Performance Qualification of HPLC Instrumentation in Regulated Laboratories

Jun 01, 2008




With the forthcoming USP monograph <1058>, many laboratories are in the process of reexamining their high performance liquid chromatography (HPLC) instrumentation qualification practices. This article demystifies the qualification procedures and proposes a well designed, easy and simple set of experiments upon which to establish internal standard operating procedures (SOPs) for the complete qualification of HPLC instruments. A key concept is the development of a consistent test system, comprised of premade test solutions, a prequalified HPLC column, standardized protocols, and validated software that can be prepared in-house or purchased commercially as a kit. This system can be applied to any HPLC system worldwide, to produce comparable test results under uniform conditions. The test system is designed to be rapid, with a comprehensive performance qualification being completed in about 2 h for isocratic, and 3 h for quaternary gradient systems.

The generation of high-quality, reliable analytical data is grounded on three fundamental components: instrument qualification, method validation, and user training (1,2). For the pharmaceutical industry, these activities fall under cGMP/GLP regulations. Although the specific regulations can vary for the environmental or other industries, the principles remain the same.

The first of these, instrument qualification, is the focus of this article. A laboratory plan for analytical instrument qualification (AIQ) is a requirement for all cGMP/GLP laboratories. The pending USP guidance document <1058> (3) reflects the evolving accepted practices for the introduction and qualification of analytical instrumentation into the regulated laboratory environment.

Instruments must be maintained systematically and proven to be precise and accurate for their intended use on an ongoing basis (4,5). However, the specific qualification procedures are, appropriately, not predetermined by regulation. Instead, the laboratory management is responsible for developing a scientifically sound, risk-based plan for the periodic maintenance and qualification of their analytical instruments. Nonetheless, the approach is subject to FDA review.

A sound instrument qualification program should be both scientifically rigorous and straightforward to use. It must be sufficiently comprehensive to capture aberrant instrument performance, yet be rapid enough to promptly return instruments to service after the maintenance or repairs have been completed. Development of the standard operating procedures (SOPs) and testing materials for the qualification program can be a daunting, and sometimes confusing task. This article presents an approach that we have developed and trialed over many years, which provides a comprehensive, rapid performance qualification for high performance liquid chromatography (HPLC) instruments.

Who Should Perform the Qualification?

The proposed USP AIQ monograph <1058> states that, "Users are ultimately responsible for instrument operations and data quality. The user's group encompasses analysts, their supervisors, and organization management." It further states that:

"Users should also be responsible for qualifying their instruments, because their training and expertise in the use of instruments make them the best-qualified groups to design the instrument test(s) and specification(s) necessary for successful AIQ."

This view of user responsibility is shared by the FDA (6).