Central Service 4/2017 RECOMMENDATIONS | 265

Recommendations by the Quality Task Group (102)

Low-temperature sterilization processes

Authors: B. Amann, T. Appel, M. Bertram, P. Bröcheler, A. Carter, D. Diedrich, C. Diekmann, A. Forster, M. Härtel, I. Mock, C. Schmid, M. Schreiner
E-mail: qualitaet@dgsv-ev.de

|| 1 Introduction
For medical device (MD) reprocessing there are various processes that must be taken
into account. The continuous, rapid pace of developments in medical technology is driv-
ing the introduction of ever more complex systems and medical devices, which in turn
make increasingly more stringent demands on reprocessing. For example, there is a
sharp rise in the number of ➜ THERMOLABILE (heat-sensitive) MDs, such as flex- ➜ THERMOLABILE MD can only be
ible endoscopes, camera heads, ultrasonic transducers and electronic sensors, which sterilized with low-temperature processes.
can only be sterilized with low-temperature processes.
Even the preceding cleaning and disinfection steps are carried out at lower tempera-
tures for the material compatibility reasons mentioned. Instead of the normally used
thermal disinfection (e.g. A0 3000 – at around 90 °C), chemothermal disinfection (ad-
dition of a disinfectant) is employed at temperatures of generally less than 60 °C.
Likewise, instead of the generally more popular steam sterilization process at temper-
atures of 134 °C, for sterilization of heat-sensitive medical devices low-temperature
sterilization at much lower temperatures (e.g. 50 – 70 °C) is used.
In the medical setting in Germany, Austria and Switzerland the following ➜ LOW- ➜ LOW-TEMPERATURE PROCESSES
TEMPERATURE PROCESSES are employed: used in the medical setting.
–– Hydrogen peroxide sterilization with and without a plasma phase
–– Low-temperature steam and formaldehyde sterilization (LTSF)
–– Ethylene oxide sterilization
–– Gamma irradiation (industrial production)
If necessary, prionicidal activity must be taken into consideration. The KRINKO/BfArM
Recommendation* 2012, Annex 7, sets out measures to curtail the risk of transmission
of CJD/vCJD via medical devices.
Other factors, e.g. cycle times, chamber volume, sterilization temperature, running
costs (such as maintenance and validation) and energy costs, should be taken into ac-
count at the time of procurement.

|| 2 Processes
2.1 Hydrogen peroxide sterilization with and without a plasma phase Hydrogen peroxide sterilization
Hydrogen peroxide sterilization is a low-temperature sterilization process with ac-
tivity in temperature ranges below 60 °C. Most sterilizers operate at a temperature of
around 50 °C – 55 °C.
The cycle times chosen will depend on the respective system (sterilizer model and de-
sign) as well as on the design of the MD (lumen, length, materials). The information
supplied by the sterilizer manufacturer and the reprocessing instructions for the spe-
cific medical device must be observed. Instrument compatibility with the sterilization
process and intended programme must be evaluated and a written record of that kept.
Partial prionicidal activity has been demonstrated for a number of processes (see also
the aforementioned KRINKO/BfArM Recommendation, Annex 7).

* KRINKO/BfArM Recommendation*: Recommendation for hygienic processing practices for medical de-
vices, jointly compiled by the Commission for Hospital Hygiene and Infection Prevention at the Robert Koch
Institute (RKI) and the Federal Institute for Drugs and Medical Devices (BfArM)
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➜ ADVANTAGES of hydrogen peroxide Hydrogen peroxide sterilization has the following ➜ ADVANTAGES:
sterilization –– Good material compatibility
–– Sterilant activity within a sterile container and/or soft packaging
–– Easy and safe handling
–– Short batch times
–– No water consumption
Hydrogen peroxide sterilization is a low-temperature process operated at negative
pressure. Hydrogen peroxide (H 2O2), the sterilant, is present in the process in gaseous
form. This gaseous environment enhances the oxidizing properties of H 2O2 promoting
the formation of free radicals endowed with potent biocidal activity. If a plasma phase
is incorporated, it generally provides for conditioning of the sterile supplies and/or in-
activation of the remaining H 2O2 or its remaining free radicals.
Few technical requirements apply here. This is a closed system that generally requires
only a power connection. During the process it must be ensured that the sterilant is able
to access all internal and external surfaces. In terms of health and safety, no additional
permit is needed for operation of a H 2O2 process.

