This article appeared in the November 2008 edition of INNsight

The FDA gets tough

 You might recall that there was a dreadful scandal in the US a few months ago when contaminated Heparin from China that was sold by Baxter was found to have caused several deaths. The contentious aspect of it all was that that the FDA had not only inspected the wrong plant where the raw material was made, but then went on to compound that error by approving the plant. It was not actually the plant that was supplying Baxter.

 At the time, the FDA was strongly criticised from several different quarters for its incompetence in overseeing GMP compliance in foreign manufacturers in general. In this particular case, the organisation was further embarrassed when it emerged that the FDA confused the application for approval of the company manufacturing the raw heparin with a company with a similar name whom they had previously checked and approved.

 So now, they want to prove that they are on the ball and still in control and generic companies have been hit by the resulting fallout. So far, the companies affected are Ranbaxy, Sandoz and Sun.

 It started in July of this year when the US Department of Justice filed papers in a Maryland federal court alleging that Ranbaxy forged parts of the paperwork that it had used to support ANDAs that it had filed for various generics. More specifically, the FDA was accusing Ranbaxy of cheating on its biostudies and plant records amongst other things.

 Apart from the dismay that this would have caused to the company at any time, it must have felt like a bucket of cold water being thrown over them while they were still basking in the warm glow of having just announced their engagement to be married to Daiichi-Sankyo. While the FDA did not demand that Ranbaxy withdraw products from the market, it did prohibit any further imports when it issued Warning Letters in September.

 In its press release, the FDA stated: “

“The Warning Letters identify the agency's concerns about deviations from U.S. current Good Manufacturing Practice (cGMP) requirements at Ranbaxy's manufacturing facilities in Dewas and Paonta Sahib (including the Batamandi unit), in India. Because of the extent and nature of the violations, FDA today issued an Import Alert, under which U.S. officials may detain at the U.S. border, any active pharmaceutical ingredients (API) (the primary therapeutic component of a finished drug product) and both sterile and non-sterile finished drug products manufactured at these Ranbaxy facilities and offered for import into the United States” (Full text is available at http://www.fda.gov/bbs/topics/NEWS/2008/NEW01886.html)

 Then in August, the FDA got tough with Sandoz. It sent a warning letter regarding the manufacturing process for their Metoprolol Succinate generic version of the AZ product Toprol XL. The FDA was worried about inadequate validation of the manufacturing process and expressed concern that this might be reflected in the manufacturing of other Sandoz generics. It stated:

"We are also concerned that the problems noted in the metoprolol validations could be indicative of problems and poor decisions made with other product validations,"

 Now in November, the FDA has found another target in the shape of the Indian company Sun. The letter related to an inspection of its US subsidiary Caraco back in May and concerned certain quality control issues that the FDA felt had not been addressed following its visit.

 Interestingly, the Indian Economic Times newspaper report on the matter included the following:

“A section of the domestic industry finds a design in Indian companies being penalised in the US market. Recently, USFDA had banned drugs which were produced at Ranbaxy’s two manufacturing plants in India. “It looks like the US is targeting Indian companies. Other Indian companies may face similar problems in the future,” an industry analyst said.”

 They are possibly correct in saying that other Indian companies may face similar problems, but then so will any other companies, whatever their origin, if they do not adhere to GMP guidelines. Proof of this comes in the fact that the FDA also targeted Sandoz, which is definitely not an Indian company.

 While the Indian companies might be developing a persecution complex, the increased stringency of the FDA is a welcome development, whatever its target. After the Heparin fiasco, the FDA needs to be seen to be doing its job and the new attitude can only serve to increase confidence in the quality of their supervision and the quality of the generic products that they monitor.

  If you have any comments or questions,

Please feel free to contact me

peter@interpharm-consultancy.co.uk

www.interpharm-consultancy.co.uk