In the line of fire

Written by Sudhir Chowdhary | Updated: Dec 8 2008, 06:34am hrs
Its been seen as a double-whammy for the Indian pharmaceuticals industry. The US drug regulator, US Food and Drug Administration (USFDA) has shown no let up in censoring Indian pharmaceutical companies for shortcomings in their manufacturing operationsLupin is the latest to draw the American drug regulators ire after Sun Pharmaceuticals and Ranbaxy. It is now the turn of our own drug regulator, Central Drugs and Standard Control Organisation, to flex its muscles. In a recent move, the drug regulatory body has withdrawn the licenses given to 17 domestic pharmaceutical companies from producing generic versions of an anti-obesity drug in India, after reports by the European drug regulatory authorityEuropean Medicines Agencyof severe side effects.

With the safety of public health foremost in the minds, the move by Indian drug regulator to stop the manufacturing of the anti-obesity drug in the country seems to have to have gone down well in industry circles. However, it is the role donned by the American drug regulator that is causing a lot of heart-burn in the domestic pharmaceutical industry.

Indian drug companies are deliberately being singled out and capital punishment reserved especially for them, says an industry insider. Little wonder, their brushes with the drug regulatorsin India as well as overseasis something they would like to forget as early as possible.

India has about 75 USFDA approved plants and is one of the most dominant players in global exports of generic formulation and active pharmaceutical ingredients. In the Asian region, China comes a distant second with 22 FDA plants, followed by Taiwan with 10 plants. With various incentives given for generic prescription in the US on a significant upswing, USFDA is in an overdrive to ensure that safe medicines enter the American healthcare system. The American drug regulator is responsible for the safety of foods, drugs and other health-related products sold in the US. Thus we need to be prepared for more USFDA inspections in the country. We could also see some more Indian drug companies being hauled up in future if they are not complying with their regulatory norms for a drugs quality, safety and efficacy, says Avesthagen founder Villoo Morawala-Patell.

It seems the woes of Indian drug companies are far from over. When contacted, Rita Chappelle from the office of public affairs, USFDA stressed, FDA will continue to do its job of protecting and promoting the publics health through inspections to ensure compliance with US current good manufacturing practices.

On the record, it is understandable that few Indian drug companies would like to speak out against the USFDA. The US, in spite of the intense competitiveness and pricing pressures, remains the largest generic market in the world.

Estimated at $29.6 billion in 2006, it is projected to rise to $52.3 billion by 2011. Besides, over $47 billion worth of drugs are expected to go off-patent over the next three years, representing a rich pipeline for Indian generic manufacturers. Thus, business interests deter Indian drug companies from publicly airing their grievances for fear of antagonising the American drug regulator. No wonder, the official line emanating from them is this: We would like to work closely with USFDA to ensure that standard operating procedures with regard to manufacturing are strictly addressed.

But how can such cases be avoided

After all, isnt a question mark dangling on the manufacturing capabilities of our pharmaceutical companies By remaining fully FDA compliant, comes the standard yet predictable reply from a Sun Pharmaceuticals spokesperson. We have to make efforts to fully comprehend FDA requirements, and then work towards remaining in line or ahead of the improving FDA standards, he adds.

But scratch the surface and advocates in the Indian pharmaceutical industry start pointing fingersof course, off the record. Who wants to upset the USFDA Nobody can afford to take on the regulator in India as well as overseas. Besides, our own regulatory infrastructure and framework is not adequate, leave aside the fact that they could talk on our behalf and put up a strong case for us, comes the cryptic reply from an industry insider. While the likes of Wyeth, GlaxoSmithKline, Pfizer and Astra Zeneca too get warning letters issued by the FDA, stark reality is only the likes of Ranbaxy, Sun Pharmaceuticals and Lupin are deliberately singled out for harsh punishment, comes the argument from another anguished source.

Before we dwell into the measures needed to overhaul the countrys drug regulatory mechanism, heres a quick look as to how and why the American drug regulator cracked the whip on Indian pharmaceutical companies. Ranbaxy was the first to be ticked off with warning letters issued by the USFDA on manufacturing deficiencies at its two production facilities in the country. Specifically, the FDA inspections revealed significant deviations from US current good manufacturing practice (CGMP) regulations in the manufacture of finished drug products. The only saving grace: nowhere did FDAs testing and review led the agency to question the safety or effectiveness of Ranbaxys drugs.

Ranbaxy was soon followed by Sun Pharmaceuticals to come under the American drug regulators scanner. Here again, a warning letter was issued to Caraco Pharmaceuticals, a US subsidiary of Sun Pharma, over the companys manufacturing facility in Detroit. The malpractice cited by USFDA stated that inadequate and untimely investigation by the quality control unit was conducted in certain incidents, contrary to Caraco Pharmaceuticals standard operating procedures. In our understanding, FDA has raised issues on which it was not satisfied with Caracos past response and actions, says the Sun Pharmaceuticals spokesperson.

Lupin is the latest to come under the USFDAs radar for manufacturing shortcomings at its Mandideep production facility in Madhya Pradesh. Here too, USFDA inspectors are believed to have detected several deficiencies which deviate from the US drug manufacturing standards.

Indian companies who market drugs in the US have to get plants approved from the FDA. Typically, USFDA inspectors or investigators undertake a thorough inspectionmonitoring, auditing and documentingof the manufacturing facilities of drug companies exporting medicines to the US. Predictably, they are on the lookout for any deviations from good manufacturing practices to ensure product quality, safety and efficacy, as specified by the USFDA. Once detected, a warning letter is issued to the drug company to ensure necessary compliance to the US standards. A harsher punishment could invite a complete ban on drug shipments to the US.

The USFDA regularly issues warning letters to drug companies. They might have detected some deviations from the US current good manufacturing practice at the manufacturing facilities of Indian drug companies. They are only doing their job and the only solution for Indian drug companies is regulatory compliance, says Sujay Shetty, associate director (pharmaceuticals and life science practice), PricewaterhouseCoopers.

Industry insiders are of the view that there might have been some shortcomings in the manufacturing of drugs by Indian companies, especially for the US market, thereby attracting FDAs attention. Nevertheless, there are a couple of developments in the making that could life simpler for Indian drug companies.

The first is the move by USFDA to have a direct presence in the country, starting with an office in New Delhi later this month and Mumbai thereafter. There are plans to post 10 FDA officials in India. The goal of the new offices would be to ensure safety standards and quality controls in drugs at the point of manufacture. Probably there would be frequent inspections and we might have fewer instances of domestic drug companies being hauled up by the FDA, stresses Villoo Patell.

The second yet eagerly awaited move is the planned revamp of the countrys drug regulatory framework. The move by the government to have in place a Central Drugs Authority for India on the lines of the USFDA seems to be gaining momentum. A health ministry official informs, Plans for a Central Drugs Authority with sweeping powers over the regulation and control of medicines at the national level will soon be a reality. The Drugs and Cosmetics (Amendment) Bill, 2007, has already been introduced in the Parliament. The parliamentary standing committee on health and family welfare has suggested some changes and we are working on them.

A broad consensus is emerging in the industry circles that there is an equivocal need to have in place a single Central agency like

Central Drugs Authority for better coordination between the State and Central authorities. Only then would the overall objective of product quality, safety and efficacy remain unblemished, informs Shetty. Probably the same level of coordination with global regulatory agencies like the USFDA or European Medicines Agency could also save Indian drug companies from the flak they have been getting in recent times.