Issue link: https://www.e-digitaleditions.com/i/1411460
28 Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2021 P h a r mTe c h . c o m Best Practices: Part 1 This is an improvement on the IUPAC 1990 Determina- tion definition in that it more clearly defines the operational steps. However, it requires a more detailed extension to fit with current regulatory expectations. Even where the terms are the same, as in "Test Result", the definitions are not identical as shown in the following: • IUPAC definition: "The value of the characteristic de- termined as a result of a test measurement(s) when de- termined by a specified test method" (4) • ASTM definition: "The value of a characteristic obtained by carrying out a specified test method and can be a result calculated from several observed values" (6). Both guidance documents specify the Test Result as being the value of a characteristic, and yet don't agree on the defi- nition of what a characteristic is, as shown in the following: • IUPAC definition: "A property or attribute of a mate- rial that is to be measured, compared, or noted" (4) • ASTM definition: "A property of items in a sample or population which, when measured, counted or otherwise observed, helps to distinguish between the items" (6). The term definitions from ASTM are shown in Table III. WHO's nomenclature for sampling and testing In 2005, WHO published guidelines for sampling of phar- maceutical products and related materials (7). It focused on only Phases 0 and 1 as illustrated in the right-hand column of Figure 2. Its definitions for the terms used are given in Table IV. The WHO guideline bears similarities to the IUPAC 1990 terminology and, importantly, empathises the need for not only a sampling plan but a sampling protocol and a sampling record. Confusingly, the document uses 'uniformity' for the commonly accepted concept of 'homogeneity' and defines homogeneity, strangely, as "A material is regarded as homo- geneous when it is all of the same origin (e.g., from the same batch) and as non-homogeneous when it is of differing ori- gins" (7). The document also calls the sample ready for the application of the test procedure as the final sample. United States Pharmacopeia requirements United States Pharmacopeia (USP) monographs are standards, not specifications and are mandatory (9). Therefore, in a com- pliance sense, USP is not concerned with Phases 0 or 1 or the batch or lot, but only with compliance of the sample tested with the monograph standard's acceptance criteria. Table II. Definitions for process flow shown in Figure 2, Phases 1 to 3. Adapted from International Union of Pure and Applied Chemistry's Nomenclature for Sampling in Analytical Chemistry (4). Term Definition 1_Consignment A quantity of material transferred on one occasion and covered by a single set of shipping documents. It may consist of one or more lots or portions of lots. The presence of different lots in a consignment is important from the point of view of the sampling plan and the interpretation of the results of analysis 2_Lot A quantity of material which is assumed to be a single population for sampling purposes. A lot may consist of one or more batches. 2_Batch A quantity of material which is known or assumed to be produced under uniform conditions 2-1_Increment(s) Physically comparable units removed from the lot or batch in accordance with the sampling plan. An increment is an individual portion of material collected by a single operation of a sampling device. 3_Primary or gross sample The collection of one or more increments or units initially taken from a population. If the increments are kept separate, these then form a gross sample 4_Secondary or aggregated sample Increments may be combined (composited) to form a secondary aggregated sample 5_Laboratory sample The gross sample(s) or aggregated subsample(s) received by the laboratory 6_Test sample The sample, prepared from the laboratory sample, from which test portions are removed for testing or for analysis 7_Test portion The quantity of material, of proper size for measurement of the concentration or other property of interest, removed from the test sample 8_Test solution The solution prepared by dissolving, with or without reaction, the test portion in a liquid 9_Treated solution or measurement solution The test solution that has been subjected to reaction or separation procedures prior to measurement of some property 10_Aliquot A known amount of a homogeneous material assumed to be taken with negligible sampling error. The term is usually applied to fluids. 11_Measurement The observed value of the characteristic when determined by a specified test method 12_Test result The value of the characteristic determined as a result of a test measurement(s) when determined by a specified test method 13_Determination The entire analytical operation on a single test portion from the measurement of the test portion to the calculation of the analyte content