Sorry I've Been Gone For a While- Still Fretting about DOXIL Shortage

It has been over a month since I last posted.  A lot has happened during that time in the drug shortage space and in my personal space.  For me personally, I thought in early March that I had recurred only three months after finishing chemotherapy without the recommended Doxil treatment.  Although my CA 125 numbers are up, luckily my CT scan showed no evidence of disease (NED) so I am still enjoying life not being pumped full with poisons.

On February 21, 2012 the FDA announced it was importing a Doxil substitute called Lipodox from overseas.  I was quoted in two articles about the announcement here and here.  At the time I was optimistic about the importation of Lipodox although I was a bit suspicious because no one I knew who was following the Doxil drug shortage had heard of Lipodox.  According to the FDA, Lipodox has not been found to be a bioequivalent of Doxil. Johnson & Johnson said that it did not know if LipoDox was the chemical equivalent of Doxil.   And the ASHP said, "Lipodox cannot cannot be AP-rated to Doxil because it is not an FDA-approved product.  However, Lipodox may be substituted with Doxil on a mg per mg basis."  AP-rated means the drugs are therapeutically equivalent.

According to a 2008 JAMA article:

The 1984 Hatch-Waxman Act first authorized the FDA to approve generic drugs demonstrated to be “bioequivalent,” which is defined as absence of a significant difference in the availability of the active ingredient at the site of drug action.​ Bioequivalency can be established on the basis of the maximum serum concentration of the drug, the time until maximum concentration is reached, or the area under the curve based on serum concentration as a function of time.

Serum concentration is the amount of a drug or other compound in the circulation.
So I understand this to mean that even if drugs are chemically equivalent, if they affect blood serum concentration differently they are not bioequivalent under the law and cannot be designated a generic version by the FDA. Clinical equivalence, according to the JAMA article, looks at health outcomes such as physiological measures or mortality.

The FDA defines therapeutic equivalence as follows:

Therapeutic Equivalence (TE)
Drug products classified as therapeutically equivalent can be substituted with the full expectation that the substituted product will produce the same clinical effect and safety profile as the prescribed product. Drug products are considered to be therapeutically equivalent  only if they meet these criteria:

• they are  pharmaceutical equivalents (contain the same  active ingredient(s); dosage form and route of administration; and strength.) 

• they are assigned by FDA the same therapeutic equivalence codes starting with the letter "A ." To receive a letter "A", FDA  

• designates a brand name drug or a generic drug to be the Reference Listed Drug (RLD).

• assigns therapeutic equivalence codes based on data that a drug sponsor submits in an ANDA to scientifically demonstrate that its product is bioequivalent (i.e., performs in the same manner as the Reference Listed Drug).

Therapeutic Equivalence (TE) Codes
The coding system for therapeutic equivalence evaluations allows users to determine whether FDA has evaluated a particular approved product as therapeutically equivalent to other pharmaceutically equivalent products (first letter) and to provide additional information on the basis of FDA's evaluations (second letter). Sample TE codes: AA, AB, BC (More on TE Codes)

• FDA assigns therapeutic equivalence codes to pharmaceutically equivalent drug products. A drug product is deemed to be therapeutically equivalent ("A" rated) only if:
• a drug company's approved application contains adequate scientific evidence establishing through in vivo and/or in vitro studies the bioequivalence of the product to a selected reference listed drug. 
• those active ingredients or dosage forms for which no in vivo bioequivalence issue is known or suspected.
• Some drug products have more than one TE Code.
• Those products which the FDA does not deem to be therapeutically equivalent are "B" rated.  

Over-the-counter drugs are not assigned TE codes.

Clear?  Again, it appears that a drug must be chemically equivalent, pharmaceutically equivalent and bioequivalent to the brand name drug to be designated a "generic" by FDA.  

Sun Pharma, the UAE company which manufacturers Lipodox in India, has sent a letter to physicians stating that the dosages of Lipodox are the same as for Doxil.  My own oncologist said that his group nonetheless did not intend to use Lipodox until there was more information about its efficacy. Some gyn/oncologists are prescribing it to ovarian cancer patients, according to posts on OCNA support community on Inspire.com. It is too soon to tell how well it is working and whether it really is "equivalent" to Doxil.

