This third, revised edition I would like to dedicate to Dr. Georg-Wilhelm Oetjen, who passed away in 2015. He introduced me to Freeze-Drying and essentially influenced my professional career.

I would like to acknowledge my supporters who helped me to complete this book. Without their continued support and effort I probably would have not been able to bring my work to a successful completion. I would like to thank Mr. Mars Ho – CEO Austar Group, Hong Kong; Mr. Austin McDonald – CEO Sterile Technology LLC, USA; Mr. Manfred Steiner – GEA Lyophil GmbH, Germany; and Mr. Anton Mangold – CEO iQ-mobil solutions, Germany.

Without the professional support of Mrs. Regine Fisher, MD Semicom Media & Communications, Germany, I would have had difficulties to finish the book. She was responsible for the text finalization and proofreading as well as for the editing and handling of images, tables, and graphics.

Peter Haseley
Dipl.-Ing.(FH)

Drying of food and herbs is one of the oldest preservation methods of humanity.

Freeze-drying was first carried out, as K.H. Neumann wrote in his book Grundriß der Gefriertrocknung, 1954, by Altmann, who freeze-dried parts of organs in 1890. In 1932, Gersh designed an effective vacuum plant for freeze-drying of histological preparations with the help of the diffusion pump just invented by Gaede at that time. Sawyer, Lloyd, and Kitchen successfully freeze-dried yellow fiber viruses in 1929. Industrial freeze-drying began, as E.W. Flosdorf shows in his book Freeze-Drying, 1949, with the production of preserved blood plasma and penicillin.

Vacuum technology and penicillin were also my own first encounter with freeze-drying. After my studies of physics at the university in Göttingen, I worked in the development department of E. Leybold's Nachf. where I had to build a freeze-drying plant for penicillin. Since that time I was engaged in vacuum process technology for almost 25 years, from 1952 on as managing director of Leybold Hochvakuum Anlagen GmbH. From this time I know Peter Haseley, whom I employed for the freeze-drying department. Later, as “Geschäftsführer” of Steris GmbH, he was actively involved with engineering modern freeze-drying plants with all their complex requirements of documentation and qualification. Together we have developed an old idea of mine to control the freeze-drying process not by predetermined time, pressure, and temperature data, but by the data measured during the process. Therefore, I was very happy when Peter Haseley agreed to rewrite the chapters “Installation and Equipment Technique” and “Trouble-Shooting and Regulatory Issues” for this second edition.

Freeze-drying has always fascinated me as the most complex vacuum process. Mechanical and chemical engineering, chemistry and biology, and sterility and regulatory issues are all part of the freeze-drying process.

After my retirement from the managing board of Drägerwerke AG, I had the time to write the German edition of this book, Gefriertrocknen, published in 1997, and the first English edition in 1999. In 2004, a translation into Japanese has also been published.

When I started to write the German edition, Mr. Wolfgang Suwelack, managing partner of Dr. Otto Suwelack Nachf. GmbH & Co., asked me to work for him as consultant in freeze-drying, and I have to thank him for the permission to use some of the results achieved in the last years. This activity was the new start of my work in freeze-drying, and I would therefore like to dedicate this book to Mr. Wolfgang Suwelack out of gratitude for a harmonic cooperation lasting for over a decade.

Several companies and publishing houses have granted permission to use drawings and photographs to which they own the copyright. Mr. Haseley and I are grateful to all of them because they have thus made it possible to present freeze-drying under many aspects.

We have tried to show the interconnection between the properties of the product, the goal to make it stable, and the necessary processes to achieve this. The problems of the different process steps are discussed with examples and the parameters influencing each step are described. We have avoided to follow the many theoretical attempts to describe one or more of the freeze-drying steps, but have restricted ourselves to a few equations that permit calculating process and product data with sufficient accuracy, or to at least allow an estimate based on measuring some of the data.

The freezing of a product is a very important step. The structure in the frozen product decides whether the product can be freeze-dried at all, and under which conditions it can be done. Therefore, the consequences of freezing rate, layer thickness of the product, and excipients are discussed in some detail. The second main point is the measurement and control of the two drying phases, the main and secondary drying, and the third point concentrates on the residual moisture content, its measurement, and the consequences during storage of the dry product. There will be critical opinions that some of the processes are unilaterally represented. I have tried to show the limits and advantages of certain procedures to enable the reader to decide for himself whether the ideas of the quoted authors or my own can be applied best to his particular task.

The approximately 270 literature references in the 1999 edition have been in part replaced and furthermore supplemented to a new total of 370.

Dr. Georg-Wilhelm Oetjen