Performance Qualification of Autoclave cum Bung Processor : Pharmaguideline

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Performance Qualification of Autoclave cum Bung Processor

Protocol and Procedure for Validation of Autoclave cum Bung Processor in sterile pharmaceuticals.

1.0  IDENTIFICATION OF CRITICAL CONTROL MONITORING PARAMETER

Before proceeding for Validation of Autoclave cum bung processor, following parameters
To be Checked –
·  Biological Indicator spore concentration must be 106.
·  Used media must be tested for its growth promoting test.
·  Calibration of Pressure Gauge
·  Calibration of Temperature Gauge
·  Calibration of PT -100 Sensors 

2.0  VALIDATION PROCEDURE

Validation of an Autoclave will be considered qualified for consistent and reliable performance (validated) on successful completion of the following –
·  Vacuum Leak Test
·  Bowie-Dick Test
·  Heat Distribution Study
·  Heat Penetration Study
·  Biological Challenge Test
·  Bung Processing
·  Flip off Seal
To qualify these tests, the equipment should fulfill the acceptance criteria described in the individual test procedures.

3.0 GENERAL CONSIDERATION/PREREQUISITE

A. Approved standard operating procedure of the equipment shall be available
B. Approved analytical methods for testing the samples collected during the processing
C. The impact analysis of the equipments shall be recorded in the summary sheet.
D. The installation and operational qualification of the equipment shall be successfully completed before the execution of the performance qualification.
E. All the deficiencies and discrepancies related to the equipment which affect the product quality and corrective action taken shall be recorded in the appropriate section of the protocol.
F. The analytical test results and other reports related with the equipment shall be attached with the performance qualification of the equipment and finally verified.

3.1 CALIBRATION DETAIL OF TEMPERATURE SENSORS

Equipment Name
Equipment I.D
Data of calibration
Due Date
Date of Pre
calibration
performed
  Date of Post
calibration
performed
Done by
Checked       by

3.2 CALIBRATION OF TEMPERATURE SENSORS:

•  Pre & Post Calibration of Temperature Sensors.
•  Pre & post calibration shall be carried out before starting and after completion of heat distribution cycles as well as heat penetration cycles.

PRE & POST CALIBRATION OF TEMPERATURE SENSORS:

•  PREPRATION OF ICE BATH:
Prepare a container with crushed ice and add enough purified water to ensure a proper
Slush allow the temperature to stabilize ensure to add sufficient crushed ice to maintain the equilibrium state of ice and water.

•  PROCEDURE :

Temperature sensors which are used for qualification study shall be calibrated in ice bath at approximately 0oc and in high temperature reference block at 50,100,121,150oc prior to its usage in qualification.
Record the temperature of all the sensors while putting them in ice bath after one minute of temperature stabilization. Put the individual sensor to the slot of high temperature reference block which is stabilized at required temperature. Record the temperature for five minute by data logger and attach the report with print outs with reports.

ACCEPTANCE CRITERIA:

No temperature sensors vary by 1oc in ice bath from the mean of temperatures shown by the calibrated thermometer during the data logging period.
No temperature sensors vary by 1oc in high temperature reference block from the mean of temperatures Shown by the calibrated thermometer during the data logging period.   

4.0  RE-VALIDATION CRITERIA:

Replacement of major component / instrument.
Major modification in the existing equipment / utility.
During monitoring if system is found to be malfunctioning.
Shifting of the equipment/Instrument from one location to another

5.0  SYSTEM DESCRIPTION:

Autoclave cum Bung processor is designed to sterilize the components which are used in the Aseptic area while processing the sterile products. Autoclave cum Bung processor having the chamber size 900×900×1500mm and is made up of SS 316L provided with 3 validation ports having 7 Nos of probes in Each validation port. Argon welding is done in joints of piping. Vacuum Break filter 5 inches long Having 0.2 micron porosity is provided Bung & flip off carriage made of SS 316L, 2 Nos. trolley made of SS 304L for keeping the components in autoclave cum bung processor provided during sterilization. All the system is controlled through PLC.

