5/16/23, 3:42 PM SOP for Handling of Out of Limit Results in Environmental Monitoring and Water Analysis : Pharmaguideline

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SOP for Handling of Out of Limit Results in Environmental Monitoring and Water Analysis
Standard operating procedure of Out of Limit results of Environmental Monitoring and Water Analysis.
1.0 PURPOSE
To lay down the procedure for handling of out of limits (OOL) results of environmental monitoring and water system monitoring results.
2.0 SCOPE
Applicable to handling and conducting investigations when out of limit results are obtained in environmental monitoring and water system monitoring
of production and microbiology laboratory facilities.
3.0 RESPONSIBILITY
3.1 Quality Control Microbiology
Microbiology Officer is responsible to notify Microbiology Head or his designee when and alert or action limit is obtained.
Head - Microbiology or his designee is responsible to notify the QA and concerned departments and initiate the investigation in the laboratory and
concerned department.
To implement any corrective action and preventive action
3.2 Quality Assurance Department
To participate in investigations
To review and approve investigation reports
To review action taken reports
3.3 Production / Engineering Department
To participate in investigations
To implement necessary corrective and preventive actions

4.0 ACCOUNTABILITY
Head of Department
5.0 PROCEDURE
5.1 Notification and allotment of number for Out of Limit Result
5.1.1 On obtaining an out of the limit result, the microbiologist shall notify the Microbiology In - Charge or his designee and they shall notify the QA
and concerned department.
5.1.2 The details of Out of Limit results shall be entered in Log Book and a number shall be allotted as M-OOL/YY/ZZZ, where
M-OOL : Microbiological Monitoring – Out Of Limit Result
YY : Represents last two digits of current year

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5/16/23, 3:42 PM SOP for Handling of Out of Limit Results in Environmental Monitoring and Water Analysis : Pharmaguideline

ZZZ : Represents serial number starting with 001

Example : First OOL reported in year 2011: M-OOL/11/001
5.2 Handling and Investigation of Out of Limits Results in Microbiological Monitoring of Cleanrooms
Note: This section is applicable for handling and investigation of out of limit results in Passive Air Sampling (Settle Plate), Active Air Sampling and
Surface Sampling.
5.2.1 Observe the plates under incubation (sampled after the date of sampling showing out of limit results) of the sample location / room showing out
of limits and check of for any out of limit results. Inform the observations to Head Microbiology or his designee.
5.2.2 Verify the negative control plate incubated along with test samples for any contamination. Inform the observation to Head Microbiology or his
designee.
5.2.3 Process the out of limit results for identification as follows:
In case of out of alert limit results, perform gram staining of morphologically similar colonies and identification of representative isolates based on
Gram Staining Results as per SOP.
In case of out of action limit results in Grade C and Grade D areas, perform gram staining of morphologically similar colonies and identification of
representative isolates based on Gram Staining Results as per SOP.
In case of out of action limit results in Grade A and Grade B areas perform identification of all isolates as per SOP and also by DNA sequencing.
5.2.4 Investigation of Out of Alert Limit Results
5.2.4.1 Review the data for the sample location/room in question for any previous instances of out of limit results in last three months.
5.2.4.2 If review of data or plates under incubation shows occurrences of out of alert limit results for more than three consecutive days or occurs
frequently then the investigation should be elevated to out of action limits.

