This sop describes the procedure to carry out routine environmental monitoring of manufacturing facility,service,and equipment to determine the level of viable and non-viable particulate contamination.
2.0
SCOPE
1.
This procedure is applicable to production and microbiology lab.
RESPONSIBILITY:
1.
It is the responsibility of the working personnel performing tests,to inform the Q.A –HOD in case of results exceeding the specified action level and to re monitor after completion of corrective action.
2.
It is the responsibility of the site Microbiology Manager to give the recommendation for taking corrective action in case of results exceeding the specified action level.
3.
It is a jointresponsibility of the Micro\Q.A and production,engg.personnel(if required) to
Carry out an investigation in case of results exceeding the specified action level.
4.
It is the responsibility of the concerned department-head to take corrective action in co-ordination with other related departments like engineering and Micro\Q.A.
5.
It is the responsibility of Q.A.Manager to take necessary action in case of results exceeding the specified action level.
PROCEDURE:
Environmental monitoring must be in place and it categorized in to two types, which are (1) monitoring as part of facility validation/re-qualification and (2) routine monitoring
1.
The following procedure is applicable for routine monitoring
1)The Q.A.Manager in co-ordination with Microbiology\production manager must prepare a environmental monitoring program which must include
a)responsibilities for sampling,testing,documentation and evaluation of data
b)Method of monitoring (active air sampling\passive air sampling\surface monitoring etc)
c)Sampling location.
d)Sampling frequency.
e)Sampling to be done during activity\at rest condition\after cleaning etc,as the case may be.
f)Alert and action level for each type of monitoring
g)Level of investigation and action to be taken in case the alert\action limit has been exceeded.
h)The results of environmental monitoring must be recorded in a manner such that it facilitates easy recognition of trends over a longer period of time.the trends must be evaluated at least once in a year.
i)Any result above the specified alert limit must trigger a communication to the person concerned(production\engineering).
J) In case the result obtained is above the specified action limit, this must be immediately notified to the Q.A.Manager or his\her authorized delegate and a formal black spot must be made and submitted to the concerned department.
k)An investigation must be performed to determine the probable causes of higher results.
l)The Q.A.Manager must recommend an appropraiate corrective and preventive action.
2)
MONITORING OF MANUFACTURING FACILITY
a)This includes monitoring of facility, services and equipment used in the manufacturing to determine the non-viable load.
MICROBIOLOGICAL MONITORING
1.
Microbiological monitoring of the facility must be undertaken as appropriate to the nature of the facility and the type of products manufactured.
2.
Monitoring must cover all production areas at a defined frequency.
3.
Manufacturing environments where product is exposed must be monitored in operation
4.
Refer to Annexure 1 for action level, recommended locations& frequencies for stores, production and packing departments
a)
ACTIVE SAMPLING
The manufacturing area must be monitored for microbial quality by using active air sampler capable of sampling of minimum of 1000 liters of air generally Tryptone Soya Agar to be used for determining total bacterial counts).
1.
This is a quantitative method for determining microbial load in the area; and result reported as cfu\m3.
2
.
Sampling must be done at (or) near areas where product is exposed and with normal operating activity. (after air sampling immediately incubate the plates at 20-25°c for not less than 72 hrs next at 30 to 35°c for not less than 48 hrs.)
B)
PASSIVE SAMPLING
This is a semi-quantitative method for determining microbial load in a facility.
1.
Monitoring must be carried out during normal manufacturing activity (Exception is processes which generate dust particles,in which sampling will be done before start of activity).
2.
Plate containing nutritive media (with suitable supplements ,if necessary) must be exposed in the critical areas for a long period of not less than 4hrs. The results reported as cfu per plate for the duration exposed. Typically,Tryptone Soya Agar should be used for determining bacterial counts(after plate collction immediately incubate the plates at 20-25°c for not less than 72 hrs next at 30 to 35°c for not less than 48 hrs.)
3.
SURFACE MONITORING
This involves testing of equipment surfaces(product-contact) and manufacturing premises(including wash areas)using the swab technique.Tryptone Soya Agar can be used to swab technique.
4.
