sop for environment monitoring program

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sop for environment monitoring program

OBJECTIVE
Lay down the procedure for environment monitoring program.
2.0 SCOPE
This procedure is applicable for Drain, Compressed air Nitrogen air, microbiological environmental monitoring of area (Dry powder injection Block I and II /Microbiology laboratory/ Oral solid dose area) and personnel at M/s abc company
3.0 RESPONSIBILITY
• Officer / Executive (QC Micro) shall be responsible for Sampling, analysis and reporting.
• Section head shall be responsible for monitoring, review, compliance and implementation of the
SOP.
4.0 ACCOUNTABILITY
• Department Head for implementation of SOP.
• Head Quality / QA for compliance of SOP.
5.0 PROCEDURE
5.1 General information:
5.1.1 In any environment where human operators are present, microbial contamination at small level is inevitable. Thus, an expectation of zero contamination at all the location during every aseptic processing operation is technically not possible.

5.1.2 Microbial monitoring program assess the effectiveness of cleaning and sanitization practice by and of personnel who could have an impact on the bioburden of controlled environment.

5.2 Good environment monitoring practices (GEMP):
5.2.1 Layout for environment monitoring locations shall be prepared as per template format no. for all type of monitoring or sampling technique.
5.2.2 Ensure visually, during preparation of microbiological monitoring kit, there shall not be any contamination Petri plates.
5.2.3 Labeling shall be labeled with media reference number.
5.2.4 Marking shall be done on the base of media plate, do not mark the lid of plate.
5.2.5 Environment monitoring Start/End time shall be mention on Ist and last exposed media plate
During plate exposure/collection.
5.2.6 Ensure area cleaning, temperature, RH and pressure differential shall be within the specified
limit before start of environment monitoring. If not found in the limit inform to respective area
in-charge.
5.2.7 Before entering into the respective area person must follow the entry/exit procedure of
respective area.
5.2.8 Status of the area (as under operation/not in operation) must be mention in the format.
5.2.9 Person shall not disturb the plates during exposure.
5.2.10 Sanitize the hands before start of plate exposing.
5.2.11 After completion of environment monitoring, plates shall be incubated in incubator and
mention the details in format no. “Incubator usage logbook” as per SOP no “Operation, Cleaning and Maintenance of Incubator”.
5.2.12 Ensure that the air sampler is charged before taking it for air sampling.
6.0 DEFINATION
6.1.1 Settle Plate Exposure:
6.1.1.1 This technique is used to qualitatively assess the environments over prolonged exposure period.
6.1.1.2 When settle plates are exposed for NMT 4 hours periods, it can provide a limit of detection for
suitable evaluation of the aseptic environment.
6.1.2 Volumetric Air Sampling:
6.1.2.1 This technique is also known as Active air sampling and used to quantitatively assess the environment and trap the microorganisms associated with light particles in the air of controlled environment that cannot be settle down on Petri plates easily. One cubic meter (1000 liter) of air is sampled in order to maximize sensitivity of technique.
6.1.2.2 Surface Sampling: This technique is used to sample the regular or irregular surface of equipment, facilities, and personnel in aseptic area of controlled environment. Surface sampling can be accomplished by the use of contact plates or by swabbing methods.

6.1.2.3 Contact plate: This method is applicable for sampling of regular or flat surface; a suitable agar surface is pressed against the test surface for a short moment. Thus, part of the microorganisms that colonizing the surface is transferred to the agar surface. Microbial counts are reported as per plate contact plate.
6.1.2.4 Swab method: This method is applicable for sampling of irregular surfaces, especially irregular surfaces of equipment. After sample collection the swab is placed in an appropriate diluents or transport medium and is plated onto the desired agar plate and microbial count are reported as per swab of defined sampling area
6.1.3 Personnel monitoring: This technique is applicable for sampling of garb and Gloved Fingertip Sampling of the personnel associated with aseptic processing. It includes contact plate method for monitoring of garbing and 90mm media filled plate for Gloves Fingertip Sampling.
6.1.4 Drain monitoring: This technique is applicable for the sampling of Drains points in critical or controlled area.
6.1.5 Compressed and nitrogen air monitoring: Compressed & Nitrogen air monitoring shall be performed by active air sampling and purging method.
7.0 ENVIRONMENT MONITORING PROCEDURE
7.1 Microbiology media required for environment monitoring shall be prepared as per SOP No.: QC04-030 “Lab Media Management”
7.2 After the completion of pre incubation period, all the pre-incubated plates shall be examined for any microbial growth, any cracks over media, raised surface in contact plates, check the media lot number on the plate before keep in SS container.
7.3 If any plate is found to have low quantity media, growth, cracks, the inadequate raised surface or air bubbles, the plate shall be discarded. Mention the detail in ‘Media Reconciliation Record” format no.: QC04-030/F08 “Media reconciliation record”
7.4 Environmental monitoring kit shall be prepared as below:
Media filled Petri plates (90 mm) for settle plate exposure and air sampling.
Media filled (RODAC) contact plates (55-65 mm) for surface monitoring and Personnel Monitoring.
Swab for surface monitoring.
Air sampler sieve (sterile).
7.4.1 The sampling kit shall be prepared as per location mention in “Format No.
Schedule for Environment monitoring Sampling”.