2.2 Low-temperature steam and formaldehyde (LTSF) sterilization processes

LTSF sterilization is a low-temperature sterilization process based on the use of a for-
maldehyde-steam mixture in temperature ranges of around 60 – 70 °C .The sterilant
activity derives from a reaction with protein groups in the cells of microorganisms. In
Germany, the Hazardous Substances Regulation (GefStoffV Section 7(3) of 26 Novem-
ber 2010) and the German Technical Regulations on Hazardous Substances (TRGS)
513 must be observed.
The cycle times chosen will depend on the respective system (sterilizer model and de-
sign) as well as on the design of the MD (lumen, length, materials). The information
supplied by the sterilizer manufacturer and the reprocessing instructions for the spe-
cific medical device must be observed.
➜ ADVANTAGES of LTSF sterilization LTSF sterilization has the following ➜ ADVANTAGES:
–– Good material compatibility
–– Sterilant activity within a sterile container and/or soft packaging
–– Easy and safe handling
–– Acceptable batch times
–– Cost-effective process (procurement and operation)
In the sterilizer the formaldehyde solution is conveyed immediately to the steam gen-
erator, i.e. directly into the sterilization chamber without any contact with the outer re-
gions of the sterilizer. Unlike a steam sterilizer, in the LTSF sterilizer there are essen-
tially more load changes (fractionated prevacuum/pulsed vacuum method).
On completion of the process steps: formaldehyde injection (several fractionation cycles
and holding time), desorption (several fractionations in which the steam is separated
from the formaldehyde) and drying, the medical device can be safely withdrawn from
the sterilizer. During the process it must be ensured that the sterilant is able to access
all internal and external surfaces.
Based on the currently valid Hazardous Substances Regulation no permit is needed for
a fully automated sterilizer for medical use, with a chamber volume of less than 1 m3
and which complies with the state of the art (e.g. DIN EN 14180).
The structural requirements are similar to those applicable to steam sterilization.

2.3 Ethylene oxide sterilization

➜ ETHYLENE OXIDE STERILIZATION ➜ ETHYLENE OXIDE STERILIZATION is used for low-temperature sterilization in
is mostly used in industrial settings. industrial settings and increasingly less in the healthcare sector. The sterilant action
of ethylene oxide in combination with water derives from a change in the protein mol-
ecules in the cells of microorganisms. Both positive- and negative-pressure processes
are employed. Modern sterilizers use a mixture of 6% ethylene oxide and 94% carbon
dioxide since at normal pressure this mixture is no longer flammable. In Germany, the
Hazardous Substances Regulation (GefStoffV Section 7(3) of 26 November 2010) as well
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as the Technical Regulations on Hazardous Substances (TRGS) 513 must be observed.

Following ethylene oxide sterilization, desorption, or degassing, must be carried out
to release the ethylene oxide that had penetrated, or adsorbed on, the devices during
sterilization. The desorption time will depend on the composition of the MDs being
sterilized and on the packaging (the manufacturer’s instructions must be noted).
In addition to the technical requirements to be borne in mind for steam sterilization, a
catalytic converter is needed for the exhaust air as well as at least six air exchanges in
the installation room for compliance with the provisions of the German Technical In-
structions on Air Quality Control (TA Luft).

|| 3 Validation and routine monitoring

3.1 Hydrogen-peroxide sterilization with and without a plasma phase
Here the provisions specified in the “superordinate/higher-level” standard DIN EN
ISO 14937 must be observed since, to date, there is no dedicated ➜ STANDARD for ➜ THERE IS NO DEDICATED STAND-
validation and routine monitoring of this sterilization process. The Cleaning, Disinfec- ARD for H2O2 sterilization processes. The
tion and Sterilization Horizontal Working Group of the German Central State Body for provisions specified in the superordinate
Health Protection with Regard to Drugs and Medical Devices (ZLG) has published a standard EN ISO 14937 must therefore
document setting out minimum requirements. This is entitled “RDS 004 – Minimum be observed.
Content of Validation Reports for Peroxide/Peroxide Plasma Sterilization Processes
for Medical Devices”.

