Shortages of Drugs for Life Threatening Illnesses- An Overview

UPDATED NOVEMBER 21, 2011

If you have followed the news and this blog, you know that there is a nationwide shortage of Doxil, a chemotherapy drug used to treat recurrent ovarian cancer, multiple myeloma and Kaposi’s sarcoma.   News of the shortage first surfaced in July 2011  with new supplies expected in mid or late August, 2011.  However, that prediction from the drug distributor turned out to be wholly inaccurate.

The drug is owned and distributed by Janssen Products, LP, a Johnson & Johnson company.  Ben Venue Laboratories in Bedford, Ohio, the manufacturing arm of Bedford Laboratories and a unit of Boehringer Ingelheim GmbH of Germany, manufactures Doxil under contract to Janssen.

To explain the Doxil shortage, Ben Venue’s representative said that the company is facing "manufacturing capacity constraints" that have held up some products, and it is working diligently to prioritize and expedite manufacturing for current orders." However, Ben Venue Labs has decided to exit the Doxil business and other contract manufacturing to focus more on its business as Bedford Laboratories, a producer of generic injectables, and avoid all the problems that have caused bans from Canada and Europe of Ben Venue products.  In the meantime, as Bedford Laboratories, the company has discontinued manufacture of mainline cancer drugs cisplatin and carboplatin and has significant shortages of Taxol. It appears to focus on commonly prescribed and presumably more profitable drugs such as those that treat migraine (generic Imitrix), indigestion (generic Zantac) and high blood pressure (generic Inderol).

With Ben Venue moving on to greener pastures, who will J&J find to manufacture Doxil and how hard will they try? Doxil reportedly represents less than 1% of Johnson & Johnson revenues.

As of today, there is no indication that the Doxil shortage will end any time soon. Janssen's president, a cancer survivor himself, sympathizes with those affected by having treatment plans interrupted or changed.  However, in 2010, Janssen chose to rely on one manufacturer to produce Doxil, even though in the past, it had a second manufacturer abroad, Schering Plough. Doxil also has no generic competition because it effectively still has patent protection in the US until 2014.  Doxil's patent expired in 2009 but J&J/Janssen still has the monopoly under the Orphan Drug Act as a reward for acquiring the company which produced a drug for a rare condition-one affecting fewer than 200,000 people.

In fact, on November 19, 2011, the Wall Street Journal reported that Ben Venue had stopped manufacturing drugs, including Doxil, altogether:

A troubled contract manufacturer, whose problems caused a shortage of Johnson & Johnson's (JNJ) cancer drug Doxil, has suspended manufacturing and distribution of products from its Ohio plant, saying routine preventive maintenance and other required actions were overdue. . . . Before its decision to halt production, Ben Venue had strained to balance factory remediation efforts with the need to continue supplying critical drugs, a newly released document shows.

See also here.

Janssen knew or should have known that Ben Venue had a history of manufacturing and quality control problems that would lead shortages and thus should not have been the sole manufacturer in the world of Doxil (called Caelyx in other parts of the world.) The FDA recently issued an unusually lengthy 483 report showing complaints about quality control since 2006 and 48 GMP (good manufacturing practices) violations.  Public records of these FDA inspections and an earlier 483  report have been available since  at least 2007.  The European Medicines Agency also inspected Ben Venue and found quality control issues.

Not only is Doxil currently unavailable for most people who need it, the mainstay chemotherapies for ovarian cancer--cisplatin, carboplatin and taxol (placitaxel) are also in shortage.  Cervical cancer and endometrial cancer are also disproportionately affected by these shortages.  The common drugs used to treat cervical cancer,  cisplatin, carboplatin, taxol (placitaxel) and fluorouracil, 5-FU, are all in shortage.  Fluorouracil is also used to treat colorectal cancer and pancreatic cancer, which are obviously gender neutral cancers.  And do not forget that Taxol is one of the mainstay treatments for breast cancer which is diagnosed in about 230,000 women per year in the U.S. with 2.5 million survivors. Endometrial cancer’s mainline chemo treatments are carboplatin, Taxol, doxorubicin and cisplatin, all of which are in short supply.  Unfortunately, another cancer whose treatment is seriously affected is testicular cancer, for which 3 of 4 mainline chemo treatments (Bleomycin, Etoposide, and Cisplatin) have shortages.  The following generic drug companies have mainline chemo shortages:

Taxol-- APP, Bedford, Hospira, Sandoz and Teva
Carboplatin-- APP, Bedford, Sandoz and Teva.
Cisplatin-- APP, Bedford, BMS and Teva.
Fluorouracil--APP, Teva, and Mylan
Bleomycin—APP, Bristol-Myers, Hospira and Teva (Bedford ceased manufacture)
Etoposide—APP, Bedford, Teva

