title: Using statistical analysis for setting process validation acceptance criteria for biotech products.
abstract: This paper discusses the challenges of setting process validation acceptance criteria for biotech products for cases where using statistical tools is appropriate. Data are analyzed under three different scenarios that are frequently encountered in biotech applications. Scenario A represents the case when a small data set around center point conditions is available for setting acceptance criteria. Scenario B represents the case when a larger data set within normal operation conditions is available for setting acceptance criteria. Scenario C represents the case when a large characterization data set is available for setting acceptance criteria and it is possible to accurately model the impact of operation conditions on performance of the step. Statistical approaches including mean +/- 3SD, tolerance interval analysis, prediction profiler, and Monte Carlo simulation are applied to the different scenarios. Strengths and shortcomings of the different statistical tools are discussed, and the best approach for each scenario is recommended. It is shown that selection of the right statistical approach is a critical first step toward setting appropriate acceptance criteria.
authors.affiliation: Process Development and Corporate Quality Engineering, Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Wang
authors.forename: Abe
authors.initials: A
authors.lastname: Germansderfer
authors.forename: Jean
authors.initials: J
authors.lastname: Harms
authors.forename: Anurag S
authors.initials: AS
authors.lastname: Rathore
mesh_terms: D001709:Biotechnology / Q000295:instrumentation* / Q000379:methods*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D019544:Equipment Failure Analysis / Q000379:methods*; D015233:Models, Statistical; D011785:Quality Assurance, Health Care / Q000379:methods*; D011786:Quality Control