SOP on OOS in microbiology

Objective:

To lay down the procedure for investigation of out of specification of test results in Microbiology Laboratory.

Scope:

This Scope is limited to out of specification results of microbial testing, sterility testing and environmental testing in microbiology section of Formulation plant.

Responsibility:

Head Microbiology

Head Quality Control

Accountability:

Head-Q.A

Procedure:

L.T / Sterility / B.E.T / Environmental monitoring.

• In case of microbiological limit test, if observation was found out of specified limit immediately inform to Head Quality control department and to the stores dept. for holding the material.
• Investigate in detail as per the checklist in annexure- QCSG308/A01.
• If turbidity is observed in samples tested for Sterility during incubation period immediately inform to Head Quality control department, Injectables Department and to the stores department for holding the material.
• Investigate in detail as per the check list in annexure- QCSG308/A01
• In case of Non-compliance of BET for the sample tested (i.e. if gel-clot is observed immediately inform to Head Quality control department and to the stores department. for holding the material.

Environmental monitoring

• If observation out of alert limit immediately inform to Head Quality control and to the concerned department for immediate cleaning and sanitization for checking any visual abnormalities (leakage, breakage or rusting etc.) in the concerned area/location / system.
• If the observations are out of action limit then proceed as follows:-
• Immediately inform to Head Quality control department and to the concerned department for immediate cleaning and sanitization of the concerned area / location observed and immediate attention to following points:
• Verify Personnel entry procedure in the concerned area.
• Preserve the organism on the solid agar nutrient media and at the same time identify the microorganism morphologically and its gram character.
• Check the positive and negative control of media, autoclave cycle load details, colour change indicators used for the specific load, environmental conditions (bio-burden), differential pressure & humidity of the area.
• Non viable particle count test, if performed on that particular day or at previous  day (as per the frequency) by the concerned department.
• Hygienic condition of the personnel.
• If all of the above being found to be within in the specified limit then instruct concerned department for checking the HEPA filter integrity of concerned area.
• Check the impact on the batch manufactured on that particular day, Also check the previous and subsequent batches.

OOS in water testing

• Immediately inform to Head Quality control department. and to the concerned department for immediate cleaning and sanitization of the concerned area / location observed.
• Check the positive and negative control of media, details of Autoclave cycle Load
• Compare the test results with other user points.
• If a particular user point is showing out of specification result, check the particular user point for any leakage, rusting, breakage etc.
• Inform, engineering / production department for sanitization of the particular user point.
• If all the points are showing out of specification results, inform engineering department for sanitization of entire water system
• Cleaning and sanitization of storage tank in case of potable water.
• Cleaning and sanitization of storage tank in case of water for injection & sanitization of distribution loops.
• Hold (retain) the material manufactured on the same day, using the water for batch processing or cleaning and perform microbiological analysis.
• Hold (retain) all the batches manufactured from the date of sampling till the result of re-test has been observed.
• Test for, microbial limit test with same number of samples.
• If the result comes within specified limit, batch can be released.
• If the result is found out of specified limit, batch can be rejected.

For OOS in compressed gas / compressed air monitoring test results.

• Proceed as per above point.
• Repeat the test with same volume of sample from the same point. Hold all the batches manufactured from the date of sampling till the result of next test been observed.
• Test the batch manufactured at the same day, using the compressed gas /air.
• If, the batch manufactured at the same day, using the compressed gas /air is found within the specified limit, the batch can be released.
• If, in the repeat analysis of compressed gas /air any microbiological growth is found within specified limit batch can be released.
• If, in the repeat analysis, microbiological growth is out of specified limit, and of the same type as previous, reject the batch.

For OOS in Microbiological Limit Test.

• Immediately inform to Head Quality control dept. and hold the batch.
• Check the positive and negative control of media, all record related to autoclave cycle environmental conditions (bio-burden), differential pressure, and humidity of the area and water quality for that particular day.
• Repeat the test with change of microbiologist with 25 gm sample. Hold the batch, till the result of next lot of the same batch.
• If, in the repeat analysis any microbiological growth is not observed batch can be released.
• If, in the repeat analysis, microbiological growth is observed out of specified limit, and of the same type as previous, reject the batch.

