Expert Details

Statistics (Pharmaceuticals (CMC): Design of Experiments, Process Validation, Stability)

ID: 731170 New Jersey, USA

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After receiving a Expert in statistics, expert has worked in the pharmaceutical industry for over 30 years as a non-clinical statistician applying statistical methodologies, performing data analysis, and interpreting results with scientists in research and development. He collaborated with scientists from many different areas including formulation, stability, process and analytical chemistry, quality control, and regulatory to apply appropriate statistics to develop new drugs. Projects have included optimizing formulations, applying Quality by Design principles, defining a "design space," validating analytical assays, identifying sources of variability, developing sampling plans, designing and analyzing stability studies, proposing specifications, responding to regulatory (internal/external) questions, and involvement with internal investigations. Many statistical methodologies were used to complete these projects including design of experiments, analysis of variance, variance components, sampling strategies, regression analysis, and in some cases, developing new methodology to solve specific problems.

Expert has been a member of the American Statistical Association for over 35 years. Over these years, his expertise in statistics has developed as a result of many professional activities such as membership on the Pharmaceutical Research and Manufacturers of America (PhRMA) Expert Statistics Team (chair for two years) and Biostatistics Steering Committee, chair of the Midwest Biopharmaceutical Statistics Workshop, member of the Product Quality Research Institute (PQRI) Container Closure Work Group, director of a Pharmaceutical Education & Research Institute (PERI) non-clinical training course, and member of ASTM International. He has displayed his knowledge of statistics by presenting at various conferences, including the American Statistical Association (ASA), International Society for Pharmaceutical Engineering (ISPE), FDA/Industry Workshop, PQRI workshop, New Jersey Pharmaceutical Association for Science and Technology(NJPhast), NJ Chromatography Group, Institute of Validation Technology, IBC Life Sciences Conference, IFPAC, Pharm Ed Resources, ISPE/FDA CGMP, and Parenteral Drug Association (PDA), on statistical topics such as design of experiments, analytical method validation, process validation and evaluation of dosage unit content uniformity.

In addition to demonstrating knowledge of applied statistics by working with scientists, involvement with professional groups, and presentations, he has co-authored articles with scientists and/or other statisticians covering a range of topics such as Design Space Development, content uniformity (methods and evaluation), process validation, and packaging. A chapter on Quality by Design for Analytical Methods is in the publication process (expected later in 2013).

Expert has developed a methodology used by pharmaceutical companies to evaluate data gathered during process validation. The method has resulted in ASTM standards (E2709 and E2810). To implement the methodology, he wrote a SAS software program to perform the computations and create tables for the user as well as led a team to validate the program.

Expert has worked in the non-clinical statistics area or Research and Development providing statistical collaboration with scientists from drug formulation, analytical chemistry, synthetic chemistry, drug stability, and manufacturing. One of the primary areas of collaboration was design and analysis of experiments. Designs were used for many purposes including optimization of formulas, methods, or processes, ruggedness, process understanding, implementation of Quality by Design, and defining a "design space." Commonly used designs were factorials, fractional factorials, split plots, nested, and response surface. He developed an 'in-house' design of experiments class at Bristol-Myers Squibb that was offered and well attended for over 10 years. The class included basic statistics, factorial designs, and advanced topics such as response surfaces, Design Space, and mixture designs.

During the 1990's, he was director of a Professional Education and Research Institute (PERI) training class for non-clinical statisticians in the pharmaceutical industry. The course consisted of speakers from industry and the FDA in all areas of non-clinical biostatistics such as experimental design, stability, animal pathology/toxicology studies, drug discovery, and analytical method validation. Expert taught the experimental design session providing examples of commonly used designs used in non-clinical statistics, "real" examples based on his experience, and consulting tips.

As a member of the PhRMA Statistics team, he co-wrote a series of three articles on statistical considerations in design space development. He wrote the section on statistical experimental design.

Recently, expert co-wrote a chapter entitled "Application of quality by design (QbD) to the development and validation of analytical methods" for the book "Specification of Drug Substances and Products" published in 2013. He wrote the section on Empirical models: DOE (screening, modeling, robustness) as well as a subsection providing general advice on design and analysis of experiments. He also performed the analysis for an example that is given in the chapter to show how to apply design of experiments using QbD principles.

Expert has also been involved with statistical design and analysis used for analytical method validations. He developed statistical methods and wrote an Excel program used by analytical chemists for validation. He was an invited speaker at an IBC Life Sciences Conference in London entitled "Achieving excellence in analytical method validation" where he presented these statistical methods.

Expert has been involved with applying statistics for process validation since the 1980's. This includes sampling plans as well as statistical tests and acceptance criteria. He developed and published a method for evaluating data collected during process validation such as content uniformity and dissolution that provides a statistical statement that passing the method criteria insures passage of the regulatory standard with a desired level of confidence. He also published a method that can be used for large sample sizes called "Large N". This method can be used when the analytical method can provided results from a large number of tablets (ex NIR). Expert has met with several regulatory agencies in Europe and US as part of a pre-approval inspection team to explain and justify this method. Expert is a member of an ISPE Blend Uniformity/Content Uniformity Group that published several papers (2015) in response to the FDA withdrawal of a stratified sampling guidance. The papers have been presented at several meetings (IFPAC Annual Meeting, ISPE Statistics Forum, Pharm Ed Resources PV Summit)

Expert has been involved with the design and analysis of drug stability studies for over 15 years. He introduced the concept of matrixing and bracketting to Bristol-Myers Squibb which significantly reduces the resources such as analytical testing to conduct a stability study. He received a president's award for the effort. He also was the primary statisical contributer to an "in-house" stability package that was written by an outside contractor. He provided the statistical methodology, test data, and was involved in the validation effort.

