Issue link: https://www.e-digitaleditions.com/i/1411460
Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2021 31 No guidance is offered on how this sample is to be generated. Specifically, the court judgement found that "Many of the practices the Court condemns today are used in the day-to- day operations of Barr and memorialized in standard oper- ating procedures. Examples include Barr's blend sampling strategy, retesting procedure, outlier technique and reliance on averaging" (15). FDA's requirement is for an original homogenous sample material to be obtained "from a batch and should be suffi- ciently large to accommodate additional testing in the event an OOS result is obtained" (16). This is called the 'laboratory sample 'in IUPAC and 'sample' in ASTM. However, the analytical process flow in the FDA guidance is defined in more detail as described in the following: • "It should be noted that a test might consist of a specific number of replicates to arrive at a result. For instance, an HPLC assay result may be determined by averaging the peak responses from a number of consecutive, replicate injections from the same preparation (usually 2 or 3)." • "The assay result would be calculated using the peak re- sponse average. This determination is considered one test and one result." • "This is a distinct difference from the analysis of different portions from a lot, intended to determine variability within the lot, and from multiple full analyses of the same homogenous sample. The use of replicates to arrive at a single reportable result, and the specific number of replicates used, should be specified in the written, ap- proved test method" (16). Note the specific distinction between individual portions— IUPAC calls them dynamic samples—and composite samples, which are called the homogeneous sample by FDA, sample by ASTM, and combined sample by WHO. The FDA guidance further notes: • "Acceptance limits for variability among the replicates should also be specified in the method." • "The term reportable result as used in this document [FDA guidance] means a final analytical result. This re- sult is appropriately defined in the written approved test method and derived from one full execution of that Figure 2 Comparison of Phase 1 Sampling Nomenclatures ASTM E2282-14 (2019) Defining the Test Result of a Test Method IUPAC Nomenclature for Sampling (1990) Compendium of Analytical Nomenclature (1997) WHO guidelines for sampling Technical Report Series, No. 929, (2005) Annex 4 AAFCO GOODSamples: Guidance on Obtaining Defensible Samples October 2015 Phase 1: Sampling Process to first item in Phase 2 5_LABORATORY SAMPLE 2_LOT or BATCH Increments 2-1 6 _TEST SAMPLE 3_PRIMARY or GROSS SAMPLE Composited increments 1_CONSIGNMENT 4_SECONDARY or AGGREGATED SAMPLE Subsample if required 6 _TEST UNIT 5_SAMPLE 2_ BATCH 6 _FINAL SAMPLE 3_ORIGINAL SAMPLE 1_CONSIGNMENT 5_COMBINED SAMPLE 2_ INCREMENTS 6 _ANALYTICAL SAMPLE 3_PRIMARY SAMPLE 1_DECISION UNIT 5_LABORATORY SAMPLE 7_TEST PORTION 7_TEST SPECIMEN or PORTION 7_TEST PORTION Figure 3. Comparison of sampling process flows from International Union of Pure and Applied Chemistry, ASTM, and World Health Organization.