A General Test Method for the Development, Validation and Routine Use of Disposable near Infrared Spectroscopic Libraries

Abstract

We have developed a novel approach for using near infrared (NIR) spectroscopy; this is to create and apply calibration models “on-the-fly”. We define a process to create, validate, implement and approve a disposable library for discriminating between active and placebo pharmaceutical dosage forms packaged for clinical studies. This approach is based on two concepts; one germane to the particular needs and requirements of the pharmaceutical industry and the second based on an observation of the proposed experimental parameters. The first is that validation, in the general sense, implies control over a method. The second is that each clinical trial is a unique event, consisting of a finite or closed population of samples. The essence of the idea behind our process is to use disposable libraries, that is, libraries of NIR spectra created for one-time use and then archived. The justification for this approach is that the population of samples used both to create the library and subsequently to be identified using that library consists of a finite set of samples. This paper describes the rationale of this approach, discusses in detail the requirements for suitable protocols for using this method of verifying the dosages used in clinical trials, and describes the application of this approach on two separate clinical trials. Many other examples exist in the authors' laboratory. We also provide formatted templates that can be used to document and report NIR analytical results for discriminating between drug product and placebo dosage forms packaged in patient kits for clinical studies. The use of these templates, carefully designed to ensure regulatory requirements for validation are met, makes the implementation of the technique both rapid and compliant with regulatory requirements.