Ask any laboratory professional where analytical accuracy begins, and most will point to the instrument. A few will mention the method. Fewer still will mention the analyst. But Dr. Rashmi Ranjan Mohanty, Director – Technical at Advent, asks us to look one step further back - to the reference material that anchors every result to something real.
In Episode 17 of the Dr. Mohanty’s Masterclass, Dr. Mohanty takes on a subject that is deceptively simple on the surface and remarkably consequential beneath it: Reference Materials and Standards. His opening provocation cuts right to the chase - every result we generate, no matter how sophisticated the instrumentation or how experienced the analyst, ultimately depends on the reference we use. Change the reference, and you change the result.
Reference Material: The Starting Point of Measurement
At its most fundamental level, a Reference Material (RM) is a substance with a known property value, used for calibration, validation, and quality control. Think of it as the fixed anchor in a moving sea of variables. Without a reliable reference, even the most advanced instrument becomes unreliable — it measures with precision, but accuracy remains elusive.
But not all reference materials are created equal. A Certified Reference Material (CRM) goes further: its value is not just known, it is scientifically established through metrological traceability, defined measurement uncertainty, and formal certification. This distinction matters enormously in regulated and high-precision analytical environments, where every measurement must be not just accurate but defensible.
The difference between an RM and a CRM, as Dr. Mohanty explains, is not merely technical. It is about the level of confidence required in the final result. Routine work may be adequately served by an RM, but when the stakes demand traceability - regulatory submissions, method validation, critical quality decisions - the CRM becomes non-negotiable.
Reference Standards and Certified Reference Standards: A Different Kind of Confidence
The conversation extends to two more terms that are often conflated in laboratory practice: Reference Standards (RS) and Certified Reference Standards (CRS). While the names sound similar, their purpose and provenance differ.
A Reference Standard is an internally qualified working standard used within a laboratory for routine quality control. A Certified Reference Standard — typified by pharmacopoeial standards from organisations like USP, IP, EP, or JP — is an official standard designed for regulatory compliance, characterised by specific analytical methods and monograph requirements.
Critically, Dr. Mohanty draws a clean line between the two frameworks these operate within: metrological traceability (linked to National Metrology Institutes like NIST or PTB, culminating in CRMs) and regulatory compliance (linked to pharmacopoeial standards, culminating in CRS-based qualification). These frameworks are complementary, not interchangeable. A CRM gives you measurement confidence. A CRS gives you regulatory acceptance. Conflating them is a risk that laboratories carry silently — until they don't.
The Invisible Risk Nobody Is Talking About
Here is where Dr. Mohanty makes his most incisive point. When something goes wrong in a laboratory — an out-of-specification result, an audit observation, an anomalous reading — the first suspects are always the instrument, the method, or the analyst. Rarely is the reference material scrutinized.
Yet this is precisely where hidden risk accumulates. A poorly selected or inadequately characterized reference material can propagate systematic error across every measurement made against it. The instrument may be perfectly calibrated. The analyst may follow the procedure to the letter. But if the reference is wrong, the result is wrong — and often nobody knows until the damage is done.
This is the invisible risk that Dr. Mohanty names directly. Poor reference materials lead to improper qualification, out-of-specification results, audit observations, and ultimately wrong decisions. In industries where those decisions carry regulatory or patient-safety implications, the cost is not just scientific — it is consequential.
Fitness for Purpose: The Guiding Principle
So what is the solution? Dr. Mohanty offers a principle that is both practical and elegant: fitness for purpose. The highest-grade reference material is not always the right choice. What matters is selecting the appropriate standard for the specific application, based on the level of confidence required.
For pharmacopoeial methods: use CRS. For validation and critical measurements: use CRM. For routine QC: RS suffices. Scientific judgment, in Dr. Mohanty's framing, lies not in defaulting to the highest available standard but in knowing which one is genuinely appropriate — and being able to justify that choice with a sound scientific basis.
This principle extends to situations where official standards simply do not exist — emerging molecules, impurities, peptides, and specialised compounds for which no pharmacopoeial reference has yet been developed. In these cases, reference materials must be developed and characterised in-house, using a combination of chromatographic, spectroscopic, and orthogonal analytical approaches to establish identity, purity, and suitability. The absence of an official standard is not an excuse for measurement ambiguity; it is a call for more rigorous characterization, not less.
Traceability: The Thread That Connects Every Measurement
Running through the entire discussion is the concept of traceability — the unbroken chain of comparisons that links a measurement result to a globally recognised standard. Traceability is what allows a result generated in a laboratory in Hyderabad to be compared with confidence against one generated in Hamburg or Houston. It is the backbone of data integrity, the enabler of regulatory acceptance, and the foundation of scientific credibility.
For CRMs, traceability is a defining attribute. It is not optional, not aspirational — it is the feature that justifies the confidence placed in the result. When Dr. Mohanty cites ISO and NABL requirements for traceability, he is pointing to an expectation that regulators around the world share: that measurement data be anchored to a verifiable, global chain of standards.
Where This Leaves Us
Accuracy, Dr. Mohanty reminds us, does not begin in the instrument. It begins with the reference you choose.
This is a simple statement with far-reaching implications. It asks every laboratory professional — from QC technician to analytical director — to examine not just how they measure, but what they measure against. It asks organisations to invest in the quality of their reference systems with the same seriousness they invest in instrumentation. And it asks the industry, collectively, to stop treating the reference as an afterthought.
At Advent, this is not a theoretical conversation. Over the years, the organisation has been building capability in reference material characterization, traceability systems, and analytical reliability — quietly, methodically, with scientific rigour. The next episode of the Dr. Mohanty’s Masterclass will explore how these principles translate into practical solutions for modern analytical science.
Until then, the question to carry forward is this: Do you know exactly what your results are anchored to?