6.0  PERFORMANCE QUALIFICATION:

The Autoclave Cum Bung Processor will be qualified after validating (As per the methods outlined in this Protocol) the equipment for desired performance and its ability to sterilize different components and/or loads at the set parameters & set loading patterns, repeatedly & consistently.
The Autoclave Cum Bung Processor will be considered qualified for consistent and reliable performance (Validated) on successful completion of the following tests.
·  Vacuum Leak test (3 Trials with probe)
·  Bowie –Dick Test for Steam penetration (3 trials on 3 different days)
·  Steam qualification tests (3 trials on 3 different days)
·  Empty Chamber Heat Distribution studies (3 trials) with temperature mapping probes at different locations of the sterilizer chamber.
·  Loaded Chamber heat penetration studies (3 trials) for each sterilization load of fixed loading pattern, with temperature mapping probes inside the innermost possible layer of the load subjected for sterilization.
·  Bio-Challenge studies using Bacillus stearothemophilus spore strips (containing 106 or more spores per strip) during the heat distribution & heat penetration studies.
·  Estimation of the FO value achieved during the sterilization hold period at each temperature-mapping probe.
·  Quality of the steam condensate collected from the sampling point provided in the sterilizer  chamber condensate drain line for all loads.
·  Vacuum break filter integrity testing.   
To qualify these tests the equipment should fulfill the acceptance criteria described in the individual test procedures.

6.1 VACUUM LEAK TEST

•  Objective:

To verify the leakage in sterilization chamber during Vacuum Hold when the sterilization chamber is empty.

•  Procedure:

·  Operate the equipment as per SOP .
·  Set the parameters in PLC.

PROCESS PARAMETERS:

PRE VACCUM                     :
DELAY BEFORE HOLD      :
VACCUM HOLD TIME       :
CHAMBER PRESSURE       :
·  Record the vacuum Hold start pressure and vacuum Hold end pressure & calculate the actual leakage by subtracting the former from later.
Three consecutive cycles shall be carried out as per above parameters and procedure.

•  ACCEPTANCE CRITERIA

Vacuum leak rate should not be more than 0.013 BAR / 10 minute.

•  RESULTS:

Record the Observations in Annexure # 1

6.2  STEAM QUALITY TESTS

A continuous supply of saturated steam is required for steam sterilization. Too high a level of non-condensable gases will prevent the attainment of sterilizing conditions; too little moisture carried in suspension may allow the steam to become superheated during expansion into the chamber, while excess moisture may cause damp loads.
For all these tests, the steam should be sampled from the steam service pipe. The measurements are taken during a period of maximum steam demand, when steam is first admitted to the sterilizer chamber.
Presence of non-condensable gases more than the desired level might get accumulated within the sterilization chamber in the form of air pockets, which might affect steam penetration this leading to probable non-sterile unit.
NOTE: Silicone rubber tubing is porous to steam and should not be used to carry steam in these tests.

