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Sterilization

Objectives and principles of sterilization

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Sterilization is intended to render  Reusable Medical Devices free from viable microorganisms.

Terminal sterilization of RMDs in healthcare facilities is based on 4 key concepts

  1. Sterility Assurance Level (SAL): As it is not feasible to control the sterility of each device, the objective of sterilization is expressed as a probability of microorganism survival: not more than 1 viable microorganisms in an amount of one million sterilised items or a 10-6 Sterility Assurance Level.
  2. Overkill : The quantity, type and location of microorganisms which may be present on a RMD even after careful cleaning is not known. Safety margins are hence taken. Studies determine the microorganisms displaying the highest resistance to the sterilizing agent (usually spores). Sterility tests are performed with highly concentrated inoculum containing more than 1 million microorganisms that have demonstrated the greatest resistance to the sterilization process. This conservative safety margin above the highest amount and nature of real life contamination is called overkill.
  3. Preservation of medical device: RMD must remains fully functional and safe for use after sterilization. Compatibility is checked by the RMD Manufacturer. Manufacturer specifies the maximal number of sterilization cycles to which the RMD can be exposed before being disposed or repaired.
  4. Preservation of sterility by packaging (terminal sterilization): Medical devices are enclosed in a sterile barrier system (SBS) which preserve sterility until use. Non terminal sterilization processes meet the SAL criteria but sterility is lost after the cycle.
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Immediate Use Steam Sterilization (IUSS) also called flash sterilization is an example of a non terminal sterilization process used for emergency point of use reprocessing. Compared to terminal steam sterilization processes, drying and cooling are shortened to limit cycle time. Risk of recontamination is increased by humidity present on the device after cycle completion. Some countries do not allow IUSS. In regions where IUSS is tolerated it is usually advised to challenge and evaluate need for emergency point of use reprocessing of RMD. WFHSS recommends to convince the surgery department that IUSS should not be used anymore.

 

International standards  propose different methods to establish the SAL according to the overkill method. The most frequently used is the half cycle approach.

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106 (6 log) inoculums (most commonly spores such as Geobacillus stearothermophilus) are exposed to the sterilizing agent at various exposure times.

The surviving germs at each exposure time are counted. Results are plotted on a semi-logarithmic graph (Log reduction versus time).

If the survivor curve is linear the inactivation kinetic can be characterized by a D-Value i.e. the time needed to divide the number of viable microorganisms by 10 (or 1 log reduction).

Doubling the time needed to kill 106 test microorganisms (half cycle) yields the 10-6 SAL (full cycle).

For example, if it is experimentally shown that a given sterilization process has  a D-value of 2 minutes,  6 log reduction is obtained in 12 minutes (half cycle) and by extrapolation, a 24 minutes exposure time yields the probability that less than 1 million items will be free of viable microorganisms.

Terminal sterilization takes place at high temperature or at low temperature (see below).

High temperature terminal sterilization

Saturated Steam sterilization (also referred to as moist heat sterilization or steam sterilization), is the preferred sterilization method for non-heat sensitive devices. Most commonly use temperatures are 134°C or 132°C (270°F) with exposure time between 3 minutes to 18 minutes (depending on local guidelines or regulation). Items that are not compatible with 132 or 134°C, may be processed at 125 °C or by low temperature sterilization.

Saturated means that steam is at equilibrium between liquid and vapor phase. The high efficacy of saturated steam sterilization is due to the release of latent heat when steam condensates on surface of medical devices.

Dry heat is the oldest high temperature steriization method. Compared to saturated steam sterilization, T°C and time required for efficacy are higher and longer (typically 17°C x 60 minutes or 15°C x 150 minutes), penetration performances are poor and cool down times are longer. Dry is protein fixative. Dry heat is banned in a growing number of countries and WFHSS recommends to not use it. Anymore.

 

Low temperature terminal sterilization

Low temperature sterilization processes are adapted to RMDs (LTS) that cannot withstand high temperatures.

