Recommended Resources – A Commentary

By Jeanne Moldenhauer, PhD

Understanding the Risk of Contamination

In Pharmaceutical Environments

Numerous talks and papers have been written relative to risk management,
assessment and mediation. The regulatory guidance provided in ICH Q9 Quality
Risk Management (QRM) as issued in 2005 are treated as law by most
pharmaceutical companies.

A recent issue of the PDA Letter included a case study describing how a
company assigned a team to develop a process to implement QRM for its
pharmaceutical subsidiaries.1 This article described three strategic imperatives2
identified by the team as necessary to accomplish their mission:
1. Drive accountability of leaders to use QRM
2. Provide clear guidance on managing and communicating risk
3. Embed QRM into business process.

As companies identify the need for risk assessment procedures in their facilities,
it is also necessary to identify where and how those procedures will be
implemented. One of the areas frequently identified by companies is the control
of microbiological contamination. This may be as part of a company wide
program for contamination control, or specific areas of microbiological control,
e.g., environmental monitoring, maintenance of sterility, and so forth.

In order to manage and communicate risks associated with microbiology, it is

necessary to understand the risks of contamination present in a pharmaceutical
facility. A new publication published by PDA/DHI, Pharmaceutical Contamination
Control: Practical Strategies for Compliance, provides a great description of
areas to consider in your contamination control program. Nigel Halls, editor of
this book, has compiled a wealth of useful information. Some of the topics
covered in this book include:
• Water Systems and the Risks of Microbiological Contamination from
Water
This chapter breaks down the various types of water used in a
pharmaceutical application and the associated compendial requirements.
It also describes in sufficient detail those areas with the risk of biofilm
formation. The discussion on biofilms is very informative, whether you are
looking at it from a microbiological, quality, engineering or other
perspective.

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 An interesting discussion on the appropriateness of alert and action levels
is provided. Guidance is also provided on how to determine the source of
contamination, based upon the types of organisms detected.

This chapter is a must read, whether you are a novice, or have had many
years experience.
• Isolator Technology
The isolator chapter describes the applications for isolator technology.
One of the unusual features of this chapter is that both production and
sterility test isolators are covered throughout the chapter.

Included in this chapter is a wealth of information on the structure of

isolators, explaining the various options available and how to select the
correct design and materials for your application. Other sections include
information on isolator validation, restricted access barriers, and sporicidal
gassing procedures.
• Caveats of Bacterial Endotoxin Testing
The various types of risk associated with endotoxin control and testing are
clearly described with examples from everyday life. As such, anyone can
understand what is written and how to apply the information.

There is a comprehensive section that describes container closure testing

and differentiating depyrogenation destruction and removal. Another
unique feature in this chapter is the discussion of non-endotoxin pyrogens
including information on recent problems with Gentamicin and some
dialysis solutions.
• Role of the QC Laboratory in the Control of Contamination
One of the key features of this chapter is a detailed table that describes
the typical pharmaceutical environment and water contaminants. The
table includes the type of organisms, their habitat, and likely sources of
contamination, safety risks, and the potential root causes for the
contamination.

Recommended training and testing procedures are also discussed.

• Risk Management: Practicalities and Problems in Pharmaceutical
Manufacture
In addition to a description of risk management, this chapter includes
several examples written in terms of pharmaceutical applications. These
examples are sufficiently detailed that even a novice can apply the
principles to other processes within their facility.
• Bacterial Retentive Filtration
An overview of filtration is provided, including validation, integrity testing,
disposable systems and a discussion about bacterial penetration or grow-

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 through. These subsections include both the principles and the practices
used.
• Cleaning and Preparation
Cleaning validation is described, as is expected in most chapters on
cleaning. What makes this chapter different is the various discussions on
topics like, cleaning after a media fill, and protection prior to, and during
sterilization (various types of sterilization are discussed).

Overall, this book is very practical and useful regardless of your technical
discipline. The authors of the various chapters are worldwide experts in the
subject matter, and reading this book is like benefiting from tens of thousands of
dollars of consulting at your site.

The only problem with the various books released by PDA/DHI this year, is
finding enough time and money to buy and read them all!

1
Managing Quality Risk Management Implementation, 2007, PDA Letter, Vol. XLIII (1), p. 1, 13-14.
2
Ibid

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