FRESH PERSPECTIVES
Enhanced Classification of
Placebo and Active Formulations via Hierarchical Modeling
Michael Dotlich,
M.Sc.1 Robert Roginski, Ph.D.2
, Richard M. Kattner,
M.Sc.1 ,
and Jeremy Shaver, Ph.D.2 1
Eli Lilly and Company 2Eigenvector Research, Inc. Introduction
Michael Dotlich,
M.Sc., is a Research Scientist in analytical research and development at Eli Lilly and Company. He works in the Lilly Research Laboratories validating methods of testing for clinical trial materials release. His active research is focused on the development of spectroscopic methods using different analytical techniques and chemometrics for identification and quantitation of raw materials and drug products. He earned his
M.Sc. in applications of Raman spectroscopy from Marquette University, Milwaukee WI.
Dr. Bob Roginski is a Senior Applications Scientist with Eigenvector Research, Inc., where he provides consulting services, instruction, and software development in the area of chemometrics. Previously, Bob served in engineering roles specializing in process analytical technology at Eli Lilly & Co., Searle/Pharmacia/Pfizer, and Amoco Corporation. Bob received his Ph.D. in Chemical Engineering from the University of Illinois in 1987, and has collaborated on numerous peer- reviewed publications and outside presentations. Bob has special interests in spectroscopy as applied to PAT and using chemometrics to determine the health of continuous processes.
Richard M. Kattner,
M.Sc., is Associate Consultant Chemist in the analytical research and development at Eli Lilly and Company.
current work in the Lilly Research Laboratories deals with developing and validating methods for the testing and release of clinical trial materials. His current focus is the development and validation of spectroscopic methods using different analytical techniques and chemometrics for testing active/placebo tablet and solutions.
earned his
M.Sc. in Chemistry focusing in Physical Organic Chemistry at the University of North Texas, Denton, TX.
Dr. Jeremy Shaver is currently the Chief of Technology Development at Eigenvector Research, Inc., which he joined in 2001. He received a BA in Chemistry from the College of Wooster in 1991 and a Ph.D. in Analytical Chemistry from Duke University in 1995.
His
A placebo-controlled study is a means of testing a drug for safety and efficacy in a group of subjects that receive the treatment. Current placebo identity tests typically utilize an HPLC identity method for the active compound to confirm the absence of the active (i.e., negative identity). In this review, the development and application of transmission Raman spectroscopy (TRS) with chemometric modeling for positive placebo identification testing will be applied to drug products, illustrated for several compounds and their respective placebos.
Placebo identification tests are a clinical manufacturing requirement, and when implemented in a negative mode, data are evaluated against the specification “There is no active detected”.
Clinical placebos share the same physical
appearance as the active tablets or capsules, as required for blinded studies, hence definitive identification of both the active and placebo (absence of active) are necessary release tests.
Spectroscopic test methods utilizing a standard
library provide a robust approach for evaluating the chemical identity of both placebos and actives.
In addition, spectral testing using chemometric models
can compare placebo results against a database of numerous placebos and active drugs instead of assaying for a single active ingredient. Spectroscopic methods utilizing rapid, chemometric-based spectroscopic technologies create efficiencies and minimize workload due to minimal sample preparation and automated data analysis. Finally, chemometric models provide benefits over traditional spectral comparisons such as eliminating a need for storage and maintenance of reference standards (e.g., API, tablets and capsules) and reduce subjectivity in determining if sample data “compares favorably to a reference standard” or demonstrates “no active XYZ present,” especially for complex drug excipient matrices.
Experimental He
For the experiments reported here, a Cobalt transmission Raman instrument (TRS100) was used with the following settings: • Laser Power: 0.65W • Exposure: 0.5 sec. • Accumulations: 180 • Detector: CCD • Read Optics: Small • Laser Spot Diameter: 2mm • Scan Range: 40 – 2400 cm-1
61 American Pharmaceutical Review | Fresh Perspectives 2013
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