Emerging antibody products and Nicotiana manufacturing.

Antibody based products are not widely available to address multiple global health challenges due to high costs, limited manufacturing capacity, and long manufacturing lead times. Nicotiana-based manufacturing of antibody products may now begin to address these challenges as a result of revolutionary advances in transient expression and altered glycosylation pathways. This review provides examples of emerging antibody-based products (mucosal and systemic) that could be competitive and commercially viable when the attributes of Nicotiana-based manufacturing (large scale, versatile, rapid, low cost) are utilized.

Biosimilars: current status and future directions.

IMPORTANCE OF THE FIELD: Expiration of patents covering biopharmaceuticals, has provided opportunities for pharmaceutical companies to develop, produce and market biosimilars or follow-on biologicals. However, there have been concerns over the degree of similarity of these complex drugs in addition to the hope that their introduction may lower the cost of such expensive medicinal products. AREAS COVERED IN THIS REVIEW: The introduction/manufacturing considerations, immunogenicity and regulatory approaches to biosimilars around the world. In addition, arguments and techniques employed by pharmaceutical companies to advance or discredit biosimilar drugs will be outlined. Issues with post-marketing surveillance programmes and their limitations are described. WHAT THE READER WILL GAIN: This evaluation outlines the controversial issues associated with introduction of biosimilar medicines across a range of pharmacological indications. Also the differences between regulatory approved medicines and biopharmaceutical products not subjected to regulatory approval ('B-NSRA') are highlighted. The review is limited by the rapid changes in regulatory approval and licencing of biosimilars. TAKE HOME MESSAGE: Hopefully biosimilar medicines will allow more widespread availability of expensive biopharmaceutical products. Clinicians need to be wary of non-transparent promotion of innovator/biosimilar products.

Biotechnology as the engine for the Knowledge-Based Bio-Economy.

The European Commission has defined the Knowledge-Based Bio-Economy (KBBE) as the process of transforming life science knowledge into new, sustainable, eco-efficient and competitive products. The term "Bio-Economy" encompasses all industries and economic sectors that produce, manage and otherwise exploit biological resources and related services. Over the last decades biotechnologies have led to innovations in many agricultural, industrial, medical sectors and societal activities. Biotechnology will continue to be a major contributor to the Bio-Economy, playing an essential role in support of economic growth, employment, energy supply and a new generation of bio-products, and to maintain the standard of living. The paper reviews some of the main biotechnology-related research activities at European level. Beyond the 7th Framework Program for Research and Technological Development (FP7), several initiatives have been launched to better integrate FP7 with European national research activities, promote public-private partnerships and create better market and regulatory environments for stimulating innovation.

Industrialization of mAb production technology: the bioprocessing industry at a crossroads.

Manufacturing processes for therapeutic monoclonal antibodies (mAbs) have evolved tremendously since the first licensed mAb product in 1986. The rapid growth in product demand for mAbs triggered parallel efforts to increase production capacity through construction of large bulk manufacturing plants as well as improvements in cell culture processes to raise product titers. This combination has led to an excess of manufacturing capacity, and together with improvements in conventional purification technologies, promises nearly unlimited production capacity in the foreseeable future. The increase in titers has also led to a marked reduction in production costs, which could then become a relatively small fraction of sales price for future products which are sold at prices at or near current levels. The reduction of capacity and cost pressures for current state-of-the-art bulk production processes may shift the focus of process development efforts and have important implications for both plant design and product development strategies for both biopharmaceutical and contract manufacturing companies.

Natural product drug discovery: the times have never been better.

The annual meeting of the Society for Industrial Microbiology (SIM) this year was held in Denver, Colorado, from July 29 to August 2, 2007. Nearly 200 oral and about 120 poster presentations kept the approximately 600 participants busy for more than 4 days. This report focuses on the 35 talks dedicated to natural products chemistry, biosynthesis, engineering, drug discovery and development, as well as neutraceuticals.

Biosimilars: recent developments.

Biopharmaceuticals are recombinant protein drugs which are produced by biotechnology. The availability of such molecules has revolutionised the way we treat many diseases. However, the patents for many originator biopharmaceuticals are expiring, and a new generation of follow-on molecules, termed "biosimilars", are under development. Health care providers perceive biosimilars to be cheap replacements for originator drugs such as recombinant human erythropoietin and human growth hormone. However, concerns have been raised about the comparability of biosimilars with originator products especially in light of the complex manufacturing process required to produce biopharmaceuticals. The complexity of protein molecules renders it impossible to produce identical copies; this in turn raises questions on the safety of follow-on biosimilar products, particularly with respect to immunogenicity. This review briefly outlines the process of biopharmaceutical production, potential problems that can arise from their long-term use in patients, and the issues facing regulatory bodies as they look to institute guidelines for new biosimilar molecules.

From natural products discovery to commercialization: a success story.

