Steam sterilization is the sterilization method using saturated steam under pressure and is the method of choice for thermostable medical devices. It works by denaturing cellular components and requires direct contact of the steam with every product surface. EN ISO 17665 specifies the requirements for the development, validation, and control of application of a moist heat process for medical devices, covering saturated steam and other moist heat variants. Regulatorily, two separate fields of application arise: sterilization by the manufacturer before placing on the market and the reprocessing of reusable products in healthcare facilities.
Cycle Types and Process Parameters
Common holding temperatures are 121 °C and 134 °C, with the required holding time decreasing as the temperature rises. A distinction is made between gravity displacement processes, where air is displaced by incoming steam, and processes with fractionated pre-vacuum, where multiple evacuation and steam admission steps actively remove air. Only fractionated pre-vacuum reliably reaches hollow bodies, porous goods, and packaged instrument sets. The lethal effect is described by the F-value relative to 121.1 °C; critical parameters are temperature, holding time, saturated steam conditions, and complete air removal. Non-condensable gases, superheated or wet steam prevent killing despite correct temperature indication.
Load, Hollow Bodies, and Lumens
Validation according to EN ISO 17665 is not performed for the sterilizer alone, but for defined loading patterns. Heat distribution in the chamber and heat penetration into the product at the thermally least favorable point must be demonstrated. For long, narrow, or unilaterally closed lumens, steam penetration is the limiting factor, which is why process challenge devices with hollow body geometry are used. Load density, arrangement, packaging type, and drying phase are part of the validated configuration; residual moisture in the load is considered a deviation because it can moisten the sterile barrier. Changes to the load, packaging, or system trigger revalidation.
Packaging and Sterile Barrier System
The sterile barrier system must be steam-permeable and form a microbial barrier again after drying. For products sterilized in their final packaging, the requirements of the EN ISO 11607 series of standards apply to the design and validation of packaging systems; in healthcare facilities, sterilization containers and sterilization wraps are additionally used. Packaging and cycle are not independent: paper-film pouches, containers, and wraps differ in air removal, steam penetration, and drying behavior. Therefore, the packaging is co-tested during performance qualification and stipulated in the release specification.
Routine Control and Release
Routine control relies on physical parameter recording and supplementary tests. These include the daily Bowie-Dick test for assessing air removal and steam penetration, the vacuum leak test, the evaluation of steam and feed water quality, and chemical indicators as batch identification. Biological indicators use spores of Geobacillus stearothermophilus and are used for validation and periodic testing. For sufficiently characterized processes, release is parametric, i.e., based on the recorded physical values against the validated specification, and not on end-product testing.
Distinction between Manufacturer Sterilization and Reprocessing
If the manufacturer sterilizes before placing on the market, the result is a product marked as sterile; for Class I, the involvement of the Notified Body, limited to the sterilization aspect, then applies according to Article 52(7) of Regulation (EU) 2017/745. If, however, a healthcare facility reprocesses a reusable product, it is considered reprocessing: the basis is the manufacturer’s instructions according to EN ISO 17664-1, the validated procedures of the operator, and, in Germany, § 8 of the Medical Device Operator Ordinance with the joint recommendation of KRINKO and BfArM. The reprocessing of single-use products is a third, distinct case and is only permissible with national authorization according to Article 17. The pharmaceutical law perspective on moist heat and terminal sterilization is presented in the entry on Sterility Assurance Level and Terminal Sterilization.
Relevance for clinical trials
In clinical trials of reusable instruments or implant instrument sets, steam sterilization is relevant to the study in two ways. Firstly, the sponsor must provide evidence of the validation of the process and packaging for sterile-provided investigational products. Secondly, if products are reprocessed at the study site, the sponsor must submit the validated reprocessing instructions and specify in the study plan how cycles are documented and deviations recorded. If reprocessing at the site deviates from the instructions, this constitutes a product defect or a study plan deviation with an impact on data quality.
Practically, this means establishing training and documentation at the site early: which load, which cycle, which evidence, and which traceability exists between the sterilization batch and the study participant. The number of permissible reprocessing cycles is also a product characteristic that must be considered in the study plan. Full-service CROs like Mediconomics support sponsors and manufacturers in aligning reprocessing instructions with the study plan, in site training and documentation requirements, in evaluating deviations, and in medical writing for study and regulatory documents.
Frequently Asked Questions (FAQ)
When is a gravity displacement process sufficient, and when is fractionated pre-vacuum needed?
For massive, unpackaged goods with a free surface, gravity displacement may suffice. For porous goods, packaged sets, and hollow bodies with lumens, fractionated pre-vacuum is required, otherwise residual air prevents steam penetration.
What is the purpose of the Bowie-Dick test?
It daily checks air removal and steam penetration in the test pack. It is not proof of the sterility of a batch and replaces neither validation nor the recording of process parameters.
May a manufacturer provide reprocessing instructions without their own validation?
No. The information according to EN ISO 17664-1 must be validated for the specific product, including cleaning, disinfection, packaging, sterilization, and the number of permissible reprocessings.
Regulatory References
- Regulation (EU) 2017/745, Annex I Chapter II Section 11 and Article 52(7)
- Regulation (EU) 2017/745, Article 17 – Single-use products and their reprocessing
- EN ISO 17665 – Moist Heat: Development, Validation, and Control
- EN ISO 17664-1 – Reprocessing information to be provided by the manufacturer
- § 8 Medical Device Operator Ordinance and Recommendation of KRINKO and BfArM on Reprocessing
