The action is being taken against Yag Mag, which supplies APIs such as platelet aggregation inhibitor clopidogrel bisulphate. The API is used to manufacture generic versions of Plavix, the blockbuster blood thinner.

FDA issued its 12 September 2011 warning letter due to good manufacturing practice (GMP) violations identified at the company’s site in Hyderabad. According to FDA, the site ‘was not adequately designed to facilitate cleaning and minimise the potential for contamination.’ During inspections there was evidence of ‘residues and corrosion on processing equipment’, ‘poorly identified and leaking piping’, problems with ‘flooding’ and ‘standing water’ and ‘unsanitary restroom facilities’.

There was a ‘failure to have appropriate procedures or practices in place to prevent cross-contamination.’ There was also a ‘failure to prepare, review and approve documents for making APIs in accordance with written procedures.’ Additionally, traceability of the finished APIs was highlighted as a problem due to the fact that completed batches were not properly identified.

FDA recommend that Yag Mag ‘conduct a complete and extensive evaluation’ of their quality and manufacturing controls ‘to ensure that all APIs manufactured at the facility meet the quality and purity characteristics they purport to possess.’ The agency adds that the company’s GMP compliance issues ‘will require significant remediation and substantial investment of time and resources.’ The areas needing global attention include, but are not limited to, facility improvements, process validation, complete and accurate manufacturing procedures, training programmes, quality unit effectiveness, and an overall effective quality system.

FDA warns that until the company complies with its GMP requirements it may withhold approval of any new applications or supplements listing the firm as an API manufacturer and that products manufactured by the company will be refused entry into the US.

This could have a knock-on effect on generics manufacturers using APIs from Yag Mag, especially regarding generic versions of Plavix (clopidogrel bisulphate), which comes off patent in the US in November 2011. There is much at stake. Plavix is the world’s second-biggest selling drug, and had 2010 sales of US$6.7 billion for Bristol-Myers Squibb and over 2 billion for sanofi-aventis.

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