Review of the book "Endotoxins and pyrogens"
As usual, I was once again accompanied on my last vacation by a technical book, which I’d now like to present. In this case, it is "Endotoxins and Pyrogens - Detection Methods, Product Testing, Inactivation", which was published by Michael Rieth at Wiley-VCH GmbH, Weinheim in 2021 as first edition (ISBN: 978-3-527-34695-0).
About the content
The book comprises 185 printed pages with appendix, abbreviations, further reading (very detailed) and index and is accompanied by 6 blank double pages at the end. What are these 6 blank pages for - is it a potential binding error of my edition or is there a purpose behind that I just can't figure out?
Apart from that, after a brief outline of the history of endotoxin and pyrogen detection methods, its variations and new developments, you will learn interesting facts about the horseshoe crab itself, the underlying reaction principles of the tests and endotoxins in general. This is followed by descriptions of the corresponding pharmacopoeia chapters. The chapters on laboratory equipment, sampling and sample preparation as well as method validation clearly illustrate the practical relevance. An introduction of the LER effect (low endotoxin recovery) and glucans provides good background knowledge. After also looking at how to deal with out-of-specification (OOS) results, chapters on other possible applications round off the book's content.
My impression
I think the choice of topics is basically successful, perhaps a little lengthy at one point or another in my opinion, but overall appropriate. It's a good all-round book. There are no chapters in this book, as in many other books, where I had to ask myself what’s the relation of this section with the actual topic. I was also very impressed by the topicality of the book, which covers the monocyte activation test (MAT) and the test with recombinant factor C (rFC) in addition to the classic methods such as the limulus amebocyte lysate (LAL) test. It’s a bit of a shame that e.g. some of the English citations are pages long and could have been better summarized...
Furthermore, some things unfortunately seemed to me like a gap filler, for example, the already detailed description of the rabbit pyrogen test (RPT) is followed by translations of the monographs of various excipients or a two-page list of the maximum valid dilutions (MVD) of various substances tested in the LAL test without any conclusions... Does this list reflect the experience of the author's laboratory, is it intended to serve as guidance for the reader or what’s the purpose? Why do I need a tabular taxonomic comparison between the horseshoe crab and the sea cucumber? And while we're about tables, some of the illustrations point into the same direction: there are pictures of the production of the lysate, of bacteria, a stamp, a photo of the kit components or calibration lines for evaluation, which are quite nice, but which are not cited in the text... Otherwise the illustrations are good.
I found the author's writing style easy to understand and interesting, but it could pose difficulties for a layperson who is not familiar with the subject, because knowledge is assumed, as sometimes unexplained or different abbreviations or technical terms are used. Does everyone know what an MHC complex is or that PPC and PPK stand for the same thing (positive product control / German: Positive Produktkontrolle)? In addition, in some sections there were almost identical repetitions of previous chapters...
Some examples are presented in great detail, but in my opinion some are also too vague: for example, information about a centrifugation is given in rpm instead of g, or in the example of the LER effect it is not clear whether CSE or RSE (control / reference standard endotoxin) was used, or in a MAT with cryo-preserved blood the calibration lines are sometimes set up with 3 and sometimes with 4 concentrations - without further explanation...
In addition to minor errors (columns of a table mixed up, two different temperatures for the same process, wording: pasteurization is not the same as UHT (ultra-high temperature / treatment)), I also have to criticize the handling of references: some references are not included in the text or the numbering jumps in an incomprehensible way, one reference has already been withdrawn but was cited, one has already been updated but you can still find the old reference in the book, and sometimes they are missing completely... In this context, especially when explaining the LER effect, a reference to the PDA TR 82 would not have been bad...
From a didactic point of view, small introductory summaries or reminder boxes might also have been good, but as this book is more of a practical than a classic textbook, this might also be ok as it is. Basically, the practical aspect and the many examples in the book appeal to me, but some things were also a bit strange to me: For example, in the validation section, there is a summarizing results table with all 3 variants of the LAL test (GelClot, turbidimetric, chromogenic) before the individual results per batch are listed for pages. Perhaps shorter presentations would have been possible? In addition, 3 validation examples are listed, where the underlying intention is not clear to me: Should the 1st example show the comparison of the 3 variants of the LAL test, the 2nd example an alternative to the RPT including calcium blocking and the 3rd example the use of Pyrosperse® including the evaluation of trueness? Another example clearly shows the LER effect but does not explain how the problem was solved. In a further example of endotoxin testing for stoppers, it is not clear whether the procedure described is based on the author's experience or on an unnamed reference. An "e.g." would have been nice, because from my own experience I can say that the test is also performed differently in other labs than described in this book ;-)
Speaking of my own experience: Does the requalification of a dry heat tunnel for depyrogenation always have to be performed every six months? Wouldn't an annual cycle also be conceivable?
I smiled a little when I come across my own professional stations while reading the book and turning full circle. As a trained dairy laboratory technician, UHT treatment of milk is of course not unknown to me and the name of one of the cited authors was still present after years at my training institution in Kiel. Mentioning Confarma as a MAT provider also makes me smile a little, as I also spent some time at Confarma... even though I gained most of my endotoxin experience in recent years as part of a larger customer project...
My conclusion
Perhaps the annotations above didn’t make it very clear, but my own expectations of the book were fully met. Although I was familiar with most of it, I enjoyed reading this book and some of the content was refreshed or deepened and some was even new - so it fits ;-)
I would recommend this book without reservation to anyone who already knows a little about the subject and wants to get a broad overview.
References
Parenteral Drug Association, Inc. (PDA) Technical Report No. 82 (2019). Low Endotoxin Recovery, ISBN: 978-1-945584-07-7