eBook: TOC and Microbial Detection Monitoring - 11

Continuous TOC Monitoring for Real-time Release

Indeed, this reading is supported by a key ICH mission
statement: "To make recommendations towards achieving
greater harmonization in the interpretation and application
of technical guidelines and requirements for pharmaceutical product registration and the maintenance of such registrations". On the contrary, if specific guidance has been
provided, no further validation steps should be considered
necessary for users to meet regulatory requirements.
A step-by-step approach to instrument selection
When determining which regulatory requirements must be
met, and which non-regulatory guidance may be beneficial for implementing a specific measurement or analytical
instrument, a simple four-step approach is recommended
(see Figure 1). It is first necessary to consider the most
foundational, relevant regulatory requirements, and then
build upon this by adding parameter-specific regulatory
requirements. And finally reach greater clarity and specificity by considering non-regulatory guidance. This allows
the development of a complete and robust measurement
requirements specification. With such a process in place,
it becomes a simpler matter to evaluate available measurement options to determine what best fits a specific
measurement use case.

4
Instrument
Selection

Global pharmacopeias define operational
standards that must be followed to meet
regulatory requirements. Once the requirements
pertaining to a specific process have been met,
no further validation is necessary to meet
regulatory requirements.

Regulatory guidance for TOC measurement in
pharmaceutical waters
Water is the most commonly used excipient in the pharmaceutical industry. It is an ingredient, a cleaning agent,
a reagent, a solvent, and a product. As a result, production
and control of Pharmaceutical Waters is a common
challenge faced by virtually any process contributing to
the manufacture of pharmaceutical products. To aid with
managing the regulations that define the requirements
placed upon manufacturers by the global pharmacopeia,
this four-step approach is suggested to determine a suitable instrument for monitoring and control of TOC for bulk
pharmaceutical waters.

Speed of response, continuous measurement,
ISM technology

3
Non-regulatory
Sources

ASTMI E2656

Parameter-speciﬁc Regulatory
Requirements

USP <643>, <1231>,
EP 2.2.44, JP 2.59

Monographs
USP

General Regulatory
Requirements

Figure 1 - Four-step approach to determine regulatory requirements

11
METTLER TOLEDO White

Paper

eBook: TOC and Microbial Detection Monitoring

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