US FDA Importing Unapproved Drugs to Ease Shortages

US Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced at a press conference on 21 February that the agency is working with manufacturers to resolve drug supply shortages of the cancer drugs Doxil (doxorubicin) and methotrexate.

Hamburg said the agency is working with domestic and foreign manufacturers to bring supply levels of both drugs back to non-shortage levels, adding that the agency has allowed the import of an unapproved replacement of Doxil called Lipodox, which is currently manufacturered at an FDA-inspected facility in India.

"We are confident using regulatory discretion to ensure the safety and utility of this product," said FDA Associate Director Valerie Jensen, who heads the drug shortage program.

FDA said in a press statement that the arrangement is "considered in rare cases when there is a shortage of an approved drug that is critical to patients and the shortage cannot be resolved in a timely fashion with FDA-approved drugs." When such a rare case occurs, FDA "evaluates the foreign-approved drug to ensure that it is of adequate quality and that the drug does not pose significant risks for US patients."

In a statement provided to Regulatory Focus, an FDA spokesman further noted that "FDA has used temporary importation to help with drug shortages eight times in the past year and a half."

While both Doxil and Lipodox are doxorubicin hydrochloride liposome injections, FDA spokeswoman Lisa Kubaska noted that the two have not been found to be bioequivalent, which prevented FDA from approving the product via the 505(j) pathway used for generic drugs.

 "We have every reason to believe that Lipodox has the same efficacy and safety as Doxil," said Kubaska. "Sun Pharmaceuticals markets Lipodox in other countries and has conducted studies that are reassuring to this effect." FDA sought out Sun Pharmaceuticals to help ease the shortage, noted Kubaska.

"FDA has utilized regulatory enforcement discretion for temporary importation to meet critical patient needs during the shortage," added Kubaska. "FDA evaluates the overseas drug to ensure that it is of adequate quality and that the drug does not pose significant risks for US patients."