The Age of Biotherapeutics

This article is partly based on my previous publication in the journal BioSpectrum titled “Serum free media - All are not created equal” August 2008 (http://www.biospectrumasia.com/content/130808ind6802.asp).

During the last century we saw major advances in controlling infectious diseases by way of vaccination as well as development of antibiotics. We also saw hundred of small chemical molecular drugs developed for various indications. Until then infectious diseases were the major killer around the world. There were many recorded incidences of Pandemic, the Black Death for example, during middle-ages probably wiped out over 50% percent of population of Europe. With the advances in medicine during the last century, the life expectancy have gone up significantly especially in the developed countries.

As the median age of the population went up, the patterns of diseases have changed. Now cardiovascular and metabolic diseases, such as diabetes and obesity, are major causes of morbidity and mortality. Also many geriatric conditions, such as Alzheimer’s disease and dementia, are becoming more prevalent.

In this century we will see developments in biotherapeutics and personalized medicine to combat these ailments. By biotherapeutics I mean drugs of biological origin such as recombinant proteins and antibodies. The pharmaceutical industry went through a major paradigm change in their product development strategy during the last decade. Until recently they were very much focused on small molecule based drug development. Things started changing over last 10 years or so when more and more protein based drugs got approvals and some became blockbuster drugs. Probably the success of Rituxan/MabThera, for the treatment of Non Hodgkins lymphoma launched in 1997 by Idec Pharmaceuticals and Genentech, initiated this shift towards biologics or biotherapeutics. Currently, monoclonal antibody development is the fastest growing segment in biotech industry recording 14% annual growth rate (versus 0.6% for small molecule), with recent recorded sales in excess of $20 billion. Over 50% of products in development are biotherapeutics that include monoclonal antibodies and recombinant proteins.

The manufacture of biotherapeutics requires live cells such as bacterial culture, yeast or mammalian cell culture. Many recombinant proteins and antibodies require mammalian cell culture for production. Cells are grown in vitro for the production of proteins they produce including antibodies. About half of all recombinant therapeutic proteins currently in the market are produced in mammalian cells. The accelerated demand of biologics also put lot of demand on bioprocessing to increase capacity, improve on efficiency and yield. Significant progress has been made in in vitro cell culture technologies during last few years. Initial commercial uses of cell culture were for the production of vaccines, such as polio vaccines.

The rapid advancement in development of biopharmaceuticals and biologics recently has forced the industry to come up better solutions to its problems and issues. Major issues are 1) safety associated with use of animal products, 2) consistency of production associated with variability from lot to lot and 3) cost. Cost of manufacturing by mammalian cell culture is high and hence the high cost of many biologics in the market currently. A small improvement in productivity of a cell line may have a significant savings in terms of cost. Currently there are 26 approved monoclonal antibodies in the market some of which can be life saving to many patients. But high cost may be keeping it from the reach of many. The challenge to the industry is to bring the cost down to be affordable to all.