Data available from the US Food and Drug Administration (FDA) website reveal that the regulator has issued about 200 warning letters since January this year to various manufacturers, both in the US and outside, at an average of about 30-35 letters every month.

These are mainly for deviating from manufacturing and quality assurance systems and for selling adulterated or misbranded products, the same charges levelled against Ranbaxy during the inspection of its Paonta Sahib facility in February 2006.

Interestingly, records reveal that only three Indian drug companies have been served with warning letters � Ranbaxy and Wockhardt in 2006 and Granules India [Get Quote] in 2001 � compared with numerous warnings to major drug makers.

Though Business Standard could not independently verify whether these companies have responded to the warnings of the regulator, sources said the companies might have responded as per the deadline for replies.

The US FDA website regularly posts responses on warning letters to the companies, but so far has not posted the feedback on most of the warnings issued this year.

Warning letters are issued by the US regulator to caution the company of punishments such as possible suspension of production at the site or withdrawal of approvals, in the case of failure to meet recommended standards.

In addition, pending new drug applications, abbreviated new drug application, or export certificate requests submitted by the company may not be approved until the violations are corrected, said sources.

"Normally, the regulator will inspect the manufacturing site before giving approval, and will convey its inspectional observations in Form 483, issued at the closeout of the inspection detailing the problems in manufacturing and quality assurance systems. If the violations are not rectified and are serious, then only the regulator will issue a warning letter," elaborated a senior regulatory expert with a major drug company.

"The US regulator maintains stringent quality standards and employ over 8,000 professionals. In comparison, our regulatory mechanism has just a few hundred people," he added.

The US is the largest drug market in the world, which accounts for almost half of the total annual global drug sales of over $700 billion.

A warning issued to the US-based Merck on April 28 this year shows FDA investigations between November 26, 2007, and January 17, 2008, regarding significant deviations from the current good manufacturing practice (CGMP) and lack of maintenance of data in the manufacture of licensed biological vaccine products, bulk drug substances and drug components.

The drugs under scrutiny include some of its major products such as combination vaccine ProQuad, cancer vaccine Gardasil, Hepatitis A vaccine Vaqta, and Haemophilus and Hepatitis B Vaccine Comvax.

Novartis Vaccines and Diagnostics was issued a similar warning in January this year for discarding CGMP norms for its anti-rabies vaccine RabAvert and Diphtheria and Tetanus Toxoids Adsorbed concentrate made at a manufacturing site in Germany, following a site inspection in September last year.

US-based Pfizer, the largest drug maker, was pulled up by the regulator recently for airing a promotional video of its blockbuster erectile dysfunction drug Viagra, for misbranding the product and failure to disclose any risk information associated with the drug.

Drug major GlaxoSmithKline was warned by the regulator for releasing promotional material that misrepresented facts and overstated the efficacy of its blockbuster breast cancer drug Tykerb.

Swiss drug major Novartis also had received warning letters from the US FDA earlier for misrepresenting the safety and efficacy data of epilepsy drug Trilepta, Exelon capsules and oral solutions to treat dementia.

Earlier, GSK [Get Quote] had received another warning for failure to report clinical data, along with other data and information, on its anti-diabetic drug Avandia.

King Pharmaceuticals, another US drug manufacturer, was also served with a notice for false claims on efficacy of its pain drug Avinza.

On May 28, the regulator issued a warning to Cardinal Health, the largest drug distributor of drugs in the US, for not meeting the standards specified for manufacturing, related to selling an adulterated medical device, due to low quality standards maintained at its manufacturing facility.