Times of India
01 November 2010
By Shobha John

As a new generation of bio–pharmaceutical drugs are undergoing trials in India, experts are asking if there is regulation enough to protect patients should something go wrong. The question is urgent. Biopharmaceutical drugs are made using living systems such as micro–organisms, plants or animal cells. If unwittingly altered while being manufactured or administered, they can cause coronary heart disease, cancer and infertility. Bio–pharmaceuticals, which are very different from synthetic drugs that are made out of simple, well–defined chemical compounds, are increasingly being used to treat cancer, multiple sclerosis and kidney failure.

But India’s Drugs and Cosmetics Rules (DCR) don’t differentiate between chemical and bio–pharmaceutical drugs, says C M Gulhati, editor, Monthly Index of Medical Specialties (MIMS). If something went wrong with a bio–pharmaceutical, there would be little succour to be had from regulations. Gulhati says it is not idle speculation. Two years ago, the US Food and Drug Administration (FDA) blacklisted and barred the import and sale of 31 synthetic medicines manufactured by Ranbaxy Laboratories at its Paonta Sahib and Dewas factories in India.

FDA inspectors had detected "multiple, serious deficiencies" in the manufacturing processes in violation of ‘good manufacturing practices.’ Gulhati says that part of the problem is the smaller trials now required before new drugs are accepted for general use. "Earlier, up to January 2005, Phase III (advanced) trials needed a minimum of 100 subjects in three to four centres. Now, this minimum has been removed on ‘friendly persuasion’ and ‘advice’ from drug companies, putting patients at risk."

Add to that the trend for pharmaceutical companies to outsource clinical trials to clinical research organizations that may not be accredited. "It is time India had a National Biotech Association of India to control all bio–products," says Dr Ranjit Roy Chaudhury, national professor of pharmacology, National Academy of Medical Sciences.

The Drugs and Cosmetics Rules require inspectors to visit every drug manufacturing plant at least once a year. But that doesn’t happen, says Gulhati. By 2016, many biopharmaceuticals will come off patent worldwide and India, Brazil and China sense a huge opportunity to manufacture and sell bio–similars, which reportedly have similar properties. In India alone, this market is estimated to touch $580 million by 2012.

Bio–similars would make health care more affordable because they cost one–third of bio–pharmaceuticals but manufacturing procedures have to be stringent. "Their safety and efficacy is highly dependent on the robustness and monitoring of quality aspects as even minor changes can affect the body," says Dr Anoop Misra, head of the department of diabetes and metabolic diseases, Fortis Hospitals. "Due to certain laxities, it’s easier for bio–similars to get into the Indian market than abroad."

M K Bhan, secretary, department of biotechnology, assures that the Biotech Regulation Authority Bill would come out with guidelines within a few months. "We are working with the Drug Controller of India for a one–window regime for drug companies." Misra says that some erythropoietins, a bio–similar that controls red blood cell production, have caused health problems abroad.Almost 500 patients given the biosimilar during trials in 1998–2003 reportedly developed lifethreatening anaemia.

Bio–similars in India
Erythropoetin
Shantha Biotechnics (Shanpoietin) LG Life Sciences India (LG Espogen Inj) Ranbaxy (Ceriton) Johnson & Johnson (Eprex) Emcure Pharma (Vintor for Nephrology/Epofer for Haematinics) Wockhardt (Wepox) Zydus Biogen (Zyrop) Hindustan Antibiotics (Hemax) Intas Pharmaceuticals (Epofit and Erykine)

Human Insulin
Wockhardt Biocon

Monoclonal antibodies
Dr Reddy (rituximab)
Source: Dr Anoop Misra