Introducing the new ISO IWA 15 agreement
Oct 28, 2015
A new ISO International Workshop Agreement (IWA 15) has been published!
This agreement, titled Specification and method for the determination of performance of automated liquid handling systems, underwent intensive technical development in 2014, followed by editorial review and finalization in 2015. This agreement pertains to volumetric performance – meaning it has relevance to anyone who is involved in understanding or testing the accuracy and precision of automated liquid handling systems (ALHS). Persons responsible for equipment calibration, verification or validation will find helpful information in this agreement document. In addition, persons writing technical specifications for purchase or calibration of ALHS will save considerable time by referring to the requirements laid out in IWA 15.
IWA 15 was developed by expert participants from 18 different leading liquid handling organizations including equipment manufacturers, user laboratories, and third party testing services. A brochure describing the IWA 15 project and goals can be downloaded here, and includes a listing of the participating organizations.
Format and wording in ISO documents
All ISO documents follow a defined format.
- The main body of every ISO document is divided into numbered clauses.
- Following the main body, there is an option to include one or more annexes which are identified by letters.
- Sections of the document may be either normative meaning they are mandatory if claiming compliance to the document, or they may be informative meaning they contain information or recommendations but not requirements.
When reading ISO documents, the words shall and should are particularly important.
- Shall indicates a requirement. ISO IWA 15 contains 37 uses of the word shall within the normative sections.
- Should indicates a recommendation. Within IWA 15 are 61 recommendations. (In case you are wondering about my sanity, I did not manually count these words – I took the easy route and used Adobe’s document search function.)
Part by part
The first three parts of IWA 15 can be viewed online at the ISO website.
Clause 1, the scope section, is straightforward and describes what the document is designed to do.
Clause 2 contains one normative reference to ISO 17025 which describes requirements for the competence of testing and calibration laboratories.
Clause 3 contains definitions for fifty terms pertaining to ALHS, along with many explanatory notes. It is good that this terminology can be viewed at no charge. Having this common terminology should enable users, manufacturers and third party service organizations to communicate more precisely about liquid handling volumetric performance.
Clause 4 covers operation of ALHS. This clause includes four subsections addressing the different types of ALHS, adjustment of delivered volume, disposable and non-disposable tips, and some requirements and recommendations regarding the importance of considering environmental conditions.
Clause 5 deals with the concepts and equations for describing volumetric performance. In a recent blog I discussed six volumetric performance terms which are presented in the first part of Clause 5. Also included is a short hand indexing system for specifying and testing volumetric performance. An indexing system is a mathematical shorthand that allows us to uniquely identify liquid aliquots. Two indexing perspectives are given. From the manufacturer’s view, it is useful to talk about liquid handler channels, and sequential dispenses per channel. This is the usual concern of manufacturers who are interested in knowing that each channel is functioning properly within a multi-channel array of liquid handling tips. An alternative view could be a plate based approach where a laboratory user is concerned with verifying the accuracy of liquid delivery along particular rows or columns within one or more microplates.
After discussing indexing, Clause 5 provides fourteen mathematical formulas for assessing precision and trueness. While fourteen equations might seem excessive, this number arises because of the great variety of ways that volume measurements can be handled. For example, when we speak of coefficient of variation (CV), it is not always clear whether we are speaking of the CV of a single channel, or of multiple channels. When multiple channels are concerned, the results of single channels must be combined in some way, for example by combining at a root mean square, or by calculating CV across an entire microplate. These different mathematical treatments produce different values. Prior to IWA 15, manufacturers and users have calculated CV in various ways which has sometimes caused confusion and conflict.
Clause 6 provides a summary of thirteen different volume measurement methods. These methods were provided by the IWA 15 participants, and are the first time that the various volume measurement methods used by a large number of manufacturers have been described and compiled into one document. Prior to IWA 15, some of these methods had been disclosed publicly, and those that were disclosed were in different places and formats. Now all 13 are in one place, and in a similar format, which should be a great aid to anyone wanting to better understand or to duplicate testing methods. While Clause 6 is a summary, more complete descriptions of test methods are given in Annex B.
Clause 7 Specification of ALHS volumetric performance discusses mandatory and optional information to be supplied by the manufacturer, and includes 8 requirements. In this way, IWA 15 creates a common expectation for the kinds of information that should be provided. These requirements are based on the information necessary for users to understand how specifications should be interpreted and applied.
Clause 8 addresses reporting of volumetric performance, with both requirements and recommendations for calibration certificates and test reports. Certificates which adhere to this clause will provide users with the information needed to properly interpret the results, and also to reproduce the testing if desired.
Clause 9, the final clause in the main body, is a list of recommendations for future work. During the development of IWA 15 it was recognized that some topics would need further research or experimental work prior to standardization. Progress on some of these recommendations will be the subject of a future blog.
In addition to a large Annex B with details of the 13 measurement methods, there are three smaller annexes with useful information. Annex A gives examples of how the concepts and equations of Clause 5 can be practically applied in an excel spreadsheet. Annex C describes the proper way to convert a weight of liquid into volume, including reference to the current best practice in this regard.
Annex D is a list of participants who developed IWA 15. This list is useful, both for contacting individual contributors, and also for gaining a sense of the number and variety of organizations involved. This list can also be found in the IWA 15 brochure download.
How to access IWA 15
IWA 15 is a detailed, lengthy document which can be purchased at the ISO webstore (link). It contains up to date information on the current state of the art in the performance verification of ALHS. This document provides the best available foundation for anyone seeking to understand what is happening now across a broad spectrum of the industry, and will provide a platform for clearer discussion between users and manufacturers. The document will also be the starting point for further international standardization in automated liquid handling.
As a participant in the process, I welcome feedback on this document. Please visit the ISO webstore, browse the definitions and, if needed for your work, please do purchase this document. The authors worked hard in an attempt to produce a usable document that is free of errors. If you have suggestions for improvement, please let us know!
About the Author
George Rodrigues, Ph.D.
George Rodrigues, Ph.D., is Senior Scientific Manager at Artel, the global leader in liquid delivery quality assurance. Rodrigues is responsible for developing and delivering communications and consulting programs designed to maximize laboratory quality and productivity through science-based management of liquid delivery. Rodrigues is Artel’s chief representative to key commercial clients, government regulatory bodies and industry organizations. His speaking and teaching engagements, along with his publications, build awareness of the challenges and solutions for laboratories in maintaining data integrity and confidence in their testing protocols. He plays a key role in developing the manufacturing and quality assurance processes for Artel products and organizes programs to assist pharmaceutical, biotechnology and clinical laboratories in improving their liquid delivery quality assurance and analytical process control. Rodrigues earned his BS in Chemical Engineering at the U.C. Berkeley, and a PhD in Chemical Engineering at the University of Wisconsin.