7.4.2 After the visual check of the media plate, each plate surface shall be wiped with 0.2µ filtered 70
% IPA sterile lint free mop.
7.5 Marking on media plates shall be done as per table-1:
7.5.1 Marking shall be done in Passbox and kept in the SS Petri plate carrier.
7.5.2 Environmental monitoring plate shall be numbered as per prototype “Media Name/Location ID/performed by initial with date/Month along with media lot number. For eg. MN001/sign14/05.
7.5.3 For drain point sampling, Drain ID/sampled by initial with date/month. For e.g. DNP06/sign14/05.
7.5.4 For Compressed air monitoring sample plate, Point ID/sampled by initial with date/month. For eg. CAA01/sign/30/08.

Test	Code
Settle plate	SP
Active Air Sampling	AS
Surface monitoring by contact plate	SM
Surface monitoring by Swab	SW
Soyabean casein digest agar	SCDA
Dey-Engley Neutralized Agar	DNA
Dry power Injection block	DPI
Oral solid dosage	OSD
Microbiology	MIC

The Inner and outer surface of the SS Petri plate carrier and poly shall be sanitized previously with 0.2 μ filtered 70 % IPA and shall be put into the sanitized polybag and carried to the respective facility.
7.6 Transportation of Kit in DPI area:
7.6.1 SS container carrying plates shall be transferred from packing pass box ID: to manufacturing area.
7.6.2 In manufacturing area , the outer polybag shall be removed inside the controlled area and SS containers carrying plates shall be transferred to the Dynamic passbox ID:
7.6.3 Microbiologist shall enter as per SOP on “Entry and Exit procedure for respective area”
7.6.4 Plates are then taken from the container and exposed to the location as per “Format No. – ” Schedule for Environment monitoring Sampling.
7.6.5 After the completion of environmental monitoring activity all the sample plates shall be kept into the SS plate carrier and transferred to the microbiology lab for the incubation.

7.6.6 Environmental monitoring shall be performed by trained person, to ensure that the environmental conditions of the area are in compliance with respect to the acceptable levels of total viable count.
7.6.7
8.0 Transportation of Kit In OSD Area:
8.1.1 Take the container from packing pass box ID: to OSD area through air shower.
8.1.2 Expose the plates as per Schedule.
9.0 ENVIRONMENT MONITORING
9.1 Microbial Monitoring by Settle Plate in DPI,OSD and Microbiology Lab:
9.1.1 Enter into the area as per respective area Entry/ Exit procedure.
9.1.2 In this method pre-incubated 90 mm Soybean casein digest media Petri plates shall be exposed for a period NMT 4 hours.
9.1.3 Plates shall be exposed on SS stand or SS plate form of equipment as per the location ID described in the respective area.
9.1.4 Before exposing sanitize the hands with 0.22µ filtered 70% IPA and aseptically expose the Petri plate by putting the lid adjacent the exposed Petri plates facing the inside down on SS stand or SS surface.
9.1.5 Care shall be taken that hands should not move over the exposed Petri plates to avoid chance of contamination.

