HPLC system qualification

Equipment qualification is a formal process that provides documented evidence that an instrument is fit for its intended used. The entire process typically consists of four parts design qualification (DQ), installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ). 

After initial qualification, the system is placed in service and is kept in a qualified state using a periodic calibration program. In addition, its performance for the specific application is also verified at the time of use using system suitability testing. This section describes the procedures and documentation used for HPLC hardware qualification. Detailed discussions of this subject can be found in books and articles elsewhere.3,4 The regulations and qualification of computerized data systems and networks with their associated software can be quite elaborate and is described elsewhere.5 7 

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Figure 9.2. A schematic diagram illustrating the timeline and documents in the various stages in HPLC system qualification.

Calibration procedures are often similar to those used in the initial operational qualification of each module of the HPLC system. While each company s procedure might differ in the details, most share these common strategies. 

The final task of the pre-installation process should be a preinstallation qualification. This is a site-readiness evaluation indicating whether the location into which the HPLC system is to be installed is actually ready to accommodate this system. This should include the following utility/spatial/environmental and safety considerations ... 

Following pre-installation qualification and the actual installation of an HPLC system, both the IQ and the OQ protocols should be implemented, back to back, soon after the installation. Again, the IQ is used to verify that the installation of the system was successful, with all instrument components powering-up properly. The OQ follows, verifying that the system components perform as they were functionally specified by the vendor. Finally, the PQ protocol serves to verify that the system as a whole performs to the URS established by the user and within the functional limitations of the system as a whole. As part of the PQ, it is recommended to test the system as a whole, called holistic validation. This... 

Operation Qualification. Operation qualification (OQ) is the process of establishing that the instrument or system modules operate according to the functional requirements in a suitable environment. For an HPLC system, operation of the pump, injector, and detector will be tested at this stage. Typical OQ tests for HPLC modules and a UV-Vis spectrophotometer are as follows ... 

The performance of an HPLC system can be evaluated by examining the key functions of the various modules that comprise the system, followed by holistic testing that challenges the performance of the HPLC components as an integrated system. The holistic testing is commonly referred to as the performance qualification (PQ). The holistic test can be as simple as running a frequently used HPLC method in the laboratory. Modular testing of various components, which is... 

Validation of HPLC instrumentation, also called qualification, is the procedure that ensures that the instrument is qualified that is, that its performance complies with the method s predetermined requirements, providing reliable and valid results. Modern HPLC systems are computerized, generally consisting of analytical hardware, computer hardware, peripherals, and software. 

Waters (1993) Guide for the system qualification of HPLC automated with detection UV... 

The present operating procedure describes the procedure and the documentation for the performance qualification (PQ) of HPLC systems It can be used for both isocratic and gradient systems with UV detection and it is independent of the instrument manufacturer. The procedure includes the tests of pump, autosampler, UV detector and column oven. It can be put into practice immediately. 

Equipment selection is often based on performance specifications, pricing, features, or vendor s technical or service support. Major companies tend to purchase HPLC from one or two vendors to reduce cost in system qualification, equipment service, and operator training. The compatibility to an existing chromatographic data-handling network often dominates the purchase decision for HPLC equipment. 

Design qualification (DQ) describes the user requirements and defines the functional and operational specifications of the instrument which are used for OQ testing. Table 9.1 shows an example of a DQ for an HPLC system used for method development. 

Table 9.1. An Example of a Design Qualification (DQ) of an HPLC System for Method Development...

This chapter discusses regulatory issues in HPLC laboratories with a focus on procedures and requirements for system qualification, calibration, method validation, and system suitability testing. Examples in a cGMP pharmaceutical environment are used to illustrate the various tools and systems used to ensure the degree of HPLC data accuracy necessary to achieve the delicate balance of regulatory compliance and laboratory productivity. 

While automated tools and software are available for system qualification, method validation, and system suitability testing, achieving regulatory compliance for an HPLC laboratory remains a complex, costly, and time-consuming process. Many companies are adopting a risk-based approach to balance productivity and compliance. For instance, many pharmaceutical research... 

The instrumentation comprises the individual elements that make up the HPLC system, including the pump, injector, column compartment, and detector. Qualification is performed on any element that, if defective, will have a significant effect on the result. Each of these elements must be assessed against a predetermined specification before it can be deemed fit for purpose and used to measure real samples. The specifications used in the qualification of instrumentation are usually provided by the individual vendors of the equipment. Care should be taken because not all manufacturers specifications are the same. 

Coupling HPLC with UVA S detection on-line to MS is state-of-the-art for quantification and qualification. If HPLC systems are coupled on-line to mass spectrometers the use of volatile buffers and solvents is required. In contrast to APCI, the yield and reproducibility of ESI depends on the presence of charged solvent molecules, hence the ionic strength -represented in most cases by organic acids- of the mobile phases used should be kept constant especially during gradient elution. 

Instrument qualification is an important element of laboratory validation. Suppliers s (retrospective) validation plans help with the equipment qualification process. Nowadays the regulatory compliance needs of industry on a global basis are well understood by the instrument vendors. For example, Duncan et al. [118] have illustrated the validation chain for benchtop LC-MS systems and Maxwell et al. [119] have applied the validation timeline to HPLC system validation. Both FDA and USP require that the proper operation of an HPLC system must be validated through a formal calibration program. The components of an HPLC that require calibration include pumps, pump mixing elements, auto-injector, detector, and column heater. 

Furman et al. discussing the validation of computerised liquid chromatographic systems, present the concept of modular and holistic qualification. Modular qualification involves the individual components of a system such as pump, autosampler, column heater and detector of an HPLC. The authors make the point that ... 

Equipment such as high-pressure liquid chromatography (HPLC) should have system-suitability checks, installation qualifications, and operational qualifications performed at a minimum. 

System calibration refers to the periodic operational qualification of the HPLC, typically every 6 to 12 months in most regulated laboratories. This calibration procedure is usually coordinated with an annual preventative maintenance (PM) program and is performed immediately after PM. A calibration sticker is placed on the instrument to indicate its calibration status and readiness for GMP work. The reader is referred to the principles and strategies behind HPLC calibration criteria published elsewhere.8 A summary of the calibration procedures and acceptance criteria, including additional procedures recommended for initial operational qualification, is listed in Table 9.3. 

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