Low-Temperature Sterilization Method Selection: EtO vs. VHP vs. Ozone

When a reusable instrument can’t tolerate steam — because heat, moisture, or pressure would damage it — sterile processing has to reach for one of several low-temperature methods instead. The problem infection preventionists, sterile processing leadership, and quality/risk teams actually face is not “which low-temperature method is best,” because none of them is universally best. It’s a selection problem: which method fits this specific device, on this facility’s cycle-time and throughput constraints. Choosing the wrong one produces either a device the method can’t legitimately sterilize (an IFU mismatch that surfaces on survey) or a bottleneck that pushes cases behind schedule.

This guide walks through the three low-temperature methods most US hospitals choose among for heat- and moisture-sensitive instrumentation — ethylene oxide (EtO), vaporized/plasma hydrogen peroxide (VH2O2, commonly marketed as hydrogen peroxide gas plasma systems), and ozone sterilization — as a decision matrix by material compatibility, lumen/channel restriction, and cycle time, not as a single-method explainer.

Why steam isn’t an option for these devices in the first place

Under the Spaulding classification, critical devices (those entering sterile tissue or the vascular system) and many semicritical devices require sterilization or, at minimum, high-level disinfection. Steam remains the default sterilization method for anything that can tolerate it — it’s fast, well-validated, and the cheapest per cycle. Low-temperature methods exist specifically for the instruments that can’t: rigid and flexible endoscopic equipment with heat-labile optics or adhesives, powered instruments with electronics or lithium batteries, certain plastics and polymers that deform or degrade under steam’s heat and moisture, and devices with long, narrow lumens where steam penetration and drying are already marginal even before heat sensitivity is considered.

The manufacturer’s instructions for use (IFU) is the actual starting point, not a preference. A device’s IFU specifies which sterilization methods it has been validated against — a facility choosing a method the IFU doesn’t list is operating outside the device’s validated use, regardless of which method is technically capable of killing the same organisms.

The three methods, compared

Each method trades speed, material compatibility, and infrastructure differently. None dominates on every axis.

Ethylene oxide (EtO)

EtO gas has the broadest material compatibility of the three — it penetrates long, narrow lumens and tolerates a wide range of plastics, adhesives, and electronic components better than the alternatives, which is why it remains the default for devices nothing else can process. The tradeoff is time: an EtO cycle runs at a low temperature over an extended exposure phase, and the gas itself is toxic and flammable, so processed items require a substantial post-cycle aeration period to purge residual EtO to a safe level before the device can be handled or used — aeration commonly extends the total turnaround from exposure to release by many hours beyond the exposure phase itself, and the exact exposure and aeration times are set per the sterilizer’s cleared cycle and the device’s IFU, not a single fixed number across all EtO systems. That total turnaround is the single biggest reason EtO has become a last-resort method in most hospitals rather than a routine one: it is reserved for the subset of instruments — long, narrow-lumen flexible endoscopic accessories and certain powered or electronic devices — that genuinely can’t be processed any other way, and facilities plan for it as an overnight or next-day turnaround, not a same-shift one.

EtO sterilization for medical devices is governed in the US and internationally by the ANSI/AAMI/ISO 11135 series, and facilities running EtO also carry real occupational-exposure and facility obligations under OSHA’s ethylene oxide standard (dedicated exhaust ventilation, area monitoring, and — depending on scale — permit and emission requirements) that the other two methods don’t create in the same way.

Vaporized/plasma hydrogen peroxide (VH2O2)

Hydrogen peroxide vapor systems — including the hydrogen peroxide gas plasma variants common in US hospitals — are the fastest of the three, with cycles typically completing in well under two hours and no aeration period required, because the byproducts (water vapor and oxygen) aren’t toxic residues that need to off-gas. That speed is why VH2O2 has become the default low-temperature method for the majority of hospital semicritical/critical devices that don’t tolerate steam but also don’t need EtO’s lumen reach.

The tradeoff is material and configuration restriction, not exposure time. VH2O2 cannot process cellulose-based materials (paper, cloth, and most standard sterilization wrap — devices go in dedicated non-woven or Tyvek packaging instead), cannot process liquids or powders, and has real lumen restrictions: each sterilizer and load configuration carries a manufacturer-defined “lumen claim” — a specific internal diameter and length combination, sometimes requiring a diffusion restrictor or booster accessory — beyond which the system is not validated to sterilize the device. A device that clears that claim processes quickly and reliably; a device with a longer or narrower lumen than the claim covers has to go to EtO instead, IFU permitting, even though it would otherwise be a good fit for VH2O2 on every other axis.

The 2022 international standard for this method, ISO 22441, sets the requirements for developing, validating, and routinely controlling a low-temperature vaporized hydrogen peroxide sterilization process for medical devices — the VH2O2 equivalent of what ISO 11135 does for EtO.

Ozone

Ozone sterilization generates ozone gas on-site from USP-grade oxygen and medical-grade water, and — like VH2O2 — breaks down to non-toxic byproducts (oxygen and water vapor) at the end of the cycle, so it doesn’t carry EtO’s aeration burden. Cycle times sit between the other two methods: longer than a typical VH2O2 cycle, but without EtO’s multi-hour aeration tail added on top, so total turnaround is usually still same-day.