Drug shortages, which according to the American Society of Health-System Pharmacists (ASHP) as of today exceed 200 drugs, (the FDA, who receives voluntary reports of shortages from drug companies, lists over 170) do not just affect people with relatively rare cancers or just people with cancer in general. The shortages include anesthetics, IV propofol used for intubation when someone cannot breathe, injectable antibiotics such as streptomycin,and norepinephrine and labetalol which regulate emergency cases of  low and high blood pressure respectively.  So these shortages may affect any of us and most likely in an emergency setting when you rely on hospitals and medical personnel having the medications necessary to keep you alive. And as shortages of one drug occur, other substitute drugs have increased demand, which then can lead to their shortages.  No relief seems to be in sight.  As NPR says, drug shortages are "the new normal".

A hearing was held on Friday September 23, 2011 in the House Energy and Commerce subcommittee on Health about the drug shortages.

FACTS FROM THE HEARING (as reported by Ovarian Cancer National Alliance):
• 54 percent of shortages are due to quality control issues
• 21 percent of shortages are due to delays in manufacturing or capacity issues
• 99 percent of hospitals report experiencing one or more drug shortage in the first six months of 2011
• 66 percent of hospitals report an oncology drug shortage
• In an April 2011 survey, more than 90 percent of anesthesiologists reported at least one drug shortage at the time of the survey and 98 percent reported a shortage at some time during the past year
• The shortages have cost hospitals $415 million in drug and labor costs

More about Drug Shortages- Get Out Those Scarves and Teal Arm Bands

What if the government and private donations pumped money into the development of drugs to treat a deadly cancer but suddenly when distribution of the drugs became unprofitable the companies making them stopped production.  What happens to the war on cancer then?  Should we just accept that in a capitalist economy, profits determine who lives and who dies?

I have written in other posts that it appears to me that the current chemo shortages are disproportionately affecting ovarian cancer, which is primarily an older woman's disease. I was please to find this American Cancer Society article that confirms my position. Unfortunately the article skews the discussion a bit about what has caused the shortages by also quoting  a large pharmaceutal distributor (McKesson) saying essentially it's all the FDA's fault.  The spokesperson claims that FDA's increased scrutiny on manufacturing processes and quality control have made certain drugs too low in profits to sustain production of those drugs.  The article further states,"McKesson’s Chief Medical Officer Dr. Roy Beveridge, MD, says there is no economic incentive for manufacturers to make or distribute low-priced generic drugs, and that unless the baseline system changes, shortages are going to continue."

J&J Headquarters designed by IM Pei

Ben Venue Labs, the manufacturer of Doxil, a critical treatment for recurrent ovarian cancer, for a subsidiary of Johnson & Johnson, claims that the problem is not one profit. An 9/22/11 article in courier-journal.com by Laura Ungar states:

Jason Kurtz, spokesman for the Ohio-based third-party maker, Ben Venue Laboratories, would only say “we’re facing capacity constraints” with a drug that is complex to make. He wouldn’t specify what type of constraints, but said examples of such problems include unplanned downtime because of machinery breakdowns and capital-improvement projects that limit manufacturing capacity.

However, Ben Venue Labs wants out of the Doxil business (and other contract manufacturing) to focus more on its business as Bedford Labs, a producer of generic injectables, and avoid all the problems that have caused bans from Canada and Europe of Ben Venue products.  Like the WSJ said, it is all about manufacturing priorities. In the meantime, as Bedford Labs, the company has discontinued cisplatin and carboplatin and has significant shortages in production of Taxol. It appears to focus on commonly needed and presumably more profitable drugs such as those that treat migraine (generic Imitrix), indigestion (generic Zantac) and high blood pressure (generic Inderol).

With Ben Venue moving on to greener pastures, who will J&J find to manufacture Doxil and how hard will they try? Doxil reportedly represents less than 1% of Johnson & Johnson revenues.  A few of my ovarian cancer sisters on inspire.com bulletin board noted that J&J makes a lot of money marketing to women, and in particular in women's products.   Here's one list of products that J& J sells.  Perhaps J&J needs to be reminded that they need to focus on Doxil as well, and quickly.  

In addition,  there are all the generic drug companies that have discontinued or have serious shortage in chemo drugs  ovarian cancer patients need. For Taxol, they are APP, Bedford, Hospira, Sandoz and Teva.  For carboplatin, they are APP, Bedford, Sandoz and Teva.  For cisplatin, they are APP, Bedford and Teva.  And with Bedford, now out of the ovarian chemo business for the most part, more of the market power will consolidate in the handful of generic companies left, who will continue to make "allocation decisions" of their manufacturing capacity based on profit. 


What can we do? Big Pharma would have us believe that the causes are all very complicated--increased reliance on outsourced ingredients, Medicare price controls, increased demand from all those pesky cancer patients, complicated manufacturing processes and lack of inspection capacity from the FDA.  But we all know that it boils down to making sure that Big Pharma makes maximum profit, even when lives are at stake.  This is unacceptable in a civilized society.


