Tuesday, December 13, 2011

The Last Dosage-- No More Doxil for the Foreseeable Future



Janssen just released the last dosages of Doxil, reportedly enough to treat 1000 people on the waiting list.  Of course, it is too late for me.  I am finished with this course of chemotherapy and hoping for the best so, if my turn on the waiting list comes up, someone will take my place .

As I stated in my last post, European Medicines Agency asked Janssen three weeks ago to notify doctors  to monitor for possible side effects, such as sepsis, in use of Doxil as a result of quality control issues at its contract manufacturer, Ben Venue Laboratories (BVL).  Janssen issued a letter to physicians today, December 12, 2011 with the release of the last doses of Doxil.  Here is what it says about quality control issues:

We are aware of some recent information about the quality shortcomings at this contracted supplier of  DOXIL®. We have performed thorough quality reviews of this additional supply of DOXIL®, which included a review of production procedures and extensive sample testing. Based on these assessments, Janssen Products, LP has now approved release of this supply from BVL for distribution through our patient allocation program.

Note that there is no mention of monitoring side effects whatsoever.  Janssen instead decided to do "extensive quality reviews . . . and extensive sample testing."  I hope they are right.  Sepsis is not something to ignore and of course, physicians receiving this letter may not have been following the warning from the EMA so they would not have the heightened level of concern that EMA wanted Janssen to communicate about Doxil.

Janssen also seems to be softpedaling the "shortcomings" at Ben Venue. The FDA last week issued another 483 report dated December 2, 2011 about extensive quality control problems at Ben Venue, including finding urine in a container, leaky roofs still not repaired and metal particles in a product.  Indeed the EMA broadened their recall to include two additional drugs and issued warnings about another two additional drugs.

And, confirming what I have been saying for some time now, Janssen acknowledges that there will be no Doxil for the foreseeable future. Janssen states in the 12/12/11 letter to physicians  (which is stated in very similar wording in the Janssen President's letter of the same date):

This limited supply represents all of the remaining DOXIL® that had been previously produced by BVL. Please be advised that this modest supply of DOXIL® will not be sufficient to supply everyone on the wait list. We want to emphasize that this limited product availability does not foreshadow the potential for any additional supply of DOXIL® in the immediate future as we have no further information from BVL on when manufacturing will resume at its facility.

The problem, as I also mentioned in earlier blog posts  (see e.g. here) and as Peter Loftus reports, is that other chemotherapies are in shortage.  I read over the weekend on an Inspire.com bulletin board for cervical cancer that women are having trouble getting cis-platin, a mainline treatment also of ovarian cancer. Carboplatin is also in short supply and was repeatedly discussed in last week's Senate Finance Committee hearing on drug shortages.

Members of the Finance Committee seemed to be angling to remove the price increase cap from the Medicare Part B drug schedules so that the marketplace would correct for the shortages because financial incentive would be returned.  Unfortunately, I think the free marketplace is why this issue has come to a head. A report issued in October 2011 by the Assistant Secretary for Planning and Evaluation (ASPE) of the Department of Health and Human Services (HHS) entitled Economic Analysis of the Causes of Drug Shortages suggests that the problem results from generic manufacturers avoiding excess capacity rather than the Medicare Part B cap.  Drug shortages only exist in 10% of sterile injectable generics covered by Medicare Part B and, contrary to testimony before the Finance Committee by the conservative American Enterprise Institute representative, consolidation of the sterile injectable generic drug industry did not cause the shortages.  The report said in a section entitled Supply:

Consolidation at the corporate level would be a significant contributor to drug shortages only if the consolidations have resulted in closures of manufacturing facilities that reduced production capacity.  Conversations with leading generic drug manufacturers, and data from the FDA, indicate that the consolidations have not resulted in decreased production capacity or in the closure of manufacturing facilities.

The ASPE-HHS report concluded that the shortages resulted from long term choices by generic manufacturers to ensure that there would not be surpluses  of certain highly specialized drugs for which they got lower prices because of limited demand.  The report explained in a section entitled "Market Behavior":

Our analysis suggests that this change in capacity utilization stems from a combination of the effects of the increase in volume of chemotherapy drugs used, the expansion of products available for generic manufacturing because of patent expiration, and the complexity of manufacture and requirements for Current Good Manufacturing Practices.  Entry cannot occur quickly in the sterile injectables industry because of the high fixed costs of specialized production and regulatory protections.  Furthermore, because shortages are uncommon and occur in drugs for which capacity is highly specialized, and because there are few penalties for failing to supply contracted drugs, there is no financial return to investing in excess capacity — that is, capacity that is not used outside a supply shortage, and thus earns no revenue except during a supply shortage.

So, according to HHS this is a market driven phenomenon completely relating to drug companies trying to maximize profits and essentially preferentially choosing to manufacture more of higher price drugs.  It is the marketplace at its best and worst, which is why I would advocate that these types of life saving drugs need to be regulated for the long term to ensure their supply when the profit seekers cannot be bothered.

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