Material compatibility is the axis to check carefully with ozone. It handles many common instrument materials — most stainless steel, many rigid plastics, and titanium — but ozone’s oxidizing action is incompatible with some rubbers, certain polymers, and copper- or zinc-based metals, which can degrade or discolor under repeated exposure. Because ozone systems have a smaller installed base in US hospitals than EtO or VH2O2, device manufacturers are less likely to have published an ozone-specific validation in the IFU at all — the practical constraint is often data availability (has this device been validated against ozone by its manufacturer?) rather than a known incompatibility. There is no single dedicated ISO standard for ozone sterilization analogous to ISO 11135 or ISO 22441; ozone systems are typically developed and validated against the general framework in ISO 14937 (requirements for characterizing a sterilizing agent and validating a sterilization process), applied to the specific agent.

A decision matrix by material compatibility and cycle time

Read the table as a filter, applied in order: confirm the device’s IFU lists the method at all; check whether its lumen dimensions clear that sterilizer’s validated claim; check for a known material incompatibility; only then does cycle time become the deciding factor between two methods that both pass the first three filters.

A practical selection framework

1. Start from the IFU, not the equipment on hand. The device manufacturer’s validated method list is the actual constraint. A facility with only VH2O2 installed cannot substitute it for a device whose IFU validates EtO only, without either the manufacturer extending validation or the facility accepting an off-label reprocessing decision that most infection prevention and risk programs won’t sign off on.
2. Check the lumen claim, not just “does it have a lumen.” VH2O2 and ozone systems publish specific validated internal-diameter/length combinations per load configuration — a device within that claim processes normally; a device outside it needs EtO, a longer-cycle VH2O2 configuration if the manufacturer supports one, or an alternate reprocessing pathway entirely.
3. Model turnaround against real case scheduling, the same way a sterile processing department sizes steam sterilizer and washer-disinfector capacity together — see CASRAI’s guide on sterile processing department equipment purchasing. A single EtO cycle’s overnight turnaround means the facility needs either duplicate instrument sets or a scheduling buffer; VH2O2’s speed changes that math substantially for devices it can process.
4. Verify biological indicator monitoring matches the method. The organism and indicator system differ by sterilization modality — EtO cycles are typically challenged with Bacillus atrophaeus spores, while hydrogen peroxide cycles are typically challenged with Geobacillus stearothermophilus spores (the same organism used for steam biological indicators). Confirm sterile processing is using the correct indicator type for whichever method a device is routed to, not a generic one.
5. Document the routing decision, not just the outcome. Where a device could plausibly go to more than one method, record why a specific method was chosen (lumen claim, turnaround need, material restriction) — this is the kind of specific, verifiable rationale that holds up under a Joint Commission or state survey tracer, versus a routing decision nobody can explain after the fact.

Where this goes wrong in practice

• Treating “low-temperature” as one interchangeable category. Sterile processing staff sometimes reroute a device from one low-temperature method to another under time pressure without rechecking the IFU and lumen claim for the new method — a device validated for EtO’s lumen reach is not automatically validated for a VH2O2 system’s tighter claim.
• Assuming ozone or VH2O2 compatibility because “it’s plastic.” Material class alone doesn’t predict compatibility; the manufacturer’s specific validation (or the absence of one) is the determining fact, not a general assumption about a polymer family.
• Underestimating EtO’s real turnaround when it’s the only validated option. A facility that keeps only one EtO-only device’s instrument set in circulation, without a duplicate to cover the overnight cycle, creates a recurring case-delay risk that a one-time purchasing decision (buying a second set, or requesting expanded IFU validation from the manufacturer) would resolve.
• Skipping the facility-side EtO obligations. Occupational exposure monitoring and dedicated exhaust aren’t optional add-ons to running EtO — they’re part of what makes running EtO at all a real facility decision, not just an equipment purchase.

Frequently asked questions

Is ethylene oxide sterilization being phased out of hospitals?

Its hospital use has shrunk substantially as vaporized/plasma hydrogen peroxide systems have taken over most of the routine low-temperature caseload, but EtO has not been phased out — it remains the only validated option for a real subset of long, narrow-lumen and electronic devices. Facilities with EtO capability keep it specifically for that subset rather than routine use.

Can a device validated for EtO automatically be processed with vaporized hydrogen peroxide instead?

No. Method substitution is only valid if the device manufacturer’s IFU specifically lists that alternate method, including any lumen claim it applies to. Absent that, switching methods is an off-label reprocessing decision, not a routine equipment choice.

What’s the difference between “vaporized hydrogen peroxide” and “hydrogen peroxide gas plasma”?

Both use hydrogen peroxide vapor as the sterilant; gas plasma systems add a plasma phase (typically generated by radiofrequency or microwave energy) at the end of the cycle to help break down residual hydrogen peroxide into water and oxygen faster. For material-compatibility and lumen-claim purposes covered in this guide, the practical constraints are the same family of considerations — check the specific sterilizer’s validated claims rather than assuming plasma and non-plasma vaporized hydrogen peroxide systems behave identically.

Does ozone sterilization require aeration like EtO does?

No. Ozone breaks down into oxygen and water vapor at the end of the cycle, the same category of non-toxic byproduct as vaporized hydrogen peroxide, so it doesn’t carry EtO’s dedicated aeration period.

For the broader reprocessing framework these methods sit inside — including where sterilization is required versus where high-level disinfection is the accepted minimum — see CASRAI’s guide to the Spaulding classification, and for the validation obligations that apply once a method is selected, see sterilization validation across steam, EtO, and radiation methods.