6.2.1 Non-Condensable Gas Test

Objective
Objective of this test is to ensure that,
·  The pure steam supply of the High Pressure High Vacuum Steam Sterilizer does not contain non-condensable gases more than the desire level (NMT 3.5%) when measured on-line during the standard sterilization cycle.
Procedure
This test is used to demonstrate that the level of non-condensable gases in the steam will not prevent the attainment of sterilization conditions in any part of the load. The method described should be regarded not as measuring the exact level of non-condensable gas, but a method by which the provision of acceptable steam quality can be demonstrated. The apparatus is shown and described in Figure No.1 (all sizes are nominal). Connect the needle valve to the steam service pipe as shown in Figure No.1. Assemble the apparatus so that condensate will drain freely from the long rubber tube into the sampling pipe. If the tube is too short, copper or stainless steel tubing may also be used. Fill the container with cold water until it overflows. Fill the burette and funnel with cold water, invert them and place them in the container. Draw out any air that has collected in the burette. With the steam sampling pipe out of the container, open the needle valve and allow steam to purge the air form the pipe. Place the pipe in the container, locate the end within the funnel, and add more cold water until it flows through the overflow pipe. Place the empty measuring cylinder under the container overflow. Adjust the needle valve to allow a continuous sample of steam into the funnel sufficient to cause a small amount of “Steam Hammer” to be heard. Ensure that all the steam is discharged into the funnel and does not bubble out into the container. Note the setting of the needle valve. Close the valve.
Ensure that the container is topped up with cold water and that the measuring cylinder is empty. Draw out any air present in the burette. Ensure that the sterilizer chamber is empty except for the usual chamber furniture. Select and start the operating cycle. When the steam supply to the chamber first opens, open the needle valve to the previously noted setting, allowing a continuous sample of steam into the funnel sufficient to cause a small amount of steam hammer to be heard. Allow the steam sample to condense in the funnel. Any non-condensable gases will rise to the top of the burette. Overspill formed by the condensate and the water displaced by the gases will collect in the measuring cylinder.
When the temperature of the water in the container reaches 70-75oc close the needle valve. Note the volume of gas collected in the burette (Vb) and the volume of water collected in the measuring cylinder (Vc).
Calculate the fraction of non-condensable gases as a percentage as follows.
When the temperature of the water in the container reaches 70-75oc close the needle valve. Note the volume of gas collected in the burette (Vb) and the volume of water collected in the measuring cylinder (Vc).
Calculate the fraction of non-condensable gases as a percentage as follows.
Fraction of non-condensable gases = 100 x (Vb/Vc).
The test should be considered satisfactory if the fraction of non-condensable gases does not exceed 3.5 %.
The test should be done two more times to check consistency. If the results of the three tests differ significantly, then the cause should be investigated before proceeding further.

Figure No.1

Acceptance Criteria:
The measured non-condensable gases in the pure steam should not cross 3.5%
Observations & Results
Record the observations and results in formats enclosed as Attachement-2, Annexure-1

6.2.2 Super Heat

Objective
This test is used to demonstrate that the amount of moisture in suspension with steam from the service supply is sufficient to prevent the steam from becoming superheated during expansion into the chamber.
The method described here uses a low-volume sample, continuously taken from the center of the steam service pipe. The level of superheat determined by this method cannot be regarded as indicative of the true dryness of the steam in the pipe since condensate flowing along the inner surface is not collected. However, devices designed to separate free condensate are incorporated into the steam delivery system to the chamber and therefore the level determined by this method is representative of steam conditions likely to prevail within the chamber during the plateau period.
Procedure
This test should normally follow a satisfactory test for non-condensable gases.
This test, and the subsequent dryness value test, requires a pitot tube as shown in figure No.2. The rest of the apparatus is shown and described in figure No.3. All sizes are nominal. Fit the Pitot tube concentrically within the steam service pipe as shown in figure No.3. Fit the sensor entry gland to the steam service pipe. Insert one of the sensors through the gland and position the axis of the pipe. Insert the second sensor through the gland in the expansion tube and position it on the axis of the pipe. Wrap lagging around the expansion tube. Push the tube on to the pitot.

Figure No.2.

Ensure that the sterilizer chamber is empty except for the usual chamber furniture. Select and start the operating cycle.
From the measured temperatures, note the temperature in the steam service pipe (for use in the dryness test) and in the expansion tube (Te) when the steam supply to the chamber first opens. Calculate the superheat in oC from the following equation:
Superheat  = Te - To
Where:
To is the boiling point of water at local atmospheric pressure.
The test should be considered satisfactory if the superheat measured in the expansion tube does not exceed 25oC.
Record the observations and results in formats enclosed as Attachement-2, Annexure-2.

6.2.3  DRYNESS TEST

The accurate measurement of the percentage of moisture content in the steam is difficult, and the traditional methods where constant steam flow is required are not suitable for sterilizers. This test should be regarded not as measuring the true content of moisture in the steam, but as a method by which the provision of acceptable steam quality can be demonstrated. 

6.2.4  Objective

This test is used to demonstrate that the dryness value is not less than 0.90 (if metal loads be processed, the dryness value should not be less than 0.95); throughout the operating cycle, the temperature measured in the steam service pipe is within 30C of that measured during the superheat test.

