Purity test procedure

Laboratory controls should include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures to ensure that raw materials and containers conform to established standards of quality and purity. Specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, including any minor changes, should be updated by the appropriate organizational unit and reviewed and approved by the QC unit. Laboratory controls should be followed and documented at the time of performance. Deviations from written specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms should be documented and justified. 

Now I would like to turn to some of the issues of operations within the manufacturing process itself and speak to certain process controls that are expected. In a chemical synthesis sequence, as I mentioned above, intermediates will need to be fully characterized. That characterization will then lead to a set of specifications for the intermediate, that is, its level of purity, its form, etc. Test procedures that demonstrate that the intermediate meets specifications must be established. Some intermediates are deemed to be more important than others and are given specific designation, such as pivotal, key, and final intermediates. In those cases, it is necessary to demonstrate that the specific and appropriate structure is obtained from the chemical reaction and that the yield of the intermediate is documented and meets the expected yield to demonstrate process reproducibility and control. Purity of the substance is to be appropriately documented. And, finally, in reactions which produce pivotal, key, and final intermediates, side products or undesirable impurities are identified and their concentrations measured and reduced by appropriate purification procedures so that the intermediate meets in-process specifications. Thus, those important intermediates become focuses of the process to demonstrate that the process is "under control" and functioning in a reproducible and expected manner. All of these activities ultimately are designed to lead to the production of the actual active ingredient which is referred to then as a "bulk pharmaceutical agent." That final product will need to be completely characterized which then will document that it meets a set of specifications ("Final Product Specifications") for qualification as suitable for pharmaceutical use. 

Type of analytical procedure characteristics Identification Impurities purity test Assay content/potency... 

Changes in input material This is an active and growing area of industrial research and development. Less toxic substitute products are being developed and tested. Procedures for increasing the purity of raw materials include material purification and material substitution. 

The requirements are as follows (1) the substance is permitted for use in food or in food processing in the United States (or, in certain cases, in other countries in which FCC specifications are recognized), (2) it is commercially available, and (3) suitable specifications and analytical test procedures are available to determine its identity and purity. 

Years of doing things the same way does not validate correctness. Many chemical tests have been proven incorrect over a period of time. Newer techniques like thin layer chromatography (TLC), high performance liquid chromatography (HPLC), capillary electrophoresis (CE) and mass spectrometry (MS) have revolutionized our standards of purity. So, too, should this testing procedure prove to be. 

As required by regulatory authorities [1-3, 6] and International Conference on Harmonisation (ICH) guidelines [7], analytical method validation is especially important in establishing the assay methods and procedures of quantitative or semi-quantitative measurement of target substances or compounds. Among the specification items for drug products, assay, content uniformity, and dissolution are typical of those which require almost full analytical validation. The purity test, related... 

The final product must be free of adventitious agents that primarily include bacterial or viral pathogens and other biologic contaminates contributed during cell culture, such as DNA from prokaryotic or eukaryotic host cells and endotoxin. Purity testing for these factors must be performed throughout the production procedure and meet defined criteria before administration into humans. 

Specifications for the finished product Two specifications at release and end of shelf-life List general characteristics, specific standards tests and limits for results for the finished product must be provided Analytical test procedures described (physicochemical properties, identity of API) Quantitative determination of active, deviations, purity tests, pharmaceutical tests, colouring antimicrobial or chemical preservatives, results of validation studies, comments on the choice of routine tests and standards provided Copy of pharmacopoeia monograph and verification data Results of batch analysis (inc. date of manufacture, place of manufacture, batch size and use of batch tested) ... 

For substances that cannot be properly characterized or products for which an exact analysis of the purity cannot be determined through routine analytical methods, the applicant should propose and justify alternative testing procedures. 

This form was designed specifically for routine analyses to test for the identity and purity of large numbers of pharmaceutically active ingredients and intermediates. The samples are weighed out on an analytical balance with no printer. All operating procedures are given in a valid testing procedure. 

Laboratory controls should include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures to ensure that raw materials, intermediates, APIs, and containers conform to established standards of quality and purity. 

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