US FDA revokes ban on Lupin’s Mandideep facility; grants tentative approval for generic memantine (Namenda) pills

United States Food and Drug Administration has revoked the ban imposed on India’s Lupin Ltd’s manufacturing facility at Mandideep in Madhya Pradesh, the company announced.

The US FDA had conducted an inspection at Lupin’s manufacturing facility at Mandideep,  in October – November 2008.

The US FDA inspection found several deficiencies in the Good Manufacturing Standards  (GMP) standards set by the agency and issued Inspectional Observations also known as Form 483 listing all the deviations.

“The USFDA issued a warning letter for the cephalosporin (antibiotic compounds) facility of the Mandideep plant (in Madhya Pradesh). The facility was inspected in November 2008 for a routine GMP (good manufacturing practices) inspection. As a result, Lupin had received 15 procedural observations,” Lupin sated in a press release while announcing its fourth quarter results for the period 2008-09.

Lupin responded to the 483 observations informing the corrective course of action through a series of letters in the subsequent months. However, US FDA did not find Lupin’s responses satisfactory and issued a warning letter dated 7th May 2009, pointing out at least eight violations regarding the manufacturing process.

“The warning letter was issued to provide Lupin with an opportunity to submit additional documentation and explanation to a few selected observations where the FDA felt that the initial responses were inadequate and could be strengthened by further evidence of compliance with enhanced documentation practices,” the announcement said.

Lupin’s Mandideep facility makes both sterile and non-sterile pharmaceutical manufacturing and sterile active pharmaceutical manufacturing factories.

US FDA has cited Lupin’s failure to maintain production, control, or distribution records and failure to follow appropriate written procedures designed to prevent microbiological contamination of drug products to be sterile.

Lupin’s Mandideep facility also found to be lacking in controls to prevent contamination in defined areas regarding operations related to aseptic processing of products. The plant managers also failed to routinely calibrate, inspect, or check according to a written programme designed to assure proper performance of automatic, mechanical, or electronic systems.

The inspectors also found deficiencies in following written procedures describing the receipt, identification, storage, handling etc of drug product containers and closures and documentation of each significant step in the manufacture, processing and packing apart from their failure to investigate the failure of a batch or any of its components to meet any of its specifications.

Mandideep is Lupin’s only plant which manufactures its cephalosporin range of antibiotics, according to a Lupin presentation to its investors made in July 2008. Cephalosporins contribute about 45% of the company’s total revenue. Lupin sells 10 products and has one pending ANDA (abbreviated new drug application) from this facility.

In the ensuing seven months, Lupin made significant enhancements and took appropriate corrective actions.

Mandideep facility was re-inspected by the US FDA officilas in November 2009. Following the inspection, Lupin has received official communication from the US FDA on the satisfactory resolution of the Warning Letter issued earlier to its Mandideep site.

Lupin was able to satisfactorily address all of the concerns related to the Warning Letter and the site compliance status was found to be acceptable, the company said in an official release.

“With the recent inspections and satisfactory resolution of all pending concerns at Mandideep, all our facilities have now been inspected in the past year and have been found to be in good shape,” Nilesh Gupta, group president and executive director, Lupin has stated.

US FDA inspected two new sites of Lupin at Aurangabad (Liquids) & Indore (Oral Solids and Oral Contraceptives) in the last quarter.

Aurangabad liquid manufacturing facility was found acceptable with no 483’s and Indore was found acceptable with one 483 observation which was satisfactorily addressed before the close of the inspection.

These recent US FDA inspections bring Lupin a step closer to launching liquids and Oral contraceptives in US market.

Earlier, the UK MHRA and the Australian TGA had also conducted a joint inspection of the Mandideep facility and had found it acceptable.

Meanwhile, Lupin Pharmaceuticals, Inc, the U.S subsidiary of Lupin Ltd has received the tentative approval for the company’s Abbreviated New Drug Application (ANDA) for its memantine hydrochloride tablets, 5mg and 10mg from US FDA.

Lupin’s memantine HCl tablets are AB-rated to Namenda (Forest Labs) tablets indicated for the treatment of moderate to severe dementia of the Alzheimer’s type.

Namenda had annual sales of approximately $1.1 billion for the twelve months ended September 2009, based on IMS Health sales data.

In December, Lupin Ltd settled all ongoing Hatch-Waxman litigation relating to memantine tablets with Forest Laboratories, Inc.

As per the terms of the settlement, Lupin Ltd. will be licensed under the relevant patents and would be free to commercially launch its generic product in January, 2015, or earlier in certain circumstances.

Lupin had earlier filed a Paragraph IV certification to U.S. Patent No. 5,061,703, contesting that the patent was invalid or had not been infringed, resulting in the subsequent litigation with Forest.

India’s Sun Pharma, Wockhardt and Orchid Pharma are among the other generic makers who got tentative approvals for memantine generic pills.

Headquartered in Mumbai, India, Lupin Limited produces a wide range of quality, affordable generic and branded formulations and APIs for the developed and developing markets of the world.

Lupin has significant market share in key markets in the cardiovasculars (prils and statins), diabetology, asthma, pediatrics, CNS, GI, anti-infectives and NSAIDs therapy segments, not to mention global leadership positions in the anti-TB and cephalosporins.

Lupin is considered to be one among the fastest growing top 10 generics players in the two largest pharmaceutical markets of the world – The U.S (ranked 9th by prescriptions & growing at 92 %) and Japan (ranked 7th and growing at 23%).

Lupin is also the fastest growing, top 5 pharmaceutical players in India (ORG IMS – March 2009) and the fastest growing Generic player in South Africa (ranked 6th and growing at over 30 % YoY – IMS)

For the financial year ended March 2009, Lupin’s Consolidated Revenues and Profit after Tax were Rs.39,145 million (US$ 851 million) and Rs.5015 million (US$ 109 million) respectively.