September 2016Carrying out a DOE correctly requires that runs be randomized whenever possible to counteract the bias that may be introduced by time-related trends. If complete randomization proves to be impossible, however, a specialized form of design—called a split plot—is useful because of its ability to effectively group hard-to-change (HTC) factors. It accommodates both HTC and easy-to-change factors in the design.Authors: Mark J. Anderson
Publication: Chemical Engineering
A generic pharmaceutical manufacturer recently hired VerGo Pharma Research Laboratories Pvt. Ltd to develop a bioequivalent with different polymorphic forms for an anti-depressant drug that had previously been patented in crystalline form only. Bioequivalence requires that a drug be pharmaceutically equivalent and that it be delivered at the same rate and same level of bioavailability so that its efficacy and safety can be expected to be the same as the original product. By using design of experiments (DOE) to reduce the number of tests required (to determine the effects of inactive ingredients on bioavailability in both fed and fasting conditions), VerGo was able to cut the development process from several years to only four months.
A variation of this case study was also printed in R&D magazine, July 2016, as Scientists Develop Bioequivalent Drug in Months instead of Years.
See also How Design of Experiments Can Improve Formulation Development by Jerry Fireman, March 2016, Scientific Computing magazine.Authors: Subrata Kundu
Publication: Pharmaceutical Manufacturing
March 2016By sizing experiment designs properly, test and evaluation (T&E) engineers can assure they specify a sufficient number of runs to reveal any important effects on the system. For factorial designs laid out in an orthogonal matrix this can be done by calculating statistical power (Anderson and Whitcomb, 2014). However, when a defense system behaves in a nonlinear fashion, then response surface method experiment (RSM) designs must be employed (Anderson and Whitcomb, 2005). The test matrices for RSM generally do not exhibit orthogonality, thus the effect calculations become correlated and degrade the statistical power. This in turn leads to inflation in the number of test runs needed to detect important performance differences that may be generated by the experiment. A generally acceptable alternative to sizing designs makes use of fraction of design space (FDS) plots. This article details the FDS approach and explains why it works best to serve the purpose of RSM experiments done for T&E.Authors: Mark J. Anderson, Wayne F. Adams, Pat J. Whitcomb
Publication: ITEA Journal
November 2015A pilot plant usually plays a key role in process development by providing essential data related to operation, safety, scale-up and other issues. The value of the pilot plant depends on the validity of the data captured. Planned experimentation is crucial to gathering meaningful data, and design of experiments (DOE) is the gold standard for finding results which are statistically significant.Authors: Ron Stites
Publication: Chemical Processing
This article offers a five-step method to finding the optimum or ‘best’ weld. The method detailed below utilizes a statistical tool known as the two-level factor approach. This well-tested method will assist an investigator in identifying what is to be optimized, choosing inputs for evaluation, running the tests so that statistically significant data is generated, analyzing data, and finally determining the settings for the significant inputs which result in the optimum weld.Authors: Chris Bertoni
Publication: Welding Design & Fabrication
Learn how DoE can help save time and money in process design and optimization with this primer. (To read this article, sign up for an account at http://www.chemengonline.com/chemical-engineering-magazine .)Authors: Wilhelm Kleppmann
Publication: Chemical Engineering Magazine
June 2014An industrial equipment supplier wanted to find the best operating conditions, as well as determine what performance its product could deliver for ethanol producers, before putting the device on the market. A DOE was run to successfully identify and validate a measurement method that has enabled the supplier to accurately evaluate the performance of the new product in a large number of plants under a wide range of operating conditions.Authors: Stites, Ron
Publication: Ethanol Producer Magazine
June 2014OMG Borchers used the design of experiments method to develop a mixture experiment to screen the effects of four candidate additives. The challenge was to find a second source for an associative thickener used in a family of waterborne coatings that matched the properties of the incumbent thickener in three different classes of products with a different chemical composition than the incumbent.Authors: OMG Borchers
Publication: Paint & Coatings Industry Magazine
March 2014Due to operational or physical considerations, standard factorial and response surface method (RSM) design of experiments (DOE) often prove to be unsuitable. In such cases a computer-generated statistically-optimal design fills the breech. This article explores vital mathematical properties for evaluating alternative designs with a focus on what is really important for industrial experimenters. To assess “goodness of design” such evaluations must consider the model choice, specific optimality criteria (in particular D and I), precision of estimation based on the fraction of design space (FDS), the number of runs to achieve required precision, lack-of-fit testing, and so forth. With a focus on RSM, all these issues are considered at a practical level, keeping engineers and scientists in mind. This brings to the forefront such considerations as subject-matter knowledge from first principles and experience, factor choice and the feasibility of the experiment design.Authors: Anderson, Mark J.; Whitcomb, Patrick J.
Publication: Journal of Statistical Science and Application V2, N3, March, pp 85-92
This article provides insights on how many runs are required to make it very likely that a test will reveal any important effects. Due to the mathematical complexities of multifactor Design of Experiments (DOE) matrices, the calculations for adequate power and precision (Oehlert and Whitcomb 2002) are not practical to do by 'hand' so the focus is kept at a high level--scoping out the forest rather than detailing all the trees. By example, reader will learn the price that must be paid for an adequately-sized experiment and the penalty incurred by conveniently grouping hard-to-change factors. (The article is not available on the ITEA Journal web site without membership. Click on the Download PDF link below to view the manuscript.)Authors: Anderson, Mark J.; Whitcomb, Patrick J.
Publication: The ITEA Journal
In an effort to recover additional copper and gold at KGHM International’s Robinson Mine located near Ruth, Nevada, an in-plant study was undertaken to quantify potential flotation recoveries from the concentrator’s final tailings stream. Tests were conducted by passing a small continuous sample of final tailings through a single 1.5 m3 FLSmidth XCELL™ demonstration flotation machine. This paper reviews the results obtained from the in-plant testing with the single 1.5 m3 flotation cell and provides a comparison to the subsequent operational performance of multiple 160 m3 flotation machinesAuthors: Redden, Lorin; Stevens,Chase; O’Brien, Mark; and Bender, Thomas
Experimental design, modeling, and data analysis methods for mixture experiments provide for efficiently determining the component proportions that will yield a product with desired properties. This article presents a case study of the work performed to develop a new rubber formulation for an o-ring (a circular gasket) with requirements specified on 10 product properties. Progress in Rubber, Plastics and Recycling Technology, Vol. 29, No. 3, 2013
Note: If interested, you may contact one of the authors, Greg Piepel, Ph.D., for a copy of the paper.Authors: Kaya, Yahya; Piepel, Greg F.; and Caniyilmaz, Erdal
Publication: Progress in Rubber, Plastics and Recycling Technology
Researchers improved the performance of an isolated ketoreductase (KRED) enzyme using directed evolution, and also performed two stages of design of experiments (DOE) to identify and optimize key process variables.Authors: Collier, Ph.D., Steve
Publication: Pharmaceutical Manufacturing
Design of experiments (DoE) incorporates statistical methods and multivariate analysis into microscale chemistry. Controlled experiments help analysts evaluate processes with that involve several variables, such as temperature and osmolality in cell culture processes. Often three variables are studied together, with the results expressed in a three-dimensional response-surface graphsAuthors: Scott, Cheryl
Publication: BioProcess International
Resin manufacturer Interplastic Corp. Thermoset Resins Div. (St. Paul, Minn.), a major gel coat producer, recently developed a new gel coat with the aid of Design-Expert design of experiments software from Stat-Ease Inc.Authors: Black, Sara
Publication: Composites Technology