5.2.4.3 Laboratory Investigation

• Interview the microbiologist who performed sampling and verify whether the sampling was performed as per SOP and if any deviations observed
during the sampling/testing/transportation and disinfection of plates.
• Verify the instruments used (air sampler) were operated properly and accessories used (air sampler head or swab template) were sterilized.
• Verify all the media used were within their shelf life and review their preparation records for results of pre-incubation and sterility checks.
• Interview the media personnel for any deviation observed during preparation/pouring of plates.
• Review the results of all EMP parameter of the particular days.(Active, Passive ,surface & personnel monitoring)
• If contamination in negative control plates is observed or laboratory investigation reveals fault in sampling, discrepancies in status of air sampler, air
sampler head/swab templates or results of media pre-incubation and sterility check are not satisfactory, then the occurrence of out of limit results
could be attributed to laboratory/sampling error.
5.2.4.4 Facility Investigation
• Review cleaning/disinfection logs, operational logs and other activities of subject area for any discrepancies.
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• If the sample location is in critical area, then review the entry exit logs for number of persons present in the area, their duration of stay in the area
and their personal hygiene and training/qualification status.
• Review of records of physical conditions like pressure differentials, temperature and relative humidity of the subject area on the day, days before
and after the occurrence.
• Contact Engineering department for any discrepancies in the functioning of HVAC and other systems or any maintenance activities undertaken or
due for maintenance
• If any discrepancies observed during the review, determine if it has any impact on the observed results.
• Record all the observations in the investigation report.
5.2.4.5 Based on the information gathered, determine if follow up monitoring is required or not as per Investigation report and proceed accordingly.
5.2.4.6 If the results of the follow-up monitoring performed are not satisfactory elevate the investigation to out of action limit investigations.
5.2.4.7 Review the identification results and verify if it is normal micro flora of the area. If the isolate is different or objectionable, initiate necessary
corrective actions.

5.2.5 Investigation of Out of Action Limit Results

5.2.5.1 Based on the criticality of operations performed in the area showing out of limit results and observations of plates under incubation, the
decision shall be taken for use of the area for critical operations. If out of action limits are observed in Grade A and B of filling area then investigation
to be trigged. Based on the risk, the production shall be stopped till completion of the investigation and after obtaining satisfactory results for three
consecutive days, given the clearance to start the production by Head Q.A with the consultation of Head Engineering and Head Production.
5.2.5.3 Quarantine the subject batches till the investigation is complete, based upon the investigation & risk assessment if finding the impact on
product quality the concern batches shall be rejected and if finding no impact on product quality then concern batches shall be release.
5.2.5.2 Review the data for the sample location/room in question for any previous instances of out of limit results in last three months.
5.2.5.3 If the data indicates previous occurrences of out of limits, then review the previous investigation reports to determine any similarities.
5.2.5.4 Laboratory Investigation
• Interview the microbiologist who performed sampling and verify whether the sampling was performed as per SOP and if any deviations observed
during the sampling/testing/transportation and disinfection of plates.
• Verify the instruments used (air sampler) were operated properly and the accessories used (air sampler head or swab template) were sterilized.
• Verify all the media used were within their shelf life and review their preparation records for results of pre-incubation and sterility checks.
• Interview the media personnel for any deviation observed during preparation/pouring of plates.
• Review the results of all EMP parameter of the particular days.(Active, Passive, surface & personnel monitoring)
• If contamination in negative control plates is observed or laboratory investigation reveals a fault in sampling, discrepancies in the status of air
sampler, air sampler head/swab templates or results of media pre-incubation and sterility check are not satisfactory, then the occurrence of out of

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limit results could be attributed to laboratory/sampling error.

5.2.5.5 Facility Investigation
• Review cleaning/disinfection logs, operational and other activities of the subject area for any discrepancies.
• If the sample location is in a critical area, then review the entry exit logs for a number of persons present in the area, their duration of stay in the
area and their personal hygiene and training/qualification status.
• Interview the ppersonnel of particular day in which the OOL Observed for any deviation observed during gowning procedure and practices in area
etc..
• Review the material movement procedure and any other deviation /Change in procedure
• Review of records of physical conditions like pressure differentials, temperature and relative humidity of the subject area on the day, days before
and after the occurrence.
• Review the preparation and sterilization records of materials used in the area for any deviations.
• If the action limit has occurred during batch activity, review the executed batch record for any discrepancies or other helpful information. Review the
batches manufactured during the occurrence of out of action limit results for microbiological parameters.
• Contact Engineering department for any discrepancies in the functioning of HVAC (Velocity, air change & HEPA filter integrity) and other systems or
any maintenance activities undertaken or due for maintenance.
• Review the non-viable particulate count results of the particular area performed on the day, days before and after the occurrence.
• Visit the subject area and verify the physical conditions, general cleanliness and any other abnormalities, which could have contributed to the
occurrence of out of action limit results.
If any discrepancies observed during, determine if it has any impact on the observed results.
5.2.5.6 Based on the information gathered, determine if follow up monitoring is required or not as per Investigation report (Annexure I) and proceed
accordingly.
5.2.5.7 If no assignable cause is identified or the follow up monitoring results are not satisfactory, in addition to above actions, appropriate additional
measures can be initiated as follows:
• Increasing of cleaning/disinfection or change of disinfectants.
• Increasing in monitoring frequencies or increase of sample points in subject area for monitoring.
• Testing for non-viable particulate counts.
• Testing of HEPA filters for integrity and air velocity
• Any other appropriate activity
5.2.5.8 Review the identification results and verify if it is normal micro flora of the area. If isolate is different or objectionable, initiate necessary
corrective actions.

