1. Scope
1. Scope This Standard describes the scientific and risk-based method validation of on-line TOC analyzers to insure suitability for use in pharmaceutical manufacturing applications. The justification for this standard follows. TOC monitoring is required for pharmaceutical water release as defined by USP 643 and EP 2.2.44 and is commonly used for cleaning validation. Laboratory TOC measurements are currently relied upon to fulfill these needs. Laboratory TOC methodologies have been validated through ASTM, EPA and other groups for use in drinking and wastewater analysis. Transitioning from laboratory to on-line TOC is a common focus for pharmaceutical companies implementing PAT initiatives due to the significant potential for improving both quality and manufacturing efficiencies. Inhibiting this transformation is the lack of a common scientifically based approach for online TOC method validation. The standard will provide the industry with a validation procedure applicable to online instrumentation that will allow pharmaceutical manufacturers to critically evaluate the performance of various technologies so that they can make an informed decision about which technology meets their needs. The gap that exists today, that this standard plans to address, is that although the elements of a scientifically-based validation protocol currently exist (e.g., ICH Q2B), there is no guidance for the industry as to how to apply it to online technologies.
2. How does this fit into the mission/scope of E55? TOC is a commonly used methodology in pharmaceutical quality control, for purified water release and cleaning validation. There is a high level of industry interest in utilizing online TOC analyzers in lieu of or in combination with laboratory TOC analyses in an effort to improve manufacturing efficiency. This standard defines a practice by which one can validate the performance of a PAT tool methodology (on-line TOC analyzer) before using it in a PAT system. 3. Practice Overview This Practice Standard describes a scientific and risk-based method validation of on-line Total Organic Carbon (TOC) analyzers for use in pharmaceutical manufacturing applications. The Method Validation Standard Practice will consider the specific application needs inherent in measuring TOC in Pharmaceutical bulk manufacturing and cleaning validation waters representing actual conditions of use. The Practice will articulate the test protocols, test compounds and concentrations, necessary test equipment, and inter-laboratory or inter-factory tests and result reporting. It will include acceptable test apparatus specifications for function, accuracy, and precision. A list of possible test organic compounds with an explanation of their appropriate use will be provided to insure the tested on-line TOC method is properly evaluated. The selected organic test compounds will be sufficient to insure the tested on-line TOC methodology is suitable for compendial bulk TOC limits, cleaning validation, or a combination of both in pharmaceutical applications. Accuracy and precision test requirements will be specified for acceptable on-line TOC methodologies. Precision and bias test requirements will be specified for inter-laboratory or inter-factory studies. Future Test Methods for various on-line TOC methodologies that meet the requirements of this Practice Standard will be embedded (or referenced) within this Standard.
Keywords
pharmaceuticals; TOC
The title and scope are in draft form and are under development within this ASTM Committee.
Citing ASTM Standards
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