DMMC/Wyeth Course MOLECULES TO MEDICINES: HOW BIOPHARMA DELIVERS

1420-1600 Tuesday 9 May 2006. UCD Conway Institute Lecture Theatre

MANUFACTURING

Dr Brendan Hughes (Director of Development, Wyeth Medica Ireland, Grange Castle)

1420-1500 Introduction to the science and technology of biopharmaceutical manufacturing

The contribution of biopharmaceuticals to medicine has grown rapidly from an early start as complex mixtures of protein preparations extracted from tissue to today’s highly purified proteins produced from cell culture. Early biopharmaceuticals were often replacement proteins such as cytokines or growth factors that were used to supplement a deficiency that contributed to the disease process. The recombinant proteins in use today have a variety of modes of action and are used to tackle a wide range of diseases. The proteins available now are often specifically targeted against identified proteins in the circulatory system and impact disease by binding molecules such as mediators of inflammation or by marking tumour cells for destruction. Together with a major impact on a number of serious disease states, these new medicinal products have had significant commercial successful with sales of non-vaccine biopharmaceuticals exceeding €37BN in 2004.

This new generation of medicines has been enabled by breakthroughs in a number of areas in science and technology. Apart from the huge explosion of knowledge in biology which has revolutionized the Discovery and Development processes, advances in cell culture technology, bioprocess technology and protein characterization have provided the platforms on which stable, reliable and economical manufacturing systems have been established.

This course will introduce participants to the biotechnology industry and review its recent history. The course will present an overview of biopharmaceutical manufacturing and discuss facility design and operation in outline. The participants will see how the various technologies operate in the plant and how they are used in the various unit operations as well as in the supporting functions such as technical support and analytical laboratories. The course will also examine the interrelationships on a manufacturing site and look at how the process of manufacturing a batch involves a wide range of participants.

1520-1600 Focus on the application of molecular technologies in manufacturing environments

A unique feature of the production of biopharmaceuticals, distinct from medicines produced by chemical synthesis, is the use of living cells as the primary unit of production of the active ingredient. This feature and the relative complexity of the molecules produced by living organisms creates a need and an opportunity to utilize modern molecular techniques in the operation and control of biopharmaceutical processes. In the upstream area of the process, where cell growth and protein production occurs, a sound understanding of cell biology and physiology allows scientists and engineers to monitor and control the growth of cells and manage their production of recombinant proteins. Building on the work carried out by Development colleagues, manufacturing technologists carefully manage bioreactor processes to ensure optimal conditions for growth and protein purification. Later, in the downstream area, where the protein is captured and purified, a sound knowledge of the physicochemical characteristics ensure that conditions here are similarly managed to maintain maximum output and quality. All of the critical processes in a plant manufacturing biopharmaceuticals should be validated usually operated under significant automated control and should not require frequent intervention. However, natural variability can occur in biological systems and the investigative scientists who support the plant will utilize a range of modern technologies to solve problems in routine manufacturing or to support planned changes. This course will outline some of the approaches that are taken and use a number of case studies to show how this work is carried out.

Suggested Reading

Walsh, G. (2003). Biopharmaceutical benchmarks – 2003, Nat. Biotechnol. 21, 865-870. PubMed Entry