eBook: TOC and Microbial Detection Monitoring - 36

Water
System Surveillance
forWater
BetterSystem
ProcessSurveillance
Control andfor
Risk
obial Detection
Enables True
Be

Peggy Banarhal
Kumby Dhliwayo, 7

Case Study

Case Study

Measur

rior to water use
so that the user
can react
immeactual bioburden
loop and reducA pharmaceutical
company
was
having contamination
is- profile in the water
A pharmaceutical company was having contamination isFeed water
Feed water
iately to out of
specification
trendssystem.
reducingThey
reguing the
abilityastoareact to an out of specification event in
sues
with their water
suspected
biofilm
sues with their water system. TheyRMS
suspected biofilm as a
* Utilizes two est
atory risk andpossible
financialroot
loss.
a timely
fashion. Using a NEW case study, this poster
cause, so they decided to use
the 7000RMS
possible root cause, so they decided to use the 7000RMS
combining them
will highlight how a company using real-time microbion a trial basis.
on a trial basis.
A second
Sampling
port
Objective: Current
compendial
plate count
monitoring
dramatically reduced the microbial risk
* 7000RMS
analyzer
was testinstalled atalthe
return of an
* 7000RMS
analyzer
was7000RMS
installed was
at the return of an
connected
the sameloop
Points
for trialAmbient
data. Water for
ng methods allowsAmbient
the assessment
microbi-(AWFI) loop
to their manufacturing process by gaining superior unWater forofInjection
Injectionto (AWFI)
sampling port with a
of
CFU reading.
l water quality 5-7
days
afterwas
sampling,
limiting
derstanding
of their water system that was not possible
* The
AWFI
passivated
1 month before
the trial.
* The AWFI was passivated 1 month before the trial.
T connection feeding
Use
he opportunity for
of the for 1 hr
with
the plate
count method.
* any
The true
waterunderstanding
loop was sanitized
every
morning
* The water loop was sanitized for 1 hr every morning
both instruments.
with hot water (~80°C)
with hot water (~80°C)
* Evaluation period: 70 days (55 days on the AWFI and
* Evaluation period: 70 days (55 days on the AWFI and
15 days on a PW water system)
15 days on a PW water system)
Blue Light
7000RMS Real-time Monitoring Beneﬁts
(high energy
* The data from the trial was analyzed every 2 weeks
* The data from the trial was analyzed
every 2 weeks
Heat
Exchanger
On-line, real-time microbial analyzers:
UV
19 July - 31 July
19 July - 31 July
* Provide better process control
Baseline: 145,451 AFU/100ml * Continuously monitor pharma water, enabling faster
Baseline: 145,451 AFU/100ml
Diagram 1
Diagram 1
CFU average: 0 cfu
CFU average: 0 cfu
response to bioburden excursions
LIF (Laser
* The high AFU readings led to *a decision
bring a sec-of sanitization and understanding
* The high AFU readings led to a decision to bring a secto a highe
Assess thetoeffectiveness
that energ
ond analyzer to run side-by-sidetheashealth
a control
unit loop.
ond analyzer to run side-by-side as a control unit
of a water
An
AFU
spike
(likely
due
to
Points
Of
Use
being
The
increased
sanitization
time
was
a
contributing
factor
* A drop in AFU number was identified
during
sanitization
* A drop in AFU number was identified during sanitization The increased sanitization time was a con
* Use the
data to
demonstrate the limitation of the plate count
flashed)
around
to the 20% baseline reduction during 1 August - 14- August
to the 20% baseline reduction during 1 A
- The microbiologists involved method
in the trial
theorized
The microbiologists
involved
in the5:30pm
trial theorized
for process
control
* 7000RMS
uses
* Thebiofilm
diagram
shows
a polishing
effect
only during
with 19 July - 31 July.
with 19 July - 31
July.
that the assumed biofilm in* the
water system
in compared
that the assumed
in the
water
system was
in notcompared
Real-time
processwas
surveillance
ensures water system
* Microorganism
the
time
of
the
sanitization
but
throughout
the
time
the
its dispersal phase and the hot
waterincreasing
was killing
the safety
its dispersal phase and the hot water was killing the
control,
product
- Fluorescence
water system was quarantined
14 August - 31 August
14 August - 31 August
planktonic bacteria
planktonic bacteria
* On-line testing enables reduced plate sampling and lab- Mie scatterin
- The lowest AFU reading during these days
was 105,777 AFU/100ml
Baseline: 105,777 AFU/100ml
Baseline:
based testing
* Fluorescence a
at 3:30pm on 3 September
CFU average: 0 cfu
CFU average: 0 cfu
1 August - 14 August (See figure 1)
1 August - 14 August (See3,749
figure AFU/100ml
1)
* Fluorescence
- At midnight on 4 September the feed water
re- of 8 hr sanitizations
* A couple of 8 hr sanitizations were performed
in the115,436 AFU/100ml
* Awas
couple
were ap
Baseline: 115,436 AFU/100ml
Baseline:
Fluorescent
Un
introduced
to
the
AWFI
in
preparation
for
use
in
the
timeframe,
but
no
other
process
changes
were
made
timeframe,
but
no
other
process
cha
CFU average: 0 cfu
CFU average: 0 cfu
water system
day.
This is when *theThe
AFUlowest AFU reading was 43,138
* The lowest AFU reading was 43,138 AFU/100ml
* A second control 7000RMS, which had been reporting
* A second control 7000RMS,
whichthe
hadnext
been
reporting
spiked
to ~85,000
* Discussion to perform a sanitization for over 48
* Discussion to perform a sanitization
256 AFU/100ml at the METTLER TOLEDO facility, was
256hrs
AFU/100ml at the
METTLER
TOLEDOAFU/100ml.
facility, was
during 1 September - 4 September
during 1 September - 4 September
installed side-by-side at the same sampling port as the
installed side-by-side at the same sampling port as the
Conclusions
trial 7000RMS for 36 hrs
trial 7000RMS
for 36 hrs
* were
Root reading
cause determination
trial(See
theorized
1 September - 4 September (See figure 2)
1 September - 4 September
figure 2t
- Both analyzers were reading within 8% of each other
- Both analyzers
within 8% of each other
- It was
determined
after
reviewing the data
the A quarantined
growtheonAWFI
the TS
* Company A quarantined the AWFI loop from 6am
on 1
* from
Company
lo
- After the side-by-side testing, the control 7000RMS
- After
the side-by-side
testing,
the control
7000RMS
that while
biofilm
bacteria
September - 12am on 4 September
September - 12am on4 The
September
was reinstalled on the same sampling port at the METwas reinstalled on trial
the same
sampling
portmight
at the have
MET- been a contributor
to was
the high
AFU counts,
the water
feeding
the facilities and QCever,
- Only facilities and QC had access to the waterTLER
sys-TOLEDO facility
- Only
had nutritio
access
TLER TOLEDO facility and was reporting within 10% of
and
reporting
within 10%
of
AWFI
was mostwithin
likely12
thehrs
root case to the hightem
AFUat this time and all
may
not sati
tem at this time and all activities were logged the previous baseline
activities
the previous baseline AFU/100ml within 12 hrs
AFU/100ml
counts.
present
in th
- An AFU spike (likely due to Point Of Use flashing)
- An AFU spike (likely due
to Point
* AFU
Limitation
plate count
method
As a
around 3:30pm on 1 September
around 3:30pm on 1biofilm.
September
With confidence in the AFU counts, company A made a proWith confidence in the
counts,ofcompany
A made
a pro- the
All the
results from
port (see diagram
de
- Hot water sanitization was performed cess
from decision
4:00pm to increase
- Hot water sanitizationmay
wasonly
perform
cess decision to increase the sanitization time to ~12 hrs on
sanitization
timethe
to sampling
~12 hrs on
1)August
were 0(non-production
cfu. The microbiologist
the 1 September to 7:00pm
presenton
in 3th
on 1 September to 7:00pm on 3 September
11 August and 8 hrs on 12 August (non-production days).
11 August and 8 hrs on 12
days). involved in on

