Some industry observers are surprised that ‘significant violations’ of this nature have not warranted an import alert or ban. Is the US regulator giving the Mylan management the benefit of the doubt?
Like any highly competitive sector, most employees in the pharma industry in India are chained to key performance indicators but there is growing realisation that KPIs should make way for KBIs: key behavioural indicators. Mylan Laboratories’ August 6 warning letter (WL) from the US FDA, concerning inspections at three of its sites in Bangalore, paint a picture of a work force unaware or unmindful of how they are expected to execute cGMP or ISO 5/6 procedures. Worse, the WL notes that some of these violations also featured in previous WLs over a period of almost two years, leading the US FDA to conclude that they were ‘recurrent and long-standing.’
The US FDA accepted that the three sites haven’t been with Mylan long: they were acquired by the US-based MNC as the Agila Specialities injectables subsidiary from Strides Arcolab in December 2013. But they also point out that Mylan was well aware of these violations when it acquired them. A change in ownership does not appear to have made too much of a difference, in spite of Mylan CEO Heather Bresch’s claim that they “have been taking extensive action to integrate the Agila business into Mylan’s One Quality Standard, and to ensure our leading position as a high quality, reliable source of injectables for the long term. … We have been and will continue to work diligently to address all of the FDA’s observations and have made important progress.”
Clearly, the US FDA remains unimpressed. For example, at the first site, referred to as ‘Mylan Laboratories Limited OTL (Onco Therapies Limited)’, the inspectors observed operators using torn gloves and frayed/torn gowns in the aseptic filling areas, during critical interventions, noting that these are a ‘direct risk to product sterility.’
Some cGMP violation practices noted in the US FDA’s WL dated September 9, 2013 reappear in the most recent WL. For instance, both letters mention inadequacy in process simulation (media fill practices and procedures) studies, environmental monitoring systems, controls of computer-based master production and control records at the second site, referred to as the Agila Specialities’ formulation facility. The US FDA thus concludes that ‘several violations are recurrent and long-standing.’
Similarly, commenting on observations at the third facility, the Agila Specialities sterile products division, the WL says that a previous investigation into discoloration was ‘inadequate’, and that ‘enhanced detection (of discoloration) on its own does not resolve the root cause of the problem.’
The agency’s comments on operator movements are also damning from a GMP point of view. Operators involved in the set-up and filling of batches were not ‘slow and deliberate …(inspectors) often saw operators bump into each other during filling operations.’ Once again, this seems to be a recurrent problem as the August 2015 WL mentions that the firm was previously cited for ‘inadequate ISO 5 behaviours and procedures during the August 2013 inspection.’
Some industry observers are surprised that ‘significant violations’ of this nature have not warranted an import alert or ban. Is the US regulator giving the Mylan management the benefit of the doubt? To be fair, Mylan has voluntarily recalled batches from the OTL facility in March and April this year, when ‘foreign particulate matter’ were discovered in certain products. This was part of a product quality assessment protocol conducted in response to the previous US FDA inspection. But it is telling that this manufacturing issue was not completely sorted out even by June and the recall had to be expanded to some more lots.
Mylan CEO Bresch has often been quoted as a staunch supporter of increased regulatory scrutiny, and was in fact one of the key advocates of The Generic Drug User Fee Act of 2012, under which pharma companies would fund US FDA inspections of overseas plants exporting to the US market. Her bet that regulatory compliance is Mylan’s differentiator could take some more time to play out in the India market. But if, nay, when it happens, it would make for an interesting case study, one that will help rebuild India’s reputation in the pharma fraternity in the long term.