In my previous posts, I have encouraged people to write to Congress.  A hearing was held on Friday September 23, 2011 in the House Energy and Commerce subcommittee on Health but the human voice of the affected cancer patient was sorely missing. We can continue to try to get our government to take some action in this area which they have been loath to regulate thus far.  Or we can take our message to the streets and protest at the offices of the companies who will not manufacture the drugs we need.  We could show up at J&J corporate offices (and the generic companies too) wearing scarves and teal arm bands, with our message that we are still here, we are still fighting and they have an obligation to get us the drugs that will keep us alive.  Who's up for a road trip to New Brunswick, New Jersey?

THE REAL DEATH PANELS?

Nexium everywhere but no capacity for Doxil

Critics of health care reform warned the government would set up "death panels" if the law was enacted.  That hasn't happened, but such panels do exist, thanks to the actions of Big Pharma. Today pharmaceutical companies are choosing who will live and die when they decide not to manufacture drugs needed by cancer patients - like me - who are at risk of premature death.

There is a nationwide shortage of Doxil, a chemotherapy drug used to treat recurrent ovarian cancer, among other cancers. I learned about the shortage from my oncologist in July when he said that the best treatment for me was Doxil in combination with carboplatinum for my now recurrent ovarian cancer, but I would have to start without Doxil.  New supplies were not expected until mid or late August.

The drug is distributed by Janssen Products, LP, a Johnson & Johnson company, and manufactured by Ben Venue Laboratories in Bedford, Ohio, a unit of Boehringer Ingelheim GmbH of Germany. Ben Venue’s representative explained that the company is facing "manufacturing capacity constraints" that have held up some products, and it is working diligently to prioritize and expedite manufacturing for current orders." (WSJ 7/21/11)  I wonder if  the priorities are set because of the lower financial return Doxil brings or the fact that it is a woman's disease that Doxil mostly treats.

I learned from an online board that women around the country were scrambling to places remote from their regular treatment centers to get the precious Doxil before it runs out.  One woman said a small supply was available in Texas; another thought some could be had in Boston. It turns out that by early August, none was available in the United States.  One person has gone to Paris to finish her Doxil treatment.

Shockingly, Doxil is only one of many drugs in shortage in the United States.  Three other mainline chemotherapies for ovarian cancer, carboplatinum, cis-platin and taxol, as well as chemotherapy drugs for breast and colorectal cancer, are in short supply.  I learned from a new friend online that her clinic in Los Angeles has run out of taxol. Luckily, I get my infusions at Cedars Sinai Medical Center, which still
has a supply of these three drugs even though it does not have Doxil.

On August 18, 2011, Janssen issued its latest update on the Doxil shortage.  It announced that it had implemented its “new allocation process for a modest and limited supply of DOXIL®” and apparently all available Doxil has been distributed to certain patients whose physicians certified in writing that the patients were already on Doxil. There is now a waiting list that will be fulfilled as new supply eventually becomes available.  However, Janssen cautioned,   “As supply will remain intermittent in the coming months, Janssen Products, LP continues to recommend that no new patients be started on DOXIL®.”

So, the original announcement that Doxil would be available again by late August proved to be inaccurate.  Doxil is available again only for special limited cases, which unfortunately do not include me because I have not yet started treatment with Doxil.

According to the American Society of Health System Pharmacists, drug shortages currently affect about 200 medications in the United States, including antibiotics. The FDA reports record shortages for 2010 and projects more record shortages for 2011.  But the FDA has no power to require drug manufacturers to explain why there are shortages and effectively must beg the manufacturers to keep it informed.

The only real reason for these shortages is the economics for Big Pharma., which makes more money from new drugs, antidepressants and potency pills than generic chemotherapy drugs.  Why make drugs for which you can only charge $3.00 per dose when you can force doctors because of shortages to prescribe new medications that cost $10,000 per dose.?

This all means I could go for an indeterminate time not getting the drug that my oncologist says best increases my odds for remission.  I am starting to feel the need to scramble myself.  For this grandmother,
the “allocation system” of who gets Doxil (and possibly the other drugs with shortages used to treat ovarian cancer) has made the drug companies the real death panels.

Senator Klobucher introduced S. 296, Preserving Access to Life-Saving Medications Act, which would require manufacturers to report shortages and reasons for the shortages to the FDA. A similar bill, HR 2245, has been introduced in the House. Both bills are still in committee.

While I support this legislation, it is unfortunately merely a band-aid over a gaping wound.  Drug companies need to become more accountable for their profit driven decisions about what drugs to produce.  My fellow cancer warriors and I cannot fight the good fight if the drugs aren't even available.