PQ for analytical equipment qualification

Performance qualification

“Performance Qualification (PQ) is the process of demonstrating that an instrument consistently performs according to a specification appropriate for its routine use (5)”. Important here is the word ‘consistently’. The test frequency is much higher than for OQ. Another difference is that PQ should always be performed under conditions that are similar to routine sample analysis. For a chromatograph this means using the same column, the same analysis conditions and the same or similar test compounds.
PQ should be performed on a daily basis or whenever the instrument is used. The test frequency not only depends on the stability of the equipment but on everything in the system that may contribute to the analysis results. For a liquid chromatograph, this may be the chromatographic column or a detector’s lamp. The test criteria and frequency should be determined during the development and validation of the analytical method.

In practice, PQ can mean system suitability testing, where critical key system performance characteristics are measured and compared with documented, preset limits. For example, a well characterized standard can be injected 5 or 6 times and the standard deviation of amounts are then compared with a predefined value. If the limit of detection and/or quantitation are critical, the lamp’s intensity profile or the baseline boise should be tested. Table 6 gives a recommendation for a PQ example. [LIST=1]

  • Define the performance criteria and test procedures.
  • Select critical parameters with some allowance to drift out of predefined specifications. For a liquid chromatography system this can be
    • precision of the amounts
    • precision of retention times
    • resolution between two peaks
    • peak width at half height or
    • peak tailing
    • limit of detection and limit of quantitation
    • wavelength accuracy of a UV/Visible wavelength detector.
  • Define the test intervals, e.g.,
    • every day
    • every time the system is used
    • before, between and after a series of runs
  • Define corrective actions on what to do if the system does not meet the criteria, in other words if the system is out of specification The analysis of quality control (QC) samples with construction of quality control charts has been suggested as another way of performing PQ. Control samples with known amounts are interspersed among actual samples at intervals determined by the total number of samples, the stability of the system and the specified precision. The advantage of this procedure is that the system performance is measured more or less continuously under conditions that are very close to the actual application. As with system suitability testing, test procedures and acceptance limits should be specified during method validation. Documented procedures should exist, that instruct the operators on what to do if the system does not meet the criteria. A frequently discussed question is whether either system suitability testing or the analysis of QC samples are sufficient to prove on-going system performance, or whether additional checks should be performed. The answer to this question depends very much on the conditions under which the control samples are analyzed. For example, if the system is used for trace analysis and the amounts of the control sample do not include trace level amounts, the capability of the system to measure low amounts should be verified. In HPLC, this could be a routine check of the wavelength accuracy, the baseline noise and the intensity of the UV lamp. System suitability checks and control sample analysis are sufficient as PQ checks, if all critical system parameters are checked as part of tests and evaluations.
  • Qualification of HPLC
    Qualification of HPLC involves all 4 Qs but OQ and PQ is performed qarterly on maintenance basis. OQ is the Documented verification of performance of each equipment component. it verifies the Actual versus expected output testing e.g. Software (Integrator), solvent delivery system (pump) and dtector. lets take the example of OQ of Solvent delivery system (Pump), it requires to check the initialization of pump after power up, high back pressure shut down functions at preset limits, purging or flushing the delivery system at prest flow rate for a set period of time and accuracy and precision of flow rate.
    PQ is the Documented verification of system (hardware & software) PQ Verifies total system control integrity of Analytical system, it involves accuracy, Linearity and Precision of operational and control functions. PQ is done with set qualification parameters, with defined instrument and processing method for each and every components. Analyte sample is kept in autosampler and PQ is run for precision repeatability and linearity of PQ samples. In injection linearity Coeffecient of corelation is checked for the Peak hight, peak area V/S concentration. In precision repeatability %RSD for peak area and peak hight is calculated to check the acceptence with in preset limits mostly it is NMT 1.5 to 2%.

    System suitablity test is always described in compendial products monograph which shows the relevence of this not only with the test method also with the set chromatographic condition, it gives the assurance of system integrity before starting the analysis. if system suitability fails then it indicates some system integrity error or it may be a reagent and sample problem as well.

    Good laboratory practices always demand to keep the maintenance of instrument by periodically (quarterly) repeating its OQ and PQ for best system integrity.

    Shahid Ali
    QA Manager
    Addis Pharmaceutical Factory SC, Ethiopia


    I would not necessarly agree that the OQ/PQ needs to be done on a quaterly basis. The practise where I work is this,

    Twice a year there is a revalidation done on each HPLC, testing includes precision, linearity etc.
    Every time an assay is run on a HPLC a system suitability test is completed with it, so in essence you are completing part of a PQ each time you run an assay.


