Monday, December 5, 2011

Update on Doxil Production-Possible Quality Issues?

According to the WSJ and our intrepid Doxil shortage reporter, Peter Loftus, the FDA is working with Johnson & Johnson to address the fact the Ben Venue Laboratories has completely shut down production of Doxil as of two weeks ago (November 19, 2011). However, the chances of Doxil being available anytime soon, in my opinion, are slim to none.  I would love to have J&J really explain, other than in the vaguest generalities, why it will take some time to fix this situation but all of these manufacturing processes are shielded by the assertion of confidentiality due to proprietary interests.  The FDA knows a little but they are not permitted to tell.   With something that affects life and death, the lack of transparency is astonishing and disturbing.

Now however we have something new to worry about in the limited supplies of Doxil that are available. In early November 2011  the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) as part a joint inspection with UK, French and US regulators found "significant" contamination and other quality control problems at Ben Venue.  Ben Venue "voluntarily" pulled the plug on itself.  EMA recommended the recall of three drugs: Velcade, (Millennium and J&J) used for multiple myeloma,  Vidaza  (Celgene) used to treat anemia, leukemia and bone marrow disease (MDS) and Busilvex(aka Busulfex), used to treat a form of leukemia.  The Hong Kong regulatory agency has joined in and expanded this recall.  The FDA has NOT issued any recall.

EMA did not recall Doxil (Caelyx) because Ben Venue was the sole source for manufacturing the drug. However, it did recommend that the drug not be used for new patients, an irony given that the drug is essentially not available except for the limited doses that have been distributed.  It also asked that doctors monitor patients for side effects like the deadly sepsis.  Janssen was asked to circulate a letter to that effect to physicians but nothing has yet been posted on the Doxil website as of today, December 4, 2011.  Here is what EMA said about Doxil (Caelyx):

For Caelyx, for which Ben Venue is the only manufacturing source, the CHMP considers the product to be essential only for patients already on treatment. It recommended that supplies should be available to maintain these patients on Caelyx but no new patients should be started on treatment with Caelyx until further notice. The CHMP advised that healthcare professionals should monitor treated patients intensively and immediately notify any relevant safety concerns that could be evidence of a quality assurance problem (particularly any cases of sepsis or suspected sepsis, such as acute pyrexia). The marketing authorisation holder, Janssen, has been asked to circulate a communication to healthcare professionals to reinforce these messages, requesting them to enhance monitoring and report any suspected adverse reaction or complaints that could be evidence of a quality assurance problem with the aseptic filling process. The CHMP will review the situation on a continuous basis.

For those of you who may still be taking Doxil, please check with your doctor about this warning. I suspect Janssen has not yet issued the letter even though EMA posted its findings almost two weeks ago.  Unfortunately, given that emergency injectable antibiotics are also in shortage (13% of all shortages; see page 14 of this FDA report), it may not be worth the risk to take any Doxil now.

Originally posted on my other blog on December 4, 2011

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