Published Reviews for Purification Tools for Monoclonal Antibodies

Every once in a while a protein purification book comes along that is a pleasure to read, is succinctly written, and clearly relates theoretical concepts to methodology. Purification Tools for Monoclonal Antibodies does this and more. Given the plethora of therapeutic monoclonal antibodies (MAbs) currently in clinical development and progressing toward the marketplace, this book should find a welcome audience in the growing body of biopharmaceutical scientists and biochemical engineers so involved.

Well-organized chapters address all of the protein purification methodologies that have been applied to MAb purification. These include precipitation methods and many chromatographic techniques: size exclusion, ion exchange, hydroxyapatite, hydrophobic interaction, immobilized metal affinity, and protein A affinity. Less commonly used chromatographic methods are described as well, including hydrophilic interaction, euglobulin adsorption, thiophilic adsorption, dye ligand affinity, Abx adsorption, and immobilized boronate ligand. A final chapter on miscellaneous biological affinity ligands covers protein G, other bacterial ligands, immunoaffinity, lectins, and carbohydrate affinity.

Each major topic is introduced with a brief historical background and theoretical explanation. Practical examples are offered, with lots of running commentary on what works and what doesn't. Gagnon's tips on regulatory issues like DNA, virus, and endotoxin clearance are useful. He includes pointers on chromatographic media sanitization, regeneration, repacking, and storage.

Gagnon comments on the effects of each method on the bioactivity of MAb products. For example, he raises several cautionary notes on using protein A chromatography resins: low pH elutions causing protein instability or adversely affecting effector functions of IgG; and protein A leachates contaminating IgG could cause aggregation or other bioresponses in vivo. Gagnon includes a sizable bibliography on the pleiotropic effects of protein A, a potent immunomodulator. Current practices in MAb purification strive for trace levels of protein A (a few ng per mg IgG) in the product. Depending on the size of therapeutic doses and frequency of administration, those levels may not be low enough. Gagnon details methods for removing trace levels of protein A.

The book includes two appendices. One contains example protocols that could initiate newcomers into the art of purifying MAbs, and the other deals with sample preparation, providing a thoughtful review of product contaminants that can foul chromatography columns and suggestions for how to deal with them.

Both seasoned and first-time practioners of MAb purification benefit from this book, because it covers many topics of regulatory interest not found in established monographs. The extensive bibliographic entries for each method are well chosen and useful. Although MAbs are the main focus of the book, the purification issues are addressed in ways that workers involved with non-MAb proteins should find useful. I recommend this book to protein purification scientists and bioengineers as well as those involved with managing therapeutic MAb project groups.

Reviewer A.H. Nishikawa is group director of bioseparations in the biological process sciences department at SmithKline Beecham Pharmaceuticals, King of Prussia, PA; email <a_hirotoshi_nishikawa@sbphrd.com>.

Reprinted from BioPharm (website 4/98) with permission.

In the area of industrial applications, it is frequently difficult to really get an idea of what is common practice. Books and scientific publications, although frequently written by scientists skilled in the art and knowledgeable about the latest theories, often reflect how things are done in a university lab. This book is written by an industrial practitioner with years of hands-on experience with monoclonals, with all their idiosyncracies, and it shows. It is a truly comprehensive review of methods for purifying monoclonal antibodies for biotechnology applications. Rarely have so many tips for avoiding problems come together in one volume. Rarely have all of the commonly applied techniques been addressed in such a balanced way. The text is easy-to-read, the layout is attractive, and the digrams and chromatograms are clear and helpful. With respect to chromatograms, full details of materials and experimental conditions have been left out, which is unusual and may be criticized. However, this has helped to make the text lighter, and an appendix gives useful buffer systems and experimental protocols for the commonest methods.

Pete Gagnon has sprinkled a number of quotations into the text including one from Benjamin Franklin, "Either write things worthy reading, or do things worth the writing." In today's world, where time seems alway to be too short, a book like this is of enormous value, condensing masses of real-life practical knowledge into an accessible single source. This book certainly makes worthy reading.

Reprinted from Downstream 24 (March '97), with permission.