3.2 Low-temperature steam formaldehyde sterilization (LTSF)

Validation and routine monitoring of LTSF sterilization processes is conducted pursu-
ant to DIN EN 14180 and DIN EN ISO 25424. Test loads are used to demonstrate the
efficacy of the process.
In 2009, the German Society of Hospital Hygiene (DGKH) published a ➜ “RECOM- ➜ A RECOMMENDATION for valida-
MENDATION for validation and routine monitoring of sterilization processes with tion and routine monitoring of LTSF ster-
formaldehyde-containing steam for medical devices”. ilization processes has been published by
the German Society of Hospital Hygiene
3.3 Ethylene oxide sterilization (DGKH).
Validation of ethylene oxide sterilization processes in industry is an integral compo-
nent of the quality management system. The standard regulating validation and rou-
tine monitoring is DIN EN ISO 11135. DIN EN ISO 10993-7 regulates the residual gas
concentration.
No further details are given here on validation of this process since it is now rarely used
in healthcare institutions.

|| 4 Packaging
A distinction is made between soft and hard packaging. ➜ SOFT PACKAGING may ➜ SOFT PACKAGING may be made from
be made of paper, paper/foil, smooth and crepe paper, nonwovens, SMS and Tyvek®. different materials.
➜ HARD PACKAGING refers to a container (sterilization container) made of chrome ➜ HARD PACKAGING refers to steriliza-
steel, aluminium or solid plastic. The packaging requirements are regulated by DIN tion containers.
EN ISO 11607

4.1 Packaging for hydrogen peroxide sterilization with and without a plasma phase Packaging for hydrogen peroxide steriliza-
4.1.1 Soft packaging tion
Transparent packaging made of polyethylene/polyester composite film and Tyvek whose
suitability has been confirmed by the manufacturer of the sterilizer and packaging ma-
terials. This may be available as a single or double wrapper
4.1.2 Hard packaging
These are containers whose suitability has been confirmed by the manufacturer of the
sterilizer and packaging materials.

4.2 Packaging for LTSF sterilization Packaging for LTSF sterilization

4.2.1 Soft packaging
–– Paper and crepe paper
–– Nonwovens with cellulose component
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–– SMS made of 100% polypropylene || 5 References

