Current Developments in Biotechnology and Bioengineering

Human and Animal Health Applications

Vanete Thomaz Soccol, Ashok Pandey, Rodrigo R. Resende

• Publisher: Elsevier
• Year: 2016
• Print ISBN: 9780444636607
• eBook ISBN: 9780444636713
• Topic: Biological Sciences
• Subtopic: Biotechnology
• Index: Biological Sciences

Current Developments in Biotechnology and Bioengineering: Human and Animal Health Applications provides extensive coverage of new developments, state-of-the-art technologies, and potential future trends, presenting data-based scientific knowledge and information on medical biotechnological interventions for human and animal health.Drawing on the key development areas in this field, the book reviews biotechnological advances and applications in immunotechnology, vaccines and vaccinology, combinatorial libraries, gene and cell therapy, tissue engineering, and parasite and infectious disease diagnostics. This title outlines why biotechnological techniques in these areas are useful in a clinical context and considers their potential uses, limitations, and the ethical considerations surrounding their use.- Provides development in human and animal health due to biotechnology- Includes immunotechnology and vaccinology- Outlines diagnostic techniques based on tissue and metabolic engineering principles- Considers potential uses of the various biotechnology based techniques and the ethical issues raised in their use

Part 1

Perspectives in Biotechnology Health

Outline

1. Biopharmaceutical Products: An Introduction

2. Biopharmaceuticals and Biosimilars

1

Biopharmaceutical Products

An Introduction

L.R. Castilho Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Abstract

Since the approval of recombinant human insulin in 1982 as the first therapeutic protein produced by means of recombinant DNA technology, the biopharmaceutical sector has grown considerably. In this chapter, the issue of the nomenclature of biotechnological products for human health is discussed and the different classes of biopharmaceutical products are described. Because recombinant therapeutic proteins (including monoclonal antibodies) represent the most mature class of biopharmaceutical products, with the largest number of approved products, the expression systems and manufacturing technologies used to obtain these products are discussed. The new era of off-patent biosimilars, as well as the wide range of new products under development, including cell therapies and gene therapies, are currently challenging the traditional conservatism of this industry and pushing manufacturing technology toward continuous bioprocessing. Thus, processes with increased productivity, improved product and process flexibility, and reduced costs can be anticipated in the future.

Keywords

Animal cell technology; Biopharmaceutical products; Expression systems; Manufacturing process; Upstream and downstream processing

1.1. Introduction

The term “biopharmaceuticals” was coined in the 1980s specifically to refer to human health products generated or produced by means of modern molecular biological methods using engineered organisms, and to distinguish these products from traditional biological products directly extracted from natural biological sources such as proteins obtained from plasma or plants [1]. Techniques usually considered to be the landmarks in “modern Biotechnology”, recombinant DNA technology and hybridoma technology, both developed in the 1970s, were important for the development of this class of products. However, besides “biopharmaceuticals,” several other terms, such as biotherapies, immunotherapies, biologics, and biological products, have been used to refer to these products [2,3]. In 2002, in an attempt to avoid the problem that the various terms have different meanings for different people, Walsh [4] discussed the issue of nomenclature and proposed the use of the following definition:

A biopharmaceutical is a protein or nucleic acid-based pharmaceutical substance used for therapeutic or in vivo diagnostic purposes, which is produced by means other than direct extraction from a native (non-engineered) biological source.

Currently, according to this definition by Walsh [4], “biopharmaceuticals” is the most widely adopted term, but it is often used interchangeably with “biologicals,” “biologics,” and “biological products” [3]. In terms of the biopharmaceutical market, recombinant therapeutic proteins largely dominate. Thus, it is also common to use the term “biopharmaceuticals” to refer to them specifically. However, if one refers to “biopharmaceutical products” or to the “biopharmaceutical sector” as an industrial segment, recombinant vaccines and nucleic acid–based therapies are usually included. Besides these, other biotechnological products for human health are cell therapies, in which the cells are the product used to regenerate or engineer tissues, and molecules used for in vitro or in vivo diagnostics.

1.2. The Biopharmaceutical Sector: Market Aspects

The first biopharmaceutical product to be approved for human use in 1982 was human insulin produced in recombinant Escherichia coli. Four years later, there were other biopharmaceutical landmarks: the approvals of recombinant tissue plasminogen activator (t-PA) produced in animal cells (Chinese hamster ovary cells, CHO), of the monoclonal antibody OKT3 produced in hybridoma cells and of recombinant hepatitis B vaccine produced in Saccharomyces cerevisiae [5,6].

Since the commercialization of insulin almost 35 years ago as the first recombinant therapeutic protein, many other products followed, leading to a continuous increase in the sales of the biopharmaceutical sector. Until July 2014, 246 biopharmaceutical products had been licensed in the United States and in the European Union (EU), containing 166 different active ingredients. In the 20 years between 1995 and 2014, the number of new biopharmaceutical products approved in these regions was approximately constant, between 50 and 60 every 5 years. Among the 54 products licensed between 2010 and July 2014, about 40% were not truly new products (i.e., they were biosimilars, improvements of existing products, or products previously approved in other regions). Thus, only 32 of them, containing 30 different new active ingredients, can be considered genuinely new products [1].

Despite the decades that have passed since approval of recombinant insulin, the biopharmaceutical sector cannot yet be considered a mature industry, and many new developments regarding new products and new technologies are under way.

In the period 2010–14, there were several important landmarks:

• A first biosimilar monoclonal antibody (mAb) (i.e., a product comparable to the innovator biopharmaceutical product whose patent has expired) was approved in the EU: infliximab biosimilar products (Remsina and Inflectra) from two companies (Celltrion and Hospira) were licensed in 2013.

• In the so-called “highly regulated markets,” for the first time, there was approval of a gene therapy product: Glybera (alipogene tiparvovec), produced by the company UniQure, licensed in the EU in 2012.

• For the first time, a biopharmaceutical produced in plant cells was approved: Elelyso (glucocerebrosidase/taliglucerase alfa), expressed in recombinant carrot cells propagated in bioreactors and licensed by Protalix Biotherapeutics/Pfizer in 2012 in the United States.

• Ruconest, produced by the company Pharming using transgenic rabbits, was the seco...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• About the Editors
• Preface
• Part 1. Perspectives in Biotechnology Health
• Part 2. Immunotechnology
• Part 3. Combinatorial Libraries
• Part 4. Gene and Cell Therapy
• Part 5. Tissue Engineering
• Part 6. Biofilms and Biosurfactants in Health
• Part 7. Vaccines and Vaccinology
• Part 8. Biotechnology Applied to Parasites
• Part 9. Biotechnology of Reproduction
• Index