9.1.6 Environmental monitoring sequence by Settle plates shall be from critical to less critical location.
Note: In DPI change room, environment monitoring shall be done as per below sequence:

Sequence for DPI area- Change room
Monitoring Sequence No.	location	Classification
01	Man air lock-4 (Room ID F45)	Grade – B
02	Man air lock-3 (Room ID F44)	Grade – B
03	Man air lock-5 (Room ID F46)	Grade – B
04	Man air lock-6 (Room ID F47)	Grade – B
05	Man air lock-2 (Room ID F43)	Grade – C
06	Man air lock-1 (Room ID F42)	Grade – D
Sequence for Sterility area –Change room
Monitoring Sequence No.	location	Classification
01	Man air lock-3 (Room ID S54)	Grade – B
02	Man air lock-4 (Room ID S55)	Grade – B
03	Man air lock-2 (Room ID S53)	Grade – C
04	Man air lock-1 (Room ID S52).	Grade – D

Note: During change room monitoring emergency switch shall be used to enter back in the change room of DPI / Sterility area.
9.1.7 After completion of exposure period the sequence of Petri plate collection shall be start from first exposed Petri plate.
9.1.8 Transfer the collected Petri plates to Microbiology laboratory for incubation.
9.2 Incubation Details:
9.2.1 Settle Plate shall be incubated in inverted positions at 20-25 °C for 72 hrs for fungus and then 30-35°C for 48 hrs for bacteria growth.
9.2.2 In case of holiday or weekly off Environmental monitoring Petri plate shall be transferred or observed on next working.
9.3 Microbial Monitoring by Air Sampling in DPI,OSD and Microbiology Lab:
9.3.1 In this method pre-incubated Soybean casein digest media Petri plates shall be fit under the sieve and 1000 liter of air (1m3) shall be sucked (sampled) and microorganisms shall be trapped due to impaction of the air on the surface of the media Petri plates.
9.3.2 Environmental monitoring sequence by Air sampling shall be from critical to less critical location.
9.3.3 Sanitize the air sampler sieve in between the change in grade of area with 0.22µ filtered 70% IPA using sterile lint free mop and after moping ensure that there should be no traces of IPA on the sieve.
9.3.4 Air sampling shall be done on specified locations and after completion of air sampling transfer the Petri plates to the SS container to Microbiology lab for incubation.
9.3.5 Incubation Details:
9.3.5.1 Air sampling plate shall be incubated in inverted positions at 20-25 °C for 72 hrs for fungus and then 30-35°C for 48 hrs for bacteria growth.
9.3.5.2 In case of holiday or weekly off Environmental monitoring Petri plate shall be transferred or observed on next working.
9.3.6 Environment monitoring of Anaerobes in DPI Area:
9.3.6.1 Air monitoring for anaerobic organisms shall also be done using soyabean casein digest agar but the incubation of the plates shall be under anaerobic conditions.
Plate exposure to check presence of anaerobic bacteria in critical areas by settle plate method shall be performed of filling area, capping area, blending area and sampling room. Sterile product open directly
9.3.7 in Grade A and its supporting areas Grade B. Inert gas nitrogen purging apply during product filling therefore this is necessary to check anaerobic bacteria possibility in anaerobic condition applying area and supporting areas.
9.3.7.1 Environment monitoring of sample locations shall be recorded as per format no.: “Environment monitoring of sample location”
9.3.7.2 The observation of anaerobic organism shall be recorded as per format no. “Environment monitoring of Anaerobes – Settle plate method (Dry Powder Injection Area) ”
9.3.8 Incubation Details:
9.3.8.1 Settle Plate shall be incubated in inverted positions at 30-35°C for 72 hrs. for anaerobic bacteria growth.
9.3.8.2 In case of holiday or weekly off Environmental monitoring Petri plate shall be transferred or observed on next working.
9.3.9 Surface Monitoring by Swab method in DPI and Microbiology Lab.
9.3.9.1 Swab sample shall be taken from the irregular surfaces.
9.3.9.2 Take ready to use sterile swab moistened with 0.9% normal saline (sterile) under LAF to maintain the aseptic condition.
9.3.9.3 Before swab samplings sanitize the hands with 0.22µ filtered 70% IPA and care should be taken not to touch the bud portion.
9.3.9.4 Select 25cm2 area of the surface and swab it by sterile cotton swab.
9.3.9.5 Take out the swab sample first with horizontal strokes and then using vertical strokes by rotating the swab bud.
9.3.9.6 After swabbing, aseptically put the swab stick back to its container.
9.3.9.7 Sanitize the swab surface immediately after swabbing with 70% IPA.
9.3.9.8 After completion of swab sampling analyze the swab under LAF