Low temperature terminal sterilization processes currently in use in healtcare facilities are:

  • Vaporized hydrogen peroxide (vH2O2)
  • Ethylene Oxyde (EO),
  • Low temperature steam formaldehyde (LTSF) ,

Cycles are specific to each low temperature technology.

EO and LTSF are not anymore used in some countries as they are carcinogenic (EO) or potentially carcinogenic (LTSF) and because of their fixative properties.

Use of EO and LTSF is country dependent.

Radiation sterilization (ionizing – gamma, e-beam or high energy X-Ray, or non ionizing (UV) ) is not used for reprocessing of RMD in healthcare facilities and will not be taken into account in the present chapter.

 

Terminal sterilization processes are covered by international standards.

Terminal sterilization process cycles

Terminal sterilization cycles may typically be divided in 3 phases.

  1. Conditioning brings the packaged RMD in conditions required for efficient sterilizing agent efficacy. It usually includes a removal of air or non condensable gases by vacuum phases to ensure direct contact between the sterilizing agent and RMD surfaces. For some sterilization modalities, a condensate layer is used to soften spore membrane (EO) or convert the sterilizing in active liquid phase (LTSF). If needed, the cycle is preceded by a preconditioning phase (for instance to bring the load at specified temperature and relative humidity level).
  2. Exposure phase brings RMD surfaces in contact with the sterilizing agent during the time required to at least achieve the SAL. Exposure phase might be unique like in steam or repeated (usually an even number of times). See half cycle approach above.
  3. Removal stage renders the load safe for unloading. Time is given to allow the load to cool down (Steam) or for chemical residues to reach level safe for operators. For some modalities using toxic chemical, additional aeration time is applied during or after the cycle to permit desorption of toxic residues.

Details for each terminal sterilization modality are provided below.

 

Saturated Steam

Saturated means that steam is at equilibrium between vapor and liquid phase. Temperatures above 100°C are obtained by increasing the pressure in the chamber. The condensation of steam on device surface releases latent heat that highly contributes to steam sterilization efficacy. Condensation and temperature decreases are compensated by pressure adjustments.

  1. Conditioning: In modern steam sterilizers, air and non-condensable gases are withdrawn by vacuum pulses and progressively replaced by saturated steam within packaging and RMDs cavities.
  2. Exposure: Temperature and exposure time are defined by local regulation and guidelines: 132°C (270°F) or 134°C with exposure times ranging from 3 minutes to 18 minutes (prion cycle). RMD which cannot withstand 132°C or 134°C may be processed at 121°C or 125°C for a minimum of 15 minutes or undergo low temperature sterilization.
  3. Removal: Vacuum and heating are used to remove condensate. After opening door, load is allowed to cool down  for safe handling by the operator.

Vaporized hydrogen peroxide

Vaporized hydrogen peroxide is obtained by vaporization of a hydrogen peroxide solution (commonly at 59% H2O2). Concentration can be adjusted at higher levels in some systems,. Cycles are specific to each manufacturer and adapted to the geometry of devices (lumen or non-lumen) and materials. Vaporized H2O2 diffuses through H2O2 permeable packaging  into device cavities and forms a thin layer of highly active condensate on surfaces. H2O2 decomposes as it interacts with surfaces. dose and diffusion processes are optimized to minimize the concentration and time combination needed to achieve the SAL on all surfaces while preserving fragile heat sensitive material.

  1. Conditioning: Air is withdrawn by low vacuum (single or multiple pulses). Measures may be taken to accelerate the elimination of residual humidity (vacuum pulse or others).
  2. Exposure: vH2O2 cycles include an even number of exposure phases (2 or more) separated by a vacuum step. The second half of the cycle achieves the 10-6 Air is admitted in the chamber to improve circulation in complex geometries before a vacuum step and new exposure phase or final removal stage.
  3. Removal: Water and H2O2 residues left or adsorbed by the load are eliminated by vacuum/venting alternations and catalytic filtering. In some equipment this process is supported by plasma phases.

