It all starts with trust.

Article 1 in the Assay Quality Assurance Series.

I think it would be fair to say that there is a lot of confusion out there about the differences between Validation, Verification, Evaluation and Qualification in a laboratory context.

There is an inter-play between Knowledge, Trust, and Risk in all services.

These terms are often (incorrectly) used inter-changeably, which only adds to the confusion.

On top of this, these terms are also used in other industries such as software management, project management and construction to name a few!

😤 "... Oh I thought validation and verification were the same thing?" 😅

This ambiguity has often resulted in consternation and friction between members of project teams who have not been appraised of the finer points and hence may have differing expectations regarding Quality, Resource, and Timelines.

Knowledge in this field is often hard-won, jealously guarded, and can come across as rather dry.

With this series of articles, which I intend to write on a fairly regular basis, I will attempt to disambiguate these terms in the context of diagnostic assays.

My musings on this topic are not to be taken as definitive or exhaustive: that is reserved for regulatory bodies and standards organisations. I hope, however, that my thoughts are informative and give a wider audience a new perspective on what can be a thorny area.

Let us begin with trust and risk.

Trust underpins all of our interactions as patients and consumers of services, medicines and products. Whether you are undergoing surgery, booking your car in for a service, or buying an electric gadget, you implicitly weigh up the risk and reward of handing over your possessions (corporeal, financial or otherwise!). When you are not able to thoroughly assess that risk yourself, because you are inexperienced, or don't have the requisite knowledge then there is a large element of trust involved. To mitigate the perceived risk of trusting an unknown, you may rely on the testimonials of others that you trust to help you make a decision about how to proceed. Such a testimonial could take the form of a recommendation, a certification, or independent assessment by a trusted regulatory authority.

Trust, therefore, is the basis of how we make decisions about how we go about our lives. We find that trust in individual people, organisations and businesses can be substituted for trust in an accepted authority.

Next, let us break this down in the context of a diagnostic laboratory service.

The end-user (generally a health professional) relies on assessment from an independent accreditation service (UKAS) that the lab's services meet (or comply with) an appropriate set of standards (ISO15189). In the absence of accreditation, an end-user has no evidence that they can trust the services they are purchasing.

The assessment by the accreditation service is, therefore, a substitute for a personal audit.

Accreditation of a service implies that said service complies with all elements of an appropriate standard within defined boundaries (a scope). Compliant elements include documentation (quality management system, training records, standard operating procedures, method verification reports, instrument qualification, ....) and operational and management behaviours (evidence of continuous professional development, continuous improvement, staff expertise, record-keeping, risk assessment ...).

It is important to note that even within molecular diagnostics, all laboratories differ. They offer different services, in different locations, with different staff, equipment and reagents. Attempts at standardising laboratory services for rapid roll-out of large scale testing during the COVID-19 pandemic faced significant hurdles (including assay supply, market competition and staff expertise), which together rendered a 'cookie-cutter', or turnkey approach unrealistic (if not impossible) for the deployment of multiple high quality laboratories.

In recognition of the differences between laboratories, standards are cleverly written such that compliance with the principles of the standard can be achieved, or proven, in many different ways, while still ensuring the safety and quality of a service. Interpretation and application of standards to a system requires creative thinking on the part of subject matter experts to show how a product or a service conforms. By being non-prescriptive on how to achieve compliance, standards ensure that only highly skilled, and hence trusted, people can:

1. develop a plan for and deliver compliance

2. assess compliance

An in-depth discussion on regulatory strategy is outside of the scope of this series of articles, but suffice to say that a tailored approach that navigates legal requirements (whether that is the FDA, the MHRA or the EMA) in an efficient and realistic manner is extremely valuable.

In this first article, I have presented trust as the 'why' of compliance with standards. Starting with this principle is, I feel, important as it establishes a solid axiom that can be used in the subsequent articles in this series, which will in the first instance seek to address definitions of the fit-for-purpose assessments of methods and equipment.