9.3.9.9 Add 1 ml of sterile saline to the swab and vortex it till all the constituents of the swab bud get properly mix in the saline.
9.3.10 Test by Filtration method:
9.3.10.1 Filtration method shall be used for aseptic area (Grade A & B).
9.3.10.2 Filter the swab sample through sterile 0.45µ membrane filter by filtering all the content of the swab.
9.3.10.3 Wash the membrane with 100 ml 0.1% peptone water.
9.3.10.4 Transfer the membrane filter on SCDA media plate.
9.3.10.5 Perform one negative control for SCDA media by filtration method using 100 ml diluent. After filtration transfer membrane filter on surface of SCDA media petriplate.
9.3.11 Test by Pour plate method:
9.3.11.1 Pour plate method shall be used for grade C & D.
9.3.11.2 Pipette out 1 ml saline to a sterile Petri dish and add approximately 15-20 ml of sterile SCDA media. Rotate it in clockwise & anti clockwise direction and allow it to solidify.
9.3.12 Result interpretation:
9.3.12.1 After completion of incubation period count the number of colony forming units and record the results as counted cfu /Swab in the respective area format.
9.3.12.2 Sample should be analyzed within 2 hrs of sampling or within 24 hrs of sampling if stored at 2°C to 8°C.
9.3.12.3 All the swab plate observation shall be recorded as per format on. “Environment monitoring – Swab method (DPI)” and format no. “Environment monitoring – Swab method (Microbiology)”.
9.3.13 Surface monitoring by contact plate method:
9.3.13.1 For the surface monitoring by contact plate RODAC plate 55mm shall be used. Open the contact plate aseptically and gently press over the surface to be monitored for 5-10 seconds after sampling immediate sanitize the surface with 0.22µ filtered 70% IPA.
9.3.13.2 Observation shall be recorded as per format no.: “Environment monitoring – RODAC plate method (DPI)” “Environment monitoring-Swab method (DPI)” and format no. Environment monitoring – RODAC plate method (Microbiology Area), Environment monitoring – Swab method (Microbiology Area).
9.3.14 Incubation Details:
9.3.14.1 Swab plates along with negative control shall be incubated in inverted positions at 20-25 °C for 72 hrs for fungus and then 30-35°C for 48 hrs for bacteria growth.
9.3.14.2 In case of holiday or weekly off Environmental monitoring Petri plate shall be transferred or observed on next working.
9.3.15 Personnel Monitoring DPI and Microbiology Lab:
9.3.15.1 Personnel monitoring shall be applicable to all personnel who are required to work in Grade A and Grade B.
9.3.15.2 Person shall do self-monitoring at the end of shift or every exit in the first exit air lock of Injection and Sterility area of Microbiology laboratory.
9.3.15.3 Personnel shall not re-use the garment after personnel monitoring.
9.3.15.4 Before personnel monitoring marking on contact plate shall be done as per below procedure
NAME/PM-XX/DD/MM,
Where
NAME=Personnel Name,
PM= Personnel monitoring,
XX= serial no (as per picture –I),
DD= Date of monitoring,
MM= Month of monitoring
For example Vikash/PM-01/23/11 shall be the marking procedure of Mr. Vikash for the personnel monitoring of location PM-01 (01 is the location for Forehead (Gown) as per picture – I) on the 23/11/19.
9.3.15.5 The lid of RODAC plate shall be opened and personnel monitoring shall be done as per picture-I. Medium of RODAC plate shall be gently pressed for 3-5 seconds on the surface of garment in such a way that the entire convex surface of agar shall touch the surface.
9.3.15.6 The monitored surface of the garment shall be disinfected with 70% IPA after personnel monitoring and garment shall be put into the bin for cleaning purpose.
9.3.15.7 After completion of personnel monitoring plates shall be collected into SS Petri plate’s carrier and exit from exit airlock.

9.3.15.8 Person shall verify the personnel monitoring plates with the logbook “Logbook for entry/exit in aseptic process area” (PR02-003/F02).
Note:
• Just before personnel monitoring personnel shall not sanitize the hands with provided disinfectant.
• Personnel monitoring shall not be performed for personnel engage in cleaning activity after completion of processing.
• Surprise monitoring shall be performed by trained microbiologist to verify the self monitoring procedure and details shall be mentioned in format no.: “Environment monitoring – Personnel monitoring “and same shall be mentioned by the microbiologist under remark column as “Surprise Monitoring”
• Frequency of surprise monitoring: Monthly±3 days.
9.3.15.9 Observation shall be recorded as per format no “Environment monitoring – Personnel monitoring”

