The US Food and Drug Administration (FDA) on Tuesday released a warning letter sent 3 April to Mylan Pharmaceuticals for its Nashik, India-based manufacturing site, which FDA said does not have a functioning quality system.
"Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture," FDA said following a nine-day inspection in September 2016.
The manufacturing site is important for supplying low- and middle-income countries (LMICs) with antiretroviral drugs for the treatment of HIV. According to the Financial Times, Mylan produces over half of all antiretrovirals for LMICs.
Mylan told Focus in a statement: “Mylan received a warning letter with two observations
from the U.S. Food and Drug Administration (FDA) and we are working closely
with FDA to respond to and address the issues raised in the letter as
comprehensively and expeditiously as possible.”
The company also noted that production
at the site "continues uninterrupted and at this time we do
not anticipate any supply issues related to any products currently being
manufactured at the site" as the Nashik site is in good standing with other global regulators,
including UK's MHRA, which inspected the site following FDA and issued a GMP
"Mylan has nine
independent sites, including Nashik, engaged in the production and supply of
ARVs, and these multiple redundancies help ensure that
we can maintain continuous supply," the spokesperson added.
The agency’s inspectors found that the site failed to monitor and investigate error signals generated by its computerized systems used for high performance liquid chromatography and gas chromatography.
"These signals indicated the loss or deletion of original CGMP [current good manufacturing practice] analytical data," the warning letter says.
FDA notes that Mylan attributed "numerous incidents to power interruptions, connectivity problems (disconnection of the Ethernet or power cord), and instrument malfunctions," but could not explain why these events occurred with frequency, and did not undertake a comprehensive investigation into the problem or seek to correct it and prevent its recurrence.
A similar issue cropped up at Mylan’s Bangalore facility, where FDA inspectors said, "Original raw data is recorded in marker on the surface of the laminated sheets. The marker can be erased."
And in this latest warning letter, FDA cautions that Mylan has not identified trends in its out-of-specification (OOS) investigations, which is a repeat observation from a March 2015 inspection.
"Because your laboratory investigations frequently invalidate initial failures without cause, your laboratory trending excludes a large proportion of data that would otherwise alert you to problems in your laboratory system," FDA said, noting that from 1 January to 30 June 2016, Mylan invalidated 101 out of 139 (about 72%) initial OOS assay results without sufficient investigation to determine the root cause.
In response to the warning letter, FDA is asking, among other things, for Mylan to conduct and provide the results of a trend analysis of all OOS results that includes both "confirmed" root causes and the initial OOS results that were previously excluded as invalid without assignable root causes.
Article updated with comment from Mylan.