Most IVD manufacturers use calibration practices designed to reduce costs, not to ensure accuracy… and here’s what that really costs you.
The calibration crisis no one’s talking about
A Mayo Clinic study found that calibration errors in a single analyte, calcium, could cost the U.S. healthcare system up to $199 million annually. Not from equipment failure. Not from operator error. From standard calibration practices that most labs consider “good enough.”
Here’s the uncomfortable truth: calibration is the most critical and most neglected step in the IVD analytical process. And the materials you’re using to calibrate? They might be undermining everything you do next.
Why your current calibration approach is a gamble
A 2024 review in Advances in Laboratory Medicine exposes a gap that should concern every IVD manufacturer: there are no clear guidelines for proper calibration procedures beyond what’s in the manufacturer’s insert.
And those instructions? “Somewhat minimalistic, aimed at saving time and, consequently, costs,” according to Sonntag and Loh, the review authors.
The industry standard… that isn’t actually standard
Most routine procedures rely on:
- Single-point calibration
- One measurement per calibrator (no replicates)
- Quality control to catch errors after they’ve already affected patient samples
This creates what the authors call “infinite regression possibilities”. With only one calibration point, any curve can theoretically fit… you’re drawing a straight line with one dot.
Worse, when QC materials come from the same source as your calibrators, they can mask calibration errors instead of revealing them. ISO 15189:2022 now explicitly recommends third-party QC materials for this reason.
The hidden risk in your calibrator supply
Beyond procedural gaps, there’s a material problem most manufacturers treat as unavoidable.
Human plasma calibrators: the triple threat
- Traceability gaps under IVDR
Regulations require traceability to reference materials, but not how often manufacturers must re-demonstrate it. A Norwegian glucose study found concentration increases over seven years across healthy and diabetic populations. The cause? Uncorrected lot-to-lot reagent drift. Not clinical deterioration. Manufacturing drift.
- 20% coefficient of variation
Plasma-based materials typically show CV around 20%. This variability doesn’t just affect your calibration curve, but it compounds with single-point measurement uncertainty to create analytical shifts that slip past QC.
- Supply chain roulette
Plasma availability fluctuates. When supplies tighten, you’re forced to switch lots mid-validation, introducing the exact drift and bias proper calibration should prevent.
What best-in-class manufacturers do differently
Leading IVD companies are solving this from two angles.
- Fix the process
The Sonntag and Loh review is clear: blank first, use two-point calibration minimum covering your analytical range, measure duplicates for each point, and recalibrate with every lot change or instrument maintenance.
Not revolutionary. Just rigorous.
- Fix the materials
Human Fc monoclonal antibodies eliminate plasma variability at the source.
BCell Design’s approach: engineered antibodies with human Fc that deliver CV below 5%, complete clone-to-vial traceability for IVDR compliance, and 10+ year guaranteed supply that decouples you from plasma market volatility.
These materials work across your entire workflow: calibrators with minimal uncertainty, third-party QC materials as ISO 15189:2022 recommends, and commercial kits where lot-to-lot consistency isn’t negotiable.
The ROI calculation you’re not making
Sonntag and Loh ask a question every quality manager should answer: “Why designate such extensive resources to quality control procedures while neglecting calibration?”
QC catches errors. Calibration prevents them.
Manufacturers investing in both proper calibration procedures and reproducible materials see:
- Fewer batch failures and reduced troubleshooting costs
- Faster regulatory approval with complete traceability
- Market differentiation through demonstrated reliability
- Protected supply chains immune to plasma shortages
The competitive wedge
IVDR compliance, ISO 15189 requirements, and customer demands for consistency are converging. The manufacturers winning are those who recognize that calibration isn’t a cost center but a competitive advantage.
What will you choose?
- Option1: invest in preventing calibration errors
- Option 2: keep spending to catch them downstream.
Next steps
If you’re still relying on plasma-based calibrators and single-point procedures, you’re playing roulette with regulatory compliance and product consistency.
BCell Design provides human Fc monoclonal antibodies that eliminate the three critical risks plasma introduces: traceability gaps, lot variability, and supply uncertainty. CV below 5%, guaranteed. Supply secured for 10+ years. Complete documentation from clone to vial.