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Regulatory Focus™ > News Articles > Exclusive: FDA to Continue Regulatory Exception for Doxil Substitute

Exclusive: FDA to Continue Regulatory Exception for Doxil Substitute

Posted 18 October 2012 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) plans to continue to allow a substitute for the anti-cancer drug Doxil, manufactured by Johnson & Johnson subsidiary Ben Venue Laboratories, into the country in the near future despite Ben Venue's 17 October announcement that it has resumed production at its Bedford, Ohio facility.

Ben Venue suspended the majority of manufacturing activities at its Bedford plant in November 2011 after inspectors from FDA identified a series of serious violations of current good manufacturing practice (cGMP) regulations. At the time, Rob Bazemore, president of Janssen Products, the J&J subsidiary in charge of marketing Doxil, said that the shortages were due to "unplanned downtime due to equipment failures at our independent specialty manufacturer."

Shortages Lead to Unusual Decision

By February 2012, shortages of Doxil had led to widespread outrage at both J&J and FDA, both of which scrambled to institute changes to address the shortage. While J&J focused its efforts on a rationing program known as Doxil C.A.R.E.S-a physician access program-FDA moved to use its enforcement discretion.

In a relatively unusual announcement in February 2012, FDA said it would allow the import of supplies of Lipodox, a chemically identical substitute for Doxil manufactured by Indian drug manufacturer Sun Pharma. In a statement, FDA said the situation was of unprecedented importance and it has evaluated the drug-unapproved in the US-and determined that it was of "adequate quality and that the drug does not pose significant risks for US patients."

As pointed out by Regulatory Focus at the time, the drug did not undergo bioequivalence testing before being allowed entry to the US.

"We have every reason to believe that Lipodox has the same efficacy and safety as Doxil," said Lisa Kubaska, a spokeswoman for the Center for Drug Evaluation and Research, told Focus. "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 at the time.

Shortages Set to End…

But Doxil's shortage situation is set to start easing-and perhaps end-shortly. In a statement released on 16 October, Ben Venue said it had, "Resumed production on a limited number of manufacturing lines in the company's Bedford, Ohio facilities."

Ben Venue also said it, "Anticipates that production will resume on additional lines as lasting corrective measures to address facility and equipment issues are implemented."

A 15 October letter from Jannsen went further, saying it is, "Restoring full access to Doxil in the US for physicians and the patients they serve."

"With this new full access, we are able to suspend the Doxil C.A.R.E.S. Physician Access Program," it continued.

…But Enforcement Discretion for Lipodox Continues

But even as the shortage situation seems poised to end, an FDA spokeswoman said the agency has no intention of stopping its enforcement discretion in the near future. "FDA is continuing its exercise of enforcement discretion for the importation of Sun's liposomal doxorubicin product, Lipodox," said FDA spokeswoman Shelly Burgess in a statement to Focus. "Doxil remains in shortage.  FDA continues to work closely with the manufacturer of Doxil as it works to resupply Doxil to the US market."

The statement could come as some relief for Sun Pharma, which Reuters reported is being hammered by worries that its ability to import Lipodox into the US will end once Janssen's manufacturing capacity improves.

Burgess also said FDA plans to continue to use its enforcement discretion to allow for limited importation of unapproved drugs in the future to combat shortage situations. "FDA will continue to consider enforcement discretion for importation in appropriate cases. Temporary importation of foreign drugs 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."

Despite not testing the products for bioequivalence, Burgess said the agency still took measures to assess the product's safety and quality. "Before exercising enforcement discretion for the temporary importation of a foreign drug to address a shortage, FDA evaluates the drug to ensure that it is of adequate quality and that the drug does not pose undue risks for US patients," she wrote.

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