Among import alerts or import bans issued by US FDA for more serious compliance issues, Indian sites constituted 30 percent, while China's share was 50 percent in 2017.
Root cause assessments and investigation failures have emerged as the leading source of regulatory non-compliance with Indian drug makers, replacing data integrity, according to a study by consulting firm McKinsey & Company.
McKinsey, which has studied the observations and warning letters issued over the last three years, found that around 28 percent of the warning letters and 483 observations that Indian companies received from US Food and Drug Administration (US FDA) in 2017 were related to root cause assessments.
Root cause assessment relates to failure to adequately investigate deviations, out of specification (OOS) results, invalidated OOS and customer complaints.
Data reliability and good documentation practices, together referred as data integrity, were major non-compliance issues two years ago, constituting around 41 percent of warning letters and 483 observations. But they have now reduced by half to around 21 percent, indicating considerable progress in strengthening data capturing systems.
The other major emerging source of non-compliance is laboratory controls, which includes failure to establish laboratory controls such as appropriate specifications, standards, sampling plans and failure to ensure that test procedures are scientifically sound.
“Regulatory expectations are evolving overtime,” said Vikas Bhadoria, Senior Partner at McKinsey & Company.
Earlier the USFDA was focusing on infrastructure-related deviations like leakages and cleanliness as Indian companies more or less addressed that they moved to data integrity. Now with data integrity concerns being addressed, the regulator is now looking for root cause assessments and investigating failures, Bhadoria said.
“This stuff around root cause analysis, problem solving, investigation capabilities, lab management systems all of them are to do with upgrading the quality management systems in the organization,” he added.
The efforts to raise overall quality standards has started to show – out of 118 warning letters received by non-US sites between 2014 and 2017, 33 percent were Indian plants, 32 percent were Chinese and the remaining were plants located in the rest of the world.
Indian sites constituted about 39 percent and 50 percent of warning letters issued to non-US sites in 2014 and 2015, respectively. But their share reduced to 29 percent in 2016 and 2017.
Among import alerts or import bans issued by US FDA for more serious compliance issues, Indian sites constituted 30 percent, while China's share was 50 percent in 2017.
India has 7 percent of the global US FDA-approved manufacturing sites. “We are at a place where we are tightening our quality systems, most sites are already in a very decent state of compliance,” Bhadoria said.
“It's a 4-5 year journey,” he added.
Six top Indian drug makers including Sun Pharma, Dr Reddy’s, Lupin, Cipla, Cadila Healthcare, and Torrent Pharma joined hands to establish the Indian Pharmaceutical Alliance (IPA) Quality forum 3 years ago, at a time when Indian drug makers were facing pressure as they struggled to keep up pace with expectations of US drug regulator. The IPA Quality Forum since then has been working with McKinsey to address quality issues.