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5.3 Handling and Investigation of Out of Limits Results in Non Viable Monitoring
Note: This section is applicable for handling, out of limit results of Microbiological lab facility.
5.3.1 On obtaining any out of limit results during non-viable monitoring, immediately do the following:
5.3.2 Check the instrument is operating properly and any disturbance or changes in room conditions is observed.
5.3.3 Check activities (specifically for particle or aerosol generating or disturbance to particle counter probe) performed around the sample location
during the time of out of limit result and evaluate if it has any effect on the reported result.
5.3.4 Verify that the instrument used was within calibration and testing performed as per procedure. If appropriate perform the zero count of the
particle counter.
5.3.5 Re-sample the location after the conditions are restored and verify the results. Record the noted observation the report. If the results of re-
sample are conforming to limits, then no further action is required. If the results are still non-conforming proceed to 5.3.6
5.3.6 Review the trend for the sample location / room in question and results of other sample locations performed on the day.
5.3.7 Review department cleaning logs, room differential pressure records, number for personal in the room at the time of testing, number of
equipment and their operation status and other activities for any discrepancies.
5.3.8 Contact Engineering / Maintenance department and review logs for any discrepancies in the functioning and maintenance of HVAC and other
systems or any maintenance activities undertaken.
5.3.9 Evaluate the information gathered and determine if it has an impact on the results observed.
5.3.10 Based on the information gathered, evaluate the actions to be performed and perform re-sampling of the concerned location or room as per
Investigation report and proceed accordingly.
5.3.11 If the re-sample results conform to limits then no further action is required.
5.3.12 If the re-sample result does not conform to limits, then carry out further investigation for determining the root cause. Following activities can be
performed to determine the root cause:
• Extensive cleaning of area
• Air Velocity verification of HEPA filters
• HEPA filter integrity testing
• Air flow studies
5.4 Handling and Investigation of Out of Limits Results in Personnel Monitoring
5.4.1 Observe the plates under incubation (sampled after the date of sampling showing out of limit results) of the sample same person(s) showing
out of limits and check of for any out of limit results. Inform the observations to Head Microbiology or his designee.
5.4.2 Verify the negative control plate incubated along with test samples for any contamination. Inform the observation to Head Microbiology or his
designee.
5.4.3 Observe the other plates of environmental monitoring performed on the day of out of limit occurrence and compare the colonies with plates
showing out of limit results.
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5.4.4 Process the out of limit results for identification along with morphologically similar colonies from environmental monitoring plates if any as
follows:
5.4.4.1 Perform gram staining of morphologically similar colonies and identification of representative isolatess based on Gram Staining Results as
per SOP
5.4.4.2 In case of out of limit results in Grade A and Grade B areas perform identification of all isolates as per SOP and also by DNA sequencing.
5.4.5 Laboratory Investigation
5.4.5.1 Interview the microbiologist who performed sampling and verify whether the sampling was performed as per SOP and if any deviations
observed during the sampling/testing.
5.4.5.2 Verify all the media used were within their shelf life and review their preparation records for results of pre-incubation and sterility checks.
5.4.5.3 If contamination in negative control plates is observed or laboratory investigation reveals fault in sampling, discrepancies in results of media
pre-incubation and sterility check are not satisfactory, then the occurrence of out of limit results could be attributed to laboratory/sampling error.
5.4.6 Facility Investigation
5.4.6.1 Review the previous data of concerned person for any out of limit results.
5.4.6.2 Verify the personal hygiene and health status of concerned person. Review the medical and training records of the concerned person.
5.4.6.3 Review the environmental monitoring data of day and days before and after the day of occurrence for out of limit results.
5.4.6.4 Review cleaning / disinfection logs, entry exits logs and other activities of subject area for any discrepancies.
5.4.6.5 Review of records of physical conditions like pressure differentials, temperature and relative humidity of the subject area on the day, days
before and after occurrence.
5.4.6.6 Review the garment preparation and sterilization records for any discrepancies.
5.4.7 Based on the information gathered, determine the actions to performed as per Investigation and Decision Flow Chart in (Annexure I) and
proceed accordingly.
5.4.8 Review the activities performed the concerned individual and if he has performed critical aseptic operations, critically review the microbiological
results of the concerned batch.

