Pertinent to specific techniques, these requirements rely heavily on the manufacturer
United States Pharmacopeia (USP) <1058> on Analytical Instrument Qualification (AIQ) is effective from August 2008. It was developed from an American
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Association of Pharmaceutical Scientists meeting in 2003. Through a white paper published in 2004 and incorporation as a potential USP general chapter in 2005, cycles of comment and revision have followed to the final version that is now effective.1 It is worth remembering at this point that USP general chapters between <1> and <999> are requirements, and that those between <1000> and <1999> are informational in nature. However, <1058> will implicitly refer to USP requirements, pertinent to specific techniques, e.g. <21> Thermometers or <41> Weights and Balances.
Qualification process and classification of instruments
The process for instrument qualification follows the four Qs model for the specification, installation check and monitoring of on-going instrument performance:
• design qualification (DQ)
• installation qualification (IQ)
• operational qualification (OQ)
• performance qualification (PQ)
One of the problems with <1058> is the reliance on the manufacturer for the specification for the instrument in the DQ phase. While this is fine for the design, build and test phases within the factory, it ignores the responsibility of the users to define their requirements and compare them with the various instruments on the market. The message in the DQ phase is for the user to ask what they want the instrument or system to do and to document it. Ignoring your specification is a high business risk and, if one looks outside the pharmaceutical industry to other standards, ISO 17025 notes that laboratory and manufacturers’ specifications may be different. Hence, the need to define your instrument and system requirements. Otherwise, you will have problems in that the purchased system may not meet your needs.
All instruments/systems are classified into one of the following three categories:
• Group A
• Group B
• Group C
Table 1 shows the criteria for classification and how each are qualified together with some typical examples in each group. There is a built-in risk assessment, as Group A are the lowest risk requiring the smallest amount of work and Group C represent the greatest risk and, hence, the most work to control.
Inadequate approach to software validation
Virtually all instruments have software, varying from firmware for the basic instrument operation to a separate data system for instrument control, data acquisition, analysis and reporting. For Group B instruments, the firmware is implicitly tested as part of the IQ and OQ phases of the qualification – this is in contrast with the latest GAMP guide which has removed Category 2 software that most closely equates to Group B instruments.
Where there is a separate data system, this needs to be validated at the same time the instrument is qualified.
However, the approach taken by <1058> for computer system validation (CSV) is too simplistic and naïve, as everything is dumped on the manufacturer to write the software, validate it and provide a summary to users for them to holistically validate in their system. While this may be ok for small firmware instruments, it is totally inadequate and deficient for complex systems, as it omits the following:
• configuration of security and access control
• configuration of software to the business process, if appropriate
• definition and testing 21 CFR 11 functions as used in your laboratory
• custom reports
• macros defined and written by the users
For Group 3 instruments with data systems, you will leave yourself exposed if you follow the computer validation approach in USP <1058>.
1. United States Pharmacopeia <1058> Analytical Equipment Qualification, USP, 2008.
R.D. McDowall is Principal, McDowall Consulting. He may be contacted at editor@ScientificComputing.com.