Rapid/Automated Environmental
Monitoring on the Manufacturing Floor
Amy McDaniel, Ph.D.
IFPAC
Arlington, VA
January 2014
Outline
• Introduction to Pfizer Biotech, Sanford
• Introduction to Rapid Microbial Methods
(RMM) for Environmental Monitoring (EM)
• Evaluation of the Growth Direct II in a
manufacturing facility –Evaluation of Consumables
–Beta Instrument Evaluation
• Conclusions
Introduction to Pfizer Biotech,
Sanford, NC
Sanford’s Role: • Commercial manufacturing for Prev(e)nar and Prev(e)nar13 conjugate
• Commercial manufacturing for CRM197 carrier protein
• Supply clinical trial materials for microbial / conjugate products
• Commercial launch and production site for microbial / conjugate products within the PGS
network
Why RMM for EM?
4
Get materials
Sample in
Manufacturing
Wait for
settle plates
Wait for
incubation
Return to lab
Read
Results
Identify samples
Get materials
Prepare on
mfg floor Collect samples
according to role
Load samples into automated
technology
Pre
sent
Futu
re?
Prepare in lab
Clean carts
Gown
Travel to manufacturing
Incubate plates
Clean up
Data entry
De Gown
QC Identifies samples
BioProcess Technicians
QC reviews results
Growth Direct communicates
with LIMS to download results,
sends alerts electronically as
programmed
Growth Direct
segregates
positive plates for
identification (in
QC lab), discards
negative plates
Reduced Time
to Results
QC micro analysts
5
Shift huddles utilize a short, routine meeting & white board to monitor/manage Micro lab operations
How are current EM sampling issues identified?
Relies on analyst knowledge and
memory to communicate any
missed samples.
The ideal technology should be programmed to
automatically read bar-coded labels, “know” what samples
to expect, and send email alerts if a sample is missing.
Error proof and time saving!
RMM for EM: Standard Work Confirms
Advantage
Break
Equipment / Process Controlled Analyst Controlled
Collecting Supplies
Travel to Area
Gowning
Cart Cleaning
Prep Equip and Materials in Manuf.
European Grade (4 carts) (20 Air sites)
Prepping Cart/Clean Up/Data Entry
Degowning/Travel to Lab
Data Download/Incubation
Collecting Supplies
Travel to Area
Gowning
Cart Cleaning
Prep Equip and Materials in Manuf.
US Classification (2 carts) (8 Air sites)
European Grade (2 carts) (9 Air sites)
Prepping Cart/Clean Up/Data Entry
Degowning/Travel to Lab
Data Download/Incubation
Collecting Supplies
Break
Travel to Area
Gowning
Cart Cleaning
Prep Equip and Materials in Manuf.
Hood Monitoring
Settle Plates (Room)
B Room
C Rooms (27 VA)
Clean Up/Data Entry/Data Download
Degown/Travel to Lab/Clean Up/Incubate
Lunch
EM
0# # # # # #12 13 14 15 16 17
Hours Evening Night
Weekly Requ
Samples /Tests
TestTask
TypeTask
Day 1
8 9 10 11
Po
ten
tia
l E
M R
ole
(3
) H
oo
ds
What technologies are available for
Rapid/Automated EM?
• Active Air Sampling – IMD (Instant Microbial Detection)
– PMS (Particle Measuring Systems)
– TSI (BioLaz)
– Growth Direct II (Rapid Micro Biosystems)
• Surface Sampling – Swabbing & preparation with:
• ScanRDI (BioMerieux)
• ATP systems (e.g., Celsis, PallCheck, MilliFlex Rapid)
• Growth Direct II
– RODACS: • Growth Direct II
– Passive Air: • Growth Direct II
Evaluating the Growth Direct II (GDII)
• Phase I: Evaluation of Consumables
• Phase II: Evaluation of Beta Unit
Growth Direct II: What is it?
9
User Interface Touch Screen
Interface to
Network or LIMS
Incubators 1 or 2 temperatures
300+ capacity/incubator
Interior
View
Input Queue
Cassette
Elevator
Slide graphics courtesy of Rapid Micro Biosystems
GDII: Evaluation of Consumables
• Why? – The intention was to train manufacturing
technicians to take EM samples
– Designed the study to compare an
experienced analyst (QC Micro) with a
new technician
– Assess handling of plates, switching
lids, general equivalence of results with
offline incubation
GDII: Evaluation of Consumables
Active air sampling
• Same sampling
apparatus able to be
used for GDII and
traditional testing
• Media accommodated
within the sampler with
an adaptor (made by
manufacturer of the
sampling device)
Passive Air sampling:
• No difference in testing set
up for GDII and traditional
• Traditional plates are
slightly larger diameter than
GDII (evaluation of impact
ongoing)
GDII: Evaluation of Consumables
Surface Sampling with RODACs:
• Currently the only technology capable of automating this
element of EM
• Same convex surface of the plate with black membrane
overlayed on agar
• Diameter of the test surface is the same, GDII plates
have a wider base
GDII: Evaluation of Consumables
15
Grade Sample Type Results (Avg CFU/plate)
Growth Direct Traditional A Active Air 0 0 Settle Plates 0 0 Surface #1 0 0 Surface #2 0 0 B Active Air 3 3 Settle Plates 1 1 Surface #1 0 0 Surface #2 1 1 C Active Air Site #1 9 11 Active Air Site #2 7 8 Settle Plates 3 1 Surface #1 0 0 Surface #2 5 1 Surface #3 0 0 Surface #4 2 1 Surface #5 0 0 D Active Air Site #1 23 24 Active Air Site #2 13 14 Settle Plates 1 2 Surface #1 5 5 Surface #2 0 0 Surface #3 1 1 Surface #4 0 0 Surface #5 0 0
Grade A: 1 active air site, 1 settling plate, 2 analysts, two reps each 2 surface sites, 2 analysts, 2 reps each
Grade B: 2 active air locations, 1 settling plate, 2 analysts, 2 reps each 3 surface sites, 3 analysts, 2 reps each
Grade C/D 2 active air sites, 1 settling plate, 2 analysts, 2 reps each 5 surface sites, 3 analysts, 2 reps each
GDII: Evaluation of Consumables: Data
• Preparation for onsite evaluation in a GMP manufacturing
facility: – Project plan
– Change control
– Impact assessment
– Evaluation Protocol
• Install the unit
• Execute evaluation protocol
GDII: Beta Evaluation
GDII: Beta Evaluation - Planning
• Proposal was to locate it within the classified area in manufacturing
– To gain the full benefit of efficiency, plates not moving out of the area, carts
not moving in
• Equipment pass through (Grade D)
– Evaluated options with project manager
– System requires water (to humidify incubators), air (to power the robotics),
230V power, gives off 4200BTU/hr of heat (all assessed for impact and
accommodated)
• Evaluated Risk of microbial growth in controlled area
– Closed incubators
– Plates are individually closed (lids lock to the base)
– Disposal chamber is contained within the instrument
– Increased monitoring around the instrument performed during evaluation
17
GDII: Beta Evaluation – Site Installation
Equipment pass through to
manufacturing. Uncontrolled
corridor looking into the pass
through.