Location	Location Description	Location	Location Description
01	Right Hand Finger dabs (Gloves)	05	Right Armpit (Gown)
02	Left Hand Finger dabs (Gloves)	06	Left Armpit (Gown)
03	Forehead (Gown)	07	Right Forearm (Gown)
04	Chest (Gown)	08	Left Forearm (Gown)

9.3.16 Incubation Details:
9.3.16.1 Personnel Monitoring Plate shall be incubated in inverted positions at 20-25 °C for 72 hrs for fungus and then 30-35°C for 48 hrs for bacteria growth.
9.3.16.2 In case of holiday or weekly off Environmental monitoring Petri plate shall be transferred or observed on next working.
9.3.17 Monitoring of Drain Points in DPI, OSD and Microbiology Lab.
9.3.17.1 Rational for selection of drain points to be monitor for Microbiological analysis: Aseptic area drains shall be monitored for microbiological analysis. Drains area situated in grade D area. Area is controlled and classified to maintain the cleanliness class. Criticality is high of these area drains. Requirement as per schedule M pathogen should be absent in specific designed drains which prevent to back flow and cross contamination in area. Therefore only classified area (Grade D) drains shall be selected for microbiological analysis.
9.3.17.2 Details of drain points & its sampling schedule shall be maintained as per format no. Format no. “Environment monitoring of sample location”.
9.3.17.3 Calendar shall be prepared as per format no “Schedule for Environment monitoring Sampling” and maintained after sampling of drain point.
9.3.17.4 Swab sampling shall be performed for total aerobic viable count and pathogen analysis.
9.3.17.5 Take required number of pre sterilized swabs. Two number of swabs sample shall be collected from one drain point ( one for total viable count and one for pathogens)
9.3.17.6 Label swab tube with the details of location No. /sampled by initial with date/month and collect the swab sample from drains and sinks in manufacturing area and Quality control.
9.3.17.7 Observation shall be recorded as per “Environment monitoring – drain point” (Format No. ).

9.3.17.8 Sample should be analyzed within 4 hrs of sampling or within 24 hrs of sampling if stored at 2°C to 8°C.
9.3.17.9 One swab sample (Pathogen analysis):
• By Direct Inoculation Method: Transfer 1 ml swab sample in 100 ml Soyabean casein digest medium tube. Simultaneously perform negative control. Incubate the Soyabean casein digest medium tube as per below table-II.
9.3.17.10 After completion of incubation period take a loop full of enriched medium (SCDM) and subculture and incubation as per table-II.

Table-II

S.No	Media	Used For	Incubation Period
01	Soyabean Casein Digest Medium	Enrichment	30-35 °C for 18-24 hours
02	MacConkey Agar	E.coli	30-35 °C for 72 hours
03	Citramide Agar	Pseudomonas	30-35 °C for 72 hours
04	Manitol Salt Agar	S.aureus	30-35 °C for 72 hours
05	Xylose Lysine Dextrose Agar	Salmonella	30-35 °C for 48 hours

9.3.17.11 Second swab sample (Total aerobic viable count):
• By Direct Inoculation Method: Sample shall be analyzed by pour plate method as per clause no-8.3.10 simultaneously performs negative control.
9.3.17.12 Acceptance criteria: Total aerobic microbial count: for information only and Pathogens – must be absent.
9.4 Compressed/Nitrogen air in DPI and OSD area:
9.4.1 Monitoring of Compressed/Nitrogen air shall be performed through active air sampling or purging method.
9.4.2 Active air sampling:
9.4.3 Active air method shall be used for grade C/D.
9.4.3.1 1000 liter air shall be released using rotameter on the solid agar surface of Soyabean Casein Digest Agar 90 mm plate.
9.4.3.2 Incubation Details:
9.4.3.3 After monitoring SCDA plate shall be incubated in inverted positions at 20-25 °C for 72 hrs for fungus and then 30-35°C for 48 hrs for bacteria growth and record the observation as per format no.: “Environment monitoring – Compressed Air”
9.4.3.4 In case of holiday or weekly off Environmental monitoring Petri plate shall be transferred or observed on next working day.
9.4.4 Purging Method:
9.4.4.1 Purging method shall be used for aseptic area (Grade –A).
9.4.4.2 Take 100 ml SWFI in the filtration tube assembly and purse about 1000 liter compressed air in the solution through inlet of apparatus as per SOP no.: QC04-042 “Sampling and Testing of Nitrogen & Compressed Air”. After sampling sample assembly shall be transferred in microbiology lab aseptically and perform the sterility test as per SOP No.: QC04-053 “Sterility Test”.
9.4.4.3 If sample shall not be analyzed within four hour then sample shall be placed in refrigerator at 2 to 8 °C and have to analyze within 24 hours.
9.4.4.4 Incubation Details:
9.4.5 After analysis FTGM Tubes including, negative control and media control shall be incubated for 14 days at 32.5˚C + 2.5˚C to detect the aerobic & anaerobic microorganism growth & incubate SCDM tubes along with negative control and media control for 14 days at 22.5˚C + 2.5˚C for the detection of aerobic microorganism.
9.5 Observation and interpretation of results:
9.5.1 Observations shall be taken after the completion of the incubation period.
9.5.2 During transfer of the plates for second incubation, all plates shall be visually verified for the excursion. If any excursion is occurred, investigation shall be initiated without waiting for complete 5 days incubation. In such case result shall be reported in remark column of the respective format.
9.5.3 Count the number of colonies observed in the colony counter and in case of air sampling plates apply the appropriate correction table.
9.5.4 If there is no count in the plate it should be considered as NIL instead of zero.
9.5.5 If any spreader colony found, it shall be consider as a single colony.
9.5.6 In case if wrong count has been entered by the analyst in the concerned document it should be verified by the reviewer by observing the plate and can rectify the concerned entry.