Ethylene Oxide

EO is a colorless, poisonous gas that attacks the cellular proteins and nucleic acids of microorganisms. EO is carcinogenic to humans and flammable. Specific ventilation and safety precautions are hence required. EO is protein fixative. EO is highly penetrative in materials but fails to cross spore envelopes. A relative humidity rate above 75 % is required to soften spore envelopes and render them permeable to EO.

 

 

  1. Conditioning: Residual air is removed by vacuum pulses and progressively replaced by  EO and steam. Pre-conditioning of the load at predetermined temperature and humidity levels may be required.
  1. Exposure: The load is exposed at stabilized gas concentration and temperature for defined times. Concentration, temperature and exposure range from 450 to 1200 mg/l, 37 to 63°C and 1 to 6 hours respectively.
  2. Removal: EO concentration in the chamber is reduced by pressure pulses. Aeration reduces toxic EO residual from exposed absorbent materials. Aeration takes place within the sterilization chamber or after transfer in secured conditions in an aeration cabinet. Aeration time ranges from 8 to 12 hours at 50°C to 48 hours at 60°C.

Low temperature steam formaldehyde

Formaldehyde (HCHO) is a colorless gas, classified as potentially carcinogenic and is protein fixative. Formaldehyde is obtained by vaporization of a solution of formalin (concentration below 35%). A relative humidity rate above 75% is required for microbial efficacy. Formaldehyde gas is highly soluble in water and combines with steam condensate to create a layer of active liquid formalin.

  1. Conditioning: An initial vacuum removes air from the chamber and load. Residual air is progressively replaced by pulses of steam and formaldehyde.
  2. Exposure: During the exposure time, the chamber is maintained at specified temperature, sterilant concentration, pressure and humidity. LTSF operates at 80, 65, 60, 55 or 50° C (176, 149, 140, 131 or 122° F) with a realtive humidity of 75 to 100 %.
  3. Removal: The formalin condensate and formaldehyde residues are removed from the load by repeated vacuum and steam flushes followed by vacuum. Formaldehyde collected in the sterilizer drain is diluted before evacuation.

Dry heat

Dry heat achieves sterilization by means of conduction. The heat is absorbed by the RMD and moves within RMD layer-by-layer. For the RMD to be fully sterilized, it needs to reach the required temperature. Compared to steam sterilization, dry heat temperature and time required for efficacy are higher and longer, the penetration performance is inferior, and cool down-times are longer. Dry heat is banned in a growing number of countries.

  1. Conditioning: The chamber is brought to the targeted temperature. Dry heat is preferably forced throughout the sterilization chamber.
  2. Exposure time: The load is maintained at the target temperature for a predetermined time. Common temperature and time are 160 °C (320 °F) for 2 hours, 170 °C (340 °F) for 1 hour, or at 190°C in the case of High Velocity Hot Air sterilizers.
  3. Removal: The chamber and load are given time to cool down for operator safety. Cooling may be prolonged after opening the door.

wfhss

WFHSS strongly recommends the rapid replacement of dry steam sterilizers by saturated steam sterilizers.

Sterilization process implementation

This paragraph describes the key process implementation concepts common to all sterilization modalities.

Before first use, the sterilizer undergoes process validation. Details of process validation and routine controls for saturated steam and vH2O2 can be found in process validation chapter.

Standard operating procedures (SOP) describe operations and controls to be performed before, during and after the sterilization cycle.

SOP takes into account equipement and RMD manufacturer IFU. All tasks are performed by trained and formally authorized personnel and in accordance with local regulations or guidelines (when required).

