Introduction
- DoE and Quality by Design
- Regulations (EU and FDA)
- A factorial experiment
- DoE vs one-at-a-time experiment
- Where is DoE applied in development and validation of analytical methods
- Where is DoE applied in manufacturing process
- development and validation
DoE by Hand Calculations: Effects and Interactions
- Factorial experiments (categorical and numeric factors)
- Two and three factorial designs
- Manual calculation of main effects
- Manual calculation of interactions
- What is an orthogonal DoE
- Exercises with Excel
Acquaintance with Minitab
- Basic structure of Minitab software
- Input of data
- Running a DoE
- Plotting output results
- Practicing with Minitab
Basic Statistical tools for Interpretation of DoE Output
- F-Test
- t-Test
- p-value
- ANOVA
- Diagnostics for goodness of fit to model
- Exercises with Excel
Are the Factors Significant?
- Deviations from normality plot
- Making replicate experiments
- Adding experiments at centre points
- Using known variability
- Exercises with Excel
Full Factorial DoE Experiments with Minitab
- Two factor full DoE experiments
- Interactions between two factors
- Plotting Main effects and Interactions
- Interpretation of DoE Minitab output
- Does the linear fit the model?
- Significance with p values
- General full factorial DoE
- Exercises with Excel
- Exercises in interpretation of Minitab outputs
Screening Design Experiments with Minitab
- Two and three factor experiments with Minitab
- Aliasing in DoE experiments
- Resolution of DoE experiments
- 4-7 fractional factorial DoE
- Blackett-Burmann designs
- Definitive screening design
- Exercises with Minitab:
- Robustness of HPLC method with fractional DoE
- Optimisation of a process with fractional DoE
Optimisation with Response Surface Methodology
- 22 factorial experiments with RSM
- Contour plot
- Surface plot
- Concept of Design Space
- Exercises: optimization of drug solubility with RSM design
- Effect of process parameters on dissolution assay and variability
Case Study DoE: Development of a Medicinal Product
- Why we use DoE in the pharmaceutical development?
- Example: DoE for formulation selection / optimization
- Example: DoE for manufacturing process optimization
- DoE vs “traditional” approach – when to use which?
Strategy of DoE in Drug Development Process
- Screening experiments
- Fractional experiments
- Full factorial experiments
- Optimisation experiments: Surface Response Methodology
- Design Space versus Proven Operating Range (PAR)
- Normal Operating Range (NOR)
- Robustness of experiments of a process/method