Statistical Applications for Chemistry, Manufacturing and Controls (CMC) in the Pharmaceutical Industry

Native size-exclusion chromatography-mass spectrometry: suitability for antibody–drug conjugate drug-to-antibody ratio quantitation across a range of chemotypes and drug-loading levels

“…The approach taken was to perform a method bridging evaluation that uses a statistically derived equivalence acceptance criteria (EAC) to define the magnitude of difference between the two methods that is practically important. 29 System suitability data for HIC were used to define mathematically based EACs because these data are expected to most accurately reflect expected method variability. Based on the HIC system suitability data, the EAC was ±0.08.…”

“…The EAC was calculated as 2 times the 80% upper confidence bound on the total variance in historical HIC system suitability data (n = 45). 29 The difference in SEC-MS and HIC means, along with a 90% CI on the difference, was calculated using data from an accuracy experiment where each sample was tested with both methods (n = 9 per method). Two one-sided t-tests were used to assess equivalence such that the 90% CI was compared to the EAC range.…”

“…HIC from two different lots tested at different times, where SEC-MS data were generated on one lot (n = 43) and HIC data were generated on a different lot (n = 45). The 90% CI on the ratio of variance was calculated using equation 2.66 in Burdick et al 29 The estimated ratio of variances is 0.2946. The upper 90% confidence bound on the ratio of variances is 0.5667, indicating that the variance of the SEC-MS method is approximately 57% of the total variance present in the HIC method.…”

Strategies for Setting Patient-Centric Commercial Specifications for Biotherapeutic Products

“…More recently, Bayesian statistical analysis may be used to compute limits, generating a probability distribution of a future reportable value a combination of prior knowledge and historical data, particularly when data is limited. 42 The specific statistical method used to derive a limit is of secondary importance: understanding of process capability must be derived from data that captures future sources of variation to reduce risk of problems in the future.…”

The current state of Bayesian methods in nonclinical pharmaceutical statistics: Survey results and recommendations from the DIA/ASA‐BIOP Nonclinical Bayesian Working Group

“…These areas include preclinical discovery, nonclinical development, translational science, safety, pharmacology, and chemistry, manufacturing and controls (CMC). Common CMC functions include assay validation, process optimization and control, dissolution testing, shelf‐life assessment, comparability studies, and specification setting 9‐12 . The nonclinical space is ideally suited for the application of Bayesian methods.…”