In order for a natural product to become a commercial reality, laboratory improvement of its production process is a necessity since titers produced by wild strains could never compete with the power of synthetic chemistry. Strain improvement by mutagenesis has been a major success. It has mainly been carried out by "brute force" screening or selection, but modern genetic technologies have entered the scene in recent years. For every new strain developed genetically, there is further opportunity to raise titers by medium modifications. Of major interest has been the nutritional control by induction, as well as inhibition and repression by sources of carbon, nitrogen, phosphate and end products. Both strain improvement and nutritional modification contribute to the new process, which is then scaled up by biochemical engineers into pilot scale and later into factory size fermentors.

The historical delivery of antibiotics from microbial natural products--can history repeat?

Microbial natural products are the origin of most of the antibiotics on the market today. However, research in antibiotics and natural products has declined significantly during the last decade as a consequence of diverse factors, among which the lack of interest of industry in the field and the strong competition from collections of synthetic compounds as source of drug leads. As a consequence, there is an alarming scarcity of new antibiotic classes in the pipelines of the pharmaceutical industry. Still, microbial natural products remain the most promising source of novel antibiotics, although new approaches are required to improve the efficiency of the discovery process. The impact of microbial biodiversity, the influence of growth conditions on the production of secondary metabolites, the choice of the best approach at the screening step and the challenges faced during the isolation and identification of the active compounds are examined in this review as the critical factors contributing to success in the effort of antibiotic discovery from microbial natural products.

Bioprocesses for the manufacture of ingredients for foods and cosmetics.

This chapter describes the rapid growth in the use of biotransformation processes to manufacture food and cosmetic ingredients. Newly introduced processes include those to produce both ingredients not previously available, and also improved processes to make ingredients previously produced by chemical synthesis, fermentation or extraction from natural sources. What can we learn from what has already been achieved that will help us in the future? This question is very important because the key challenge is not just to do innovative research, but also to develop such research into cost-effective industrial scale processes that deliver products of proven utility to the end customer, and at prices that give good returns on R&D investments to the manufacturer. Therefore biotransformation R&D information is presented in the real-life context of manufacturing, IP, regulatory and safety, product costs and quality etc. Examples of new ingredients and processes are given that illustrate the great variety of ingredients produced biochemically, and the range of raw materials and enzyme reactions used to make them. These examples also illustrate how the technical advances made in developing these processes and products are inseparable from economic factors, especially production costs and functional benefits that create the demand and set the performance, cost, and quality standards for the product. Many of the key factors necessary for the translation of research into commercial successes are identified and described, as well as some special features that have helped individual processes to become successful. This review also proves that a key factor for success is management that can successfully integrate and implement the large number of different technical and commercial factors involved. The wide range of examples provided also prove that very many of the technical advances made in the field of applied biocatalysis have actually been made while developing processes for food and cosmetic ingredients; rather than for pharmaceuticals as is very often assumed. Consequently it is hoped that this review will help future research efforts, and especially aid the development of research into commercial success in this field.

Plant molecular farming: systems and products.

Plant molecular farming is a new and promising industry involving plant biotechnology. In this review, we describe several diverse plant systems that have been developed to produce commercially useful proteins for pharmaceutical and industrial uses. The advantages and disadvantages of each system are discussed. The first plant-derived molecular farming products have reached the marketplace and other products are poised to join them during the next few years. We explain the rationale for using plants as biofactories. We also describe the products currently on the market, and those that appear likely to join them in the near future. Lastly, we discuss the issue of public acceptance of molecular farming products.

An overview of health-related industrial biotechnology in Latin America and the Caribbean.

There is some uncertainty about the extent to which Latin America and the Caribbean have participated in the advances of health-related industrial biotechnology. This article reviews the available literature and seeks to provide an overview of the prevailing situation. In general, national governments and multinational agencies have provided most of the health-related biotechnology investments within this region. Efforts to achieve technology transfers, a subject of prime concern, have been developed by a number of programs including the WHO Special Program for Research and Training in Tropical Diseases, the UNDP/UNESCO/UNIDO Regional Biotechnology Program for Latin America and the Caribbean; PAHO's Program for the Regional Development of Biotechnology as Applied to Health; The PAHO/WHO Expanded Program on Immunization (EPI); and PAHO's Regional System of Vaccines (SIREVA). Regarding current production capacity, some successful efforts have been made to produce a variety of therapeutic products including recombinant and natural interferons, interleukins, insulin, and recombinant streptokinase; but in general the region's current potential in this area is at best incipient and uncertain. However, the region does have a limited ability to make diagnostic products and a well-established capacity for vaccine development. Overall, this picture suggests that the region has the potential to play a small but significant role in health-related biotechnology.

The importance of cell physiology to the performance of animal cell bioreactors.

This report has pointed out the following: (1) the new animal cell products that will be produced commercially will have large dollar markets and will, together with cost containment and competitive pressures, place a greater emphasis on the reduction of the cost of production through the selection of appropriate culture technology; (2) the benefits to be gained by working with basic biological processes in animal cell culture that will increase cell density, cell productivity, and product quality; (3) the need to work with reactor technologies that can affect the basic biology of the cell in these positive ways; (4) it appears worthwhile to explore immobilized, high cell density culture technologies as a possible means to achieve the objectives by affecting the basic regulation of the cell through fundamental cell/cell environment biological processes.