In aseptic manufacturing, no surface is exempt from regulatory scrutiny. The 2022 revision of EU GMP Annex 1 reinforces the expectation that contamination control be approached holistically, encompassing not only cleanroom environments and personnel, but also the equipment that supports critical processes. The regulation distinguishes between cleaning — the physical removal of dirt and particulates — and bio-decontamination, which involves validated microbial reduction. Facilities must demonstrate both where relevant, based on risk.
While cleanroom surface bio-decontamination is typically managed through robust procedures, support equipment often receives less structured attention. Many legacy facilities continue to rely on manual cleaning, such as spray and wipe techniques, for pass-through or benchtop devices. Under Annex 1, this may still be acceptable in low-risk or low-bioburden areas, provided the approach is risk-assessed and appropriately documented. However, where surfaces are hard to access or microbial risk is higher, manual cleaning and bio-decontamination may not be robust and repeatable.
Find out more about how ProXcide HPV System can benefit your facility
Cleaning vs. Bio-decontamination: Understanding the Difference
Annex 1 requires facilities to distinguish between cleaning and bio-decontamination as part of a defined contamination control strategy. Cleaning is the prerequisite physical removal of residues and debris. Bio-decontamination follows, reducing bioburden to acceptable levels using validated disinfection methods employing disinfectants effective against bacteria and fungi, including spore forms. Where bio-decontamination is required, its efficacy must be demonstrated through validated studies.
Risk Factors in Clean Air Devices: What to Consider
Certain equipment types have historically received less rigorous decontamination attention. These include:
- Pass-through chambers, which frequently transfer materials between different grades of rooms
- Incubators and fridges/freezers, which can support microbial growth if not properly and routinely decontaminated
- Non-gassed biosafety cabinets and isolators, which contain glove ports, filters, and recessed surfaces
- Portable or benchtop equipment, often moved between zones and at risk of cross-contamination
When these risks go unaddressed, even a single overlooked surface can compromise a contamination control strategy. This can lead to environmental monitoring failures, batch deviations, or audit findings that challenge the effectiveness of your Contamination Control Strategy (CCS).
This is particularly relevant in cleanrooms where manual cleaning remains the norm, especially for support equipment. While manual methods can be acceptable under Annex 1 when properly validated and documented, they must be applied with consistency and supported by a clear risk-based rationale. With the reliance on operators to execute them, the risk of human error increases — making the process inherently less robust and more difficult to defend during inspection.
What Makes a Bio-Decontamination Method 'Validated' Under Annex 1?
Validation under Annex 1 is not simply about demonstrating microbial reduction. It demands a structured, documented approach that proves a method performs consistently under defined conditions. A validated bio-decontamination process must:
- Establish efficacy across representative surfaces and geometries
- Demonstrate reproducibility across multiple runs
- Account for worst-case loads and material compatibility
- Provide traceability through protocols, test data, and reporting
Annex 1 places the burden of proof squarely on the cleanroom user. Process validation is a core responsibility, and regulators expect data to support each element of a contamination control strategy.
Questions to Ask When Selecting a
Bio-Decontamination Approach
- Is there a means to automate the decontamination process?
- Are all surfaces accessible for cleaning and bio-decontamination?
- Is the equipment moved between zones or used across
different product lines?
- Can the equipment be disassembled easily, or does it
include enclosed volumes?
- What level of consistency and traceability does the
current method provide?
- Can the solution scale across multiple facilities or operational models?
- What is the risk to my contamination control
strategies when decontamination goes wrong?
These are strategic contamination control decisions, central to both compliance and operational efficiency. The right solution should meet compliance expectations and integrate seamlessly into your operational flow.
Hydrogen Peroxide Vapour (HPV) for Robust Bio-decontamination: Aligning with Annex 1 Principles
Annex 1 also broadly requires that ‘Where fumigation or vapour disinfection (e.g. Hydrogen Peroxide Vapour) of cleanrooms and associated surfaces are used, the effectiveness of any fumigation agent and dispersion system should be understood and validated.’ This underscores the fundamental need for robust validation for any vapour-based bio-decontamination.
Adherence to the principle of validated effectiveness is paramount. HPV technology, with its inherent characteristics, is well-suited for achieving reliable bio-decontamination for a range of support equipment and surfaces within controlled environments.
A validated HPV approach offers:
- Consistent, uniform coverage of irregular and enclosed surfaces
- Automated cycles that remove risk of operator variability
- Traceability and data capture to support audit readiness
Consistency in microbial reduction, documentation, and execution distinguishes a regulatory-aligned process from a routine SOP. It’s also essential that bio-decontamination cycles are tailored to the specific enclosure size, surface load, material compatibility, and expected bioburden to ensure efficacy and safety.
The Value of Portable
Bio-Decontamination Systems
Fixed bio-decontamination systems have been shown to serve large-scale environments effectively but are not always suitable for enclosed or small-volume equipment. Portable, validated systems offer:
- Deployment within sealed units like pass-through chambers, isolators and other containment enclosures
- Decontamination of equipment that cannot be readily disassembled like incubators and fridges
- Faster turnaround without disrupting production schedules
By integrating portable bio-decontamination units, facilities can achieve validated, sporicidal cycles without manual intervention in targeted areas. This not only maintains robust microbial control and supports cleanroom compliance but also preserves operational flow, ensuring that all critical equipment within the Contamination Control Strategy (CCS) is addressed with verifiable efficacy.
Embedding Equipment Decontamination Into Your CCS
- Conducting risk assessments to define appropriate decontamination requirements
- Selecting technologies compatible with the equipment’s materials, geometry, and location
- Validating the chosen approach and maintaining thorough documentation
Manufacturers must take a risk-based approach—considering each asset’s design, intended use, and potential to impact contamination levels in controlled areas. What matters is a clear, defensible rationale for every decision within the CCS.
Raising Standards Without Increasing Risk
Annex 1 signals a shift toward risk and evidenced based contamination control. Whether essential to production or supportive to process, clean air devices now demand the same level of scrutiny as other environmental risks.
If your current approach to equipment decontamination relies on legacy assumptions, now is the time to re-evaluate. Compliance isn’t about doing what’s familiar, it’s about adapting to what’s required. In an Annex 1 world, the bar isn’t where it used to be. It’s higher and it’s probable.
References:
European Medicines Agency. (2022, August 25). Annex 1: Manufacture of sterile medicinal products (PE 009-15, Part I). European Commission. https://health.ec.europa.eu/system/files/2022-08/20220825_gmp-an1_en_0.pdf