    Dear Ruth
    I think we shud not mix up system suitability test with PQ of instrument. To set the frequency of OQ/PQ for instrument depends on u its not a hard and fast rule to do it quarterly or bianually, well good organization go for quarterly what i have seen in different multinational companies.

    Shahid Ali
    QA Manager
    APF SC, Ethiopia

    Can you please explain the risk that has been perceived to warrant so much testing? Is anyone finding an HPLC that does not pass a PQ each quarter? Especially, when you do suitability daily or prior to each test.

    Also, validating something typically makes it so you have to do less testing not more. It seems that there is no confidence that the instrument will perform as intended.

    Is this just a mixup in terminology, periodic maintenance or calibration for PQ

    If HPLC doesn`t pass the PQ then definitely it means that it needs some maintenance and service. System suitability test as i have already told before that its in fact a compendial requirement for the test method and this is done to check the suitability of entire system relevent typically to the test requirement.

    Shahid Ali
    QA Manager
    APF SC, Ethiopia

    Having A PQ every quater I think is over kill. Yes a system suitability is performed to test the system using the testing method standards. If your system suitability fails then you have a problem with your system not your method.

    I have never seen a HPLC fail a revalidation (twice yearly).

    Dear All
    Operation qualification and performance qualification for the Equipment and System Suitability Tests for Quantitative Chromatographic Methods.

    1. Introduction
      Despite the importance of the system suitability test to ensure the performance of the analytical system, in many cases this is overlooked by scientists when they develop analytical methods. This article will summarize
      the strategy used to develop a sound system suitability test. In addition, different approaches to set suitable limits will be discussed.
    2. Definition
      The purpose of the system suitability test is to ensure that the complete testing system (including instrument,
      reagents, columns, analysts) is suitable for the intended application. The USP Chromatography General Chapter <621> states:
      “System suitability tests are an integral part of gas and liquid chromatographic methods. They are used to verify that the resolution and reproducibility of the chromatographic system are adequate for the analysis to be done.
      The tests are based on the concept that the equipment, electronics, analytical operations and samples to be analyzed constitute an integral system that can be evaluated as such.”
    3. System Suitability, Operational Qualification and Performance Qualification
      3.1 Operational Qualification (OQ) and Performance Qualification (PQ)
      Within the analytical community, system suitability is sometimes confused with the OQ and PQ, performed during instrument qualification. OQ/PQ are used to demonstrate that all components of the instrument, and/or the complete instrument system, are meeting performance standards (i.e., specifications). The testing methodology for OQ/PQ is specific to instrumental performance. In order to ensure that the chromatographic system is tested in a manner not affected by the analytical method, the system is usually qualified in a well-controlled environment. Therefore, the analytical HPLC column is removed in order to remove it’s contribution to the variability of the system, and a simple mobile phase should be used in the OQ/PQ of HPLC systems.
      3.2 However, unlike OQ/PQ, the system suitability test is method specific. The system, which should already be qualified during IQ/OQ/PQ, is tested using the test conditions described in the method.
      OQ/PQ focuses on the analytical instrument operation and performance. System suitability, however, encompasses the complete testing system including instrument, reagents, columns and analysts.

    Shahid Ali
    QA Manager
    APF SC, Ethiopia

    For equipment case, there is no such requirment or need to initiate qualification studies quarterly, biannualy or annualy. It should be perform at th beginning stages like DQ, IQ, OQ and PQ, system suitabilty test must be perform before start up the analysis to check whether the system is in proper working condition according to their specfication, and perform calibration on regular interval, but in some cases qualification studies has perform on regular basis for instance, in area qualification especially aseptic area, it is more prefable that area qualification is perform before conducted the media fill trail , the area should be throughly qualified besides personel qualifications.In HPLC case, there is no requirement to perform PQ on every quarter but must conduct system suitablity test daily before starting the analysis and perform calibration on regular basis i.e biannually or quarterly. but there is any major change or repairing done in equipment or shifting the equipment from one place to another then qualification studies must be perform from some extent.

    [quote=Shahid Ali]Dear Ruth
    I think we shud not mix up system suitability test with PQ of instrument. To set the frequency of OQ/PQ for instrument depends on u its not a hard and fast rule to do it quarterly or bianually, well good organization go for quarterly what i have seen in different multinational companies.

    Shahid Ali
    QA Manager
    APF SC, Ethiopia[/quote]

    As i have already posted my comments that its not a hard and fast rule to set frequency quarterly, u can set the frequency bianually or quarterly.