Hearing: Is Sampling Solution to Shortage of Foreign FDA Inspections?

The House Energy and Commerce Oversight Subcommittee held a hearing Feb. 6 on shortcomings in the FDA's foreign drug inspection program.

Subcommittee Chairman Rep. Morgan Griffith, R-Va., said we don't know exactly how much of our drugs rely on foreign sources; even domestic manufacturers may import active pharmaceutical ingredients.

"Congress passed a provision in the 2020 CARES Act that requires any manufacturer who is registered with the FDA to annually report drug substance and volume data, including API. Only about 50% of manufacturers are in compliance," Griffith said in his opening statement.

The FDA has struggled to inspect foreign factories for decades, and virtually all inspections stopped during the period of the pandemic before vaccines were available. “Whatever fitful, halting progress the FDA made towards strengthening its foreign inspection program has been undone by the COVID-19 pandemic and, to date, the FDA has been slow or unable to get foreign inspections back on track," Griffith said.

During that period of halted inspections, 54 of 64 import alerts were the result of product sampling.

Paul Tonko, D-N.Y., asked witness Mary Denigan-Macauley, director of the Government Accountability Office's public health area, if sampling should be used more, given that track record.

She said Government Accountability Office should "assess sampling to be sure it’s being used to its maximum capacity. The best use is to have that information to go into its risk-based model. They don’t have the resources to inspect everything."

Witness Dinesh Thakur received millions after serving as a whistleblower when he was an employee at an Indian manufacturer, Ranbaxy Laboratories, which sold adulterated drugs and committed fraud to cover up its practices (see 13091621).

Thakur suggested Congress should require mandatory testing of all imported drugs from countries "where past inspections have demonstrated a consistent pattern of data fraud and GMP violations." Thakur said it wouldn't necessarily have to be every shipment -- there could be random statistical sampling, or the sampling could be limited to the highest-risk drugs, such as injectable drugs, which must be sterile. He said the purchaser would be responsible for the testing, such as a pharmacy benefit manager.

He noted during the hearing that the Pentagon is doing a pilot program, testing generics in particular. "We know there is batch to batch variability [in generics], that has been conclusively established," Thakur said. "We don't know how big the problem is."

When asked in a brief interview after the hearing about this idea, Griffith said, "I certainly think it's a tool we ought to look at. We've got to learn how to be a little more quicker on our feet. I think sampling is certainly one of the tools."

Witness John Claud, counsel at Hyman, Phelps & McNamara, a boutique firm for FDA cases, was more skeptical. "Testing every drug that comes in, testing all of it, that seems to me to be a logistical problem, to say the least, and I think there are probably other tools that are available to reduce risk." He said the system is set up for voluntary compliance.

Thakur said he's worried that the issues seen in warning letters to Indian pharmaceutical manufacturers are similar to the issues at Ranbaxy.

Denigan-Macauley said that the GAO has been pointing out for years that there are three major problems with foreign inspections -- lack of local staffing, that the inspections are pre-announced, or known because of visa or other travel arrangements, and that inspectors rely on translators provided by the companies.

Claud testified that there is only one investigator in China and five in India. About one-third of all imported drugs come from those two countries.

"This workforce shortage presents a huge problem when trying to comb through the backlog of foreign facilities," he said. "It is little wonder that in the absence of regulatory inspections and actions, that we’ve seen numerous quality control failures in imported drugs."

He said it's good that the FDA has now done 35 unannounced or short-term notice inspections in India as part of a pilot program.

Griffith said it was alarming that even with advance notice, "the FDA still found deficiencies during 66% of foreign inspections, including serious deficiencies in 16% of those inspections."

Energy Committee Chairwoman Rep. Cathy McMorris Rodgers, R-Wash., noted in her opening statement that, last year, imported eye drops spread bacteria among 81 patients, four of whom died and 18 of whom lost their eyes or their vision.

The FDA "is not adequately executing its foreign inspection program, which was questionable before the pandemic, became non-existent during the pandemic, and has seen little improvement since," she said.

She said it was unacceptable that no one from the FDA was made available for the hearing.

Griffith said there will be another hearing in the late spring or early summer, and he hopes to have an FDA witness there. Subcommittee ranking member Rep. Kathy Castor, D-Fla., said the FDA wasn't given enough notice to appear.

Rodgers brought up a report from the Coalition for a Prosperous America on Aurobindo, an Indian generic drugs manufacturer. She said it showed Aurobindo suppliers are linked to forced labor in Xinjiang.

She asked Denigan-Macauley how far down in the supply chain FDA inspectors go, and if they are only concerned with drug quality, or if they also look for evidence of abusive working conditions.

Denigan-Macauley said the FDA is only looking at drug quality issues.

In his opening statement, Griffith noted that in 2019, it took the FDA, on average, 136 days to issue an import alert after discovering quality problems. After the hearing, when asked if the FDA issues enough import alerts, he replied, "I can't answer that question, and that's a problem. I should be able to answer that question, I don't have enough data, because we're not getting reports from the field that we really ought to have."