The operational issues between the US drug regulator and Ranbaxy Laboratories do not seem to have been limited to its Indian facilities and the term of its former promoters.
The company was indicted for violations at one of its US facilities in 2009, even after Daiichi Sankyo took over as majority shareholder in 2008. In 2009, even as the company received information of contamination in some of its drug batches, it failed to give the required reports to the Food and Drugs Administration (FDA), the US regulator. This has been alleged in a complaint for a permanent injunction, filed by the US Department of Justice and the FDA. According to the complaint, filed in a district court at Maryland on January 25, 2012, Ranbaxy’s US subsidiary, Ohm Laboratories, failed to inform the regulator about at least two failures of drug batches within the time specified. The relevant US law, the Food, Drugs and Cosmetics Act (FDCA), requires drug manufacturers to notify FDA within three working days after receiving any information concerning a failure of distributed batches. This notification is called a ‘field alert report’.
The FDA discovered the violations during its inspection of the Gloversville facility in 2009, one of the facilities under Ohm. “(The) inspection revealed Ranbaxy failed to submit at least two field alert reports within three working days of receiving the information concerning a failure of one or more distributed batches of a drug to meet the specifications established for it in its drug application,” the complaint said.
Ohm got a complaint on March 23, 2009, on the presence of particles in metformin oral solution, confirmed on April 1. “This event was not reported as a field alert report,” the complaint said. Through investigation it was concluded that the particles could be attributed to a worn nozzle seal on the filling machine. Again, in a separate incident, Ohm became aware of “an out-of-specification result for an antioxidant at the 24-month stability point on March 17, 2009, for sertraline hydrochloride oral concentrate”, but did not file a field alert report until March 26. While metformin is prescribed for a certain treatment of diabetes, sertraline is used in treatment of depression.
The complaint noted that FDA, during its earlier inspection of Ranbaxy’s corporate headquarters in Princeton, New Jersey, in December 2007, had also documented similar delays in drug annual reports for medicines manufactured at the company’s Paonta Sahib unit in Himachal. “The inspection further revealed that Ranbaxy submitted 115 late (past the 60-day window after the approval date anniversary) annual reports between 2005 and 2007,” it said.
FDA, during its inspection of Ohm’s Gloversville facility between July 13 and August 12, 2009, also found the unit was making and distributing prescription drug Opium Tincture USP (Deodorised, 10 mg/mL), without proper approval. Subsequently, the FDA had issued a warning letter to the US subsidiary in December 2009. Unlike FDA’s standard warning letters, which refer to the particular unit in question, this one asked the company for a comprehensive assessment of its global manufacturing operations. “We note that the CGMP (Current Good Manufacturing Practice) violations listed include similar violations to those cited in the June 2006 and September 2008 warning letters issued to other Ranbaxy Laborataries facilities. Ranbaxy’s attempts to make global corrections after past regulatory actions by the FDA have been inadequate. We remind you that Ranbaxy is responsible for ensuring that all drug manufacturing operations comply with US requirements, including the CGMP. FDA expects Ranbaxy immediately to undertake a comprehensive assessment of its global manufacturing operations to ensure all sites manufacturing drugs for the US market conform to US requirements,” the warning letter had said. In 2011, the Ranbaxy management decided to close the Gloversville unit. Then Managing Director Arun Sawhney had said it was operating at a “sub-optimal level”.
Ranbaxy says its manufacturing facilities in India and other parts of the world are routinely inspected by leading global regulatory agencies. Since 2009, the company has undergone at least 175 regulatory agency inspections across its global facilities, it added.
* Ranbaxy’s US subsidiary Ohm Laboratories failed to report to the US Food and Drug Administration (FDA) on time in March 2009 on a complaint about particles in metformin oral solution
* In March 2009 again, FDA said, Ohm didn’t report timely on “an out-of-specification result for an antioxidant for sertraline hydrochloride oral concentrate”
* In its inspection of Ohm’s Gloverville facility in July-August 2009, FDA found the unit was making and distributing prescription drug Opium Tincture USP (Deodorised-10 mg/mL) without proper approval