FDA Fumbles Abroad, Leading a University Health Plan To Ban an Imported Drug

By Kenneth Rapoza, CPA Industry Analyst

The University of Kentucky health plan banned an imported drug this week coming from India and Portugal. They’ve highlighted problems our members think need attention at the Food & Drug Administration. We believe the answers can be found right here at home.

Researchers at the University of Kentucky (UK) filed a petition on September 30 with the Food and Drug Administration to recall one lot each of Mylan and Hikma’s versions of injectable diuretic acetazolamide after finding high impurity levels in tested lots.

After testing performed in August, University researchers found that samples of Mylan’s version of acetazolamide contained only between 80% and 87% of the listed active pharmaceutical ingredient (API). The rest was composed of “unknown impurities” that University Health Care Chief Pharmacist Philip Almeter called “obscure chemicals that could result from breakdown of product or from reagents used in the manufacturing process.” In other words, a faulty product imported into the US under lackluster quality control standards.

Acetazolamide is an injectable diuretic available as a generic medication that is commonly used to treat glaucoma, epilepsy, altitude sickness and fluid retention.

The petition requested that the FDA recall a particular lot number of acetazolamide that was made in India by Mylan Laboratories, and another lot number made by Hikma in Portugal. Both of these drugs showed impurities in initial testing by the University.

“Drug quality in the United States is ensured by maintaining control of the manufacturing process,” said University pharmaceutical professor Robert Lodder. “The fact that the process is producing samples of varying composition indicates that process control is not being maintained.”

Drugs made abroad and sold here should be held to the exact same standards as Made in America pharmaceuticals are held. When they are not, it opens the door to potential problems, including death.

Three pharmaceutical companies that sold the generic drug, valsartan, agreed to recall a blood pressure medication in 2018 after the FDA said it might be tainted by N-nitrosodimethylamine (NDMA), considered a probable human carcinogen. The FDA said at the time that the contamination was believed to be related to changes in the way that valsartan was manufactured in China.

All of the valsartan under question was made in China by the same company, Zhejiang Huahai Pharmaceuticals and it was distributed in the US by Teva Pharmaceutical and Solco Healthcare, which is owned by Huahai Pharmaceutical.

Our members have been saying that FDA rules for products made overseas are not the same as those made here. They are not asking for the rules to be more lax; but they are asking for the same rules to apply to companies manufacturing elsewhere for the US market. If not, it puts US producers at a disadvantage. Put simply, they play by different rules when compared to China and India in particular.

CPA member Nexus Pharmaceuticals’ CFO Usman Ahmed told us that US firms are more heavily regulated. And one of the issues that stood out for Ahmed was the FDA requirements are not as tough in India and China, thought this may not be entirely the FDAs fault. Regulatory hurdles also make it more financially interesting to source outside of the US. India has had some run-ins with drug irregularities. Portugal tends to be as tough as the US, however.

Currently, companies with the largest drug portfolios, like Pfizer, Mylan, and Aurobindo all rely on India labs for their injectables. Last year, Aurobindo was part of a list of 13 warning letters sent to Indian companies regarding issues like misbranding, selling unapproved medicine, and violating the FDAs Current Good Management Practices guidelines.

“A lot of the generic injectables have gone overseas, mostly to India – the largest – and now China is getting into it,” Ahmed says, adding that inspection requirements need to be matched. Accountability is too weak. If it is not going to be matched, then depending on the drug, we should be bringing it home.

Says Ahmed, “We get announced inspections and China and India do not. Anything you’re not doing correctly, you have time to put all those skeletons in the closet. We don’t have that option. They just show up for as long as they want, which is fine. Some of those overseas companies have had run-ins with FDA inspectors and are still exporting to the US even after getting warning letters. The quality is different here because the FDA does a better job here.”