Biopharmaceuticals from Plan to Production

Product development and manufacturing operations in biotechnology companies come from historical developments in natural-product extractions and purification. These processes evolved into sophisticated genetic manipulations and accompanying extraction, purification, formulation, and processing into sterile clinical products. The development of operations for biopharmaceutical products required the concurrent development of technology, pharmaceutical management, regulations, and quality requirements. A recent book captures those evolutions and their resulting state of the art.

Biotechnology Operations: Principles and Practices, by Michael J. Roy, CRC Press, Boca Raton, FL, 2011, 416 pp., ISBN-13: 978-1439830277

Biotechnology Operations: Principles and Practices presents a structured overview of pharmaceutical operations that includes specific details needed for biopharmaceutical production. The book builds from a pharmaceutical business-management mode into regulatory requirements and the quality operations that are needed to achieve regulatory compliance. Included in each chapter are details about how biological products are different from traditional small molecule pharmaceuticals, and about how these differences require attention. The author emphasizes the management of business planning, regulatory operations, and quality control and assurance as essential parts of biopharmaceutical operations. The application of project-management methods, as well as regulatory and quality requirements for biopharmaceuticals, is also examined.

The book’s first five chapters give a thorough assessment of how both biotechnology and traditional pharmaceutical operations would function in a fully integrated company. A complete overview of the product-development pathway and its functional areas emphasizes the need for intimately managed planning. Product-development objectives are thoroughly outlined for companies that are well staffed and have in-house experience. For small and medium-sized biotechnology companies, the book offers an ideal approach that is rarely followed and could be somewhat unrealistic because of staff or skill limitations.

Chapters 3 through 5 offer a thorough assessment of regulatory requirements and quality systems needed for successful product development and manufacture. FDA’s evolution and its current organization are outlined, as well as the laws used to initiate regulations.

The chapter titled “Biomanufacture” contains a complete overview of manufacturing methods and technical requirements. The book has many well written sections on biomanufacturing, including “Design in Biomanufacture” and “Technical Considerations for Biomanufacture.” The chapter section titled “Phases and Scale Up” of development tries to integrate the problematic issues of management, regulation, and quality into an explanation of the relationships between those entities and how they interact and influence each other.

The chapter titled “Biomanufacture” does not provide extensive details about how the manufacturing process evolves from the development process. Although the part of the book dedicated to biomanufacturing is complete, each individual production method could have been expanded into its own book, had it covered topics, such as production methods, process development, and integration into manufacturing and technology transfer, in much more depth.

A thorough discussion titled “Biomanufacturing Process for Biotechnology Products” examines recombinant-protein expression, various cell-expression systems (including host cell selection issues), master and working cell banks, and recovery and purification methods. Further discussion of plasmid DNA, live-organism (e.g., bacterial or viral) processes, somatic cells, pluripotent (i.e., stem) cells, transgenic plant and animal sources, and bioactive peptides could each have entire books devoted to their current state of the art and production process. The brief attention given to final-product formulation, fill-finish, labeling and facilities, utilities, and equipment and validation shows how difficult is it to incorporate all of the needs of biopharmaceutical production into one book.

The chapter on quality control outlines the selection of analytical procedures needed to define quality attributes, including specification development, an array of methods for biological product testing, cell banking, stability, raw-material operations, quality in the manufacturing environment, and assay qualification and validation. This section is quite comprehensive, but might have benefited from an expanded discussion on bioassays and their validation.

The last chapters of the book explain the preclinical and clinical components of pharmaceutical and biopharmaceutical development. Discussion of preclinical and nonclinical studies includes all of the needed information on delivery, pharmacology and toxicology, and in vitro safety needs. It also includes an outline of the integration of nonclinical studies with a biopharmaceutical development program. This chapter leads into a chapter on clinical studies that include components of clinical trials from Phase I through Phase IV and notes the special needs of biopharmaceuticals in clinical settings.

The discussion of clinical trials for biopharmaceuticals is appropriately based on clinical trials for small-molecule and nonbiological products and includes details of potential biological interactions that may evolve during early and advanced clinical trials.

Overall, the book emphasizes the components needed in traditional pharmaceutical development and describes the significant differences in the requirements for biopharmaceutical development and operations. A more thorough discussion of the integration of development processes into a defined, validated manufacturing process for biotechnology products would have been a welcome addition.

Many recent books have been written to address the production of pharmaceutical proteins, and most have had problems in portraying the entire topic without missing a component or digressing into tangents. This book presents a complete review of biotechnology operations and would be an exceptionally useful overview for the experienced—and quite instructional for the uninitiated.

Jim Fernandez is president of Fernandez and Associates, 1480 Moraga Rd. #280, Moraga, CA 94556, jfernandez365@aol.com