9.5.7 The observation of settle plate, air sampling, surface monitoring & personnel monitoring in manufacturing facility area shall be recorded in the current version of their respective format.
9.6 Environment monitoring limits:
Recommended limits for microbial contamination

Area	Air sample (Cfu/m³)			Settle plates (Cfu/ 90 mm plate/*4 hours )			Surface monitoring (Cfu/55mm Plate or Cfu/Swab)			Personnel Monitoring (Cfu/Glove print 5 fingers)
Area	Alert	Action	Limit	Alert	Action	Limit	Alert	Action	Limit	Alert	Action	Limit
Grade-A	1	1	<1	1	1	<1	1	1	<1	1	1	<1
Grade-B	4	6	10	3	4	5	2	3	5	02	03	05
Grade-C	41	52	100	27	34	50	18	22	25	NA
Grade-D	106	130	200	52	63	100	38	43	50	NA

*Where settle plates are exposed for less than 4 hours the limits in the table shall still be used, no recalculation shall be done.
9.7 Frequency of environment monitoring for Dry Powder Injection & Microbiology Area

Grade	Air Monitoring by Settle Plate	Air Monitoring By Active Air Sampler	Surface Monitoring	Personnel Monitoring
A	* Each operating shift	Each operating shift	After end of the operation	Every Exit
A	**Quarterly	NA	NA	NA
B	* Each operating shift	Each operating shift	After end of the operation	Every Exit
B	**Quarterly	NA	NA	NA
C	Daily once	Daily once	Weekly	NA
D	Once in week	Fortnightly	Fortnightly	NA

(a) * Continuous monitoring shall be done by exposing the Petri plates till completion of filling activity in A/B Area of filling and sealing room, in case filling activity goes more than 4 hrs then plates shall be replaced for another next 04 hrs or till completion of filling activity.
** Anaerobes monitoring frequency for DPI area
NOTE:
• If there is no activity in the area: Microbiological monitoring shall be performed once in 72 hrs by settle plate & active air method

• In case after media fill, Environment monitoring shall be performed consecutive 3 days , there after as per frequency defined in clause no.: 8.7
9.8 Frequency of Environment Monitoring for OSD Area:

Grade	Air Monitoring by Settle Plate	Air Monitoring By Active Air Sampler
A	Fortnightly	Fortnightly
D	Bi- Monthly	Bi- Monthly

9.9 Frequency of Compressed/Nitrogen Air Monitoring:

	Frequency
Grade	Nitrogen	Compressed	Remark
A	Daily	NA	Before filling (If there is no filling activity then Compressed /Nitrogen shall be not be sampled and analyzed).
B	Daily	NA
D	Monthly	Monthly	OSD/DPI/Micro

9.10 Frequency of Air Shower Monitoring:

Area	Grade	Frequency	Method
DPI	D	Weekly	Active air sampling
OSD	D	Monthly	Active air sampling

9.11 Frequency of Drain Monitoring for OSD and DPI area:

Grade	Frequency
D	Monthly

9.12 Environment monitoring shall be done as per schedule ±3 days. If there is any holiday/weekly off, monitoring shall be done on next working day.
9.13 Monitoring schedule shall be prepared every year in last week of December as per format no.: QC04-011/F27 and after monitoring executed date shall be filled in the schedule regularly.
9.14 Trend preparation:
9.14.1 Trend preparation and graphical presentation of observed microbial values in the form of trends shall be prepared on respective area as per SOP QC04-052) “Trend analysis of Microbiology data”.
9.15 Environment Isolate:
9.15.1 Colonies of similar morphology and repeatedly observed during environment monitoring shall be isolated and recorded as per SOP QC04-032 “Handling of Microbial Isolates”.