Sterility Test (For any false +ve test results)

• Immediately inform to Section head with all the data and hold the batch.
• Carry out the assessment of OOS results before doing the retest
• Retain the test preparation if available
• Have a discussion with analyst to confirm the procedure used in the test and to find possibilities of laboratory error.
• If laboratory error is revealed, train the analyst to perform the test as per SOP, GLP and document the same.
• Check if surface decontamination of LAF has been followed correctly and if rinse fluids are freshly prepared and taken for single use.
• Check for transfer of materials to the work area as per SOP
• Check whether cleaning and sanitization of testing area is followed correctly
• Check the positive and negative control of media, all record related to autoclave cycle environmental conditions (bio-burden), differential pressure, and humidity of the area and water quality for that particular day.
• Check if the sample vials/container used in the test are closed properly
• Identify the flora, if observed on the exposed plates of finger-dab test of person performed the sterility test and the exposed plates under LAF of sterility testing area. Preserve those plates.
• Identify the flora, if observed on the exposed plates of finger-dab test of persons involved for filling and plugging in sterile vial filling area and the exposed plates under LAF of sterile vial filling area. Preserve those plates.
• Repeat the sterility test of the batch with change of microbiologist with double number of samples. Hold the batch, till the result of next lot of the same batch.
• If, in the repeat analysis any microbiological growth is not observed batch can be released and if growth observed, and micro-organism is identical as in the previous test, which matches with the flora, if observed on the exposed plates of finger-dab test of persons involved for filling and plugging in sterile vial filling area or the exposed plates under LAF of sterile vial filling area, reject the batch.

Bacterial Endotoxin Test:

• Carry out investigation as per checklist in annexure – I.
• Proceed as per following flowchart.

 

              

List of Annexure / Format: 

S. No.	Format Title	Format Number	Annexure Number	No. of Pages
1	Investigation of out of specification of microbiological test results	F01-00	I

References (if any)

• SOP on SOP’s

Reason for Revision

• Not applicable due to first version.

Abbreviation and Definition

• DOP: Di-octyl phthalate test
• HEPA: High efficiency particulate air filter.
• MLT: Microbial Limit Test
• LAF: Laminar Air flow.
• B.E.T: Bacterial Endotoxin test

 

 

Investigation of out of specification of microbiological test results

Product Name:				Tested On:
Batch NO:				Tested by:
OOS Observed in(Test):				OOS Observed on:
S.NO		PART A (Lab Investigation)			Yes	NO
1.0		Sterilization of Glassware is carried out as per procedure
2.0		Preparation of media is carried out as per procedure
3.0		Growth Promotion test Carried out
4.0		Calibration of incubators and Autoclave is carried out as per established frequency
5.0		Analyst is being certified
6.0		Error in Dilution
7.0		Error in sampling tubes
8.0		Media Positive Control
9.0		Blank Positive Control
10.0		Media Negative Control
11.0		Blank Negative Control
12.0		Surface Decontamination of LAF has been followed correctly
13.0		Rinse fluids are freshly prepared and taken for single use
14.0		Transfer of material to the work area as per SOP
15.0		Cleaning and sanitization of testing area is followed correctly
16.0		Entry/Exit procedure followed properly
17.0		Environmental monitoring test report
17.1			Passive Air sampling
17.2			Active air sampling
17.3			Surface monitoring test
18.0			Personnel monitoring test
18.1			Identification of microorganisms
18.2			Gram nature of microorganisms
18.3			Morphological Characteristics
18.4			Biochemical Test
19.0			Positive Product Control
20.0			Control of LRW is satisfactory
21.0			Control Curve of CSE is satisfactory
22.0			Expiry date CSE is satisfactory
23.0			Expiry date of Lysate is satisfactory
24.0			Expiry date of LRW is satisfactory
25.0			Is that Lysate lot no is matching with desired CSE lot no (as per COA)
26.0			Spilling of sample
27.0			Error in Dilution
PART B (Product investigation )
28.0	The U.V Sanitizers are working properly
29.0	Sanitization of membrane filters is to be carried out as per procedure
30.0	IF there is any leakage in loop system
31.0	IF there is any leakage in vaccum break filter
32.0	Test result of purified water
33.0	Cleaning and sanitization of area/system
34.0	Particle count test
35.0	Particulate matter of compressed air
36.0	Viable Count of Compressed air
37.0	Sanitization Record of filters
38.0	Entry and Exit procedure followed properly
39.0	Environment monitoring reports
40.0	Active air sampling
41.0	Passive air sampling
42.0	Surface monitoring test
43.0	Personnel monitoring test
44.0	Any other abnormal observation

Observation:
Conclusion:
Action to be taken
Investigation done by	Checked by	Manager Head

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