Modular installation of unit
was preceded by vendor
assessment of area.
GDII: Beta Evaluation – Site Installation
Stacked incubators showing location of plates (the
parking deck), touch screen and keyboard interface.
GDII: Beta Evaluation – Site Installation
Installation nearing completion, right side imaging unit
installation, front components and loading stations
(input queues)
GDII: Beta Evaluation - Project Plan
• Month 1: – System install
– Train technicians on EM
– Program the test methods (two tiered incubation, load sampling sites,
load trend rules, load response to growth – output queue)
– Evaluate LIMS interface capability, network interface capability
• Success criteria – Successful install (operational without rework) – June 26-28 (sample
ran successfully)
– Successful test method input (methods are accepted without rework
or computer issues, or with successful & timely resolution)
– Integration with LIMS is assessed as feasible
– Integration with network is assessed as feasible (“Pfizerized” PC on
7/2, connected to network)
21
√
√
√
√
• Months 2/3:
– 156 samples completed
– Inconsistencies evaluated (no discrepancies in action limits reached
by one system and not the other)
– Results indicated acceptability of the technology
GDII: Beta Evaluation - Project Plan
1133 C Air Site 2 3 6
1133 C Tank 120185 Top 0 0
1133 C Tank 120180 Top 2 0
1134 C Air Site 1 2 0
1134 C Air Site 2 2 2
1134 C Air Site 3 7 2
1134 C Tank 120110 Bottom 0 0
1134 C Wall 0 0
1134 C Counter 1 0
1134 C UP-1134 0 0
1135 C Air Site 1 4 1
1135 C Air Site 2 2 3
1135 C Air Site 3 8 1
1135 C Door to Rm 1131 0 0
1135 C Door to Rm 1145 11 0
1135 C Door to Rm 1153 0 0
1135 C Wall 0 0
1137 C Air Site 1 0 0
1137 C Air Site 2 0 1
Room Grade Sample Location
Growth
Dire/methodct
Result #CFU
Traditional EM
Result #CFU
GDII Beta Evaluation:
Potential Standard Work Efficiencies
Break
Equipment / Process Controlled Analyst Controlled
Collecting Supplies
Travel to Area
Gowning
Cart Cleaning
Prep Equip and Materials in Manuf.
European Grade (4 carts) (20 Air sites)
Prepping Cart/Clean Up/Data Entry
Degowning/Travel to Lab
Data Download/Incubation
Collecting Supplies
Travel to Area
Gowning
Cart Cleaning
Prep Equip and Materials in Manuf.
US Classification (2 carts) (8 Air sites)
European Grade (2 carts) (9 Air sites)
Prepping Cart/Clean Up/Data Entry
Degowning/Travel to Lab
Data Download/Incubation
Collecting Supplies
Break
Travel to Area
Gowning
Cart Cleaning
Prep Equip and Materials in Manuf.
Hood Monitoring
Settle Plates (Room)
B Room
C Rooms (27 VA)
Clean Up/Data Entry/Data Download
Degown/Travel to Lab/Clean Up/Incubate
Lunch
EM
0# # # # # #12 13 14 15 16 17
Hours Evening Night
Weekly Requ
Samples /Tests
TestTask
TypeTask
Day 1
8 9 10 11
Po
ten
tia
l E
M R
ole
(3
) H
oo
ds
X X
X
X X
X X
X
X X
*
*
*
*
*
*
* Timing/collection supplies (carts)
could be reduced
X Step could be eliminated
Conclusions
• Rapid/Automated methods for EM can add value: – Standard work efficiencies
– Environmental control (with faster results and notifications of trends
or events)
– Right First time (by automating receipt of expected samples and
counting errors)
• Moving EM technology and sampling to the
manufacturing area: – Increases efficiencies mentioned above
– Decreases movement of materials in and out of controlled area
– Improves awareness of technicians to EM
– Ownership of the EM program resides with QC, Manufacturing is a
sampling resource
• The Growth Direct II is a feasible technology for
implementation in a GMP facility