I am of the opinion that few or any people other than reviewers ever read the prefaces to books. Nonetheless my publisher has asked me to write one!
Contamination control in pharmaceutical clean rooms is a curious subject in the sense that the way in which it is achieved in any particular application is a jumble of science and engineering, of knowledge of what has worked well or badly in the past, of the technology available at the time the clean-room was built, and of subsequent technological developments. Surrounding it all is a blanket of regulations, some of which were written years ago and stood the test of time, some of which are currently evolving through drafts published for review, and some of which are appearing as if by spontaneous generation as inspectors and auditors feel obliged to react to situations they fear to be posing unacceptable risks (real or imagined).
Successful contamination control in pharmaceutical clean rooms calls for a multidisciplinary approach. Within an operational facility the microbiologists have their part in contamination control and monitoring, and the engineers theirs; so too have the production personnel, the quality, validation, logistics, technology transfer and compliance specialists. They have to communicate well and understand each other's difficulties, they have to share knowledge, and they have to accept that responsibilities often overlap. They should appreciate that the greatest risks to contamination control most often occur at interfaces, not just at physical interfaces between areas designated for activities of differing vulnerabilities in the factory, but also at organisational and cultural interfaces between departments, and around topics where personnel with differing educational and vocational backgrounds are obliged to interact.
This book does not and was never intended to comprehensively address all aspects of contamination control in pharmaceutical clean rooms. It is a collection of monographs written by authors who want to share their knowledge, their experience and their opinions on topics that I believe are of importance and should be of interest to all those who are involved in contamination control in pharmaceutical clean rooms.
I have written the first several chapters. When I began to write these chapters, I set out to get back to the basics of contamination control and relate them to practical situations pertinent to a general readership. Now, with 20:20 hindsight, I fear this is an impossible task because in the end no two pharmaceutical clean rooms are the same and what I have grown to believe is the "norm" is, from my experience, actually completely different from what others have come to believe to be the "norm," but frequently via routes of different experience. I also have developed a greater sympathy for the writers of regulatory guidance than I might have had in the past. It must be a very difficult job to create generic rules for an essentially eclectic industry.
I have tried to indicate what is scientifically factual, what is opinion born of personal experience and what is regulation, but I should emphasise that it is well advised in a highly regulated commercial arena to take a conservative tack when interpreting regulations. For instance, a delay of six months in gaining regulatory approval for new drug product should in my opinion be perceived in terms of the profit to be made from that product at its peak volumes under patent protection; let us imagine perhaps $1,000,000. Who would gamble that sort of sum in relation to saving $10,000 dollars on a piece of monitoring equipment, which if purchased, would guarantee compliance with the most conservative interpretation of current regulation?
We have a chapter by Dennis Fortune from Foster Wheeler on clean-room finishes and materials of construction. This is an intensely practical work, providing information that is difficult to find in any published regulatory or other standard source. It emphasises the importance of an integrated design approach to the selection of finishes and materials of construction, while at the same time frequently referring back to cost control and practical operability.
Two chapters approach contamination control in pharmaceutical clean rooms from more of a laboratory angle. They remind us that contamination control has a principally microbiological focus, and that all forms of microbiological monitoring ultimately rely on competent and knowledgeable laboratory practices and personnel.
Norman Hodges from the University of Brighton, U.K., writes about bioburden determination. John Thompson (Lord Kelvin of Largs) is reputed to have said something along the lines of "When you can measure what you are speaking about and express it in numbers, you know something about it, but when you cannot measure it in numbers your knowledge is of a meagre and unsatisfactory kind."
While not wishing to appear to be in dispute with a long-dead great of world science, this view is not necessarily true of microbiology. Numbers (concentrations) of microorganisms in pharmaceutical products and starting materials and in intermediates are important but so too are the types of microorganisms present. One colony of Pseudomonas (Burkholderia) cepacia per gram in a drug product might be of more consequence than 25 colonies per gram of Bacillus cereus. Norman's work emphasises that bioburden has a meaning which, although sometimes forgotten, embraces both numbers and types.
The chapter by Stewart Green and Christopher Randell of Wyeth covers rapid microbiological methods. The traditional means of monitoring the microbiological end-product of the physical, engineering and personnel systems that actually control contamination gives results that come just too late after the time the sample was collected, often four or five days later. This is not just an irritation; current regulatory thinking is placing more and more emphasis on environmental microbiological monitoring, particularly in critical areas of aseptic clean rooms, to the extent that it is known that in at least one major pharmaceutical company more batches of sterile drug products have been rejected for environmental microbiological noncompliances in recent years than have been rejected for failures in the Sterility Test. This is because two or three more product batches may be made on the same line with the same microbiological problem in the period between the problem first arising and its being detected some days later. Significant progress has been made in recent years in developing quicker methods of getting microbiological results. Their application in environmental monitoring and contamination control is still in its infancy. Stewart and Christopher's work brings the reader up to date on the various types of techniques that are becoming available, the scientific principles that underpin them, and gives pointers to the practicalities and limitations of each.
Finally, I hope that somewhere in this book you find something new, that there is something that will be of benefit to you and, for those of you working in the pharmaceutical sector, that there is something that will be of benefit to the company or organisation that employs you. Enjoy.
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