5.5 Handling and Investigation of Out of Limits Results in Microbiological Analysis of Water
5.5.1 Observe the plates of same type of water sampled and analyzed on the same day and those under incubation (sampled after the date of
sampling showing out of limit results) of the sample location / sample type showing out of limits and check of for any out of limit results. Inform the
observations to Head Microbiology or his designee.
5.5.2 Verify the negative control plate incubated along with test samples for any contamination. Inform the observation to Head Microbiology or his
designee.
5.5.3 Process the out of limit results for identification as follows:
• In case of out of alert limit results, perform gram staining of morphologically similar colonies and identification of representative isolates based on
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Gram Staining Results as per SOP.

• In case of out of action limit results, perform gram staining and identification of all colonies for WFI and Pure Steam Condensate and
morphologically similar colonies isolates based on Gram Staining Results for Purified Water and other water samples as per SOP.
5.5.4 Investigation of Out of Alert Limit Results
5.5.5.1 Review the data for the sample location / system in question for any previous instances of out of limit results in last three months.
5.5.5.2 If the data indicates previous occurrences of out of limits, then review the previous investigation reports to determine any similarities.
5.5.5.3 Laboratory Investigation
• Interview the microbiologist who performed sampling and verify whether the sampling was performed as per SOP and if any deviations observed
during the sampling/testing.
• Verify the materials used for sampling and testing was properly sterilized and handled.
• Verify all the media used were within their shelf life and review their preparation records for results of pre-incubation and sterility checks.
• If contamination in negative control plates is observed or laboratory investigation reveals fault in sampling and testing results of media pre-
incubation and sterility check are not satisfactory, then the occurrence of out of limit results could be attributed to laboratory/sampling error.
5.5.5.4 Water System / Facility Investigation
• Contact Engineering and Production Department for any discrepancies in the functioning of water systems or any maintenance undertaken. Verify
the operation and sanitization log books for concerned system / area.
• If the out of limit result is observed in only one sample location and rest of the system is conforming to specifications, then verify the sample location
for any discrepancies in the sample/user point and the location.
5.5.5.5 Based on the information gathered, determine the actions to be initiated as per Investigation report and proceed accordingly.
5.5.5.6 Review the identification results and verify if it is normal micro flora of the water system or of human commensal or from environment. If
isolate is different or objectionable, initiate necessary corrective actions.
5.5.5.7 If the results of follow up sampling are satisfactory after carrying out corrective actions (if any) conclude the investigation.
5.5.5.8 If the results of follow up sampling are not satisfactory carry out further investigation take necessary actions accordingly.
5.5.5 Investigation of Out of Action Limit Results
Note: This is also applicable for any non-conformance to test for specified organisms.
5.5.5.1 Review the data for the sample location / system in question for any previous instances of out of limit results in last three months.
5.5.5.2 If the data indicates previous occurrences of out of limits, then review the previous investigation reports to determine any similarities.
5.5.5.3 If the subject sampling location is a daily monitoring sample location and results of subsequent days are also showing out of limit results or
the sample location is on sampling rotation, them immediately schedule for three consecutive day sampling.
5.5.5.4 Laboratory Investigation
• Interview the microbiologist who performed sampling and verify whether the sampling was performed as per SOP and if any deviations observed
during the sampling/testing.
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• Verify the materials used for sampling and testing was properly sterilized and handled.
• Verify all the media used were within their shelf life and review their preparation records for results of pre-incubation and sterility checks.
• If contamination in negative control plates is observed or laboratory investigation reveals fault in sampling and testing results of media pre-
incubation and sterility check are not satisfactory, then the occurrence of out of limit results could be attributed to laboratory/sampling error.
5.5.5.5 Water System / Facility Investigation
Contact Engineering and Production Department for any discrepancies in the functioning of water systems or any maintenance undertaken. Verify
the operation and sanitization log books for concerned system / area.
If the out of limit result is observed in only one sample location and rest of the system is conforming to specifications, then verify the sample location
for any discrepancies in the sample/user point and the location.
If the water from the specific location was used for batch manufacturing, then verify the results in-process and finished product samples of concerned
batch(es).
• Bio-burden results of bulk sample before filtration
• Microbiological tests results of Oral Solid Dosages
5.5.5.6 Evaluate the information gathered and determine if it has any impact on the observed results.
5.5.5.7 Based on the information gathered, determine the actions to be initiated as per Investigation report and proceed accordingly.
• Review the identification results and verify if it is normal micro flora. If isolate is different, then include it micro flora stock for use in different tests.
• If isolate identified is of objectionable, then investigate the possible source of contamination and take necessary corrective and preventive actions.
• If the results of follow up sampling are satisfactory after carrying out corrective actions (if any) conclude the investigation.
• If the results of follow up sampling are not satisfactory carry out further investigation take necessary actions accordingly. Following activities can be
performed to determine the root cause:
- Sampling and analysis at different stages of generation and distribution system to identify the contamination.
- Sanitization of generation, storage, distribution and heat exchangers as applicable.
- Verification of air vent filters.
- Verification of gaskets, valves and other components.
5.5.5.8 The system can be released for use after obtaining satisfactory results for consecutive three days.

