ISO 8655:2002, was written specifically to define the requirements necessary to produce accurate and reliable calibrations of piston pipettes and other closely-related measurement equipment. It details the required methods, test conditions, test equipment, reporting requirements and includes requirements for reporting the required measurement uncertainty values. Today, it is the most critical ISO standard for calibrating piston-operated pipettes, burettes, diluters, and dispensers.
How is it different than ISO 17025?
The ISO 8655 standard was written by the International Organization for Standardization’s (ISO) Technical Committee 48 to complement and complete the well known ISO 17025 standard. While ISO 17025 is a set of generic requirements calibration providers must follow to be deemed “competent” by a suitable accreditation body, it has no requirements for how good or effective those processes must be. Nor are the guidelines specific to any device; they apply equally well to a broad range of equipment requiring calibration, including not just pipettes, but also medical devices, communication equipment, electronic devices, weight scales, pressure meters, calipers, and more.
ISO 8655, on the other hand, is a very detailed set of standards, methods and controls that a pipette calibration provider must follow to correctly and accurately calibrate piston pipettes. This difference explains how traveling or onsite pipette calibration providers can be accredited to ISO 17025 but not to ISO 8655. For more on the differences between the two ISO standards, see Why ISO 8655 Compliance Should Be Your Litmus Test.
ISO 8655 Defined
Adherence to the ISO 8655 standard covers air displacement pipettes and positive displacement pipettes, single channel and multichannel pipettes (both fixed and adjustable volume) as well as both manual pipettes and automated pipettes, often called motorized pipettes or electronic pipettes. Let’s look deeper into the quality that is ISO 8655.
The ISO 8655 standard precisely defines 6 elements required for accurate, repeatable, ISO-compliant measurements:
Acceptable Measurement Uncertainties
Measurement uncertainty is defined as a quantitative value representing a calculated level of ‘doubt’ or potential measurement error occurring from external influences, and based on the quality, standards and controls maintained or omitted from a calibration event. ISO accredited laboratories like TTE are required to verify, calculate and report measurement uncertainty for every calibration.
Maximum Permissible Errors
Maximum Error Limits for piston-operated pipettes are clearly defined in ISO 8655. The standard characterizes both the maximum permissible systematic error, as well as the maximum permissible random error limits for a device at specific volumes ranging from 1-10,000uL. These errors are doubled for multichannel pipettes. Most pipette manufacturer’s tolerance specifications fall well below these limits, but at low volume measurements, meeting ISO 8655 tolerances can be a challenge for many service providers.
Maximum permissible errors for Air Displacement and Certain Positive Displacement pipettes – [Reference: ISO8655-2:2002, pg. 6]
ISO 8655 states that the primary methodology for measurement of piston-operated pipettes and related measurement apparatus is through gravimetric measurement analysis. Included are the minimum balance requirements at each test volume, important for reporting measurement accuracy at the appropriate resolution. For example, you wouldn’t weigh yourself on a truck scale. Pipette measurements face the same challenge for many providers. This standard also requires control (not just monitoring) of test conditions, along with minimum data points for a valid representation of device performance and measurement analysis.
Minimum Balance Requirements – [Reference: ISO8655-6:2002, pg. 2]
Lab and Environmental Conditions
To be considered valid by ISO 8655, pipette measurements must occur in a strictly controlled, vibration-free test environment. The acceptable ranges of environmental conditions are defined as:
- Temperature – constant [±0.5°C], 15-30°C
- Relative Humidity – ˃50%
- Air Flow – draft free
- Static – ~0
- Evaporation Rate – ~0
- Vibration – ~0
- Altitude – Ground Level
The ISO 8655 standard defines a step-wise procedure for generating valid, reliable measurement data. Procedures include proper technique for tip installation, pre-wetting, aspiration and dispensing technique, measurement container requirements, required number of measurements, evaporation rate determination and time lapse for test completion.
ISO 8655 and FDA Audits
Regular FDA audits are required for all drug development labs, helping to ensure data integrity and proof of efficacy. However, supporting your science with the assurance of an ISO 8655 compliant pipette calibration service provider, ensures that the pipette measurements are accurate and reliable. As FDA audits validate proper drug development and quality controls, ISO 17025 accreditation audits provide the same integrity for pipette calibration providers. However, when an auditor evaluates compliance of a pipette service provider to ISO 8655 standards and controls, they are raising the bar and promoting standards-based calibration. For pipette service providers, ISO 8655 compliance improves service integrity, so drug development labs provide quality products, supported by trustworthy, reliable service providers. Metrology standards make all the difference.