MICLAB-095 Sterile Sampling Procedure for Microbiology Laboratory

General

All samples, charts and Settle plates (Fallout plates) are to be delivered to the Micro. Lab. Sample Cabinets and logged into the relevant logbooks, i.e. Sterility Logbook, Chart Logbook, Non-sterile Raw Material Logbook and Environmental Monitoring logbook.

Each group of samples taken from a Batch Production Number, (BPN) must be accounted for by noting the quantity and signing the BPN document when the samples are taken.

1. All sampling is to be done by Authorized Persons.
2. Samples selected for the Sterility test, the Bacterial Endotoxin test, Bioassay test or the Microbial Limit test are not to include any rejects, i.e. they are to be saleable product.  They are to be taken after the Inspection (where possible).
3. Only saleable product is to be sampled for the Micro. Lab., that is, NO REJECTED material is to be sent to the Micro. Lab. for testing.
4. Sample security must be maintained by placing the samples of small containers in a clean, NEW plastic bag and adequately labelling it with PRODUCT NAME, MATERIAL CODE Number (include all Material Code numbers if the batch has split codes), BPN and number of samples.  If a single BPN samples are unable to be collected into one single bag, ensure that there is a new documentation for the second bag to clearly identify the samples.
5. Samples of large containers of non‑sterile products, e.g. Jars of tablets, must be adequately labelled with PRODUCT NAME, MATERIAL CODE Number, BPN Number and date and time of fill where appropriate.
6. When Settle plates (Fallout plates) are being exposed during the manufacturing Filling shift, the Sterile operator is to check the filling machine for any leaks.  If breaches to the filling environment take place the sooner they are identified the better, it is the responsibility of all personnel working in the filling room to report any breaches to both the Process Manager and to the Micro. Lab.

NOTE: Environmental Monitoring (see MICLAB 045)

If Environmental Monitoring is to be conducted due to reasons stated in MICLAB 020 by production personnel in the place of Micro. Lab Staff, please take Air samples of both the filling machine room and Laminar Flow using the Air Sampling equipment, located inside the Sterile areas, using TSA Agar plates.  Take surface samples, using contact plates, of the machine surface, wall and floor.  Deliver samples to the Micro. Laboratory sample Cabinets.

1. Solution Preparation Area – Details of Specific Responsibilities

NOTE:   Only saleable product is to be sampled for Micro. Lab., that is, NO REJECTED material is to be sent to the Micro. Lab. for testing.

Specific Requirements for sampling:

Bulk Bioburden samples, i.e. Solution Prior to Membrane filtration are to be sampled near the end of filling for all batches manufactured in the Solution Preparation Rooms.

Samples are to be stored in the Solution Preparation Room fridges immediately after sampling.  These samples are to be logged into the appropriate logbooks.

1.1.             Each day the Micro. Lab. will collect the samples and either test immediately or place inside the Micro. Lab. fridge until testing is ready to take place, (MICLAB 075).  The Micro. Lab. will ensure samples are logged as being collected.

1.2.             Injectable Batches for filling

All injectable solution batches are to be sampled by Production personnel in the Solution Preparation Rooms for a bioburden sample at the conclusion of the filling of the batch if possible.  The Bioburden sample is obtained at the conclusion of the filling of the batch prior to the filtration (the bioburden reduction filter) of the solution by aseptically disconnecting the hose from the filter assembly and aseptically filling one sterile 500ml bottle.

1.3.             Vessel and Line Steaming Charts

1.3.1.       All vessel and line steaming charts are to be delivered and logged into the Vessels and Lines Chart Logbook (Form 645). Upon delivery to they are to be logged into the “Bioburden, Samples, Holding Tank and Production Line Steaming In Process Reports” logbook.

1.3.2.       Please ensure all Steridose Vessel charts have recorded the BPN and Material Code Number of the batch for which it is prepared and are signed and dated by the Operators.

1.3.3.       Other Vessels and Line steaming charts are printed and need to have signature and date.

1.3.4.       All sterilization charts are to be inspected before delivery and a Deviation Report (DR) generated if required.  The DR No. is to be written on the chart.

1.3.5.       Please advise Micro. Lab. staff ASAP of changes to vessel dedication of BPN so all necessary alterations to Micro. Lab. documentation can be made.

2. Sterile Filling Area – Details of Specific Responsibilities

NOTE:   Only saleable product is to be sampled for Micro. Lab., that is, NO REJECTED material is to be sent to the Micro. Lab. for testing.

Specific Requirements for sampling:

Sterility samples, Bacterial Endotoxin (Pyrogen) samples, Settle (Fallout) plates, sterilising charts and Biological Assay test samples (if necessary are to be delivered to the Micro. Lab. Sample Cabinets.  On delivery, all items are to be logged into the appropriate logbooks.

Personnel Monitoring plates are to be left in the Sterile Scrub Preparation Rooms. Label the finished units with the appropriate date, time, start, middle, end, sterility, pyrogen, assay.

2.1.             Pre sterilization bioburdens

“X” units from each batch are to be randomly selected immediately prior to the autoclaving of the final load.  When collecting Pre-Sterilization Bioburdens samples, please fill out Form 640 and place them into a NEW plastic bag and deliver to the Micro. Lab. Sample Cabinets.

2.2.             Sterility Test Samples

When collecting Sterility test samples please fill out the sterile area Sample Identification Checklist (Form 625).

