Lupin Limited has earned the unique distinction in getting an approval from the US FDA for its Mandideep multi-prils bulk manufacturing facility without actually undergoing an inspection. The regulator was so confident that a deemed approval was given to the facility for the manufacture of lisinopril which was commissioned in April 2001, according to a company source. The date of approval was not available.
Mandideep, an industrial growth centre spread over 1400 hectares, is located 23 kms away from Bhopal, the capital of Madhya Pradesh. The plant, a multi-purpose one, has gone through several capacity enhancements. The company is already exporting the active pharmaceutical ingredient lisinopril to Europe and Canada.
Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, a family of drugs used to treat high blood pressure and some types of heart failure. Lisinopril is also used in some cases to improve survival after a heart attack. The annual sales for the combined branded markets of lisinopril and lisinopril hydrochlorothiazide (HCTZ) is approximately $1.64 billion. The patent for lisinopril expired in June 2002. Lisinopril has been sold under two brands in the US market, of which Zestril, a registered trademark of Astra Zeneca UK Ltd, sales accounted for $0.66 billion.
Lupin's rifampicin plant is one among three plants in the world to receive US FDA certification and the only one to get it outside Europe. The other plants are based in Ankleshwar (Gujarat) and Aurangabad and Tarapur (both in Maharashtra). These facilities have been approved by the USFDA and UKMCA, according to the company.
"Such is the faith that the US FDA has in us that they have granted approval to the plant without conducting an inspection," Lupin Chairman and Managing Director Desh Bandhu Gupta declared at the 20th annual general meeting of the company in Mumbai on September 2, 2002.
When contacted a US FDA official said, "Our records show that the Lupin manufacturing facility in Mandideep has been inspected by FDA as recently as 2000. The result of that inspection was a finding that it was acceptable for cGMP.
According to the US FDA official, they reported the facility to the CDER review division in 2001 for cGMP determination while evaluating an application for a lisinopril tablet product.
Based on the satisfactory outcome of the 2000 inspection, the interval of less than 2 years, the ordinary nature of the process of the product lisinopril, and no adverse information about the facility, it was declared as acceptable for cGMP in the manufacture of lisinopril.
"This is a routine procedure for us within our risk assessment strategy. We do not give acceptable for cGMP determinations based on "good faith", the US FDA official added.
According to an industry source, such approvals are not given for plants. But if the firm has a long history of good quality dossier submissions- product submissions without queries -- then further product dossier clearance may not require a trip from the US regulator's inspectors.
The company has four plants and is in the process of setting up one for the production of cardiovascular drugs. This plant will be commissioned this financial year.
Lupin is a leader in anti-TB drugs with a market share of 40.9 per cent. It is one of the leading global manufacturers of Rifampicin (through the complex fermentation process) with an Indian market share of 45 per cent.