5.6 Investigation of Out of Limits Results in Chemical Analysis, BET of Water

5.6.1 On obtaining out of limit results in any chemical analysis (except for TOC) and BET, inform to Head Microbiology. Do not discard the original left
over the sample (if any).
5.6.2 Verify the status (cleaning or depyrogenation) of the glassware used for sampling and testing.
5.6.3 Verify the status of the chemicals, reagents and instruments used in the analysis.

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5.6.4 Verify the test is performed properly as per procedure for any analyst error during testing.
5.6.5 If any discrepancy is observed in glassware used for sampling and testing, then take necessary corrective actions and arrange for re-sampling
from particular sample point from glassware conforming to requirements.
5.6.6 If the any discrepancy is observed in chemicals, reagents or instruments, then take necessary corrective actions and retest using original
sample if available or with a fresh sample.
5.6.7 If the analyst error is observed, then the second analyst shall perform the test.
5.6.8 If the results of the resample conform to specifications, then record the results and water may be released.
5.6.9 If the no assignable cause is determined above or the test results show non-conformance on re-sampling and testing, then inform the
concerned department and QA.
5.6.10 Perform the investigation to determine the root cause and take necessary corrective actions. Following activities can be performed to
determine the root cause:
• Testing of input water and at different stages in the treatment and generation system.
• Cleaning and sanitation of generation, storage and distribution system.
5.6.11 The system can be released for use after obtaining satisfactory results for consecutive three days.
5.6.12 For investigation of chemical analysis follow the chart.
5.7. Investigation of Out of Limit Results in TOC
5.7.1 Investigation out of Alert Limit Results
5.7.1.1 If TOC results exceed the above Alert level then the following actions shall be initiated.
5.7.1.2 Any samples exceeding the alert limits shall be immediately informed to the Head Microbiology & QA and do not discard the original left over
the sample (if any)
5.7.1.3 Review the data for the sample location /system in question for any previous instances of out of limit results in last three months.
5.7.1.4 If the last data indicates previous occurrences of out of limits, then review the previous investigation reports to determine any similarities.
5.7.2 Laboratory Investigation
5.7.2.1 Interview the microbiologist who performed sampling and verify whether the sampling was performed as per sop and if any deviation
observed during the sampling/testing.
5.7.2.2 Verify the glassware used for sampling was properly cleaned.
5.7.2.3 Verify that sample was intact during transportation.
5.7.2.4 Verify that the instrument used was within calibration and testing performed as per procedure.
5.7.2.5 If laboratory investigation reveals a fault in sampling/glassware used/and transportation then the occurrence of out of limit results could be
attributed to laboratory /sampling error.
• An immediate repeat test of the original sample together with an additional sample from the same location shall be performed.
• If the TOC re-sample show results over the alert limit then additional user points shall be immediately sampled and tested.

