Radioisotope manufacturer International Isotopes has received a warning letter from the U.S. Food and Drug Administration (FDA) that cites several "significant violations" of current good manufacturing practice (cGMP) regulations regarding the company's sodium iodide I-131 product, which is used to treat thyroid conditions.
International Isotopes said it plans to have completed virtually all corrective actions this month related to the October 26 letter, which stems from a July inspection of its facility in Idaho Falls, ID. Stephen Laflin, president and CEO, said the company requested the FDA inspection last year based on its desire to clearly establish regulatory requirements for I-131.
International Isotopes imports I-131 from a manufacturer in South Africa and repackages the product at the Idaho Falls facility for distribution in the U.S. The FDA, however, has classified the company as a manufacturer rather than a repackager and, therefore, conducted the inspection under stricter GMP guidelines.
"While we had a rigorous quality program in place, we did not have a full GMP compliance program in place for this product," Laflin said. "So, it was no surprise that [the FDA] cited some shortcomings in the GMP compliance aspects."
Among the half-dozen deficiencies listed in the warning letter, the FDA noted that International Isotopes did not perform "identity tests" for each batch of incoming I-131 shipments. The company also was cited for failing to calibrate instruments and other devices in a timely manner, and for not having provisions in place to correct for any such inaccuracies.
In addition, the software for the company's production record had not been validated. The software is responsible for generating batch production records, performing calculations to produce varying concentrations of the drug, and detailing label information for customer vials.
The FDA also cited International Isotopes for manufacturing sodium iodide I-131 without an FDA-approved application. However, the FDA has allowed International Isotopes to continue to ship the product to its customers.
"Although there is no FDA-approved application on file for this drug product, we will allow you to continue manufacturing this product pending correction of your current GMP violations," the letter read. "This decision is consistent with FDA's commitment to take action against marketed unapproved drugs without imposing an undue burden on patients."
Laflin confirmed that there was no disruption in service to customers.
Over the past several months, the company has been providing updates to the FDA approximately every 30 days on the status of its corrective actions, addressing all the issues the agency identified, Laflin said. The FDA did not acknowledge a September response from International Isotopes because the company's communiqué was received late.
"We plan to resend the September update and the October update along with the November update next week," Laflin said. "By the time we respond, we will have completed virtually all of the corrective actions and issues [the FDA] identified."
There is one corrective action that will likely take until the end of the month to complete due to testing requirements.
"Ultimately, we are not going to quibble with [the FDA] about the significance of whether we should or shouldn't be GMP-compliant," Laflin added. "We think it is an appropriate step forward to prove the quality program of the company. It does nothing but improve the quality of the product and the integrity of the product in the customers' eyes, so we will put it in place."
International Isotopes also plans to conduct an independent assessment of its corrective actions to ensure compliance.
