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).
The AIQ Process
The AIQ process is often summarized as "The Four Qs" — that is, the design, installation, operational, and performance qualifications, referred to as DQ, IQ, OQ, and PQ. For a new installation, the instrument vendor often will be responsible for the IQ and OQ procedures, albeit under laboratory SOPs governing this operation. Depending upon the vendor, some abbreviated form of a system check also might be performed. Some vendors refer to this as a performance verification (PV). The exact procedures used will vary with each manufacturer. This IQ–OQ–PV process essentially is performed once per installation. Upon completion, responsibility for routine maintenance and periodic qualification is transferred to the user, even if outside contractors are employed for future preventative maintenance and service. Logically, because each instrument vendor has their own particular qualification routines, a master-level set of laboratory PQ testing protocols must be created to generate uniform performance data across the different brands of HPLC systems within the laboratory, while specifying measures that are required due to instrument maintenance, repair, or change. Such protocols must be consistent with the company's overall change control policy.
Table I summarizes the AIQ process and typical situations in which each stage might be applied. Specific choices will vary from laboratory to laboratory, and this is not purported to be a comprehensive plan for all contingencies. However, some rational, prewritten plan must exist to govern whatever procedures are decided upon.
Note that unlike the OQ, PQ testing is performed frequently, for many different events. System suitability of a particular method is not a substitute for a PQ, although its procedures might be incorporated into a PQ testing protocol. A system suitability is method specific, and serves a very different purpose than a full PQ.
OQ and PQ also have different purposes, although similarities often exist in tests used for these qualification steps. A distinguishing feature of the OQ is its focus on testing the individual instrument module, and often is driven by the manufacturer's design specifications. PQ testing on the other hand, is holistic, and documents the performance of the working system, which, thus includes both hardware and software issues.