ASTM E2656: Process Control and Real-time Release Testing Using Total Organic Carbon0 pages

GE Power & Water
Water & Process Technologies

Application Note

Analytical Instruments

ASTM E2656: Process Control and Real-time
Release Testing Using Total Organic Carbon
Pharmaceutical Industry
Pressures

“FDA describes
what needs to be
done to meet the
requirements and
the companies may
use standards to
describe how it is
done.”

The Role of Consensus
Standards in Filling the Gap

The 21st century has ushered
Realizing that guidance documents
in unique challenges for the
only provide generalized information
pharmaceutical industry. As cost
to assist in implementation, the
pressures continue to mount
FDA encouraged pharmaceutical
with the proliferation of generics
companies to participate in voluntary
and the “patent cliff,” worldwide
consensus standards organizations
regulatory bodies have placed
and develop “best practices” for
renewed emphasis on patient
the industry. In response, ASTM
health. Whether speaking about
International formed the E55
Process
Validation,
Quality
- Helen Winkle, Director of
committee in 2003. Comprising federal
by Design (QbD), or Process
CDER, May 2006
agencies, equipment vendors, pharAnalytical Technologies (PAT),
maceutical manufacturers, design
manufacturers
have
been
professionals, and professional societies;
directed to build a higher degree of quality, safety,
the E55 committee has issued eight consensus standards
and efficacy into their manufacturing processes and
since 2004 to promote innovations in quality and
products to assure compliance. This involves a greater
pharmaceutical manufacturing. These standards provide
process understanding and strict control of key
practical steps for implementing specific technologies
process variables to assure that the finished product
and processes. They are recognized by regulatory
meets the intended quality attributes.
bodies and cited specifically in guidance documents to
While the intent of the guidance is quite clear, the
pharmaceutical industry as a whole has been slow to
adopt new quality and manufacturing practices. In an
understandably risk-averse environment, companies
have been hesitant to change processes without
more concrete templates for success. This has
been especially true in the monitoring and control of
Purified Water and Water for Injection systems. Many
companies continue to rely on legacy laboratory
sample plans for attributes such as Total Organic
Carbon (TOC) without a clear path to implementing
real-time process control. However, a well-designed
and executed transition to on-line TOC can deliver
both better quality and reduced costs.

the industry.1

Practical Implementation of On-line TOC for
Process Control – ASTM E2656
Published in October 2010, ASTM E2656 provides a
comprehensive framework for implementing on-line TOC
instrumentation within pharmaceutical water systems.2
The use of the standard allows users to comply with
pharmacopoeia requirements while also meeting the
regulatory expectations of greater process understanding
and control.