In one of the more eye-opening warning letters issued recently by the Food and Drug Administration, an Indian drug maker was rebuked for failing to correct serious quality-control problems, some of which apparently management knew about thanks to an anonymous email.
Moreover, the letter to Ipca Laboratories documented a laundry list of manufacturing issues at three different plants, which either make finished pharmaceutical products or active ingredients that are supplied to many other drug makers. Among its domestic customers are Merck, Pfizer (PFE), and AstraZeneca (AZN).
And unlike other agency warnings, the Jan. 29 missive that the FDA sent to Ipca also included at least two instances where company employees acknowledged either that certain problems were “critical” or admitted that falsifications took place, according to the letter.
“You typically don’t see warning letters with email excerpts and noting how employees admitted to lying,” said Vince Sunjea, chief executive of TwoFour Insight Group, a consulting firm that works with Indian drug makers.
At one plant, for instance, FDA inspectors found Ipca relied on incomplete records to evaluate drug quality. More specifically, Ipca employees deleted analytical data, routinely retested samples without justification, and manipulated testing parameters to obtain passing results. The quality assurance manager conceded the magnitude of the problems.
Making matters worse, an anonymous email sent on Aug. 5, 2013, which was nine months before an FDA inspection, alerted Ipca management. “[T]here is no control of data in the department … Falsification is going on … Take action as early as possible,” the email warned, according to the FDA letter.
Meanwhile, an employee admitted that he had manipulated processes used during certain testing. A supervisor admitted to directing an employee to completing logbooks after the fact. And a microbiologist admitted that microbial sampling was falsified.
Although Ipca management maintained that it investigated various problems, the FDA wrote that “in the limited time available during the inspection, our investigator found serious deficiencies and questionable data management practices that your own four-month investigation did not identify.”
At another plant, FDA inspectors found lab controls failed to establish scientifically sound test procedures to ensure products conformed to standards of identity, strength, quality, and purity. At the third plant, the agency said Ipca failed to ensure lab records included complete data derived from all tests necessary to assure compliance with established specifications and standards.
We asked Ipca for comment and will update you accordingly.
As we have noted previously, this is the latest instance in which the FDA has scolded an Indian drug maker or ingredients supplier for quality control problems. Over the past several years, there has been mounting concern over the safety of the pharmaceutical supply chain after the agency cited several companies for production failures.
The most notable example involved Ranbaxy, which is now part of Sun Pharmaceuticals and last year paid a $500 million fine to US authorities as part of a settlement. The deal included pleading guilty to two charges of violating drug safety laws that, for example, involved manipulating data. Several companies have also been hit with import alerts in which the FDA bans products made at a facility.
Such ongoing issues prompted several congressional lawmakers late last year to ask the US Government Accountability Office to review FDA oversight of foreign manufacturing plants. As of December, the FDA had three full-time employees based in its India office performing inspections of medicines and medical products. However, US-based inspectors often travel to India to conduct inspections.
Although the FDA is trying a new approach in which inspectors also note where Indian drug makers exceed expectations, the scrutiny has upset Indian drug makers. They complain the FDA has singled them out for especially tough inspections, which occur too frequently and haphazardly, depriving them of the opportunity to make substantive changes.