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Calibration · No. 20A Team Artifact

Calibration — a shared record

A calibration curve is a team artifact

One analyst’s tight replicates describe one analyst. The lab’s real precision is the spread across people, days and instruments, and the curve every result depends on belongs to all of them.

By Medrado Analytical Innovations · Foundations, No. 20 · for the working analyst

In this piece · 5 min read
  1. Three kinds of spread
  2. Check the curve, or rebuild it
  3. Chart the curve itself
  4. The failed point
  5. Protect it like the record it is
  6. The judgement

Ask an analyst how precise their method is and they will usually quote a number from their own hands: five injections, one afternoon, a relative standard deviation (RSD, the scatter as a percentage of the average) under 1%. It is a true number. It is also the most flattering one the lab will ever produce, because it leaves out everything that changes when the work is shared: the second analyst, the other balance, the Tuesday column, the standard made last month by someone on nights. In most labs a calibration curve is not one person's work. It is built, checked, reused and relied on by a team, and the precision that matters is the team's.

Three kinds of spread

Run the same sample several times and the results scatter. How much depends on what changes between runs.

If the same person runs it with the same equipment on the same afternoon, the tight spread you see is called repeatability. If a different laboratory runs it, the much wider spread is reproducibility. Between the two sits the one a working lab lives with. When the same lab runs the method on different days, with different analysts and different equipment, the spread is wider than repeatability; that spread is called intermediate precision.1 It is at least as large as repeatability, often larger, and it is the precision that matches how the lab actually reports: a result from whoever was on shift.

The same pattern shows up one level higher: collaborative studies, which send the same samples to many laboratories, exist precisely to measure the extra spread that appears between labs.2 The general lesson carries down into a single lab: every source of variation you leave out of a precision study makes the number smaller than the truth.

So the precision study that matters is one where the people who run the method each prepare and run the same standards across several days. Validation guidance such as ICH Q2 describes how intermediate precision is studied when a method is validated, and your quality system says how it is watched afterwards; the point here is simply that "analyst" is a real source of variation and belongs in it. Small differences in technique (how a syringe is rinsed, how a bubble is cleared, how long a flask is left to reach temperature) are real effects, and they only show up when more than one person does the work.

Check yourself

Answer in your head first, then open the answer. Any question can go into your Quiz me.

  1. Which spread is the precision a working lab actually has?

    Show the answer
    “When the same lab runs the method on different days, with different analysts and different equipment, the spread is wider than repeatability; that spread is called intermediate precision.”

    See it in the article ·

  2. A calibration check fails. What does that mean for the curve?

    Show the answer
    “A calibration check asks whether the existing curve still holds; when it fails, the curve is no longer evidence, and you recalibrate.”

    See it in the article ·

  3. A chart of slopes steps every time the analyst changes. What is it showing?

    Show the answer
    “A slope that steps when the analyst changes is a people effect, and a chart of slopes is how you see it.”

    See it in the article ·

Glossary

Repeatability
The spread when the same person runs the method with the same equipment in one sitting.
Intermediate precision
The spread within one lab across different days, analysts and equipment.
Reproducibility
The spread between different laboratories.
Audit trail
A secure, time-stamped record of who created, changed or deleted what, and when.

Sources

  1. ICH Q2(R2), Validation of Analytical Procedures (2023): intermediate precision.
  2. D. Harvey, Analytical Chemistry 2.1, ch. 14, "Developing a Standard Method": collaborative (interlaboratory) testing (LibreTexts).
  3. US Code of Federal Regulations, 21 CFR 11.10(d) and (e).
  4. US FDA, Data Integrity and Compliance With Drug CGMP: Questions and Answers, Guidance for Industry (December 2018).