9.15.2 These Microorganisms shall be used in growth promotion test of media.
9.16 Excursions / deviations:
9.16.1 In case the results are found above the alert and action level, proceed for Investigation of results as per the current version of SOP QC04-048 “Handling the out of specification of microbiology results”.
9.17 Incidental breakage of plate exposure period:

9.17.1 In case of any incidental breakage of plate during the exposure period, the microbiologist shall inform the breakage to the microbiology in-charge.
9.17.2 Cover the broken plate and media with sterile mop and immediately poured with filtered 70% IPA.
9.17.3 Collect the broken plate along with the media from location immediately without leaving any residue of the media in respective aseptic area.
9.17.4 Clean the location with sterile mop containing sanitize with filtered 70% IPA.
9.17.5 Transfer the media through the dynamic passbox for decontamination in microbiology laboratory.
9.17.6 Decontamination shall be done as per SOP QC04-008 “Decontamination and Disposal of Microbial Waste”
9.17.7 Report incident and make necessary entries in Format “Incidental breakage during plate expose” (Format no. ).
10.0 FORMATS:

Sr. No.	Format No.	Title of the Format
1.		Environment monitoring by Settle plate method
2.		Environment monitoring of “Anaerobes” (DPI-I &II)
3.		Environment monitoring – Contact plate (DPI –I & II)
4.		Environment monitoring – swab method -Aseptic & control area by Membrane Filtration / Pour Plate Method (DPI-I & II)
5.		Environment monitoring – Personnel Monitoring (DPI & MICRO)
6.		Environment monitoring – Air Sampling
7.		Probable count table chart for Hi petri air sampler system Mark-II
8.		Sampling Location For Environment Monitoring
9.		Environment monitoring – Drain point
10.		Incidental breakage during plate Exposure
11.		Layout of area ______________method ______________.
12.		Environment monitoring – Settle plate (Microbiology Lab- Sterility area )
13.		Environment monitoring – Active air (Microbiology Lab- Sterility area )
14.		Environment monitoring – Aseptic Area – Settle plate (DPI-I & RM)

1.		Environment monitoring – Aseptic Area – Active Air (DPI-I)
2.		Environment monitoring – Compressed Air
3.		Environment monitoring – Settle plate (OSD)
4.		Environment monitoring – Air sampling (OSD)
5.		Schedule for Environment monitoring Sampling.
6.		Environment monitoring – Settle plate (Microbiology Lab – Control area )
7.		Environment monitoring– Active Air (Microbiology Lab – Control area)
8.		Environment Monitoring Control Area – Settle Plate (DPI-I &II)
9.		Environment monitoring-Control area & RM Store- Active air (DPI-I, II & RM Store
10.		Environment monitoring – Contact plate (Microbiology Lab )
11.		Environment monitoring – Swab method (Microbiology Lab)
12.		Probable count table chart for SAS air sampler
13.		Sampling locations for Personnel monitoring
14.		Environment monitoring – Aseptic Area – Settle plate (DPI-II)
15.		Environment monitoring – Aseptic Area – Active Air (DPI-II)

11.0 REFERENCES:

As per GMP

12.0 ABBREVIATIONS :

SOP	Standard Operating Procedure	No.	Number
QA	Quality Assurance	F	Format
QC	Quality control	%	Percentage
IPA	Isopropyl alcohol	RODAC	Replicate organism detection and count
SS	Stainless steel	PVC	Polyvinyl chloride
cGMP	Current good manufacturing practice	SCDA	Soyabean casein digest agar
USP	United standard pharmacopoeia	SEP	September
OOS	Out of specification	HVAC	Heating ventilation and air condition
CFU	Colony forming unit	m	Meter
ºC	Degree centigrade	µ	Micron
DPB	Dynamic pass box	SW	Swab