6.2.5  Procedure

The test is conveniently carried out immediately after the superheat test.
This test requires a pitot tube as shown in Figure No.2. The apparatus is shown and described in figure No.4. All sizes are nominal. A laboratory balance is also required, capable of weighing a load up to 2 kg with an accuracy of 0.1g or better. If it is not already fitted, fit the Pitot tube concentrically within the steam service pipe as shown in figure No.3. If it is not already fitted, fit the sensor entry gland to the steam service pipe. Insert a temperature sensor through the gland and position it on the axis of the pipe.
Connect the rubber tube to the longer of the pipes in the stopper, place the stopper in the neck of the vacuum flask, weigh the whole assembly and note the mass (M1). Remove the stopper and tube assembly and pour 650 +50 ml of cold water (below 27oC) in to the flask. Replace the stopper and tube assembly, weigh the flask and record the mass (M2). Support the flask close to the pitot, and ensure that the rubber tube and flask are protected from excess heat and draughts, do not connect it to the pitot tube yet.
Introduce the second temperature sensor through the shorter of the two pipes in the stopper and into the water in the flask. Note the temperature of the water in the flask (To). Ensure that the sterilizer chamber is empty except for the usual chamber furniture. Select and start the operating cycle.
When the steam supply to the chamber first opens, connect the rubber tube to the pitot discharge and wrap lagging around it. Arrange the rubber tube to permit condensate to drain freely into the flask. Not the temperature in the steam service pipe (TS).
When the temperature of the water in the flask is approximately 80oC, disconnect the rubber tube from the pitot, agitate the flask so that the contents are thoroughly mixed, and note the temperature of the water (T1).
Weigh the flask and stopper assembly and note the mass (M3).
The initial mass of water in the flask is given by Mw = M2 – M1
The mass of condensate collected is given by MC = M3 - M2.  
Calculate the dryness value of the steam from the following equation:
D= (T1-T0) (4.18MW + 0.24) / LMC - 4.18 (TS-T1) / L
Where:
T0 = Initial temperature of the water in the flask (oC);
T1 = Final temperature of the water and condensate in the flask (oC);
TS = Average temperature of the steam delivered to the sterilizer (oC);
MW = Initial mass of water in the flask (Kg);
MC= Mass of condensate collected (Kg);
L= latent heat of dry saturated steam at temperature TS (kJ Kg-1).

6.2.6 Acceptance Criteria

The test should 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 should not be less than 0.95);
B) Throughout the operating cycle, the temperature measured in the steam service pipe is within 3oC of that measured during the superheat test.

6.2.7 Observation and results

Record the observations and results in formats enclosed as Attachement-2, Annexure-3 See next page for fig no.4.

6.3 BOWIE-DICK TEST

•  Objective:
To ensure that the vacuum pulses applied before the sterilization hold period are sufficient to remove the entrapped air or non condensable gases so as to facilitate the event and rapid steam distribution into all parts of load and maintaining these conditions for specified temperature holding time.

 6.3.1 PROCEDURE

·  Operate the equipment as per SOP.
·  Set the following parameters in PLC.
PRE VACUUM
PRE PRESSURE
STERILIZATION HOLD TEMPERATURE
STERILIZATION HOLD TIME
·  Place one Bowie dick test kit pack in the center (Near drain) of the sterilization chamber supported approximately 100 to 200 mm above the sterilization chamber base.
·  The printouts taken during Bowie dick test cycle & bowie dick indicator shall be attached as per exhibit.
·  Compile the observation and take three consecutive cycles.
Acceptance Criteria
The Bowie Dick test indicator shows the uniform color change. No change, no uniform change and / or Air entrapment (bubble) spot on the test pack indicate inadequate air removal from the sterilization base chamber.
Results
Record the Observation

Related: Low Temperature Sterilization Process (115°C)

