1. Lower costs through a reduction in labor due to
reduced sampling, and reduced conventional testing and materials.
2. Fewer investigations of, and improved responsiveness to, microbial excursions.
3. Greater process understanding via historical data
profile, and product safety through real-time
4. Real-time release of ingredient water, product
intermediates, and process buffers/solutions.
5. Less frequent heat sanitization cycles through verification of system capability.
6. Increased storage times for WFI/PW and reduction in dumping prepared water on a time cycle.
The workgroup has also issued technical system
requirements that include specifications for instrument sensitivity and a limit of detection that equals
that for culture-based methods ( 10 CFU/100 mL,
the limit for Water for Injection and 100 CFU/mL
for Purified Water).
Laser-induced fluorescence (LIF) is a bioburden
measurement technique that has the ability to meet
industry needs. All microorganisms use metabolites (e.g., nicotinamide adenine dinucleotide,
riboflavin) to regulate their growth and development. These metabolites produce intrinsic fluorescence emissions when exposed to light of certain
wavelengths. LIF is a highly sensitive technique
that exploits this phenomenon to detect microbes,
indeed, analyzers that employ LIF to detect airborne contamination have been available for some
years. Advances in the technology means that it is
now possible to use LIF to measure microbial levels
Real-time bacterial detection
Online analyzers may use LIF to measure microbial
contamination, and to measure microbes that are
not cultivatable by conventional lab-based methods.
They may also be capable of quantifying inert particles in the water that can come from diaphragms,
filters, O-rings, etc.
Most inert materials do not fluoresce, but some
(including certain polymers) do, therefore there is a
risk that inert particles could be counted as biological. By analyzing both the emitted fluorescence and
the Mie scattering, microbes are distinguished from
Reduced reliance on lab testing
USP <1231> Water for Pharmaceutical Purposes
recommends that pharmaceutical water systems
should be monitored at a frequency that ensures
the system is in control and continues to produce
water of acceptable quality. The general information
chapter endorses operating monitoring instruments
continuously in order that historical in-process data
can be recorded for examination. Over time, trend
analysis can be used as a basis for conducting loop
Real-time and historical data from online
bioburden analyzers enables rapid identification of
deteriorating or improving microbiological conditions. Monitoring of various POUs or distribution
sampling points will help pinpoint the source of any
problems and provide rapid assurance of successful
Such bioburden systems enable risk reduction
and greater process control, and offer significant
costs savings from the combined decrease in laboratory testing and false-positive results.
1. “Advancing Regulatory Science at FDA — A
Strategic Plan: August 2011,” http://www.fda.gov/
James Cannon is Mettler Toledo Thornton’s Head of
OEM and Markets. He has over 35 years of experience in
the management, design, and technology development of
ultrapure water treatment and technology for pharmaceutical, laboratory, and microelectronics ultrapure water
against a traditional plate count
of R2 > 0.9.