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• If results suggest that only one point is affected and it is an isolated incident then the result will be recorded and used for trending analysis &
investigate for corrective and preventive action.
• If the retest results from the additional user points are found out of Alert limit, the results shall be informed to Head QA, Production and Engineering
department to carry out the detailed investigation and take immediate corrective and preventive actions.
5.8
• If results suggest that only one point is affected and it is an isolated incident
• Investigation shall be initiated to identify the root cause.
• If the retest results from the additional user points are found out of Action limit, the results shall be informed to Head QA, Production and
Engineering department to carry out the detailed investigation and take immediate corrective and preventive actions.
• Until and unless the investigation is complete, and immediate corrective actions is completed no further batches will be manufactured.
• The system can be released for use after investigation & obtaining the satisfactory results.
• A trend of OOL shall be prepared and review for repetitive nature & Effectiveness of CAPA on half yearly basis.
6.0 ABBREVIATIONS
6.1 SOP - Standard Operating Procedure
6.2 OOL - Out of Limit
6.3 OOS - Out of Specification
6.4 TOC - Total Organic Carbon
6.5 BET - Bacterial Endotoxin Test
6.6 CAPA - Corrective and preventive action

Annexure I

Investigation Report No: M-OOL/___/_____

Date of Initiation:
Sign: _____________ Date:____________
Details of OOL

Test in which OOL result is :

found
Results :

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Specification limit (concerned :

test)
SOP No. :

Date of Sampling :

Sampling Room/location ID :

Sample ID :

Type of water :

A.R. No. :

Sampled By :

Test Date :

Tested by :

Observed by/Date :

Results of negative control :

Plates

Product/Material details (if any)

Product/Material name :
Product Batch No. / A.R No. :

Date of Mfg. :

Investigation starting date :

QC-Supervisor Head-QC Head-QA

(Sign. & Date) (Sign. & Date) (Sign. & Date)

Phase I investigation
1.0 Observation of plates under Incubation (Sampled after the date of sampling showing out of limit results of the particular sample location)
Remarks/Summary:

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2.0 Review the Historical Data

Previous instances of OOL Yes No N/A
Remarks/Summary:

3.0 Analyst Interview

(a) Analyst trained & qualified for the particular Procedure/technique as Yes No
per the SOP

(b) Sampling was performed as per procedure Yes No

(c) Any Deviation Observed during sampling/Testing Yes No

(d) Any deviation observed during transportation of samples Yes No
Remarks/Summary:

4.0 Media Details

4.1 (a) Media Lot No.

(b) Autoclave Run No.

(c) Media Preparation Date
(d) Media Expiry Date

4.2 Personnel Interview:

(a) Analyst trained & qualified for the particular Yes No N/A
Procedure/technique as per the SOP

(a) Media was prepared as per Procedure Yes No N/A

(b) Any Deviation Observed during Preparation Yes No N/A

Remarks/Summary:

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4.3 Review of Media Preparation Record:

(a) pH Meter used within calibration (ID­­_________ ) Yes No N/A
(b) Balance used within calibration (ID__________ ) Yes No N/A
(c) Correct weight of media Taken Yes No N/A
(d) Correct volume of water taken Yes No N/A
Remarks/Summary:

4.4 (a) Autoclave validation Status Date of Validation Due date of Validation

Remarks/Summary:

(b) review of sterilization record of Media & plates/Sampling bottles/other acessories

Remarks/Summary:

(c) Any Deviation observed during sterilization

Remarks/Summary:

4.5 Bio safety cabinet /LAF used for media preparation Date of Validation Due date of Validation

4.6 Review of Biosafety cabinet /LAF records in which media is poured, for velocity, Diff. Pressure & validation document etc.
Remarks/Summary:

