1Allison Scott, Ph.D.; 2Jeremy Graham; 2,3Lisa J. Graham, Ph.D., P.E.1Azbil North America Research and Development, Inc. -BioVigilant, Tucson, AZ; 2Alkemy Innovation, Inc., Bend, OR; 3 Seeq, Seattle, WA

Case Study on the Use of an Online Water Bioburden Analyzer to Support a Reduction in Traditional Grab Samples

New continuous bioburden monitoring technologies can be used to support a move toward a reduction in traditional grab sampling. These online water bioburden analyzers (OWBAs) provide real-time bioburden data that can be used to monitor the health and performance of a pharmaceutical water system. Continuous data collected over an extended period of time is used to establish a baseline understanding of typical water loop particle and bioburden levels. Deviation from this baseline can be used to identify changes in loop health as they occur, resulting in more proactive monitoring and continuous improvements. Established alert and action levels and a continuous understanding of water loop counts can be used to reduce the number of routine traditional grab samples performed. Data is presented from an initial eight-month period after install where baseline count levels were determined, alert and action levels established, and then levels applied to continuous water loop monitoring data.

Conclusions

IMD-W, instantaneous microbial detection, BioVigilant, and the BioVigilant logo are trademarks or registered trademarks of Azbil Corp. in the U.S. and elsewhere. Other trademarks noted are property of others.

o OWBAs provide continuous information and a data rich assessment of particle and bioburden counts that can be obtained side-by-side with traditional grab samples.

o OWBA alert and action levels can be established after gaining a baseline understanding of water loop counts.

o An alarm monitoring strategy can then be established, traditional grab samples reduced, and indication provided of when grab samples should be obtained.

o Continuous, online water sampling and bioburden monitoring.

o Uses a laser, and detection of light scatter and intrinsic fluorescence - not growth dependent, capable of broader detection, requires no staining or reagents.

o Detects total particle counts and biologic (i.e. bio-fluorescent) particle counts in units of AFU (Auto-fluorescent Unit).

o Data output up to every second, counts reported per user selected time or volume.

Online Water Bioburden Analyzer (OWBA)

OWBA Total Particulate, Bioburden, and Additional Information

IMD-W total particulate and biologic counts per 1mL, reported continuously and in real time.

Understanding Your Water SystemIntroduction

Background

SEEQ

o IMD-W system reports total particle and biologic (i.e. bio-fluorescent) counts per second or chosen analysis volume.

o System provides real-time data on flow pressure, flow temperature, flow rate, water fluorescence level, and ambient temperature, among others.

o Non-zero biologic counts permit data-rich bioburden trending opportunity.

o Obtain continuous OWBA monitoring data and traditional culture-based results concurrently over an extended period of time.

o Calculate OWBA alert and action levels appropriate to data (e.g. alert level of ±3σ and action level of ±5σ).

o Consider frequency-based implementation of alert and action levels.o Apply OWBA alert and action levels and frequency-based monitoring approach.o Continue side-by-side OWBA and traditional grab sampling with goal of reducing

grab samples; add targeted grab sample use if OWBA alarm is triggered.

Identify Relevant Data

Establishing Alert and Action Levels

IMD-W™ OWBA System

Different Bioburden Signal

Colony-forming unit (CFU) - unit used to estimate number of viable and culturable bacteria or fungal cells in a sample.Auto-Fluorescent Unit (AFU) - unit that reflects both size and fluorescence of particle.

INCLUDETotal Particle and/or

Biologic Countsper Time, per Volume, or

per Second

EXCLUDECounts during sanitization

cycles, periods of preventive maintenance,

etc.

Observe Transient Changes Impacting

Performance

Determine and Confirm Alert and Action Levels

Days

o Data analytics tool designed for analyzing process data.o Capable of easily integrating data from multiple historians, such as OSIsoft PI

and GE Proficy.o Rapidly investigate operations and manufacturing data to gain insights that

enable continuous operation and quality improvement.

CFU ≠ AFUMicroseconds

Long-term, Continuous Monitoring

o Over seven months of continuous IMD-W monitoring data shown.o Average, max., min. and standard deviation of particle and biologic counts/100mL per week

monitored.o Seeq data analytics tool can be used to exclude periods of data (e.g. during sanitization),

monitor trends and delve into data on dates with higher average counts (e.g. Jul 16)

Average Counts per 100mL per week – Excluding Periods of Sanitization

Apr ‘18 May ‘18 Jun ‘18 Jul ‘18 Aug ‘18 Sep ‘18 Oct ‘18Mar ‘18

Seeq is used to monitor IMD-W biologic counts per second data (blue regions) during normal loop operation and exclude biologic count data during sanitization cycles.

Bio Count per second

±3 σAverage per hour of Bio Counts per second

CFU Results

Implement OWBA Alarm Monitoring Strategyo Frequency-based alarm strategy is used so

that a single spike in counts doesn’t trigger an alarm.

o Monitoring strategy focuses on hour increments. o Alert is triggered if counts exceed 3σ more

than five times per hour. o Action is triggered if counts exceed 5σ more

than five times per hour. o Grab samples are obtained when alarm is

triggered.

+ 3 σ

+ 5 σ

Bio count/s Avg per hour

LAST HOUR