WFI

WFI

Storage
Tank

Storage
Tank

up

1

2

ﬂow is not to eliminate bioﬁlm, but to manage the growth
phase.
Sanitization: weakens the EPS to allow the water ﬂow to
gradually scrape off layers, exposing bacteria to harsh
conditions or diffusing through the EPS to kill bacteria in
the bioﬁlm.
Continuous water ﬂow: keeps planktonic bacteria moving, making it difﬁcult for them to attach to a surface, and
slows bioﬁlm formation or maturation.
USP <1231> 5.3.1 "Although thermal methods control biofilm development by either continuously inhibiting its growth or, in intermittent applications, by
killing the microorganisms within developing biofilms, they are not effective in removing established
biofilms. Killed but intact biofilms can become a nutrient source for rapid biofilm regrowth after the san-

4
Figure
1

3

Figure 1

5

itizing conditions are removed or halted. In cases
of infrequent thermal sanitizations that allow biofilm
development between treatments, a combination of
routine thermal treatment and periodic supplemen12 hr.
8 hr.
tation with chemical sanitization
may be
more effecSanitization
Sanitization
tive. The more frequent the thermal sanitization,
the
more likely it is that biofilm re-development can be
eliminated."

4

Figure 2

≈ 5012hr.hr.Sanitization
Sanitization

8 hr.
Sanitization

Flashing
Point of Use
ports

Maturity: A well-established, happy, and healthy
bioﬁlm structure.

Water system
quarantined

38,521 AFU/100 ml

Release: Like any living organism, after survival
and growth, bioﬁlm's next stage is proliferation. A
mature bioﬁlm in a water system will intentionally
and strategically release planktonic bacteria into the water
system. The released planktonic bacteria will in turn ﬁnd an
appropriate surface to attach to, and start making new bioﬁlm structures.

5

Flashing
Point 38,521
of UseAFU/100 ml
ports

W
qu

3,749 AFU/

36
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