6.4 HEAT DISTRIBUTION STUDY (EMPTY CHAMBER)

•  Objective:
Objective of this test is to verify that the temperature uniformity throughout the chamber and to Locate the cold spot in empty Chamber.
·  The sterilizer is capable of attaining the temperature of 121.0oc during the sterilization
Hold period.
·  The profile point having the lowest temperature or slowest to heat is designated as the cold spot.
Procedure:
Insert 16 nos. of temperature sensors inside the chamber through the validation port of sterilizer .seal the port with silicone sealant to ensure that no steam leakage during operation of sterilizer.
Fix the probe at the location at the location in the sterilizer so that sensors do not touch the metallic surface of the chamber. Connect the temperature sensors to the data logger which can scan and print the actual temperature at different locations. Set the following parameters & operate the autoclave cum bung processor and also start the data logger to record the actual temperature.
SET PARAMETERS :
Sterilization Hold temp  =  121.0oc
Sterilization Hold time   =  30 min
Chamber high pressure = 1.5 BAR
·  After completion of sterilization collect thermograph from the multipoint temperature recorder of the autoclave cum bung processor.
·  Download the data from data logger to the computer for data analysis & graph prep.
·  Perform the three consecutive cycles to demonstrate the consistency of sterilizer. 
•  ACCEPTANCE CRITERIA:
1.   Throughout the cycle time, all temperature measured in the chamber do not fluctuate by more than 20C.
2.   Throughout the cycle time, all temperatures measured in the chamber do not differ from each other by more than 20C.
3.   The interval of time between the attainment of the sterilization temperature in the hottest and coldest part of the chamber does not exceed 60 seconds.
•  Results: Record the observations.
LOCATION OF TEMPERATURE SENSORS INSIDE THE CHAMBER
SENSOR NO.
LOCATION OF SENSORS IN THE CHAMBER
S1
In the drain of autoclave chamber
S2
Lower left front corner of the non sterile side
S3
Upper left front corner of non sterile side
S4
Upper right front corner of non sterile side
S5
Lower left front corner of non sterile side
S6
Middle left side of the chamber
S7
Middle right side of the chamber`
S8
Middle front non sterile side of the chamber
S9
Middle back sterile side of the chamber
S10
Lower left sterile side of the chamber
S11
Upper left sterile side of the chamber
S12
Upper right sterile side of the chamber
S13
Lower right sterile side of the chamber
S14
Middle of upper most surface of the chamber
S15
Middle of lower surface of the chamber

6.5  HEAT PENETRATION STUDY

•  Objective
Objective of this test is to ensure that, the steam is sufficiently penetrating into the innermost portion of the load subjected for sterilization to achieve desired temperature i.e. 121.40C during the sterilization cycle.
Heat penetration studies shall be carried out with the following different loads:
a.     Maximum garment load
b.     Minimum garment load
c.     Accessory load (filling machine parts load)
d.     Bung load
e.     Flip off seal
Temperature probe and biological indicator placement in the maximum garment load   
 Load details –
 Sterile garments    - 24 pieces
 Booties                    - 48 Nos.
 Head Gear              - 24Nos.
Gloves (7 inches)   - 24 pairs
LOAD CONFIGURATION:
One Perforated box (C1) containing 8 pair of garments placed on lower front of trolley (non sterile door side).
One Perforated box (C2) containing 8 pair of garments placed on lower back side of trolley (sterile door side)
One Perforated box (C3) containing 8 pair of garments placed on upper front of trolley (non sterile side)
One perforated box (C4) containing 24 pair of gloves wrapped in parchment paper & 04 pair of garments placed on upper back side of trolley (sterile door side)
Temperature Sensors with Chemical & Biological Indicator Placed In Maximum Garment Load
Sensor no.
Location of sensors in the chamber
S1
In the drain of autoclave chamber
S2
Center of the garment pack located at the lower surface in C1
S3
Center of garment pack located in the middle of C1
S4
Center of the garment pack located at the upper surface in C1
S5
Center of the garment pack located at the lower surface in C2
S6
Center of the garment pack located in the middle of C2
S7
Center of the garment pack located at the lower surface in C2
S8
Center of the garment pack located at upper surface in C2
S9
Center of the garment pack located at lower surface in C3
S10
Center of the garment pack located in middle of C3
S11
Center of the garment pack located in middle of C3
S12
Center of the garment pack located at upper surface in C3
S13
Center of the garment pack located at lower surface of C4
S14
Center of the garment pack located at upper surface in C4
S15
Center of gloves pack in C4
Temperature probe and biological indicator placement in the minimum garment load
Load Details
Sterile garments – 6 pairs
Gloves (6 inches) – 8 pairs
Load configuration:
One perforated box containing 6 pairs of garments & 8 pair gloves wrapped in parchment paper placed on lower middle of chamber.
TEMPERATURE SENSORS WITH CHEMICAL & BIOLOGICAL INDICATOR PLACEMENT IN PARTIAL GARMENT LOAD                        
   SENSOR NO.
LOCATION IN THE CHAMBER
S1
In the drain of autoclave chamber
S2
Center of the garment pack located at the lower surface in C1
S3
Center of the garment pack located in the middle of C1
S4
Center of the garment pack located at the upper surface in C1
S5
Center of glove pack located at upper surface in C1
Temperature probe and biological indicator placement in the accessory load (Filling machine parts)
•  Load details
·  Powder Hopper- 2 Nos.
·  Piston Wheel- (2 Nos.)
·  Piston- (32 Nos.)
·  Piston Tips- (36 Nos.)
·  Spoon-(2 Nos.)
·  Scoop-(2 Nos.)
·  Tubes (4 Nos.)
·  Bung Boxes- (2 Nos.)
·  Forceps- (4 Nos.) 
·  Sterile Garments – 12 pieces
·  Booties – 12 pairs
·  Gloves (7 inches) – 24 pairs
•  Load configuration:
·  12 sterile garments, 12 Booties & 24 Pairs Gloves (6 inches) in SS Perforated Container placed on Top.(Non Sterile Side)
·  One Perforated box containing 2 Piston Wheel, 32 Nos. Piston and 36 Nos. Piston Tips., Placed on Bottom.(Sterile Side)
·  One Perforated box containing 4 Nos. Tubes, 4 Nos. forceps, 2 Nos. Spoons, 2 Nos. Scoops, Placed on Top.(Sterile Side)
·  Powder Hopper 2 Nos. & 2 Nos. Bung Boxes Placed at Bottom (Non Sterile Side).

