Manufacturing of Pharmaceutical Proteins

From Technology to Economy

Stefan Behme

• Publisher: Wiley-Blackwell
• Year: 2015
• Print ISBN:
  9783527337668
• Edition: 2
• eBook ISBN:
  9783527683086
• Topic: Biological Sciences
• Subtopic: Biotechnology
• Index: Biological Sciences

Structured like a textbook, the second edition of this reference covers all aspects of biopharmaceutical manufacturing, including legal and regulatory issues, production facility design, and quality assurance, with a focus on supply chain management and regulations in emerging markets and cost control.
The author has longstanding industrial expertise in biopharmaceutical production and years of experience teaching at universities. As such, this practical book is ideal for use in academia as well as for internal training within companies.

Part I

Introduction

1
Biopharmaceutical Production: Value Creation, Product Types, and Biological Basics Introduction

1.1 Role of Production in Pharmaceutical Biotechnology

Over recent years pharmaceutical biotechnology has developed very dynamically. An important driver for this success has been the enormous increase of scientific know-how in the areas of genetics and immunology, which has created huge expectations for the development of innovative medicinal treatments.

The scientific pioneer spirit has been fueled by public and private sponsorship, resulting in a biotechnological landscape that has long been dominated by highly innovative, venture capital-based, small- and mid-size companies. However, before patients can benefit from scientific achievements it is necessary that the identified molecule is transformed into a medicine – fit for achieving the therapeutic target – and tested in comprehensive trials in the field. The production of such a medicine has to be carried out in officially licensed, often tailor-made technical manufacturing facilities.

This¹ path from project to product usually lasts several years, and is associated with enormous costs and risks. On average, the development costs of a new compound are in the region of US$500–1000 million and only 10% of all projects that enter clinical trials find their way into the market.

Owing to these immense investments in drug development, the costs of drug manufacturing often seem acceptable, particularly as the costs are absorbed by sales of the marketed drug in the same accounting period; however, safe and efficient product supply is the cornerstone of a company's success. In biotechnology, the overlap between development and market launch is particularly intensive, motivating companies to take care of manufacturing early on:

• Many targets of process development result from requirements of large-scale manufacturing.
• The classical separation of development (pre-marketing) and production (post-marketing) does not work for biologics, as both the manufacturing process and plant are factors that determine the quality of the final medicinal product.
• Production is the basis for long-term market supply. Decisions about capital investment or outsourcing of manufacturing mostly have to be taken long before the market launch of the product.
• Biotechnological processes are much more difficult to control than small-molecule preparations. The limited ability to monitor and characterize the product results in increased manufacturing risks.

The main target of production is to supply the product safely and cost-efficiently.² It is positioned between the development and marketing of a product. Figure 1.1 illustrates its significance in the value chain.

Figure 1.1 Role and tasks of production.

The chain starts with research that has a clear focus on the identification of targets, which involves analyzing the interaction between the biochemical molecule and its potential therapeutic functionality. In the subsequent development phase, a process for the scale-up and more consistent manufacturing of the molecule is designed. Here, the target structure is developed into a pharmaceutical form, and tested in animals and humans as to its safety and efficacy. Once this is achieved, production kicks in, taking care of a high-quality and profitable product supply, addressing the following main tasks:

• When, where and in what quantities should the drug be produced? (Production concept)
• How should market supply be organized? (Supply-chain organization)
• How should the quality of the product and Good Manufacturing Practice (GMP) compliance be assured? (Quality assurance)
• What are costs of manufacturing and how can these costs be controlled? (Manufacturing costs)
• How attractive is an investment in one's own facilities? (Investment decision)

The marketing of the product stands at the end of the value chain; from this position, essential goals are formulated for production: supply safety and cost efficiency.

The³ integrated position of production in the value chain results in interdisciplinary tasks that are best treated by multilateral teams managed by experts in different disciplines like biology, engineering, chemistry, economics, law, pharmacy, and medicine.

Figure 1.2 shows the subject areas that are important for the understanding and control of production processes and workflows. This volume provides an overview of these subject areas, while special emphasis is given to the interaction between these areas.

Figure 1.2 Subject areas in production. Inner circle = sections of this book; outer circle = subject areas treated in the sections.

Following this introductory part, Part 2, “Technology,” focuses on processes and analytics. This section illustrates why the manufacturing process plays such a large role in biotechnology, and to what extent product quality is determined by processes and analytics. Moreover, essential technologies for industrial manufacturing as well as methods and areas of application of analytical testing are described.

Part 3, “Pharmacy,” briefly elaborates on the basic principles of drug effects on humans and the essential steps of pre-clinical and clinical drug studies. The successful end of the clinical test marks the starting point of commercialization.

Product quality plays a crucial role in pharmaceutical manufacturing. Part 4, “Quality Assurance,” elucidates the organizational and operative workflows for quality assurance, including the rules of GMP.

Almost all activities of commercial production happen in the framework of legal regulations. Part 5, “Pharmaceutical Law,” describes drug regulations and laws as well as institutions and enforcing official authorities.

The translation of process technology into large-scale manufacturing capacities is described in Part 6, “Production Facilities.” Basic principles of the design of GMP-complia...

Table of contents

• Cover
• Related Titles
• Title Page
• Copyright
• Dedication
• Preface
• Preface to First Edition
• List of Abbreviations
• Part I: Introduction
• Part II: Technology
• Part III: Pharmacy
• Part IV: Quality Assurance
• Appendix A: Case Study Part 4:Warning Letters by FDA
• Part V: Pharmaceutical Law
• Appendix B: Case Study Part 5: Clinical Trials for Protein Products
• Part VI: Production Facilities
• Part VII: Economy
• Appendix C: Examples Part 7: Manufacturing Cost Calculation
• References
• Index
• End User License Agreement