1.1Background
1.2Biopharmaceutical Development
1.3Statistics in Bioprocess Development
1.4Statistical Inferences
1.4.1Example
1.4.2Random Variables
1.4.3Continuous Distributions
1.4.3.1Gaussian Distribution
1.4.3.2Student’s t-Distribution
1.4.3.3Chi-Square Distribution
1.4.3.4F-Distribution
1.4.4Discrete Distributions
1.4.4.1Binomial
1.4.4.2Poisson
1.5Sampling Considerations
1.5.1Non-Random Sample
1.5.2Simple Random Sampling
1.5.3Stratified Sampling
1.5.4Systematic Sampling
1.6Statistical Estimation
1.6.1Point Estimate
1.6.2Interval Estimation
1.6.2.1Confidence Interval
1.6.2.2Prediction Interval
1.6.2.3Tolerance Interval
1.7Hypothesis Testing
1.7.1Type I and Type II Errors
1.7.2Significance Test
1.7.3Statistical Significance
1.7.4Equivalence Test
1.7.4.1Issues with Significance Test
1.7.4.2Alternate Test
1.8Sample Size
1.8.1Sample Size for Estimation
1.8.2Sample Size for Significance Test
1.8.3Sample Size for Equivalence Test
1.9Selection of Method for Data Analysis
1.9.1Example
1.9.2Test Model Assumptions
1.9.2.1Q–Q Plot
1.9.2.2Nonparametric Test
1.9.3Data Transformation
1.10Removal of Outliers
1.10.1Definition
1.10.2Outlier Tests
1.10.2.1Grubbs’ Test
1.10.2.2Dixon’s Test
1.10.2.3Other Outlier Tests
1.10.2.4Model-Based Method
1.11Bayesian Inference
1.12Concluding Remarks
References
1.1Background
The biopharmaceutical industry is strictly regulated. According to governmental regulations, before marketing approval of a new drug by regulatory agencies such as the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), the drug must be shown to be both safe and efficacious (Peltzman 1973). For this reason, sufficient clinical and non-clinical data are generated in support of the premarketing approval. Furthermore, regulations such as the U.S. current Good Manufacturing Practice (cGMP) also stipulate that modern standards and technologies be adopted in the design, monitoring, and control of manufacturing processes and facilities to ensure a consistent supply of high-quality drug products to the consumer or public (FDA 1995). These include use of statistics for process validation, justification of process changes post-approval, product release testing, and root cause analysis. Adherence to government regulations such as cGMP is an essential step in ensuring a consistent supply of high-quality drug products to patients, as shown in following sections.
1.2Biopharmaceutical Development
Bioprocess development is an integral part of the overall biopharmaceutical research and development phases. For a biological drug to be tested in preclinical and clinical studies, it has to be formulated to ensure bioavailability and hence the activity...
