Single-Use Technology in Biopharmaceutical Manufacture

Regine Eibl, Dieter Eibl, Regine Eibl, Dieter Eibl

• Publisher: Wiley
• Year: 2019
• Print ISBN:
  9781119477839
• eBook ISBN:
  9781119477778
• Edition: 2
• Topic: Medicine
• Subtopic: Pharmacology

Authoritative guide to the principles, characteristics, engineering aspects, economics, and applications of disposables in the manufacture of biopharmaceuticals

The revised and updated second edition of Single-Use Technology in Biopharmaceutical Manufacture offers a comprehensive examination of the most-commonly used disposables in the manufacture of biopharmaceuticals. The authors—noted experts on the topic—provide the essential information on the principles, characteristics, engineering aspects, economics, and applications.

This authoritative guide contains the basic knowledge and information about disposable equipment. The author also discusses biopharmaceuticals' applications through the lens of case studies that clearly illustrate the role of manufacturing, quality assurance, and environmental influences. This updated second edition revises existing information with recent developments that have taken place since the first edition was published. The book also presents the latest advances in the field of single-use technology and explores topics including applying single-use devices for microorganisms, human mesenchymal stem cells, and T-cells. This important book:

•    Contains an updated and end-to-end view of the development and manufacturing of single-use biologics

•    Helps in the identification of appropriate disposables and relevant vendors

•    Offers illustrative case studies that examine manufacturing, quality assurance, and environmental influences

•    Includes updated coverage on cross-functional/transversal dependencies, significant improvements made by suppliers, and the successful application of the single-use technologies

Written for biopharmaceutical manufacturers, process developers, and biological and chemical engineers, Single-Use Technology in Biopharmaceutical Manufacture, 2nd Edition provides the information needed for professionals to come to an easier decision for or against disposable alternatives and to choose the appropriate system.

Part I
Basics

1
Single‐Use Equipment in Biopharmaceutical Manufacture: A Brief Introduction

Dieter Eibl and Regine Eibl

School of Life Sciences and Facility Management, Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, Wädenswil, Switzerland

1.1 Background

The term “biopharmaceutical” was first used in the early 1980s [1] when recombinant, commercially manufactured insulin, a therapeutic protein for diabetes patients, was introduced. In the United States and Europe, the most frequently used definition is that of a pharmaceutical manufactured by biotechnological methods with organisms, or their functional components, which have a biological origin. Following this definition, all recombinant proteins, monoclonal antibodies (mAbs), vaccines, blood/plasma‐derived products, nonrecombinant culture‐derived proteins, and cultured cells, in addition to tissues from human or animal origin and nucleic acids, are considered to be biopharmaceuticals [2–4]. The majority of the above are classified as biologicals (or biologics) by regulatory agencies [5]. Traditional pharmaceutical products, such as chemical compounds extracted from plants, secondary metabolites from microbial and plant cell cultures, and synthetic peptides, which may not comply with the above definition, are more often regarded as non‐biopharmaceuticals. Irrespective of differences in definition, recombinant protein pharmaceuticals constitute an important category of biopharmaceuticals.

The most significant protein pharmaceuticals available include hormones such as erythropoietin, enzymes such as the human plasminogen activator, vaccines such as Flucelvax, and mAbs such as bevacizumab. It is worth mentioning that the top 10 best‐selling drugs are dominated by therapeutic mAbs today [5].

In most cases, protein pharmaceuticals are produced with mammalian cell lines. During the last few years, Chinese hamster ovary cell lines have increasingly displaced earlier mammalian cell production systems such as hybridomas or embryonic feline lung fibroblast cell lines [6, 7]. Further production organisms of choice for protein pharmaceuticals are microbial cells [8] (see also Chapter 21), plant cells [9] (see also Chapter 28), and insect cells cultivated in conjunction with the baculovirus expression vector system [10].

The worldwide demand for protein pharmaceuticals (and, in particular, protein therapeutics) has resulted in increased efforts to expand the process efficiency over the past 10 years. It is undoubtedly the case that the huge growth in knowledge in molecular and cell biology has led to high‐productivity cell lines and improved culture media. These cell lines provide product titers exceeding 3 g/l in fed batch mode and contribute to shrinking bioreactor size, which is associated with cost savings [11]. Further cost savings can be achieved by replacing stainless steel with single‐use equipment in the production process [12, 13].

The present chapter introduces the reader to the area of single‐use technology. In addition to terminology, advantages and disadvantages of existing single‐use devices will be described. Based on a schematic of a typical production process for a protein therapeutic, an overview of currently available single‐use devices and a categorization approach will be presented. Moreover, the main criteria for implementing single‐use systems in biopharmaceutical production processes are summarized, and current concepts concerning single‐use production facilities are briefly explained.

1.2 Terminology and Features

As the term “single‐use” (or “disposable”) implies, such systems are only ever used once. Disposables currently in use originated in the fields of medical care (e.g. rubber gloves, sterile swabs, and the technology for intravenous applications) and infant care (e.g. paper towels and disposable diapers). With the exception of special protective clothing and consumables (e.g. swabs and paper towels), single‐use products are typically fabricated from plastics approved by the Food and Drug Administration (see also Chapter 8), such as polyethylene, polystyrene, polytetrafluoroethylene, polypropylene, or ethylene vinyl acetate. These materials are typically supplemented with additives to aid performance and/or prolong usable life [14, 15], thereby ensuring their suitability in biopharmaceutical manufacturing applications. In all cases, the product contact surfaces are free of animal‐derived components.

Disposables can be rigid (molded systems) or flexible (bags made from multilayer films) and are often supplied presterilized, having been gamma irradiated at dose levels between 25 and 50 kGy [16, 17], although some are autoclaved or sterilized with gas. This eliminates the need for subsequent sterilization of the equipment, such as the steam sterilization normally required for stainless‐steel components. Disposables can, therefore, quickly be brought into operation. On completion of the process operations, the disposables used are decontaminated and discarded. Thus, time‐consuming and expensive cleaning procedures which may require the use of corrosive chemicals (which could potentially pose a health hazard to the operator) and water‐for‐injection, often considered as a bottleneck in traditional biopharmaceutical facilities, are no longer required.

Disposable technology is often regarded as greener, due to the reduced requir...

Table of contents

• Cover
• Table of Contents
• List of Contributors
• Preface
• Part I: Basics
• Part II: Application Reports and Case Studies
• Index
• End User License Agreement