  • Periodic controls of sterilizer equipement are recommended by international standard or defined by local rules (for example daily leak test, air removal and steam penetration tests for steam sterilizers).
  • Expiry dates of consumables (sterilant, packaging and others) are checked. Items past expiry date are discarded according to manufacturer IFUs and local regulations.
  • Load composition and cycles are in accordance with instructions for reprocessing provided by the medical device manufacturers. Total mass of load, number of items are within limits specified by sterilizer manufacturer IFUs. Packaging manufacturer IFUs also need to be taken into followed.
  • Use of chemical indicators (CI) is according to applicable guidelines. Many guidelines recommend or require a visible type 1 chemical indicator on each package to differentiate processed from non processed items. Type 3, 4, 5 or 6 indicators may also be placed within packages. Chemical indicators types are defined by International standard ISO 11140-1. The classification from 1 to 6 has no hierarchical significance.
  • Use of Biological Indicators (BI) is according to local guidelines or regulation. Recommendations or requirements depend on countries regulation or guidelines and sterilization technology. BI comply to international standard ISO 11138. Biological Indicators and CI may be combined to a process challenge device (PCD)
  • Load distrbution allow a uniform distribution of the sterilizing agent. Mass is distributed evenly according to sterilizer manufacturer recommendations, usually with heavier items on the bottom. Items do not touch chamber walls.
  • Loading operations takes into account occupational health and safety considerations to avoid injuries.
  • After the end of the cycle, door chamber opening and unloading are according to sterilization modality and sterilizer manufacturer instructions. Time is allowed for load cooling or residue elimination.
  • Cycle parameters are controlled and automatically recorded.
  • Unloading starts after load cooling or elimination of chemical residues. Operators wear gloves.
  • Each item is visually controlled (for humidity, packaging integrity). If not done before sterilization at the packaging stage, labelling is implemented for traceability. Color changes of Type 1 CI are controlled. BI (see below) are incubated according to manufacturer IFUs.
  • Load release responsibilities are described and assigned. Back-ups are organized to ensure process continuity.
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Load release (i.e. formal authorization to distribute the RMD for storage and use) is performed by an accredited person.

The person in charge of load release is ideally different from the one in charge of unloading controls.

Requirements for load release vary between countries and sterilization technologies. Minimum requirements are:

  • Cycle parameters are within specified tolerances
  • Color changes of Type 1 CI are conform to CI manufacturer IFU
  • No damage of package, no humidity detected by visual inspection of items.

When additional CI are required by the SOP, they are analysed according to CI Manufacturer IFU. CI placed in packaging are controlled by operating room personnel at point of use. In case of positive CI at point of use, a risk analysis determines if some or all items must be reprocessed or recalled.

When BI are used, they are incubated and read according to BI manufacturer IFU. In case of a positive BI, a risk analysis is performed. Depending on the documented outcome of the risk analysis, the load may be entirely or partially released, additional controls may be required, and the load or items for which doubts remain are reprocessed.

For saturated steam sterilization, use of BI at each cycle is not required in most countries. In some countries like US, BI controls are recommend daily or weekly and with every implant. In Europe, BI are not routinely used for steam cycles. For other sterilization modalities, practices depends on national best practices or rules.

In any case, BI and CI cannot be used to avoid control of cycle parameters.

Sterilization and quality management

Sterilization processes are defined, validated and implemented in accordance with quality management and process validation principles:

  • Sterilizers are installed in accordance with manufacturer recommendations. Instructions for use and certificates are available. It is verified that equipment operates as intended and that conditions for SAL are met.
  • Updated Standard operation procedures (SOP) are available.
  • Routine controls are specified.
  • Occupational health & safety measures are in place (in particular for sterilizer loading and unloading)
  • Training on SOP, routine controls, occupational health & safety and waste management takes place and knowledge is periodically verified.
  • Maintenance plans are in place for sterilizers and ancillary equipments.
  • Traceability is operational.

WFHSS key recommendations for sterilization

  1. Steam at 134°C or 132°C is the preferred sterilization method  when allowed by medical device manufacturers. Exposure times vary according to country regulations or guidelines. Dry heat sterilization must be replaced by steam and IUSS (flash steam sterilization) must be avoided
  2. For RMDs that are not compatible with steam at 132°C or 134°C, RMD manufacturer IFUs specify the low temperature ssterilization methods and cycle that can be used. When several methods are approved by the RMD manufacturer, choice may be guided by applicable regulation and guidelines and occupational health and safety considerations.
  3. Sterilization process validation , routine control and load release are in accordance with quality management principles and IFUs of RMD and sterilizer manufacturers.
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