Suez Total Organic Carbon - March 2020 - 18

application note

online cleaning validation for real-time
equipment release using total organic
carbon, inorganic carbon, and
conductivity data
overview
Cleaning validation is an important element to cGMP manufacturing
to ensure purity, quality, and potency of drug product. Above all,
patient safety is the primary concern. Demonstrating a validated
cleaning process has been a regulatory requirement for many years.
Today, many manufacturing facilities still follow the historical practice
of capturing grab samples and swabs for laboratory analysis for total
organic carbon (TOC) and conductivity to satisfy this requirement.
While compliant, this traditional method of cleaning validation is time
consuming, leaves room for error, and reduces capital equipment
utilization. Thus, the industry is embracing online cleaning validation
as a more efficient and sustainable monitoring program for cleaning
validation and verification. The following outlines SUEZ's solution for
a lean, well-defined, defensible cleaning validation and verification
program using the Sievers M9 Analyzer for TOC and conductivity.

today's challenges
Traditionally, cleaning validation and verification have been
accomplished by manual sampling and laboratory analysis. This
workflow poses significant quality and efficiency shortfalls:
*

Grab samples are time consuming and require analyst
resources to prepare sample containers, print sample
labels, collect samples, transport samples to the lab to
begin analysis, and complete data entry and review. Swab
technique also requires extensive validation and training for
proper recovery.
Sample integrity can be compromised by sampling and
laboratory workflow. Contamination risks and sample
storage stability need to be assessed in any program taking
grab samples.

Laboratory workflow frequently results in delayed data
release, prolonging equipment downtime.

Grab samples have the limitation of representing a
single timepoint rather than providing a comprehensive
understanding of cleaning cycles.

Process Analytical Technology
In 2004 the FDA published a guidance document on Process
Analytical Technology (PAT).1 This document contains non-binding
recommendations and serves to encourage cGMP manufacturers to
deploy PAT to achieve process understanding, process control, and
continuous demonstration of a validated state. PAT allows for realtime measurements of desired quality attributes. Using real-time
data enables process understanding and demonstration of a validated
state without manual sampling or laboratory analysis.
Rather than testing to a predetermined timepoint, PAT allows for
the evaluation of cleanliness based on an acceptable measurement
of quality attributes. Deploying PAT enables companies to optimize
their cleaning validation programs to reduce cleaning time, cleaning
agents, water usage, equipment downtime, and human error involved
in a cleaning program. PAT is subject to the same level of scrutiny
from the FDA, so it is critical to have a fully validated and compliant
system to assess cleanliness and release equipment.

analyzer versus sensor
When choosing appropriate online technology, it is important to
understand the application and regulatory guidance. To use PAT to the
full capability of real-time equipment release, it is essential to have
a validated instrument that satisfies instrument qualification, method
validation, and Data Integrity requirements.

Suez Total Organic Carbon - March 2020

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