Biosimilars can be defined as biotechnological drugs that have been shown to have comparable quality, safety and efficacy as the original biological product on the lines of a generic version of a patent drug following its expiry.

Unlike chemical-based small molecular weight medicines, biosimilars mostly consists of heavy  proteins and their manufacture involves principles of genetic engineering such as recombinant DNA technology rather than chemical synthesis. These are manufactured using living micro-organisms such as bacteria.

In general development of biosimilar takes seven to eight  years with an estimated expense of US$ 75-250 million with clinical trials involving around 500 patients. Although the cost involved in developing and manufacturing of biosimilars is high, their usage is increasing especially in the treatment of diseases like cancer, anaemia, hepatitis, diabetes etc. This is because these drugs have a unique ability to bind to specific target within the body and thereby improving the survival rates resulting in better quantity of life.

 Some of the common biosimilar products available include: Human Growth Hormone (hGH) ,Interferons , Erythropoietin, Recombinant insulin, Filgrastin, Interleukins and  TNF-alpha antibodies. The very importance of biosimilars can be explained from the fact that in the overall pharmaceutical market , biologics have approximately 15 per cent of the total  sales and nearly a third of the total global development.

India, a potential market for biosimilars
Ever since Dr. Reddy’s laboratories launch India’s first biosimilar product, Grafeel (Filgrastin) in 2001, there has been a boom in the biosimilar market of India and now India’s biotechnology sector is the third largest in the ‘Asia Pacific Region’ after Australia and China. It is now worth more than US$ 4 billion and is tripling in size.

Issues concerning biosimilars
Although biosimilars are becoming more and more popular today, a major problem associated with them, is the difficulty of getting an exact replica, every time the drug is manufactured.

This is primarily because biosimilars are structurally proteins – which possess intricate structure with heavy poly peptide chains. Also, the manufacture of biosimilars requires the use of living micro-organism and since no two cells are identical, there is always - however minute - some variation in the biosimilars produced. This is unlike the synthetic drugs, where every product manufactured can be tuned to the same specification and strength and are identical.

These differences are what make the evaluation of biosimilars more complicated. The therapeutic equivalence has to be shown to be comparable to the original patented product. Due to these variations, the safety and efficacy of biosimilars have to be closely monitored. Another concern with the usage of biosimilars is their potential immunogenicity. The use of biopharmaceuticals to replace endogenous proteins may posses a serious threat of triggering an immune reaction.

This is why some doctors express concern over the use of biosimilars. Questions arise such as – whether the biological generic would match up with the original innovator product in terms of safety and efficacy. More over doctors are reluctant to switch from the original product to the biosimilars as they are worried about the effect it would have on the established relationship between them and the manufacturing companies.

Regulation of biosimilars
Bringing a biosimilar from developmental stage to a market stage is any day more complicated than a generic product. Different governing bodies such as The European Medicines Agency (EMA), Food and Drug Authority (USFDA) and World Health Organization (WHO) have very stringent policies for approval of a biosimilar drug. The EMA led the way internationally in 2004 by introducing the regulatory framework which includes product specific guidelines. In the year 2010 EMA also introduced draft guidelines for biosimilar monoclonal antibiotics. The various guidelines include:

Guideline on similar biological medicinal products which came into effect in October 2005.

Guideline on similar biological medicinal products containing biotechnology derived product as active substance which came into effect in June 2006.

Guideline on similar biological medicinal products containing biotechnology derived proteins as active substance; non clinical and clinical issues which came into effect in June 2006.

Guideline on immunogenicity assessment of biotechnology derived therapeutic proteins which came into effect on April 2008.

Various annexures to this were added to focus on Recombinant Somatotropin, Recombinant Human insulin, Recombinant Granulocyte-Colony-Stimulating factor, Recombinant Erythropoietin, all of which came into effect in June 2006.These guidelines, in principle could apply to all biologicals. However, in practice it will mostly be applicable to the product that can show similarity through characterization and non clinical/clinical studies and contain well characterized therapeutic protein as an active substance. The quality evaluation includes manufacturing process, comparability and stability. Clinical evaluation includes pharmacokinetic pharmacodynamic and efficacy, safety immunogenicity. The efficacy data are extrapolated to other indications.

The way ahead
India being fore front in biotechnology, is in a unique position to offer cost effective biosimilars as like in chemical-based small molecules. The corporate greed of MNCs has made the biomedicines so expensive, that even the insurance companies offering coverage for health had a fear of going  bankrupt. Hence many drugs are not affordable This has made the governments across the globe to encourage the manufacture of biosimilars.

As biologic drugs have proven their mettle in the field of health sciences, one need to put a thought as to what more use can a biosimilar be brought to. They are already being used to treat various life threatening situations and it can be said without  doubt that this is the drug of the future. There lies a long path of research and development for biosimilars in the area of science in the coming years.