A minimum area of about 25 cm square cm should be selected in case of surface swab technique(for non-flat\regular surfaces a representative area should be sampled)and results reported as cfu\swab.
5.
Surface monitoring should be done after cleaning activity and before start of manufacturing.
6.
Recovery of microorganisms using swab testing should be validated;recovery should not be less than 75%.Validation exercise must be carried out only in the laboratory by addition of known number of organisms to surfaces similar to those used in manufacturing (such as S.S plate\glass plate etc) followed by swabbing the surface and checking the number of organisms recovered from the surface.
6.
Monitoring of drains located in the manufacturing area must be carried out to check for absence of objectionable organisms (such as E.coli,Salmonella spp,P.aeruginosa and Staphylococcus aureus.
3.
MONITORING FREQUENCIES
Refer to annexure 1 &2 for monitoring frequencies for production and packing area.
NOTE:
Apart from the routine monitoring exercise,monitoring must also be carried out after AHU-shut down \after power failure and after area fumigation procedure
4.
ALERT AND ACTION LEVEL
There should be a two-tier approach for approach for expressing microbiological environmental monitoring level viz.alert limit and and action limit.
1.
ALERT LIMIT
This represents a limit more stringent than the action limit; monitoring results beyond the alert limit should trigger a communication to the concerned department production\engineering in order to make them aware of any potential problem and take an appropriate action to avoid recurrence.The Q.A.Manager in coordination with Micro.Manager should assign alert level for different type of monitoring based on the trend.
2.
ACTION LIMIT
Action limit is the limit above alert limit and when exceeded must lead to formal communication to the concerned department(production\engineering).Counts beyond action limit will represent a black spot and may warrant stoppage of activity until corrective action has been completed.
3.
NOTIFICATION REPORT:
In case the environmental monitoring results exceeds the specified action level,a formal communication in the form of notification report must be initiated to the concerned department personnel.
4.
Such results must trigger a detailed investigation to determine the probable cause; this will include a laboratory investigation. Refer to annexure 3 for the format of notification report.
5.
The report should be initiated by the microbiologist and the Micro Manager in consultation with microbiologist should give a recommended corrective action based on the type of isolate obtained
6.
This report should further be filled by the production personnel starting the corrective action taken within a stipulated time frame(with in 2 days)
7.
Re-monitoring of the location must be carried out after corrective action has been completed by the production
8.
Impact of the notification results on the product batches that have been manufactured during that period must be assessed by the site micro\QA Manager to determine further course of action.
9.
The impact for for batches manufactured in the area must be considered and remedial action identified.
10.
All investigations into the root cause and potential impact of the contamination,together with the proposed corrective and preventive actions must be documented.
11.
Corrective and preventive actions must be completed in a timely manner.
5.
IDENTIFICATIONS OF ISOLATES
1.
Identifications of isolates obtained during environmental monitoring is necessary to develop a database of typical microorganisms associated with the manufacturing and testing facility.
2.
Identification is classified in to two types viz.presumptive and confirmed identification depending on the extent to which it is carried out.
3.
Presumptive identification up to the genus-level and confirmed identification up to the species level.Level of identification required for any isolate will depend upon source\location from where it has been isolated.
4.
Periodic identification to genus level must be undertaken for microbiological isolates to establish a baseline of local environmental isolates.
5.
Identification to species level must be undertaken if the monitoring result is a typical. result is when the colony type is different from normal, when the action level is exceeded or if the isolate is suspected of being objectionable.
6.
There should be a database to include all the morphologically different organisms isolated and identified for a period spread over one
7.
Level of identification required for different types of isolate is given in Annexure 4.
Environmental monitoring review and trends
1.
Regular reviews of environmental monitoring data must be conducted and the results presented in internal management quality meeting.
2.
Environmental monitoring results should be trended to facilitate easy assessment of results.
3.
Such trends should be reviewed during the site committee meeting(site quality meeting)and must be included as part of periodic product review.
4.
Trends must be evaluated atleast every 3 months and alert and action levels re-valuated atleast annually.
5.
For areas under initial evaluation,the re-valuation period for levels must be defined in the validation protocol.this period should not exceeded one year
ANNEXURES:
Annexure 1- Schedule for microbiological monitoring of manufacturing areas.
