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1. PURPOSE
1.1 To specify the procedures for environmental monitoring during aseptic filling
operations.
1.2 To specify the environmental and personnel monitoring alert and action level
specifications for aseptic
filling events and contamination investigation procedures when these levels are
exceeded.
2. SCOPE
2.1 This procedure applies to the Aseptic Fill Room 114K during aseptic filling
operations.
3. RESPONSIBILITY
3.1 It is the responsibility of the Quality Control and Manufacturing departments to
perform environmental
monitoring.
3.2 It is the responsibility of the QC and Manufacturing supervisors to ensure that
QC and Manufacturing
personnel performing environmental monitoring have been properly trained in
aseptic technique and the use
of all monitoring equipment and procedures.
4. REFERENCES AND APPLICABLE DOCUMENTS
4.1 09-0035-SOP-1.0, Environmental Monitoring Using The Biotest Centrifugal Air
Sampler
4.2 09-0036-SOP-1.0, Environmental Monitoring Using RODAC Plates
4.3 09-0037-SOP-1.0, Routine Environmental Monitoring Program in Manufacturing
Facility
4.4 09-0038-SOP-1.0, Aerosol Particle Counting Using the MetOne 200L
4.5 Documents used to develop the aseptic fill environmental program include:
4.5.1 Pharmacopial Forum. Page 440. Mar-Apr 1995. Volume 21, Number 2. 1116
Microbiological
sterilized supplies (i.e. vial trays, caps or stopper containers etc.) that are brought
into the class 100
zone. Record on the RODAC data sheet the time and description of sampling
locations.
8.1.11 Perform non-viable particulate counting for site locations 1 and 2 per 090038-SOP-1.0 during the
baseline and set-up phases. Perform additional counting at set-up for sites 3 and 5
after all
processing equipment has been appropriately disinfected and introduced into the
class 100 zone.
8.1.12 To monitor non-viable particles during aseptic processing, place the sensor
on a suitable tripod or
stand. Place the sensor no more than one foot away from the bench top and within
12 inches of
where filtering or filling occurs. This monitoring is represented as non-viable site
location 4. Set
the counter to sample continuously by taking at least one sample every five
minutes.
8.1.13 Specific placement of airborne viable settling plates and the isokinetic
particle counting probe with
tripod stand for media fills and clinical vial filled antibody is given below in figures 1
and 2.
These placements reflect the class 100 zone monitoring procedures that should be
employed during
aseptic processing per 02-0031-PVP-1.0, and as specified in MBR 850005-02
(ascites), MBR
850016-02 (TC), and MBR 850022-01 (Tryptic Soy Broth Filling). Ensure that the
particle count
sensor is not less than 12 inches from the pump equipment.
Receiving Vessel
(Filtrate)
Watson-Marlow 505Di Pump
with 505LA Pumphead
Bulk Product
Vessel
Filtration Tubing Millipak Filter
Assembly
Room 114K
Class 100 Area
Front
Particle
Counter
Settling Plates
Figure 1. Standard Configuration During Product Filtering (Clinical Antibody, Media
Fill)
Watson-Marlow 505Di Pump
with 505L Pumphead
Filtered
Product
Filling Tubing
Assembly
Filling and Stopper Seating Crimping
Settling Plates
Particle
Counter
Stand
Vial Tray Front
Room 114K
Class 100 Area
Figure 2, Standard Configuration During Product Filling (Clinical Antibody, Media Fill)
which is the location that is generally in closest proximity to product materials and
vials during
processing and pose a greater exposure risk to open containers.
8.2.4 Use RODAC plates for monitoring the operators hands. Sample the gloves
across the fingers and
finger tips where filling materials and containers are predominantly handled.
8.2.5 Technicians performing monitoring shall also be monitored initially as
described above at set-up,
and once more prior to exiting the filling room.
8.2.6 All sampled areas should be thoroughly and carefully wiped clean using 70%
IPA and sterile wipes
immediately after sampling before resuming manufacturing or monitoring duties.
Avoid excessive
wetting of the Tyvek gown with the disinfectant.
8.3 SAMPLE HANDLING, RECORDING, AND STORAGE
8.3.1 Immediately after all aseptic fill monitoring has been completed, all Tryptic
Soy Agar air strips,
RODAC plates, and Tryptic Soy Agar settling plates should be placed in a 30-35C
incubator in
the QC laboratory for 48-120 hours.
8.3.2 Place all Rose Bengal air strips and Sabouraud Dextrose settling plates in a 2830C incubator in
the QC Laboratory for 5-7 days.
8.3.3 Manufacturing or QC personnel should record on the environmental
monitoring data sheets the
name, part number and lot number of product being filled. Also record the test date,
time of
sample, initials of technician performing sampling, and all the test media
information including the
name of the manufacturer, lot numbers, expiration dates,
8.3.4 Record the results of non-viable particle counting on the test report
attachment and fill out the
Particle Counting Data Sheet Attachment. Photocopy the particle count printouts
and paste on the
data sheet.
8.3.5 After the appropriate incubation period, QC microbiology personnel shall
remove the media plates
and airstrips and count the number of colonies per 09-0035-SOP-1.0 and 09-0036SOP-1.0.
Record the count numbers and calculations in the corresponding place on the data
sheets.
8.4 CHARACTERIZATION OF MICROORGANISMS
8.4.1 Isolates recovered from from each site and operator during aseptic filling
events, including media
fills, require identification of all different types present in terms of Gram stain and
colony
morphology (09-0040-SOP-1.0); as well as genus or species identification if possible
(09-0065SOP-1.0).
8.4.2 In cases of multiple CFUs on a single plate or airstrip where colony type is
visually the same, pick
an isolated colony for Gram stain from each quadrant. Identify to the genus and
species level if
possible all different types obtained.
8.4.3 If plate results show a lawn of colony growth, pick a representative section
and streak for colony
isolation. Perform Gram stain and identification on different organism types.
8.4.4 All original sample isolates shall be labeled and stored in a 2-8C refrigerator
as retain samples
until: positive identifications are completed; product sterility testing is completed;
and, if
8.5.5 When non-viable particle count alert levels are exceeded in the class 100 zone
during aseptic
processing, the particle count instrument will sound an alarm notifying operators
that levels have
been exceeded. If possible, operators shall note by description any activities
occurring before and
during the time of exceeded levels that may have contributed to the particle counts.
This notation
may be referenced in an investigation if applicable.