Small Pharmacyֺ’s Role in Ranitidine Concerns

Start-up pharmacy Valisure (New Haven, CT) has made a name for itself by chemically validating drugs it purchases from wholesalers before fulfilling prescriptions for consumers. The pharmacy's laboratory analysis is behind the ongoing recall of ranitidine, (see earlier story) and it has detected dozens of other quality concerns related to the medications it dispenses, according to the Washington Post.

Since late 2018, Valisure has detected over 50 safety/quality concerns with drugs it has purchased from drug wholesalers. It routinely rejects more than 10% of the batches purchased “because their tests detect contaminants, medicine that didn’t dissolve properly or pills that contain the wrong dose, among other issues,” the Post says.

“We know impurities in medicines are of great concern to patients and consumers who rely on safe and effective medicines approved by the FDA, and we are working with manufacturers and global regulators to provide clear and actionable information,” CDER director Janet Woodcock said in a statement. “These investigations take time and do not provide instantaneous answers.”

FDA has cast some doubt on Valisureֺ’s methods. While overall supporting the safety of the drug supply, the agency said that Valisure’s conclusion — that ranitidine turns into a cancer causing impurity (NDMA) in the stomach — is not supported by the agency’s testing. An FDA update earlier this month said that preliminary testing on numerous ranitidine products has found NDMA levels that are similar to levels consumers would normally be exposed to in foods like grilled or smoked meats.

“We also conducted tests that simulate what happens to ranitidine after it has been exposed to acid in the stomach with a normal diet and results of these tests indicate that NDMA is not formed through this process,” Woodcock said in the update. “Similarly, if ranitidine is exposed to a simulated small intestine environment, NDMA is not formed. However, we still must test the drugs in the human body to fully understand if ranitidine forms NDMA.”

Woodcock recently answered questions about drug safety and concerns with foreign-sourced active pharmaceutical ingredients (APIs) during a 10/30 House Energy and Commerce Subcommittee on Health hearing (see story). She said that “advanced manufacturing technologies” could reduce U.S. drug maker reliance on foreign APIs and thus “enable U.S.-based pharmaceutical manufacturing to regain its competitiveness with China and other foreign countries.”

Over the past few years, FDA has seen an uptick in the number of Warning Letters issued to foreign drug manufacturers after inspections. Former FDAer and now-Valisure chief medical officer David Gortler told the Post that inspections simply aren’t sufficient in foreign factories. He thinks the agency needs to test each batch of drug that enters the country. “It’s really becoming a national health crisis,” Gortler said, “and eventually it’s going to become a national security crisis.”

While investigations continue with ranitidine, FDA is asking that manufacturers continue conducting their own laboratory testing to determine NDMA levels in ranitidine and to send samples to FDA to be tested by its scientists. “We are still working with manufacturers to investigate the true source of NDMA and to understand the root cause of the low levels of NDMA present in the drugs,” Woodcock said.