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#SEROscience: Why Accelerated Stability Studies Can Be Misleading for Serum Biomarkers

Accelerated stability studies are widely used in pharmaceuticals and in vitro diagnostics (IVD) to predict product shelf-life. Based on the Arrhenius equation, these tests assume that degradation rates double for every 10°C increase in temperature. But is that assumption valid for complex biomolecules like enzymes and proteins in serum controls?

In this article, we explore how accelerated stability testing can sometimes misrepresent real-world product performance and how to interpret these results wisely.

The Problem: Non-linear Behavior in Real-World Conditions
Many assume that results from high-temperature storage can be linearly extrapolated to normal storage conditions (typically +2 to +8 °C). However, this is often not the case for biological materials like serum-based quality controls. Why? Because biomarkers don’t always behave predictably under heat stress. Elevated temperatures can trigger molecular changes - such as protein denaturation, enzyme inactivation, or light-induced degradation - that don’t occur under recommended storage conditions. This can lead to:

  • False negatives: assuming a product won’t meet shelf-life requirements when it actually does.
  • Poor decisions: discarding stable biomarker sources or altering formulations unnecessarily.

Study Insights: What We Observed at SERO
We conducted a series of accelerated (+20 and +30 °C) and real-time (+4 °C) stability studies on lyophilized clinical chemistry (CC) and cardiac immunoassay (IA) control materials. Here's what stood out:


🔹 Mismatch Between Accelerated and Real-Time Stability

  • Biomarkers like ALT, AST, ALP, LDH, CK, glucose, and bilirubin failed accelerated testing - but were stable for 4 years at +4 °C.
  • In contrast, creatinine and total protein showed consistent stability in both settings.

🔹 Cardiac Immunoassay Controls

  • 8 out of 15 markers failed accelerated testing.
  • Yet all passed real-time testing over a 3-year period.

Key Takeaways for Labs and Manufacturers

Don’t Rely on Q10 Alone
The common Q10 = 2 rule oversimplifies degradation in biological systems. Protein folding, enzyme activity, and oxidation are not purely temperature-driven.

Use Accelerated Studies for What They Are Good At

  • Identifying vulnerable biomarkers early in development
  • Screening alternative sources (e.g. PTH variants)
  • Monitoring lot-to-lot consistency or formulation changes
  • Investigating transport-related temperature excursions

Always Validate with Real-Time Data
Accelerated testing is valuable - but only when supported by long-term, real-time data. Relying on one without the other risks underestimating product performance.

Conclusion
Accelerated stability studies can’t fully predict the shelf-life of serum-based control materials, but they can guide smarter decisions when used correctly. Understanding the non-linear behavior of biomarkers is essential for developing robust, reliable IVD controls.

Read the poster here.