6.5.1 PROCEDURE

Conduct the study with loaded chamber cycles with temperature probes and Biological Indicators. Transfer the load to sterilizer and connect the 15 probes & Biological Indicators as per the locations. Connect the outputs of all the probes to the temperature data logger and close the door of sterilizer. Switch ON the MAINS of the control panel and set the parameters –
Temperature                      :        121.4°C
Chamber Pressure High      :        1.5 BAR      
Hold time                          :        30 minutes
Simultaneously Insert new chart in chart recorder provided on the control panel of an autoclave and adjust the start time and temperature of the instrument. Now start the cycle as per SOP for Operating Instruction. After attaining temperature 121.40C, record the chamber temperature and pressure for every minute. Simultaneously start the recording with data logger and take print outs
At the end of the cycle Switch OFF the cycle. When pressure becomes -0.04 BAR, open the door with the help of safety gloves. Remove the load. Repeat the same cycle three times and compile the data.

6.5.2  Acceptance Criteria:

Throughout the cycle time all temperature measured in the chamber do not fluctuate by more than 20C.
Throughout the cycle time, all temperatures measured in the chamber do not differ from each other by more than 20C.
The calculated minimum F0 value should be more than biological F0 value for the Biological indicator.
Each autoclaved Biological indicator gives the ‘-ve’ test during the incubation.
Results:
Record the Observations.

6.6  Biological Challenge Test

Objective
To demonstrate the degree of Process Lethality provided by the Sterilization Cycle.
Test Requirement
Spores of Geobacillus Stearothermophilus
Procedure
After determining the worst case items and worst locations i.e. cold spots, challenge these items/locations with biological indicator (spore Geobacillus Stearothermophilus)
Carry out the Microbial Challenge Studies concurrently with Loaded Chamber Heat penetration studies.
Previously population validated biological ampoule indicators of specified 106 or more spores of Geobacillus Stearothermophilus should be issued for validation as per procedure.
Place the biological indicators along with the probes at the same locations, within each load type of the specified loading configuration and pattern, as in the Loaded Chamber Heat penetration studies. Retain 2 biological indicators as positive controls. Operate the Autoclave cum Bung Processor as per SOP.
Switch ON the Mains of the control panel and set the parameters –
Temperature                     :        121.4°C
Chamber Pressure High  :           1.5 BAR      
Hold time                           :      30 minutes
Simultaneously insert new chart recorder provided on the control panel of an Autoclave and adjust the start time and temperature of the instrument.
Now start the cycle.
After attaining temperature 121.4°C, record the chamber temperature and pressure for every 60 seconds.
Simultaneously start the recording with data logger and take printouts. At the end of the cycle Switch OFF the cycle. When pressure becomes -0.04 BAR, open the door of an Autoclave with the help of safety gloves. After incubation observe the indicator for growth. (+ve when purple color change to yellow color, -ve when purple color remain as such) Conduct the test until a cycle time results in three consecutive runs where the biological indicators show on growth.
•  Acceptance Criteria
1.  Visually observe the ampoules, test +ve when purple color change to yellow color, test   -ve when purple color remain as such).
2.  If no evidence of growth observed in any of the inoculated tube and growth observed in positive control tube, the test meets the criteria to achieve the Sterility Assurance Level (SAL) 10-6.

