 Application in Process Development 2.

Hold some factors constant

- Improve process yield  Ex. Raw material type/ supplier
- Reduce variability  Selecting Factor Level Values
- Reduce development time - Spanning entire region likely to yield the
- Reduce overall costs most understanding
 Applications of Experimental Design  If factor’s level are close, measured
- Evaluate and compare alternatives effect may be statistically
- Evaluate material alternatives insignificant
- Product robustness - Moving off currenr operating points
- Determine key design parameters presents a risk
- Formulation of New Products  Probing techniques: Response
 Basic Principles Surface Analysis Evolutionary
- Replication Operation (EVOP): converge on best
1. Error Estimation Solution
2. Accuracy  Effects of Aliasing : Confounding
- Blocking - Aliased Parameters are CONFOUNDED
1. Unimportant Signigicant Error  Cannot be estimated independtly of
2. Precision one another
- Randomization  Estimates are linear combination of
1. Independence confounded parameters.
2. Even out uncontrollable factors - Aliasing creates other confounded pairs
 Steps  If ABC = D, then A=BCD ; B=ACD;
- Problem statement C=ABD; AB=AD; AC=BD; AD=AC
- Choice of factors,levels,and ranges  Desirable Designs
- Choice of response variable - Provide sufficient distribution of
- Choice of experimental design information throughout region of interest
- Performing the Experiment - Provide model that predicts the response,
- Statistical Analysis as close as possible to true response, at all
- Conclusions and Recommendation points within region of interest
 Resource Allocation - Provide ability to detect model lack of fit
- Don’t commit all resources to one design  Design Performance Considerations
1. Start with Screening Design - Number of runs
2. Only 25% of resources on any one - Design Resolution
experiment - Minimum Detectable Effect
- Learn from each design - Orthogonality & Balance
1. What did you do wrong? - Other : D-Optimal, A-Optimal & G-Optimal
 Excluded factors,wrong conditions ,  Orthogonality
etc. - Orthogonality refers to the property if a
2. What to do next? design that assures that all specified
 Sometimes next stage of parameters may be estimated
improvement isn’t worth cost of independently of any other
another experiment - Some wrutes lump balance as part of
 Selecting Factors orthogonality
- For each response , brainstorming likely  Balance
factors - Balance implies data is properly distributed
- For screening , if more than 5-7 factors over design spare
1. Reduce factor list through ranking  Uniform physical distribution
 Nominal Group Technique,  An equal number of levels of each
Prioritization Matrix factor
 - Some design sacrifice balance to achieve  These design are used to investigate
better distribution of variance or predicted which factors are important
error - “ Response surface designs “
 Ex: Central Composite  These designs are used to determine
- Balance may be sacrificed by avoiding the optimal settings of the
extreme combinations of factors significant factors
 Ex: Box-Behnken
 Sample Designs
- Box Behnken
- Placket Burman
- 2^k designs (fractional, confounding, fold
over, projection)
- 3^k designs
- Mixed level Designs
- Latin Squares
- Central Composite( with axial Points)
- John’s ¾
- Nested Designs
- Split Plots
- Simplex Lattice Design
- Simplex Centroid Design
- D-Optimal
- A-Optimal

 Modern approach: DOE

- DOE= Design of Experiments
- Key Ideas
 Change several factors
simultaneously
 Carefully choose which runs to
perform
 Use regression analysis to obtain
effect estimates
- Statistical Software (Statgraphics,JMP,SAS,)
allows to
 Choose or construct designs
 Anlayse experimental results
 Short History of Statistics and Experimentation
- 1920’s – introduction of statistical methods
in agriculture by Fisher and co-workers
- 1950’s – introduction in chemical
engineering
- 1980’s – introduction in Western industry of
Japanese approach ( Taguchi,Robust design)
- 1990’s – Combinatorial chemistry , high
throughput processing
 Types of Experimental Designs
- Screening Designs