The Valisure Study — How the NDMA Problem Was Discovered

Who Is Valisure and What Do They Do?

Valisure LLC is an independent analytical pharmacy and pharmaceutical testing laboratory founded in 2015 and based in New Haven, Connecticut. Valisure operates as a pharmacy that purchases commercial pharmaceutical products, tests them for purity and safety before dispensing, and publishes its findings publicly. Valisure has become known for identifying pharmaceutical safety issues that had not been detected by standard FDA oversight mechanisms, including NDMA in ranitidine (2019), NDMA in metformin (2020), and benzene in sunscreens (2021). Valisure is funded through its pharmacy operations and does not accept pharmaceutical industry funding, making its research financially independent of the companies it tests.

What Valisure Found in 2019

In 2019, Valisure's laboratory routinely tested ranitidine products as part of its standard pharmaceutical quality testing protocol. Using liquid chromatography-mass spectrometry (LC-MS/MS) — a highly sensitive and specific analytical chemistry technique — Valisure detected NDMA in all ranitidine products tested, at levels up to 304,500 nanograms per tablet. To put this in context: the FDA's acceptable daily intake limit for NDMA from all sources is 96 nanograms. A single Zantac tablet at Valisure's highest detected level contained more than 3,172 times the daily NDMA limit. Valisure then tested whether the NDMA was a degradation product of the tablet itself (shelf degradation) or was produced during metabolism. By dissolving ranitidine in simulated gastric acid at 37°C (body temperature), Valisure found that NDMA generation increased dramatically under these conditions, indicating that additional NDMA is produced in the stomach after ingestion.

The Citizen Petition and FDA Response

In June 2019, Valisure submitted a Citizen Petition to the FDA (Docket No. FDA-2019-P-2396) formally requesting that the FDA recall all ranitidine products from the market. The petition included Valisure's analytical data, methodology, and scientific reasoning. The Citizen Petition process allows any member of the public, including companies, to petition the FDA to take regulatory action. The FDA is required to respond to Citizen Petitions but is not required to grant them. In this instance, the FDA confirmed the core finding — NDMA was present in ranitidine at concerning levels — and ultimately took the requested market withdrawal action in April 2020, approximately 10 months after the petition was filed.

Subsequent Validation of Valisure's Findings

Valisure's initial findings were scrutinized and contested by pharmaceutical industry defendants, who argued that Valisure's simulated gastric condition testing was not accurately representative of in vivo conditions. However, subsequent independent research — including studies from Stanford University and other academic institutions — confirmed that ranitidine metabolism in the human body generates NDMA at levels far exceeding safe limits. A 2020 Stanford study using a pharmacokinetic approach found NDMA levels in human urine exceeding 47,000 nanograms following a standard ranitidine dose — consistent with Valisure's findings and inconsistent with safe human use. While the exact magnitude of NDMA generation under specific physiological conditions continues to be researched, the fundamental finding — that ranitidine use results in substantial NDMA exposure in the human body — has been confirmed by multiple independent research groups.