6.7  Bung Processing

Objective:
Objective of this test is to ensure that, the bung washing is proper and bung load subjected for sterilization to achieve desired temperature i.e. 121.4°C during the sterilization cycle.
Load details
·  Maximum Bungs cycle (Approx 80000)
·  Minimum Bungs cycle (Approx 5000)
Load configuration
·  Bungs in Bung Carriage (Approx 80000)

6.7.1  Procedure

•  Load the bungs in Bungs Carriage cassettes. Approximately 8000 Bung Load in each cassette.
•  Place one biological indicator in each cassette and transfer the load to Autoclave cum Bung processor.
•  Switch ON the MAINS of the control panel and run cycle as per HPHV Process Parameters.
Simultaneously Insert new chart in chart recorder provided on the control panel of an autoclave and adjust the start time and temperature of the instrument after attaining temperature 121.4°C, record the chamber temperature and pressure for every minute. At the end of washing cycle send WFI rinse sample to QC for Analysis of Non Ionic Detergent Content. At the end of the cycle switch OFF the cycle.
When pressure becomes -0.04 BAR, open the door with the help of safety gloves. Remove the load. Repeat the same cycle three times and compile the data.
Acceptance criteria:
The calculated minimum F0 value should be more than biological F0 value for the Biological indicator. Each autoclaved biological indicator gives the ‘-ve’ test during the incubation. WFI rinse sample should be free from non ionic Detergent.
Results:
Record the Observations

7.0  F0 Calculation
The actual observations obtained during the heat penetration studies at different temperature sensing locations were compiled in the table and the observed temperature were subjected for calculation of F0 values at that particular location. The calculations are done by using the following formula and the lethality factor computed (during the sterilization period) are given in the following table.
F0=dt ∑ 10(T-121)/Z  __________ (a)
F0=dt ∑ (Sum of lethality factors)
Where,
Dt = The time interval between successive temperature measurements (1 min).
T  = The observed temperature at that particular time (as per the actual temperatures recoded                       
Z  = The change in the heat resistance of Bacillus stearothermophilus spores as temperature is Changed (10°C)
The calculated minimum F0 value (by equation a) should be more than the biological F0 value for the biological indicator strip exposed for the bio-challenge study. The biological F0 value for biological indicator strip exposed during the sterilization can be calculated as follows.
F0 = D121 (log A – log B) ……… (b)
Where,
D121
D value of the biological indicator at 1210C
A
Biological indicator concentration or spore population
B
Desired level of sterility

8.0  INTERPRETATION OF RESULTS

All test results shall be compiled and evaluated. Compliance of all the results with empty chamber and loaded chamber with different loads to the acceptance criteria shall establish that the sterilization practices, control and facility are suitable for various required loads.

9.0  REVALIDATION FREQUENCY

Schedule Revalidation
Twice in a year.                                                                   
Unscheduled Revalidation
Unscheduled revalidation shall be carried out in following situation:
When major changes in the load is taken place.
After major maintenance of existing equipment.

10.0  DOCUMENTATION

Results and reports shall be compiled in a binder. Binder shall contain the following sequentially:
Summary Report
Test Reports

11.0  CONCLUSION

Based on the rigorous studies performed during the execution of the qualification protocol and as per the results obtained, it is concluded that the Autoclave cum Bung Processor is qualified / not Qualified for consistent results.
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