SOP for Qualification of Biological Indicator : Pharmaguideline

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SOP for Qualification of Biological Indicator

Standard operating procedure to quality the biological indicators containing Geobacillus stearothermophilus (Bacillus stearothermophilus) ATCC 7953 and Bacillus atrophaeus (Bacillus subtilis) ATCC 9372 spores.

1.0 OBJECTIVE

To lay down a Procedure is to provide guidelines for qualification of Biological Indicator.

2.0 SCOPE

This procedure is applicable for qualification of Biological Indicators i.e. Geobacillus stearothermophilus (Bacillus stearothermophilus) ATCC 7953 and Bacillus atrophaeus (Bacillus subtilis) ATCC 9372, which is used for autoclave and tunnel validation.

3.0 RESPONSIBILITY

Microbiologist

4.0 ACCOUNTABILITY

Head QA & QC

5.0 PROCEDURE

5.1 Identification test of the culture of Biological Indicator

5.1.1 Microscopic examination – Suspend one strip or ampoule of the biological indicator in sterile 10 ml Normal saline. Gently shake the suspension and transfer a loopful of suspension on a glass slide. Carry out Gram staining and observe the slide under the microscope. Gram-positive rods with oval endospores in sub terminally swollen cells indicate the identity of Geobacillus stearothermophilus. Bacillus atrophaeus is Gram-positive, rod shaped with oval & central endospores & cells are not swollen.

5.1.2 Growth Characteristic

5.1.2.1 Suspend one strip (one ampoule) of the biological indicator in 10 ml nutrient broth and incubate at 37ºC for 48 hrs. Streak a loopful content from the tube onto each two petridishes containing Soybean Casein Digest Agar Medium. Incubate one Petridish at 30ºC to 35ºC and the other at 55ºC to 60ºC for 24 hours.
5.1.2.2 The identity of Geobacillus stearothermophilus is indicated if the plate incubated at 55ºC to 60ºC shows evidence of microbial growth whereas the plate incubated at 30ºC to 35ºC dose not shows any evidence of microbial growth.
5.1.2.3 The identity of Bacillus atrophaeus is indicated if the plate incubated at 30ºC to 35ºC shows evidence of microbial growth whereas the plate incubated at 55ºC to 60ºC does not show any evidence of microbial growth.

5.2 Total Viable Spore Count in Biological Indicator

5.2.1 Randomly select four spore strips of Biological Indicator from its original individual container.
5.2.2 Place each spore strip in a sterile, screw capped, flat – bottom tube with three 6 mm glass beads, and 5.0 ml of sterile purified water.
5.2.3 Vortex 4 to 7 minutes until the paper carrier is macerated to pulp.
5.2.4 Add 5.0 ml sterile purified water. Vortex again.
5.2.5 Transfer 1 ml of the suspension to a test tube containing 9 ml of sterile purified water & vortex.
5.2.6 Place the dilution tube in a preheated bath at 95ºC – 100ºC for 15±1 minutes for Geobacillus stearothermophilus & for Bacillus atrophaeus 80ºC – 85ºC for 10 minutes.
5.2.7 Remove tubes and cool rapidly in an ice bath (0ºC – 4ºC).
5.2.8 Vortex each heat-shocked tube for at least ten seconds. Now serially dilute these tubes to yield 30 to 300 colonies. Vortex each dilution tube for at least ten seconds.
5.2.9 Prepare a separate series of plates for each aliquot. Place 1.0 ml of each selected dilution in each of two Petri dishes.
5.2.10 Pour approximately 20 ml of melted Soybean Casein Digest Agar cooled to 45º to 50ºC into the petri plates. Swirl to assure adequate mixing and allow the agar to solidify.
5.2.11 Invert and incubate plates at 55º – 60ºC for Geobacillus stearothermophilus & for Bacillus atrophaeus 30ºC – 35ºC for 48 to 72 hours. Units incubated at 55ºC to 60ºC may be placed inside a plastic bag to prevent the plates from excessive drying.
5.2.12 After incubation count CFU.
5.2.13 Average counts and then multiply by the dilution factor to calculate population per original unit.
5.2.14 Record all information on Population Determination Record for Biological Indicator.
5.2.15 For Biological indicators, sealed ampoule, take 4 ampoules in a sterile 250 ml conical flask and break the ampoules by shaking against the sides of the flask. Add sufficient sterile purified water to make 100 ml & vortex or sonicate vigorously to achieve a homogeneous suspension. Transfer 10 ml to a sterile screw capped tube. Carry out the procedure as described above.

5.3 Spore Survival Time & Kill Time Test

For Geobacillus stearothermophilus
5.3.1 For Survival time place one Biological Indicator in a suitable container like a lid of the petridish and place the same in a previously qualified autoclave. Do not close the dish so as to expose the biological indicator completely to steam. Run the steam sterilization cycle at 121°C (±0.5ºC) for minimum survival time as per the certificate of analysis of biological indicator. Immediately unload the Biological Indicator from the autoclave and aseptically transfer to sterile SCDM & incubate the Biological indicator at 55°C to 60°C for 7 days.
5.3.2 For kill time place one Biological Indicator in a suitable container like a lid of the petridish and place the same in a previously qualified autoclave. Do not close the dish so as to expose the biological indicator completely to steam. Run the steam sterilization cycle at 121°C (±0.5ºC) for minimum kill time as per the certificate of analysis of biological indicator. Immediately unload the Biological Indicator from the autoclave and aseptically transfer to sterile SCDM & incubate the Biological indicator at 55°C to 60°C for 7 days.
5.3.3 Also apply positive & negative controls.
5.3.4 There should be visible growth in Survival time test & positive control & no growth in Kill time test & Negative control.
For Bacillus atrophaeus
5.3.5 For Survival time place one Biological Indicator in a suitable container like a lid of the petridish and place the same in a previously qualified DHS. Do not close the dish so as to expose the biological indicator completely to dry heat. Run the DHS cycle at 160°C (±1ºC) for minimum survival time as per the certificate of analysis of biological indicator. Immediately unload the Biological Indicator from the DHS and aseptically transfer to sterile SCDM & incubate the Biological indicator at 30°C to 35°C for 7 days.
5.3.6 For kill time place one Biological Indicator in a suitable container like a lid of the petridish and place the same in a previously qualified DHS. Do not close the dish so as to expose the biological indicator completely to dry heat. Run the DHS cycle at 160°C (±1ºC) for minimum kill time as per the certificate of analysis of biological indicator. Immediately unload the Biological Indicator from the DHS and aseptically transfer to sterile SCDM & incubate the Biological indicator at 30°C to 35°C for 7 days.
5.3.7 Also apply positive & negative controls.
5.3.8 There should be visible growth in Survival time test & positive control & no growth in Kill time test & Negative control.

5.4 Precaution

5.4.1 Do not use agar that has been melted and held longer than 8 hours.
5.4.2 To avoid inaccurate plate counts, it is important to perform the serial transfer using 2.0 ml pipette or whichever pipette has the larger bore size. This will help avoid clogging of the pipet tip with cotton fibers.

5.5 Limits/ Acceptance Criteria

The requirement of the test are met if the log average number of the viable spores per carrier is not less than 0.3 log and does not exceed the log labeled spore count per carrier by 0.48 for total viable spore count.
Related: New Genetically Engineered Biological Indicators

6.0 ABBREVIATIONS

SOP: Standard Operating Procedure
QA: Quality Assurance
QC: Quality Control
NA: Not Applicable
SCDA: Soyabean Casein Digest Agar
IPA: Isopropyl Alcohol
CFU: Colony Forming Unit
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