A surge in the number of FDA-issued data integrity violations to overseas drug manufacturers is prompting concerns about ramifications and conversations about solutions.

A recent PricewaterhouseCoopers (PwC) report stated the number of warning letters by regulators has risen from five in 2010-2012 to 24 in 2013-2015—and all but one were issued to facilities located outside of the U.S. “That, to me, is just an astonishing increase,” said Alexander Gaffney, PwC Senior Manager, Life Sciences and New Entrants, Health Research Institute, and lead author of the report.

Companies found to have data integrity issues could have their drug rejected or banned from being sold in the U.S. If the company has a drug pending approval, the FDA could refuse to approve it. Lawsuits could result if patients are harmed by a drug for which quality is disputed. “The ramifications of data integrity issues can not be overstated,” Gaffney said.

The FDA issues data integrity warning letters if companies are found to have falsified, altered or failed to protect essential quality data about how their drugs are made and tested. The situation raises serious concerns for global pharmaceutical companies that are moving facilities overseas or contracting with offshore partners.

“If those companies aren’t exercising good data integrity, it’s not just a problem for that contracting company, but a problem for the outsourcer as well. Your supply chain can be at substantial risk of losing access to your active pharmaceutical ingredient,” Gaffney pointed out. “It’s not necessarily your name on the warning letter, but at the end of the day it’s still your product that you wanted to ship, so it’s a business loss for you.”

In addition, the loss of reputation and exposure to legal action are enormous consequences, experts say. “It’s all about public health,” said Glen Potvin, senior director, Quality & Compliance Services at Quintiles and author of a 2015 report on data integrity risks, causes and solutions. “With pharmaceuticals, ultimately you’re relying on data. When you have a breakdown in the quality of that data, it’s a sign of a much bigger potential problem involving trust.”

Data integrity issues have always existed, but the FDA is now better equipped to uncover evidence of these problems. The FDA Safety and Innovation Act of 2012 expanded the FDA’s authority and provided substantial funding to increase inspections of foreign facilities.

Of the 29 data integrity violations from 2010 to 2015 identified in the PwC report, 18 were issued to companies in India, six in China and two in Italy. The two most common issues identified in the FDA warning letters were insufficient control over data changes and improper data maintenance.

Sam Venugopal, partner, Healthcare Industries Advisory at PwC and a coauthor of the report, said a major reason for data integrity problems overseas has much to do with culture. For example, growing foreign companies often employ workers who have never had a professional job before and may be the first in their family to have one.

“There’s a learning curve in conducting these operations under a quality system,” Venugopal explained. “Many of these individuals haven’t been in an environment where they’ve had to work under a mature quality system operated in a way that the FDA would expect. It leads to these issues where personnel, whether on purpose or inadvertently, make mistakes that would be categorized as data integrity violations.”

Added to this is the hierarchical nature of how many firms are structured, especially in India and China, and the element of fear if a mistake is made. “Say you have a young, inexperienced individual who makes a mistake on a batch record,” Venugopal said. “Raising the mistake to the boss is absolutely the right thing to do and how the quality system should operate. But rather than going to the boss and admitting the issue, they may go ahead and make a correction that could compromise data integrity.”

Cost pressures also come into play. According to the National Center for Policy Analysis, generic drugs now account for roughly 88% of prescriptions in the U.S., and about 40% of drugs are being manufactured outside the U.S. Potvin said, “There are a lot of new players getting into drug development and manufacture, and not everyone has the necessary capacity or capability to understand what it means to manufacture products and document the work they do in an accurate way.”

Taking steps to curb the increase in data integrity violations is increasingly vital. Last year, the FDA’s Center for Drug Evaluation and Research created the Office of Pharmaceutical Quality, which will be releasing a new guidance document on data integrity in 2016, and regulators will be stepping up their vigilance even more.

The FDA is moving toward a metrics-based approach to risk-related inspections and, as a result, will be requiring manufacturers to provide additional data, Gaffney explained. “A lot of that data is the same kind that we see getting targeted for data violations,” he said. “If the FDA thinks they’re going to use this data more in the future, they’re starting to ramp up their focus to make sure that they’re able to rely on it.”

Experts believe that solving the challenge of data integrity failure involves a three-pronged approach: change cultural norms to encourage compliance, ensure that quality systems and standard operating procedures are in place and followed, and use new technology to help prevent data errors and catch them if they do occur.

PwC is investigating solutions to automate the prevention of common data integrity issues, including concepts based on the experience of the financial services industry, in which technology is used to identify fraudulent or inconsistent practices. Other technological systems could employ enforced valid values, where if data is out of spec, the batch process cannot continue.

“We’re working through various solutions with our forensics group to see what kind of technology can be leveraged within pharma,” Venugopal said. “We’ve got a lot of tools and technologies that clearly have worked within these other industries. Now it’s just a matter of seeing how can we leverage that same technology and apply it within our space.
“The solution is going to be a combination of multi-dimensional factors,” he continued. “Technology won’t solve everything. It will be technology coupled with the change in culture and in hierarchical attitude. If companies can get all of that put together in a cohesive and effective manner, you’ll start to see results.”

This article was reprinted from Volume 20, Issue 15, of CWWeekly, a leading clinical research industry newsletter providing expanded analysis on breaking news, study leads, trial results and more. Subscribe »