Residual Hydrogen Peroxide: Everything You Need to Know

What Remains After Sterilisation and Why Does Residual Hydrogen Peroxide Matter?

If you’ve ever worked in a lab long enough, you’ll know that the smallest details often carry the biggest weight. I was reminded of this recently while reviewing the latest regulations on vapourised hydrogen peroxide (VHP) sterilisation. It took me back to a moment in our lab when we were validating cleaning instructions for a complex device. We were confident in the sterilisation process – but what about what’s left behind? 

That lingering question, what remains after sterilisation, is at the heart of toxicological risk assessments for VHP residues. And it’s not just a theoretical concern. Residual hydrogen peroxide, if not properly assessed, can pose a real risk to patients. 

What is VHP Sterilisation and Which Standards Govern it?

VHP is widely used for low-temperature sterilisation of medical devices. ISO 22441:2022 sets the benchmark for how these processes should be developed, validated and monitored. But even when a medical device sterilisation cycle meets all the requirements, trace amounts of hydrogen peroxide can remain on or within the device. 

That’s where toxicological risk assessment comes in. ISO 22441 requires manufacturers to demonstrate that any residuals, especially under worst-case sterilisation conditions, fall below safe limits. But here’s the catch: there’s no universal limit for hydrogen peroxide residues. Instead, ISO 10993-17 provides a framework for assessing toxicological risk based on the specific device, patient contact and exposure.

How do Chemical Characterisation and Risk Assessment Work Together?

Before we can assess the risk, we need to know what we’re dealing with. ISO 10993-18 guides the chemical characterisation of medical devices, helping us identify and quantify extractable substances – like hydrogen peroxide – under simulated clinical conditions. 

Once we’ve identified the compound, ISO 10993-17 steps in to assess its toxicological impact. This involves: 

• Hazard identification: What kind of harm could hydrogen peroxide cause? Genotoxicity? Irritation? Systemic toxicity? 

• Exposure estimation: How much of the substance could realistically reach the patient? 

• Risk determination: Is the exposure below the Toxicological Screening Limit (TSL)? If not, we need to calculate a Tolerable Intake (TI) or Tolerable Contact Level (TCL). 

Why is the Margin of Safety (MoS) the Final Checkpoint?

One of the most practical tools in ISO 10993-17 is the Margin of Safety (MoS). If the MoS is greater than 1, the exposure is considered safe. If it’s 1 or below, further analysis is needed. It’s a simple number, but it represents a complex interplay of extraction data, toxicological thresholds, and clinical use scenarios. 

Why do Extraction Studies Matter for Hydrogen Peroxide Testing?

Extraction studies are the backbone of chemical characterisation. ISO 10993-18 offers several approaches, from exhaustive extraction to exaggerated or simulated conditions. But with hydrogen peroxide, we need to be cautious. Elevated temperatures, for example, might cause decomposition, leading to misleading results. 

Choosing the right extraction method isn’t just about following a standard. It’s about understanding the medical device, the sterilisation process, and the clinical context. And yes, it needs to be justified and documented. 

How do Patient Contact and Device Design Influence Residue Risk?

Not every part of a medical device contacts the patient. ISO 10993-17 focuses only on those regions that do. For example in flexible endoscopes only the insertable portion and lumen are relevant for residue testing. Identifying these regions is critical for meaningful validation. 

Similarly, the composition of the test article must reflect the actual product. Different materials absorb and release residues differently. So the test item must include all relevant materials in the correct ratios. 

Why do Product Families and Worst-Case Scenarios Matter?

Testing every single medical device isn’t always feasible. ISO 22441 allows for the creation of product families, where one worst-case item is tested to represent the group. But again, the rationale must be solid and documented. 

Worst-case sterilisation conditions, like maximum dosage or exposure time, must also be identified. These are the scenarios most likely to leave behind residual hydrogen peroxide, and they form the basis for extraction and risk assessment. 

How Should Volatile Residues Like Hydrogen Peroxide be Handled?

Hydrogen peroxide is volatile. That means it can degrade or evaporate before analysis, leading to underestimation of risk. ISO 10993-7 offers guidance on sample handling to ensure accurate results. Whether that means immediate analysis, freezing eluents, or simulating pre-use conditions. 

What Should MedTech Leaders Take Away from This?

At Test Labs, we know that medical device sterilisation doesn’t end when the cycle finishes. What remains – however small – can have a big impact. That’s why we take toxicological risk assessment seriously, especially when it comes to VHP residues. From extraction studies to Margin of Safety calculations, every step matters. 

Because in the end, it’s not just about meeting standards. It’s about protecting patients.