OBJECTIVE:
- To provide a procedure for the Performance Qualification and the Periodic Verification of Steam Sterilizers.
SCOPE:
- The procedure is applicable to the performance qualifications and the periodic Verifications for the Steam sterilizers installed in KPL.
RESPONSIBILITY:
- Microbiologists/Trained personnel
- To perform the activities as per procedure.
- To report any non compliance to the procedure
Head-Respective Department (Location)
- To ensure the activities are performed as per procedure
- To investigate any non compliance to the procedure
ACCOUNTABILITY :
Department Head :
- To ensure the procedure is implemented at their site
- To investigate any non compliance to the procedure.
Head Quality Assurance –
- To ensure implementation of procedure at their site.
- To verify investigation of any non compliance to the procedure
- To ensure the implementation of procedure at KPL.
- To revise the SOP on need base
Performance Qualification of Steam Sterilizer :
| Test | Stage | No. of Run or Cycle during Performance Qualification | |
| Chamber Integrity test applying vacuum (Vacuum leak test). | Start of equipment -Prior to the insertion of Thermocouples sensors | One cycle daily during PQ or the cycle run in routine can be considered. | |
| Chamber Integrity test applying vacuum (Vacuum leak test). | After insertion of thermocouple sensors | One cycle | |
| Steam Quality test | Non Condensable gases, Superheat test, Dryness fraction test, Chemical and Microbial Quality of Steam | Once at start of PQ or can be done separately through protocol based study prior to sterilizer qualification. | |
| Determine the air pockets (Bowie dick test) | After confirmation of Chamber Integrity test | Daily during performance qualification or the cycle run in routine can be considered. | |
| Air detector Test (if facility is available) | After confirmation of Bowie dick test | Once at start of PQ | |
| Heat distribution study of empty chamber | After confirmation of Air detection Test | Consecutive three cycle for each type of cycle (e.g. Standard, HPHV and cycle for 115ºC) | |
| Air filter sterilization (if facility is available) | During the qualification study | Once at start of PQ | |
| Heat Distribution cum Penetration study or only Heat Penetration study with chemical and microbiological challenge test. | After confirmation of Heat distribution of empty chamber | Three cycle for each type of load or when separately done one cycle of Heat distribution and 3 cycles of Heat Penetration | |
| Chamber Integrity test applying vacuum (Vacuum leak test). | After removal of thermocouple sensors | One cycle | |
| Steam Condensate Analysis | During the qualification study | One sample testing from the drain port of the steam sterilizer. | |
| Thermal door lock override test (esp. For the Lab sterilizers) | At the end of the liquid cycle/media cycle | One cycle review. (If facility is available) |
| Test Frequency | Test to be performed periodically | No. Of cycle during periodic verification |
| Daily | Vacuum Leak test | One cycle (Routine cycle can be considered) |
| Bowie Dick Test (Automatic Control Test) | One cycle (Routine cycle can be considered) | |
| Weekly | Weekly safety checks | – |
| Bowie Dick Test (Automatic Control Test) | One cycle (Routine cycle can be considered) | |
| Quarterly test | Weekly safety checks | – |
| Verification of calibration of sterilizer instruments | – | |
| Yearly and re-qualification test | Yearly safety checks | – |
| Vacuum leak test (without temperature sensors connected) | One cycle (Routine cycle can be considered) | |
| Vacuum leak test (with temperature sensors connected) | One cycle (Routine cycle can be considered) | |
| Bowie Dick Test (Automatic Control Test) | One cycle (Routine cycle can be considered) | |
| Verification of calibration of sterilizer instruments | – | |
| Empty cycle Heat Distribution | One cycle of each type (e.g. Standard, HPHV etc.) | |
| Air filter sterilization test (if facility is available) | One cycle | |
| Tests for periodic verification as per the validated load patterns of Loaded chamber heat distribution cum penetration in Performance Verification/ Re-qualification | One cycle for each load pattern | |
| Vacuum leak test (after sensor removal) | One cycle (Routine cycle can be considered) |
| Test Frequency | Test to be performed periodically | No. Of cycle during periodic verification |
| Daily | During the holding time of the first cycle of the day, observe and note the reading on the cycle counter, chamber temperature indicator and chamber pressure indicator Bowie Dick Test (Automatic Control Test) | First cycle of the day (Routine cycle can be considered) One cycle (Routine cycle can be considered) |
| Weekly | Weekly safety checks | – |
| Vacuum leak test | One cycle (Routine cycle can be considered) | |
| Bowie Dick Test (Automatic Control Test) | One cycle (Routine cycle can be considered) | |
| Quarterly test | Weekly safety checks | – |
| Verification of calibration of sterilizer instruments | – | |
