Controls, sterility testing

Hie AAMI B2 Method The AAMI B2 method assumes far less than the AAMI BI method. It assumes exponential inactivation. It does not assume any standard but arbitrary distribution and it does not require estimation of bioburden. It docs, however, continue to require well controlled sterility testing meth-... 

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. 

M. J. Akers, in Parenteral Quality Control Sterility, Pyrogen, Particulate, and Package Integrity Testing, Vol. 1 (J. R. Robinson, ed.), Marcel Dekker, New York, 1985, pp. 207-209. 

For nonpharmacopeial materials a full specification should be included in the application. This should include appropriate tests and requirements for physical characteristics, identification, relevant purity tests, and performance-related tests. Characteristics likely to influence bioavailability of the finished product should be controlled. Routine tests and specifications should be described. Methods should be validated. The material should be fully characterized, with full data on the chemistry concerned and including consideration of the safety of the excipient. Any relevant European Directive requirements or other international specifications should be met, but additional requirements might apply depending on the intended use of the product—e.g., for materials to be used in sterile products. 

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. 

USP 24 Testing Chapters (51) Antimicrobial Effectiveness Testing, (61) Microbial Limit Tests and (71) Sterility Tests, United States Pharmacopeial Convention, Inc., Rockville, MD, 2000. USP 24 Informational Chapters (1116) Microbiological Evaluation of Clean Rooms and other Controlled Environments, (1111) Microbiological Attributes of Pharmaceutical Articles, (1151) Pharmaceutical Dosage Forms, (1225) Validation of Compendial Methods, and (1231) Water for Pharmaceutical Purposes, United States Pharmacopeial Convention, Inc., Rockville, MD, 2000. 

In a test group the product is subjected to the neutralization method, and then a low level of challenge microorganism (less than 100 cfu) is inoculated for recovery. In a peptone control group the neutralization method is used with peptone or diluting fluid A (Sterility test 71) as the test solution. In a viability group the actual inoculum is used without exposure to the neutralization method. 

This document contains information related to the liquid aseptic fill operation used in the manufacture of (product name), USP, at ABC Pharmaceutical Industries located at (provide postal address). Additional information to support the liquid aseptic filling validation includes but is not limited to environmental monitoring and controls, as well as product-specific testing such as bioburden and sterility testing. The main subsections are ... 

Level V. Level V areas are noncontrolled. They include research and development laboratories, offices, quality control laboratories, microbiological laboratories (with the exception of the sterility test area), lunchroom, toilet facilities, and other nonmanufacturing areas of the facility. 

Area G Sterility test LFH (quality control microbiological lab) Class 100... 

All finished products are tested for sterility in a controlled-access clean room environment in a laminar flow hood, which provides no greater level of a microbial challenge than that encountered in the fill environment. The testing environment consists of a gowning room and sterility test suite that meets the same air quality standards as the hlling suite. 

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. 

Negative controls for SteriDILUTOR, antibiotic membrane hlter, diluting fluid sterility, and all other components of the sterility test should be conducted. 

The negative control contamination rate should be calculated and recorded. The results of negative product control tests facilitate the interpretation of sterility test results, particularly when used to declare a test invalid because of contamination in the negative product controls. 

During each working session (i.e., that uninterrupted period of time in which a sample or group of samples is tested) in which sterility testing is carried out, at least ten negative product control containers should be tested. For a direct inoculation test, these controls should be tested when possible at regular intervals during the test session. 

A suitable negative product control for an aqueous product could be distilled water in a similar container. A negative product control for testing an ointment could be a container of liquid paraffin or ointment base that has been sterilized by dry heat pouring the liquid paraffin from a container would be adequate to simulate squeezing of ointment from a tube. 

Appearance, assay, and degradation products, preservative, and antioxidant content as applicable should be considered for all dosage forms. The microbial bioburden of sterile dosage forms must be controlled and tested in compliance with pharma-copeial and/or internal specifications. The microbial bioburden of nonsterile dosage forms should be controlled, with appropriate sampling and testing. 

Parenteral Quality Control Sterility, Pyrogen, Partioulate, and Paok-age Integrity Testing Third Edition, Revised and Expanded, Michaei J. Akers, Daniei S. Larrimore, and Dana Morton Guazzo... 

Integrity test the filter medium using a sterile 0.1% peptone solution or saline solution to wet the medium. The wetting solution also serves as a negative control sterility check. The entire wetting solution is... 

The entire volume of the challenge filtrate is subsequently forced through a sterility test filter system and incubated in the same manner as the negative control filtrate. 

Compendial micro-organisms—the micro-organisms referenced in the USP for sterility test growth promotion tests—are suitable for use as controls. These include the following ... 

Therefore quality control (QC) testing of vaccines normally includes the following assays, which must be passed prior to material being released for use in preclinical toxicology studies sterility, endotoxin, general safety, identity, mass, potency, purity, and stability [62], These assays should be performed on the final product using the clinical formulation. 

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