1.0 Purpose : To provide an instruction for environmental monitoring in production department.
2.0 Objective : To provide a documented procedure for environmental monitoring. The objective
of environmental monitoring program is to be obtained representative estimates
of bio-burden of the environment for all controlled process areas and to maintain,
Control and to provide high quality of environmental standards.
3.0 Scope : This procedure is applicable for all controlled process areas and its surroundings in production department of ----- pharmaceutical Ltd,.
4.0 Responsibility:
· Primary : Production chemist.
· Secondary : Production Officer.
5.0 Procedure:
· Following parameters are to be covered for Environmental Monitoring:
Ø Temperature Monitoring. (Between 25 to 30°C, once in a day)
Ø Relative Humidity Monitoring. (Not more than 70 %, once in a day)
Ø Differential Pressure Monitoring. (Not less than 0.5 mm, once in a day)
Ø Microbiological Monitoring. (Once in a month)
o Settle Plate Method
o Air Sampling Method
o Surface Test Method
Ø Area identification for Settle Plate Method – as per attached Annexure I
Ø Area identification for Air Sampling Method – as per attached Annexure II
Ø Area identification for Surface Test Method – as per attached Annexure III
· Settle Plate Method:
Ø This is an inexpensive way to qualitatively assess the environments over prolonged exposure time. People are the major source of microorganism in controlled process area, people constantly shed skin particles, moisture droplets and hair which serve as vehicle for the transfer of body flora into the controlled process area which can be identified and monitored by exposing the media plates for long period of time
· Test Procedure
Ø Prepare the media, Soybean Casein Digest Agar as per the SOP of Media preparation.
Ø Preincubate the plates for 48 hours at 30 0C to 35 0C and check for any microbial contamination before exposure.
Ø Expose the Petri plates as per the location chart. Ensure that the surface of the agar media is open to the environment, by removing the lid of the Petri plate and placing it in the adjacent position.
Ø After completion of exposure time, place the lid of each plate back in place. Incubate the exposed plates at 30 0C to 35 0C for 2 days for bacterial growth & further 3 days at 20 0C to 25 0C for fungal growth in inverted position.
Ø Count the number of colonies per plate and record the observations as cfu/plate in the record format.
Ø Exposure Time : 1 hour.
Ø Frequency : Quarterly
Ø Following observations to be noted.
o Note the actual time of exposure on record format.
o Note down the activity in area/ no. of personnel involved at the location of exposure on record format.
Ø Check the time when sanitization of the area was last carried out.
Ø The record format or graphical representations of the environmental monitoring results are intimated to Q.A., Production, & Engineering department.
· Air Sampling Method:
Ø Determination of airborne microbial contamination using the air sampling equipment is generally carried out for process areas and is used according to the location chart.
Ø Open and place the Preincubate media plates of Soyabean casein digest agar media plate on autoclaved stainless steel cone and then on it place the autoclaved stainless steel feeder cone circular clamp assembly.
Ø Set the instrument for sampling 1000 liters of air and start it and operate it as per the SOP of Operation of air sampler.
Ø After completion of exposure time, place the lid of each plate back in place. Incubate the exposed plates at 300 C to 350 C for 2 days for bacterial growth & further 3 days at 20 0C to 25 0C for fungal growth in inverted position.
Ø Count the number of colonies per plate and record the observations as cfu/m3 in the recording format.
Ø Exposure Time : 1000 liters of air.
Ø Following observations to be noted.
o Note down the actual start time of exposure on the record format.
o Note down the activity in area at the location of exposure on the recording format.
o Check the time when sanitization of the area was last carried out.
· Surface Test Method
Ø Surface monitoring is generally performed on areas i.e. surface of equipments, facilities and personnel gears that come in contact with the product and on areas adjacent to those contact areas of controlled environment. The swabbing method may be used for sampling of irregular surfaces especially for equipments .The area to be swabbed is in the range of 24 to 30 cm2 and is to be taken in a sterile normal saline or sterilized purified water. Surface testing is more closely related to effectiveness of cleaning and sanitization methods.
Ø Test Procedure
o Contact plates filled with Soybean Casein Digest Agar are used during sampling of regular and flat surfaces and sterile swabs wetted with sterile normal saline or sterile purified water are used for irregular surfaces especially equipments.
o During contact plate sampling, ensure that the surface of the agar plate is opened and is in contact to the surface of the wall/floor to be sampled & then press it slightly and then close it immediately.
o The area to be swabbed is in the range or 24 to 30 cm2 and is to taken in sterile normal saline or sterilized purified water.
o The estimate of microbial counts in done by plating of an appropriate aliquot on or in Soybean Casein Digest Agar plate.
o After completion of test, incubate the plates at 30 0C to 35 0C for 2 days for bacterial growth & further 3 days at 20 0C to 25 0C for fungal growth in inverted position.
o Count the number of colonies observed & record the observations in the worksheet.
o Frequency: Surface test and Air sampling will be done alternatively once in Six Month
o Following observations to be noted:
o Note the time of contact on record format.
o Note down the activity in area at the location of exposure on record format.
o If any abnormality found in the results, it should be notified to Production, Q.A. & Engineering department for corrective action and following remedial action should be taken:
ü To perform cleaning immediately after the completion of the current ongoing in process stage in that area by validated process, on crossing the action and alert limit.
ü To check the filter integrity by measuring the pressure difference across the filters.
ü To check the pressure gradient of the area.
ü Do not proceed for the next batch till the microbiological result is achieved below the Action / Alert limit.
ü The products manufacture on that particular day to be hold till the Microbiological testing release.
· Limits of Environmental Count:
GRADE-D
| LIMITS | SETTLE PLATES | CONTACT PLATES | AIR SAMPLING |
| Action limit | NMT 25 cfu / 90 mm diam.Plate / 1 Hour | | NMT 100 cfu / m3 |
| Alert limit | NMT 20 cfu / 90 mm diam.Plate / 1 Hour | | NMT 75 cfu / m3 |
| Target limit | NMT 15 cfu / 90 mm diam.Plate / 1 Hour | | NMT 50 cfu / m3 |
v EC GMP Guide, Annex 1 “manufacture of sterile medicinal products” revised
April 2002