–– Transparent packaging made of paper or nonwoven material with PET/PP foil 1 Verordnung zum Schutz vor Gefahrstoffen
–– Transparent packaging made of Tyvek and PET/PE (Gefahrstoffverordnung – GefStoffV).
2 Technische Regeln für Gefahrstoffe –
Only soft packaging whose suitability has been confirmed by the manufacturer of the TRGS 513 «Tätigkeiten an Sterilisatoren
sterilizer and packaging materials is used. mit Ethylenoxid und Formaldehyd.»
3 KRINKO/BfArM-Empfehlung «Anforde-
4.2.2 Hard packaging
rungen an die Hygiene bei der Aufberei-
These are containers whose suitability has been confirmed by the manufacturer of the tung von Medizinprodukten»
sterilizer and packaging materials. 4 DIN EN ISO 10993-7 «Biologische Beur-
teilung von Medizinprodukten – Teil 7:
4.3 Packaging for EO sterilization Ethylenoxid-Sterilisationsrückstände»
5 DIN EN ISO 11135 «Sterilisation von
4.3.1 Soft packaging Produkten für die Gesundheitsfürsorge -
–– Paper and crepe paper Ethylenoxid – Anforderungen an die Ent-
–– Nonwovens with cellulose component wicklung, Validierung und Lenkung der
Anwendung eines Sterilisationsverfahrens
–– SMS made from 100% polypropylene für Medizinprodukte»
–– Transparent packaging made from paper or nonwovens with PET/PP foil 6 DIN EN ISO 11607-1 «Verpackungen für
in der Endverpackung zu sterilisierende
–– Transparent packaging made from Tyvek and PET/PE Medizinprodukte – Teil 1: Anforderungen
Only soft packaging whose suitability has been confirmed by the manufacturer of the an Materialien, Sterilbarrieresysteme und
sterilizer and packaging materials is used. Verpackungssysteme»
7 DIN EN ISO 11607-2 «Verpackungen für
4.3.2 Hard packaging in der Endverpackung zu sterilisierende
Only containers whose suitability has been confirmed by the manufacturer of the steri- Medizinprodukte – Teil 2: Validierungsan-
lizer and packaging materials are used. forderungen an Prozesse der Formgebung,
Siegelung und des Zusammenstellens»
8 DIN EN ISO 14180 «Sterilisatoren für
medizinische Zwecke – Niedertemperatur-
Dampf-Formaldehyd-Sterilisatoren – An-
Table: Compatibility with the sterilization process forderungen und Prüfung»
VH202 9 DIN EN ISO 14937 «Sterilisation von
EO FORM Produkten für die Gesundheitsfürsorge –
STEAM (vaporized Dry heat
(Ethylene (Form- Allgemeine Anforderungen an die Cha-
(steam) hydrogen (hot air)
oxide) aldehyde) rakterisierung eines sterilisierenden Agens
peroxide)
und an die Entwicklung, Validierung und
Paper (paper bags, Lenkung der Anwendung eines Sterilisati-
YES YES YES No No onsverfahrens für Medizinprodukte»
crepe paper)
10 DIN EN ISO 25424 «Sterilisation von
Produkten für die Gesundheitsfürsorge –
Nonwovens with cellu-
YES YES YES No No Niedertemperatur-Dampf-Formaldehyd
lose component – Anforderungen an die Entwicklung,
Validierung und Routineüberwachung
SMS Material made of von Sterilisationsverfahren für Medizin-
YES YES YES YES No
100% PP produkte»
11 HAK RDS 004 «Mindestinhalte von Va-
Transparent packaging lidierungsberichten für Peroxid/Per-
made of paper or non- oxid-Plasma-Sterilisationsverfahren für
YES YES YES No No
woven material with Medizinprodukte»,Zentralstelle der Länder
PET/PP foil für Gesundheitsschutz bei Arzneimitteln
Transparent packaging und Medizinprodukten (ZLG), Horizonta-
les Arbeitskomitee Reinigung, Desinfek-
made of Tyvek® and No YES YES YES No
tion und Sterilisation (HAK RDS)
PET/PE
12 Handbuch Sterilisation – von der Reinigung
bis zur Bereitstellung von Medizinprodukt
Container* YES YES YES YES No Guido Wismer – Aarau/Toni Zanette, mhp
Verlag,Wiesbaden, ISBN 978-3-88681-
129-8
(Source: Recommendation by the Quality Task Group No. 79 – Central Service 3/2013)
13 Deutsche Gesellschaft für Krankenhaus-
*Evidence of the intended sterilization process must be available hygiene e.V. (DGKH) «Empfehlung für die
Validierung und Routineüberwachung von
Sterilisationsprozessen mit formaldehyd-
haltigem Wasserdampf nach dem NTDF-
Verfahren (Niedertemperatur Dampf und
Formaldehyd) für Medizinprodukte»
14 Wallhäußers Praxis der Sterilisation, Anti-
septik und Konservierung: Qualitätssiche-
rung der Hygiene in Industrie, Pharmazie
und Medizin; Hrsg. Axel Kramer, Ojan
Assadian, Thieme Verlag, Stuttgart, ISBN
9783131411211