Innovations at INTERPHEX Guide 2022 - 13

today which drastically reduces the number of manual setup
steps for BET assays. Microfluidic automation leverages a
network of microchannels to direct and mix fluids to automate
endotoxin assays, thus significantly reducing hands-on time.
By minimizing pipetting steps, centripetal microfluidic
automation decreases the complexity of assay setup and
mitigates risks and opportunities for errors that lead to costly
retests. Preloaded standards and positive product controls
(PPCs) are used to automate standard curves and PPC spikes,
saving labs significant amounts of time and reducing pipetting
steps and opportunities for error. In addition, microfluidic
liquid handling precisely measures all liquids for the end user,
which means that the precision typically required during the
physical action of pipetting is reduced.
Overall, with microfluidic automation, compendial endotoxin
assays are performed effortlessly, quickly, and with fewer
opportunities for error. Manual steps are limited to pipetting
water for BET, samples, and 1 mL LAL - and fully compliant
endotoxin assays are set up in 9 minutes and 27 pipetting
steps, with up to 21 samples and up to a 5-point standard
curve. Microfluidic automation enables labs to achieve the
high throughput and easy assay setup they want, without
having to be concerned about footprint, complex validations,
or compliance. When an assay is running, data is transmitted
to software every five seconds, allowing analysts to check
progress frequently throughout the assay and see the data
in real time. This example of automated testing paired with
21 CFR Part 11 compliant software demonstrates the drive
for labs to achieve efficiency along with data integrity using
simple and customizable platforms.
Online Monitoring
Significant value can be captured by moving to online QC
testing and continuous monitoring of quality parameters.
Online water monitoring is a great example. With the
release of the 2004 PAT guidance document, companies
began considering what water testing would look like in a
fully automated/online state. Not until recently have these
technologies been implemented on a larger scale. The
industry is now transitioning to PAT tools and applications
such as real-time testing for Total Organic Carbon (TOC) and
conductivity, and it is only a matter of time before technology is
released that automates the testing of four compendial water
attributes - TOC, conductivity, endotoxin, and bioburden.
This real-time data from PAT ensures a controlled and well
understood process, while saving sampling and analysis time,
and allowing for fast, informed decision-making.
Example 1: Real-Time Testing (RTT) of
Pharmaceutical Water for Production
Online water monitoring has become prevalent
in the
pharma and biotechnology industries to provide a realtime
measurement of water quality and align with PAT;
however, in order to release water into production with
an online instrument, the online water monitoring system
must be properly validated in accordance with compendial
requirements for RTT. Current state laboratory practices and
online monitoring require the isolation of grab samples
for compendial testing and release. This introduces the
potential of contamination and delays the release of
water into production. RTT eliminates these inefficiencies,
saving pharma and biotech companies time and money.
To implement RTT, there are various elements that must be
considered to build Quality by Design (QBD) into the process
and mitigate patient risk, process risk, and business risk. Key
benefits and considerations for real-time testing and release
of water include:
Ë Online
instruments can be installed
for
process
monitoring, process control, and process understanding.
RTT achieves these actions by migrating from laboratory
grab sample monitoring and release of water to online
monitoring and release of water in real time.
Ë Compared to standard lab grab sampling practices, RTT
provides real-time process control and understanding,
mitigating production risks and patient risks. RTT
establishes the parameters to defend process
decisions in real time, reduces time to release batches,
eliminates intermediate sample handling, and saves
time and money.
Ë To successfully implement RTT, there are many elements
that need to be considered such as technology choice,
validation, method transfer and equivalency, etc.
Leaning on solution providers or consultants in the
industry can provide a better understanding of the steps
to incorporating RTT into pharmaceutical water testing.
www.americanpharmaceuticalreview.com |
| 13
http://www.americanpharmaceuticalreview.com
Innovations at INTERPHEX Guide 2022

Table of Contents for the Digital Edition of Innovations at INTERPHEX Guide 2022