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4.7 Pre incubation Details

(a) Date of Pre incubation

(b) Date of completion of pre incubation

(c) Details of contaminated plates after pre incubation
(d) Results of sterility check plates

(e) Review of Incubator Data used for pre incubation Date of Validation Due date
of
Validation

Remarks/Summary:

4.8 Growth Promotion Test

(a) Date of Growth Promotion Test
(b) Results of Growth Promotion Test Ok Not Ok N/A
Remark/Summary

5.0 Incubation Details

(a) Incubation done as per procedure Date of Validation Due date of Validation

(b) Review of Incubator Temp. data Used for Incubation

Remark/Summary:

6.0 Additional observations/ comments

Note: Attach additional sheet, if required

7.0 Conclusion
Assignable cause identified
No assignable cause identified

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8.0 If assignable cause(s) identified, describe the cause(s) in details and give justification:

Note: Attach additional sheet, if required

9.0 Most probable cause identified (in case of non-assignable cause)

Note: Attach additional sheet, if required

10.0 Signatures

QC-Supervisor Head of QC
(Sign. & Date) (Sign. & Date)

11.0 Retest procedure (according to retest plan)

Remark/Summary

12.0 Justification for retest procedure

Note: Attach additional sheet, if required

13.0 Justification for resampling

Sampled by
Sampling Date
Observations during resampling
14.0 Signatures

Head of QC Head of QA
(Sign. & Date) (Sign. & Date)

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15.0 Retest results

16.0 Signatures

Analyst 1 Analyst 2 Analyst 3

(Sign. & Date) (Sign. & Date) (Sign. & Date)

OC Supervisor Head of QC
(Sign. & Date) (Sign. & Date)

Conclusion of phase I investigation

17.0 Results of phase I investigation
OOL confirmed Yes No
Assignable cause identified Yes No
Phase II investigation needed Yes No

18.0 Conclusion

19.0 Assessment of impact on other samples

Note: Attach additional sheet, if required

20.0 CAPA Identified

Note: Attach additional sheet, if required

21.0 Signatures

Head of QC Head of QA
(Sign. & Date) (Sign. & Date)

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Phase II investigation
1.0 Review of Sanitization / Operation Record of concern system

Remark/Summary

2.0 Interview of Water System /Production Personnel for any discrepancies in the functioning of water system or any maintenance undertaken
Remark/Summary

3.0 Verify for leakage in loop/tank

Remark/Summary

4.0 If one Sample location is out of limit then verify the sample location for any discrepancies

Remark/Summary

5.0 Review the identification results.

Remark/Summary

6.0 Cleaning status of raw water / other storage tank

Remark/Summary

7.0 Possible Source of Contamination

Remark/Summary

8.0 Additional observations/ comments

Note: Attach additional sheet, if required

9.0 Conclusion
Assignable cause identified (refer to point 32)
No assignable cause identified (refer to point 34)

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10.0 If assignable cause(s) identified, describe the cause(s) in details and give justification

11.0 Most probable cause identified (in case of non-assignable cause)

Note: Attach additional sheet, if required

12.0 Signatures

Head of Q.C Head of Engineering Head of QA

(Sign. & Date) (Sign. & Date) (Sign. & Date)
Further actions that should be taken

13.0

Note: Attach additional sheet, if required

14.0 Documents / data that should be reviewed

Note: Attach additional sheet, if required

15.0 Describe outcome of points

Note: Attach additional sheet, if required

16.0 Signatures

Head of Production Head of Q.C Head of Engineering Head of QA

(Sign. & Date) (Sign. & Date)
(Sign. & Date) (Sign. & Date)

Conclusion of phase II investigation

17.0 Results of phase II investigation

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Assignable cause identified Yes No

18.0 Assessment by QA

Note: Attach additional sheet, if required

19.0 Assessment of impact on concern batches/other batches

Note: Attach additional sheet, if required

20.0 CAPAs identified

Note: Attach additional sheet, if required

21.0 Final conclusion

Note: Attach additional sheet, if required

22.0 Signatures

Head of QC Head of Engineering Head of Production Head of QA

(Sign. & Date) (Sign. & Date) (Sign. & Date) (Sign. & Date)

Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of pharmaguideline.com, a widely-read pharmaceutical
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