Expert was involved with statistical analysis to develop product specifications based on the stability data. He was also involved in responding to regulatory agency questions concerning proposed product specifications.

Expert was an invited presenter (twice) at an Institute of Validation Technology Workshop on Stability Testing. His presentation was "Statistical Design and Analysis of Stability Studies".

Expert has provided design of experiments (DOE) and analysis for over 30 years. Central composite designs were often used to develop response surfaces to optimize the process. Expert has presented Composite designs as part of a PERI course for non-clinical statisticians as well as a workshop at the AAPS national meeting. He also has co-authored a series of three "Design Space" papers ("Statistical Considerations in Design Space Development Parts I, II, III", Pharmaceutical Technology) and co-wrote a chapter (“Application of Quality by Design(QbD) to the Development and Validation of Analytical Methods” in the book "Specification of Drug Substances and Products: Development and Validation of Analytical Methods, Elsevier).


Year Degree Subject Institution
Year: 1981 Degree: PhD Subject: Statistics Institution: Montana State University
Year: 1976 Degree: MS Subject: Statistics Institution: Montana State University
Year: 1971 Degree: BS Subject: Mathematics Psychology Institution: Bemidji State University

Work History

Years Employer Title Department
Years: 2012 to Present Employer: Undisclosed Title: President Department:
Expert provides statistical consulting primarily to the pharmaceutical industry (Research/Development and Manufacturing). Research and Development clients are generally in the functional areas contributing to the Chemistry, Manufacturing, and Control (CMC) sections of a New Drug Application(NDA).
Years Employer Title Department
Years: 1995 to 2012 Employer: Nonclinical Biostatistics Title: Associate Director Department:
He was responsible for statistical support to Pharmaceutical R&D (Analytical, Process Chemistry/Engineering, Pharmaceutics, and Stability) providing statistical design and analysis for formulation/process scale up and optimization experiments and long term stability studies.
Years Employer Title Department
Years: 1988 to 1995 Employer: Bristol-Myers Squibb Company Title: Senior Statistician - Manager Department:
He was responsible for statistical support to Pharmaceutical R&D (Analytical, Process Chemistry/Engineering, Pharmaceutics, and Stability) providing statistical design and analysis for formulation/process scale up and optimization experiments.
Years Employer Title Department
Years: 1986 to 1988 Employer: Nonclinical Biostatistics Title: Manager Department:
Provided statistical support to R&D formulators, analytical chemists and process validation scientists.
Years Employer Title Department
Years: 1981 to 1986 Employer: Ayerst (Became Wyeth) Title: Senior Statistician Department:
Provided statistical support to R&D formulators, analytical chemists and process validation scientists.
Years Employer Title Department
Years: 1971 to 1974 Employer: Enderlin School District Title: Math Teacher Department:
Taught Mathematics

Career Accomplishments

Associations / Societies
American Statistical Association, ASTM

Additional Experience

Training / Seminars
Expert developed an "in-house" design of experiments course. He has presented seminars on statistical design and analysis of stability studies, a design of experiments, basic statistics, statistical methods for analytical method validation, and statistical methods for process validation (sampling plans, criteria).

Fields of Expertise

applied statistics, biostatistics, statistics, statistical data analysis, design of experiments, statistical design of experiments, analysis of experiments, analytical method optimization, analytical method validation, process validation, quality-by-design, drug stability, stability prediction, central composite design, linear model, estimate, education statistics, quality statistical method, Graphical Statistical System, analysis of covariance, Type II error, statistical graphics, statistical computing, fitting models to data, analysis of variance, process capability index, process capability ratio, statistic, Student's t statistic, Student's t test, Food and Drug Administration validation, statistical process control software, F distribution, acceptable quality level, statistical estimation, SAS programming language, drug degradation, experimentation, probability distribution, normal distribution, stability, numerical data, statistical sampling plan, flexible statistical model building, statistical median, root-mean-square value, numeric digit, statistical degree of freedom, process capability study, pharmaceutical research, sampling plan, measurement error analysis, data correlation, drug development, acceptance sampling, statistical sampling, probability theory, gage R&R test procedure, statistical simulation, statistical method, statistical computer software, chemical process modeling, statistical quality control, SAS software, statistical inference, accuracy, continuous distribution function, binomial mathematical distribution, shelf life, mixture experiment, response surface methodology, parameter, arithmetic mean, Food and Drug Administration regulation, data, process, mathematical function, statistical process control, skewed density function, quality control, Poisson density function, pharmaceutical manufacturing, normal density function, mathematics, Latin square, histogram, discrete distribution function, curve fitting, computer software, chi-square method, calculus, algebra

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