EU Recalls Cancer Meds Made By Boehringer Unit
6 CommentsBy Ed Silverman // November 23rd, 2011 // 8:06 am
The manufacturing problems engulfing the troubled Boehringer Ingelheim unit have just grown worse. The European Medicines Agency has just issued a ‘precautionary’ recall for the remaining batches of three cancer meds - Busilvex, Velcade and Vidaza - that were manufactured at its Ben Venue Laborartories facility in Ohio. And no new patients are to be treated with yet another med, Doxil.
The move comes just four days Ben Venue disclosed plans to “voluntarily and temporarily” suspend production and distribution at its Bedford, Ohio, plant, and one month after reluctantly putting a halt to its contract manufacturing activities, exacerbating shortages of various life-saving meds for which alternate sources are not always available (read here).
The EMA took this step following a joint inspection by regulators from the EU and France, as well as the FDA, earlier this month, which obviously precipitated the decision to halt production at the Bedford plant. The inspection “highlighted several shortcomings in the quality-management system,” according to the EMA, which is reviewing “all centrally authorized medicines that are manufactured at the site.”
“The potential risk of batch contamination due to the shortcomings in quality management at the North complex (which is part of the Bedford facility) means that only medicines which are absolutely essential to meet patients’ needs can be used and which are currently not available from another source,” according to the EMA’s Committee for Medicinal Products for Human Use.
The recalls are the latest blow to the Boehringer unit, which publicly blamed capacity constraints for chronic shortages until we reported last June that inspectors from both the EMA and FDA had visited its facilities and cited Ben Venue for various deficiencies that contributed to production slowdowns. At the time, a spokesman insisted the inspections did not cause a change in production capability (see this).
As for doctors and patients, the EMA is concerned about side effects that may result due to treatment with Doxil, which is made by Johnson & Johnson and marketed as Caelyx in Europe. Ben Venue is the only supplier for the drug, and J&J has so far been unable to offer alternatives. For this reason, the EMA opted against a recall; alternate supplies do exist for the other cancer meds.
“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),” according to the EMA (here is the complete statement).
Greg Pawelski
This is what happens when you produced an entire generation of investigators in clinical oncology who believe that the only valid form of clinical research is to perform randomized ‘GoodHouseKeeping Seal of Approval’ clinical trials in which patients are randomized to receive one empiric drug versus another empiric drug.
There is no proven standard first line therapy which has been shown to be superior to the many choices of drugs which exist. The same situation exists in the setting of 2nd, 3rd, and 4th line therapy. The therapies are equivalent on a population basis. There are a myriad number of choices of drugs that exist for each cancer.
There are alternative drugs that can be used and there are alternate supplies that do exist for the other cancer meds. Oh! But they can’t use these alternaive drugs because they haven’t gotten their ‘GoodHouseKeeping Seal of Approval’ and they can’t give those drugs without that. And you wonder why we have drug shortages!
Biotech Observer
Greg,
How do you know a drug is “equivalent on a population basis” if you don’t conduct randomized trial?
Frank Sett
Greg,
The reason for the recalls is not because the company hasn’t received the good housekeeping seal of approval; they originally had to receive it in order to market the drugs in the first place. The reason is because the company could not comply with current regulations by the EMEA and FDA.
I work with a number of “drug shortage” companies and many of these companies place quality behind production, leading to products that are out of compliance. Out of compliance per se does not necessarily mean the drugs are not safe (from a microbiological and chemical perspective) - it could indicate the drugs were made with inappropriate documentation or controls, causing them to be “adulterated”, again from a compliance purview.
Either way the results of the clinical trials are not the reason for the recalls in this case. The inappropriate manufacturing of the drugs is the reason.
original industry insider
Frank may already know this, but I know from personal experience that Ben Venue used to be a high quality contract manufacturer. The fact that they are suspending activities exemplifies what Frank says, that quality is being deemphasized in favor of meeting production quotas.
Greg Pawelski
Biotech Observer
The problem is not with using the prospective, randomized trial as a research instrument, the problem comes from applying this time and resource-consuming instrument to address hypotheses of trivial importance (do cancers prefer Coke or Pepsi?). It is crucial to work on reducing their inherent limitations, including uncertain generalizations, and to expand the use of the randomized clinical trail paradigm to areas beyond proving biological activity, like diagnostic testing (test the tumor first).
Frank
It’s just that big pharma likes to develop, patent, get it’s good housekeeping seal of approval from a population study to establish it product as the “standard” and make millions of bucks to boot that precipitates this. There is no proven standard first line therapy which has been shown to be superior to the many choices of drugs which exist.
Robert
This is just a case on an inept German company…Their love of $$ caused them to make shortcuts that now costs patients….
This is such a poorly run company in my opinion.