caa a22 4500 477128238 CHVBK 20180405111656.0 cr unu---uuuuu 170330e19970201xx s 000 0 eng 10.1023/A:1012088308307 doi (NATIONALLICENCE)springer-10.1023/A:1012088308307 Bunnell Richard aut Using Computer Simulated Results of a Bulk Drug Substance Assay to Determine Acceptance Criteria for Method Validation [Elektronische Daten] [Richard Bunnell] Purpose. To determine the statistical variability expected for a well designed HPLC assay of a bulk drug substance (BDS). The results are used to develop appropriate acceptance criteria for a method validation protocol as well as to evaluate the level of uncertainty expected for assay results using a variety of sampling/injection schemes. Methods. Computer simulation was used to generate a large quantity of data and the variability of the mock results was evaluated. Error propagation was also calculated, whenever possible, to confirm results obtained from the simulations. Results. Protocol acceptance criteria were developed that were consistent with the expected variability for data resulting from the execution of the validation protocol. In certain cases simulations provided the only avenue of obtaining results that could not otherwise be readily determined. Conclusions. Computer modeling can be used to obtain suitable acceptance criteria for validation results which are consistent with method variability. This is particularly significant in the case of linearity where it has been difficult to develop acceptance criteria based on anything other than analyst intuition and experience. Assay simulations clearly demonstrated that the variability expected for a typical BDS assay is large relative to the average specification range and therefore little insight about relative purity can be gained comparing individual passing assay results. Plenum Publishing Corporation, 1997 method validation nationallicence HPLC assay nationallicence statistics nationallicence computer simulation nationallicence Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 156-163 0724-8741 14:2<156 1997 14 11095 https://doi.org/10.1023/A:1012088308307 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012088308307 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Bunnell Richard aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 156-163 0724-8741 14:2<156 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer