit sterility assurance and information data for submission to FDA in ANDA and NDA submissions. 

Section Val. 1700 provides 14 exclusive procedures describing critical monitoring operations to ensure sterility assurance. 

The second volume and CD-ROM are designed for individuals specifically involved in writing and execution of master validation plans, development of protocols, and applicable procedures. This book provides a complete, single-source reference detailing conceptual design elements and 139 explicit procedures to provide sterility assurance. 

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