NEW DELHI: The US drug regulator's inspection teams had late last year found deviations from its prescribed manufacturing practices at two RanbaxyBSE -1.38 % plants, a development that shows the Indian drugmaker's US regulatory woes continue despite attempts to implement preventive and corrective actions at its manufacturing facilities.
The US Food and Drug Administration(FDA) had in December 2012 written to the company identifying eight violations in the manufacturing practices at its main API (active pharmaceutical ingredient) unit at Toansa in Punjab. The Toansa plant is crucial for Ranbaxy as about 70% of APIs used in its formulations are said to be manufactured there.
In September 2012, the FDA investigators had identified 11 deviations at Ranbaxy's newest facility at the Mohali SEZ. These observations were communicated by the regulator to the company through what is called 'Form 483'. This is a form used by FDA to document and communicate concerns discovered during inspections, but it does not mean the regulator has concluded that the plants are guilty of manufacturing malpractices or has banned products from them.
Companies are given an opportunity to respond and it is only if its concerns are not adequately addressed does the FDA proceed to the next step of issuing a warning letter and subsequently an import ban. ET has reviewed Form 483 for both the Toansa and Mohali units.
A Ranbaxy spokesman said "all 483s have been satisfactorily responded by the company", but declined to comment specifically on whether the company had addressed all the concerns to the satisfaction of FDA and if the matter stood resolved. Some analysts said delays in some product launches in the US could be the outcome of these adverse observations, though this could not be independently verified.
Three of Ranbaxy's India-based plants at Paonta Sahib, Batamandi and Dewas are under import alert and the company cannot export to the US from them. Ranbaxy signed a consent decree with US FDA in December 2011, pledging to take corrective action and improve its good manufacturing practices. A few months ago, it pleaded guilty to charges of falsifying data and marketing 'adulterated drugs'in the US, and agreed to pay a $500-million penalty.
In a letter addressed to TL Easwar, senior vice-president, API manufacturing, US FDA has complained that at the Toansa API plant, equipment maintenance programs were deficient..(and)..sampling plans and procedures were not scientifically sound and appropriate to ensure that raw materials and APIs conformed to established standards of quality and/or purity. "Specifically, there is no evidence that samples taken according to sampling SOPs (standard operating procedures) are representative of the batch of material from which they are taken," said Form 483.
Form 483 in the case of the Mohali plant, addressed to Naresh Gaur, said: "Adequate exhaust systems or other systems to control contaminants are lacking in areas where air contamination occurs during production," adding that "investigation conducted by your firm from January 2011 through present do not always determine a root cause, do not have adequate data to support the root cause, and/or lack adequate corrective actions and/or follow-up".
A drug industry quality expert who reviewed these Form 483s for ET said these observations appeared to be serious.
"As a general policy, FDA does not comment about inspections that may or may not be ongoing, on inspectional findings, or on possible subsequent regulatory actions," a US FDA spokesperson said.
Daiichi Sankyo-owned Ranbaxy has not yet been able to launch in the US market a generic version of Novartis' blockbuster hypertension drug Diovan, for which it holds a six-month exclusivity and whose scheduled date of launch was last September.
The company has not specified any reasons for the delay. Ranbaxy CEO Arun Sawhney in a recent interview to ET said the exclusivity opportunity was still safe with the company and it was awaiting US FDA's approval for the product.
Analysts are now looking forward to the fate of Ranbaxy's launch of the generic version of Valycte and Nexium, for which, too, the company has 180-days exclusivities. "The launch of the generic Valycte is scheduled for September. It would be interesting to see whether the company is able to launch the product on time and whether the filing has been made from the Mohali facility," said an analyst who did not wish to be named.