Challenge

Pharmacological therapy usually includes only a single or few therapeutics to treat the selected pathology, such as infection, cancer or inflammation (Walsh, 2010). After the application of these therapeutics medicine relies on our body’s ability to heal and regenerate. With daily advances in basic research, we are able to unravel mysteries concerning the biochemical pathways governing different stages of diseases. We now know many growth factors and other endogenous mediators are involved in the regeneration and healing processes. Often a defined temporal sequence of different factors is required for the best therapeutic effect, however they are very seldom used in current medicine.

Some of biopharmaceuticals used in therapy have side effects that range from mild to serious, requiring discontinuation or modification of therapy. For example the systemic inhibition of tumor necrosis factor-alpha used to treat arthritis may increase the risk of infection, application of interferon-alpha for treatment of hepatitis C infection causes nausea in patients, while some biological drugs may promote hepatic dysfunction or have other serious side effects.

Probably the most important aspect connected to the application of biological drugs is the high cost of therapy. The annual cost of biological therapy for rheumatoid arthritis ranges from 15,000 – 25,000 dollars in comparison to nonbiologic therapy cost of 100 – 300 dollars per annum, 6,000- 15,000 dollars for hepatitis C and for some others it may exceed 100,000 dollars, which is out of reach of most patients, even in wealthy countries.

Many biopharmaceutical proteins are expressed in bacterial systems, which can be excellent producers, however bacterial endotoxins must be thoroughly removed before the administration to patients as even picomolar concentrations of an endotoxin may activate immune cells. In the production of biologics, downstream processing and formulation of the drug is very demanding. For example, an interferon (IFN-α) formulation was found to oxidize at room temperature, changing the tertiary structure of the protein, decreasing its effectiveness and raising the immune response to the modified protein. The formulation and storage procedures had to be optimized to reduce antibody formulation. Similar post-manufacturing structural changes have been implicated in other immune-mediated responses to recombinant proteins (Purcell et al., 2008).