| Yearly and re-qualification test | Yearly safety checks | – |
| Vacuum leak test (without temperature sensors connected) | One cycle (Routine cycle can be considered) | |
| Vacuum leak test (with temperature sensors connected) | One cycle (Routine cycle can be considered) | |
| Bowie Dick Test (Automatic Control Test) | One cycle (Routine cycle can be considered) | |
| Verification of calibration of sterilizer instruments | – | |
| Empty cycle Heat Distribution | One cycle of each type (e.g. Standard, HPHV etc.) | |
| Tests for periodic verification as per the validated load patterns in Performance Verification/ Re-qualification (i.e. HDHP) | One cycle for each load pattern | |
| Vacuum leak test (after sensor removal) | One cycle (Routine cycle can be considered) | |
| Thermal door lock override test. (if facility is available) | One cycle (Routine cycle can be considered) |
| Test | Stage | No. of run or cycle during Performance Qualification |
| Heat distribution study of empty chamber | After Operational Qualification | Consecutive three cycle for each type of load |
| Heat Distribution cum Penetration study or only Heat Penetration study with chemical and microbiological challenge test. | After confirmation of Heat distribution of empty chamber | Three cycle for each type of load or when separately done one cycle of Heat distribution and 3 cycles of Heat Penetration |
- Time
- Temperature and Pressure
- Moisture
- Direct steam contact
- Air removal Drying
Type of Loads and Load Configurations :
Type of Loads:
- Non Porous Load/ Hard Goods Load
- Porous Load
- Liquid Load
Load Configuration:
- Fixed Load/Fixed Configuration
- Fixed Load/Variable Configuration
- Variable Configuration
Justification of Sensor locations :
- As per HTM 2010- 12 external temperature sensors are required for Qualification of Steam Sterilizer.
- Example: Locations mentioned in SOP-16 minimum locations.
- The farthest point from the inlet of steam in the steam sterilizer. (i.e. Normally towards the Non-Sterile side of the steam sterilizer).
- All the corners of the steam sterilizer & Center. (e.g. 8 corners and 6 centers i.e. On the horizontal and vertical planes, if the sterilizer is provided with two shelves).
- The locations of the probes shall preferably be near to the inbuilt sensors of the sterilizer.
- Drain point of the steam sterilizer where, hypothetical temperature shall be lowest.
- At a point nearest to the steam inlet port.
- The 16 locations from the above can be selected for heat distribution studies based on site specific requirements or any other justified locations can be incorporated.
Acceptance Criteria for various tests :
Overkill Approach :
A risk based justification/assessment shall be performed if Overkill approach is followed for sterilization and/or if the time period for sterilization is extended beyond the desired/specified timelines for the product/media or any accessories.
If any adverse impact is observed on the product/media or accessories during sterilization then the overkill approach shall not be followed and only 6 log reduction (6D) sterilization approach shall be followed.
Vacuum Leak Test (Chamber Integrity Test): The Vacuum leak rate shall not exceed 1.3 mbar/min (0.0013 bar/min) for porous load sterilizer and laboratory sterilizer.
Air Detector Test: A leak rate sufficient to depress the temperature in the test pack shall not be more than 2 ° C from the temperature in active chamber discharge.
Bowie Dick Test (Automatic Control Test): Bowie Dick test indicator shall show a uniform color change to black throughout the entire pattern or as per the manufacturer recommendation.
Steam Quality Test:
Non condensable Gases: The test shall be considered satisfactory if the fraction of non-condensable gases does not exceed 3.5%.
Superheat Test: The test shall be considered satisfactory if the superheat measured in the expansion tube does not exceed 25°C.
Dryness Fraction: The test shall be considered satisfactory if the following requirements are met:
a. the dryness value is not less than 0.90 (if metal loads are to be processed, the dryness value shall not be less than 0.95);
b. throughout the operating cycle, the temperature measured in the steam service pipe is within 3° C of that measured during the superheat test.
Chemical Quality of Steam: Quality should comply WFI Specification.
Microbial Quality of Steam: Quality should comply WFI Specification.
Air Filter Sterilization:
- The temperature shall be within 121.1 to 124 ºC after achieving the sterilization hold temperature.
- All exposed biological indicator shall not show any growth or color change as per the instruction given in the supplier manual.
- Color change of chemical indicator shall be observed as per the vendor instruction after exposure to the sterilization cycle.
Empty Chamber Heat Distribution Study (ECHD):
- Equilibration time for heat distribution study shall not be more than 30 seconds for chamber size more than 800 L and 15 seconds for chamber size less than 800 L.
