Changes in regulations, expiring patents, and growing competition are placing ever-growing pressures on pharmaceutical companies. These stresses are resulting in an increasing focus from
drug manufacturers and regulators on how modern
production methodologies can be applied in the production of pharmaceuticals that will enable greater
efficiencies alongside improving product safety.
The FDA’s Process Analytical Technology (PAT)
initiative, EMA Guidance on Real Time Release,
ICH Guidelines Q 8-10, etc., all offer approaches to
raising production efficiency for even the most conservative drug company. It is not surprising, then,
that there has been growing adoption of continuous
analytical technologies that can rapidly identify
out-of-specification conditions and lessen the workload burden on laboratories.
The requirement for real-time microbial analysis
Maintaining the quality of Purified Water and Water
for Injection is vital in the pharmaceutical industry.
Here, online analytics plays a major role in real-time
monitoring of water conductivity and total organic carbon (TOC). However, due to a lack of such
instrumentation for the determination of microbial
contamination, this vital measurement has been
dominated by laboratory culture-based methods. This
situation causes great frustration in drug production
facilities as online conductivity and TOC sensors
allow real-time release of pharmaceutical waters; yet
any bioburden excursions may not be identified for
many days as lab personnel wait for cultures to grow.
In addition, certain microbes are not cultivatable
in agar-based growth mediums and therefore can
Further, manual sampling of a Pharmaceutical
water distribution loop or multiple points-of-use
(POU) to conduct traditional bacterial culture tests
can result in a high percentage of false-positive
results. The investigation of false-positives is time
consuming and can be very expensive.
Furthermore, due to the high number of POUs in
a production facility, a single point may only be tested
a few times in a month. This can make identification
and remediation of local microbial issues very challenging, and is compounded by the fact that when
a sample is collected for testing, it represents only
a small volume of the water system or POU at that
Unsurprisingly, the pharmaceutical industry welcomed advances in technology that have led in recent
years to the development of microbial analyzers that
significantly reduce the need for culture-based methods. Measurement techniques such as polymerase
chain reaction amplification are significantly faster
than traditional lab methods; however, they require
the use of dyes and reagents to treat water samples
and cannot be used online.
Industry workgroup supports online analyzers
In 2011, the FDA published their “Advancing
Regulatory Science at FDA” document in which
they support the need to “Develop sensitive, rapid,
high-throughput methods to detect, identify, and
enumerate microbial contaminants and validate their
utility in assessing product sterility.”1
In recognition of this and the pharmaceutical
industry’s requirement for online microbial measurement instruments, a group of seven leading
pharmaceutical companies formed the Online Water
Bioburden Analyzer (OWBA) workgroup in 2013.
Their objective is to provide guidance to instrument
manufacturers regarding the development of new
microbial measurement systems in order that such
equipment satisfies the needs of industry and regulators.
The OWBA believes that pharmaceutical companies can benefit from an online real time microbial
detection system in a number of ways, including:
Maintaining the quality of Purified Water and Water for Injection.
Analysis of fluorescence
and scattered light distin-guishes microorganisms
from inert material.