Samples are to be collected with the minimum of handling and placed into a NEW plastic bag with the sterile area Sample Identification Checklist filled in and placed inside the bag with the samples.

2.3.             Bacterial Endotoxin (Pyrogen) Samples

When collecting Bacterial Endotoxin Samples please record the information on the sterile Area Sample Identification Checklist (Form 625).

2.4.             Biological Assay Test Samples – (if required)

When collecting Bacterial Endotoxin Samples please record the information on the Sterile Area Sample Identification Checklist (Form 625).

2.5.             Sterilization Charts

All charts that are generated from the steaming of the sterile preparation machines and transfer lines are to include the following details:

• Machine Number
• Shipper Label to be signed and dated by Operator
• The details of BPN, Material Code, User ID, Product Type are to be entered onto the chart at the header section.

The chart is to be checked before the commencement of filling of product.  Once the chart has been checked, it is to be signed and dated by the Operator.

If, for any reason a machine is not steamed (because of filling a product of the same Code and there has been no break in sterility of the line), It is still require the header section of the chart to include all details and a signed and dated Shipper Label. If no Shipper label has been generated for the BPN, or the machine does not require steaming, the Operator still needs to send a completed copy of Form 630 to the Micro. Lab., to enable Micro. Lab. personnel to enter the steaming details into the steaming log. Include the information that the machine has not been steamed, (i.e. N/A for Steaming).

If at the start of filling a batch, the machine does not require steaming, but during the filling of the batch it does require steaming, due to a break in sterility, then a Deviation Report (DR) is to be raised.  The DR number is to be written onto the chart.

All sterile preparation and transfer machine chart records are to be inspected before delivery to the Micro. Lab. Sample Cabinets.  The charts are to be logged into the Chart Logbook (FM 0635).
Micro. Lab. staff is responsible for the daily collection of the charts from the Sample Cabinets and the checking of the charts.

2.6.             Settle Plate (Fallout plate)

2.6.1.       Each Filling Machine is required to have exposed at least one Settle plate (Fallout) for 4hours + or – 15minutes/ per shift/ per BPN/ per number of days of filling, (i.e. if filling over 3 shifts then you are required to have at least 3 Settle plates).  If for some reason the exposure time is less due to the batch finishing on that shift or due to breaks, major stoppage then indicate this on Settle plate.  Settle plates are not to be exposed for longer than 4hours + or – 15minutes due to the possibility of the plates becoming dehydrated. NOTE: If a batch has only just started or about to end on a shift and the exposure time is less than 4hours + or – 15minutes, then the plate should be identified with start and end of batch to avoid a deviation being raised for insufficient exposure time on that individual shift of manufacturing.

2.6.2.       Nutrient Agar plates are exposed to sample the air quality during filling.  Written details required on the plate are as follows:

• BPN
• Material Code Number
• Date of Filling
• Sterile Preparation Machine number
• Start time of Exposure
• Finish time of Exposure
• Position on machine, i.e. Left, Right side.

2.6.3.       Plates are to be available from the production or Micro Lab. fridges.

2.6.4.       Settle (Fallout) plates are to be sealed with tape before being delivered to the Micro. Lab. Sample Cabinets and placed on the appropriate shelf.  On delivery to the sample cabinet they are to be logged into the Sterility Logbook.

2.6.5.       They will be collected by the Micro. Lab. staff and placed in the correct incubator in the Micro. Lab. for incubation.

2.7.             Personnel Monitoring

All personnel monitoring, if related to a batch, must have the BPN indicated on the plates.

Operator’s Clothing – Personnel exiting the Sterile areas are to monitor their clothing using contact plates supplied by the Micro Lab.  These plates are to have person’s name, area worked and date written on the plate.  The areas to be sampled are the hood, sleeve and the chest part of the uniform as was demonstrated during Sterile training and in Annual Sterile Retraining.

Note: Once you have tested your garment, you must change your uniform if wanting to return to Sterile area, you cannot go back in the Sterile area with agar on your clothing.

Glove Prints – Personnel exiting the Sterile areas are to conduct glove prints onto sterile agar plates as per the method demonstrated during the training sessions.

Finger Print Impressions testing is conducted by the individual operator in the Sterile Scrub Preparation Room environment, to evaluate the sterile working background.

Sterile area limits are applied.

a) Place plate on bench with line to center of your body.

b) Raise lid with two fingers.

c) Dab the four fingers of one hand on one side of the divided plate and then dab the thumb of the same hand in the center of that half of the plate.

d) Repeat with the other hand on the opposite side of the plate.

e) Label the plate – against the corresponding headings.

Full Name _________________________
Date _____________________________
Area/Team ________________________

BPN ___________

f) Change gloves if returning to the Sterile work area.

Note: This will have been demonstrated and taught to the Operator during Sterile Training and in Annual Sterile Retraining.

Note:
After recording the fingerprint impression, the Operator must don a new pair of sterile gloves in the Sterile Scrub Preparation Room and disinfect their gloves with Hexifoam (brand) prior to re-entering Sterile Areas. This is to be done daily.

All equipment to be used for personnel monitoring is sterile and the correct aseptic technique must be used to gain valid information.

Note: When exiting the Sterile Scrub Preparation Room, fill in Form 635.

3. Summary of Changes