- The temperature inside the steam sterilizer shall be within 121.1 to 124 ºC throughout the sterilization hold period.
- Variation of temperature within the particular external temperature sensor during hold time shall not fluctuate more than ± 1ºC.
- Variation of temperature between external temperature sensors during hold time shall not be more than 2ºC.
- Fluctuation in temperature in 02 temperature mapping probes during the Empty chamber heat distribution cycle beyond 121.1 to 124 ºC shall be acceptable and the probes shall then only be considered for the validation/qualification studies with a proper justification. But fluctuation shall not be applicable for the Drain/Active chamber discharge probe.
- If pressure measurement is verified (i.e. If facility is available) , the pressure on the pressure gauge and that recorded on the printer during the holding/plateau period shall be within the acceptance criteria as specified by the manufacturer of steam sterilizer.
- Biological Indicators are not required in the evaluation of empty chamber temperature distribution.
- The F0 Calculation for the evaluation of lethality shall begin at 100°C and shall continue till the completion of the cycle i.e. Process End Temperature.
Loaded Chamber Heat Penetration and Distribution Study (HPHD):
- Fluctuation in temperature in 01 temperature mapping probes during the Loaded chamber heat distribution cum penetration cycle beyond 121.1 to 124 ºC shall be acceptable and the probes shall then only be considered for the validation/qualification studies with a proper justification. But fluctuation shall not be applicable for the Drain/Active chamber discharge probe.
- If pressure measurement is verified (i.e. If facility is available) , the pressure on the pressure gauge and that recorded on the printer during the holding/plateau period shall be within the acceptance criteria as specified by the manufacturer of steam sterilizer.
- The F0 Calculation for the evaluation of lethality shall begin at 100°C and shall continue till the completion of the cycle i.e. Process End Temperature.
Loaded Chamber Heat Penetration and Distribution Study (HPHD):
- For sterilization of Laboratory Media ensure slow exhaust (to reduce the stress on container integrity and minimize boil over)
- As the laboratory media are considered self indicating with respect to sterility, the use of internal biological indicators during the validation cycle is not required for the Media loads.
- When sterilizing the Bio waste /Decontamination media ensure that the sterilization is done in sealed containers.
- Employ an Overkill method for the bio waste/Decontamination media sterilization preferably at 121.1°C for minimum of 30 mins such that the materials sterilized are safe for contact and disposal.
- If the process under validation is for Terminal Sterilization in terminal sterilizer then the samples from the hottest regions of the load shall be used for evaluation of material stability and quality.
- The evaluation should encompass the essential quality attributes with attention focused on known and potential new impurities and those materials that receive the most heat input.
Loaded Chamber Heat Penetration and Distribution Study (HPHD):
- Appearance, other physical property and container closure integrity shall also be evaluated.
- The location of the sensor inside the glass or plastic containers filled with fluid, media or powders etc. should be as mentioned in the Figure
- The sensor shall be firmly supported and the container should not leak while sterilization.
- The sensor should be located on the vertical axis and inserted to a depth of 85±5% of the height of the container.
- If flexible material or containers are used then the sensor should be located as near as practicable to the centre of the fluid and if required shall be supported with a support to its position.
Biological F0 value :
The biological F0 value for biological indicator strip exposed during the sterilization can be calculated as follows.
F0 = D121.1 (log A – log B) … (b)
Where, D121.1 = D value of the biological indicator at 121.1ºC
A = Biological indicator concentration or spore population
B = Desired level of non-sterility (Sterility Assurance level- 10-6)
For example:
Biological indicator strips supplied by … Co., Lot # … Expiry …
D121.1 =1.7min, Z value=8.8 min
Spore population (A) = 2.7 x 106
F0 = 1.7 x (log (2.7 x 106) –log 10-6)
F0 = 21.13 min.
Therefore, the minimum F0 value required for more than 12 log reduction of the Geobacillus stearothermophilus indicator shall not be less than 21.13 minutes.
Calculation of Biological F0 value calculation shall be done as per the formula mentioned in 5.6.13.4 and record the details in SOP.
Routine frequency for Bowie Dick Test & Vacuum leak test :
Steam sterilizer available in Sterile manufacturing sites and it’s Microbiology lab
– Vacuum Leak Test (VLT) – Daily once during operation (First cycle of the day)
– Bowie Dick test – Daily once during operation (First cycle of the day)
Steam sterilizer available in Microbiology lab of Non sterile manufacturing sites.
– Vacuum Leak Test (VLT) – Once in a week
(If history of VLT failure, it should be Daily)
– Bowie Dick test – Daily once during operation (First cycle of the day)
If any sites are following the site specific stringent frequency shall continue the same.