In the meantime, Johnson & Johnson continues to claim, while telling patients not to confuse Lipodox with Doxil,  that it is working expeditiously to get Doxil back on the market:

Importantly, we are making progress toward our long-term solutions to bring DOXIL® back to the market, via our transition to an identified alternate supplier, additional new external manufacturing capabilities, and other, alternate solutions. To validate and qualify each of these options to produce DOXIL®, there are many critical steps, each with related timelines -- from tests to confirm the facility can produce DOXIL® to our exact specifications, to global health authority reviews of any new facilities and sites. We are moving forward as quickly as we can to advance the process.

I do not believe J&J is doing everything it can to expedite production of Doxil.  It is hardly being transparent about why it will take a year to bring it back to market.  J&J has no trouble spending huge sums of money on William Weldon who is leaving the company this month (April 2012).  Weldon's retirement package is valued at $143.5 million.  Surely J&J could make things happen more quickly in the return of Doxil if it were to spend even a fraction of this payoff to Weldon on the manufacture of Doxil.  We already know that J&J cut corners on Doxil by having only one manufacturer with a sketchy record of product quality.  I believe J&J continues to cut corners while hoping that public opinion will not turn against it, particularly now that the FDA has found a purported substitute in Lipodox.

I have been encouraging people to  sign the petition to J&J to bring back DOXIL for months. Even with the availability of Lipodox, I think it is still important to keep pressure on J&J because, for example,  Lipodox may not be covered by insurance and as I mentioned above, not all gynocological oncologists will prescribe it.  Please sign if you have not already done so.
 http://www.change.org/petitions/janssen-products-lp-bring-back-doxil-to-the-market-immediately

Guest Post on Drug Shortages- Very Moving!

 ANOTHER GUEST POST-- THIS ONE FROM A COLLEGE CLASSMATE ABOUT DRUG SHORTAGES

Testimony of Betsy Garson Neisner, patient advocate, before the Massachusetts Legislature’s Joint Committee on Public Health, February 13, 2012

Honorable Members of the Joint Committee on Public Health:

I am honored to echo for you the voices of the people whose health has been compromised by drug shortages, the voices of those who have died for lack of the prescribed drug, who fear they may die, and whose loved ones cannot get the treatment they need to survive and to thrive.

The shortage of essential drugs in the United States is a national crisis with pernicious implications for Massachusetts. There have been intermittent drug shortages for the past decade, but this year, a record 246 drugs have become unavailable in the U.S. They include at least 180 drugs that are crucial for treating childhood leukemia, breast, colon and ovarian cancer, multiple myeloma, Kaposi’s sarcoma, infections and other diseases. According to a November 2011 report issued by IMS Institute for Healthcare Informatics, the shortage of cancer drugs alone will affect almost 550,000 patients this year. Patients are dying as a result of the shortages. Each of these patients affected by the drug shortages has family members, colleagues and friends who make up a huge constituency seeking a solution from corporate America and from our political leaders. 

My own situation is a case in point. I was a forty-eight-year-old mother of two and a practicing attorney in 2002 when I was diagnosed with Stage III ovarian cancer (OVCA). 80% of the 22,000 women in America who are diagnosed with OVCA each year are diagnosed, as I was, in late stage when there is no possibility of a cure. I had a 22% chance of living five years. My first call was to the elementary school psychologist to ask how to tell Charley, my 7-year-old son, and Melaina, my 10-year-old daughter. As adopted children, they had already experienced the primal loss of their birthmothers. I was devastated that I might be the cause of another profound loss.

Since my diagnosis, I have undergone major surgery and four rounds of chemo, four seasons of my life fettered by an IV bag and hobbled by the toxic cocktail fed by gloved and masked nurses directly into my bloodstream. The gold standard chemo treatment (a drug called Carboplatin) gave me a two-year remission the first time through, and then a three-year remission after the second round, but as soon as I finished the third round, my numbers started to climb and my tumor grew back. The obvious next step was Doxil, the chemo of choice for recurrent OVCA that no longer responds to the first-line treatment. It is generally an effective drug with low toxicity, keeping the cancer at bay in a kind of peaceful coexistence with a good quality of life.

I was started on Doxil in April 2010. You can no doubt foresee the end of the story: last July, I went in to Massachusetts General Hospital for my infusion and the cupboard was bare. I was given Adriamycin in place of Doxil and suffered seven weeks of nausea along with losing my hair (for the third time). Fortunately, I was "accepted" into the selective Doxil C.A.R.E.S. program orchestrated by Janssen, the pharmaceutical division of Johnson & Johnson which distributes Doxil. Of the 2,800 women with ovarian cancer who applied to the Doxil C.A.R.E.S. program, 1,600 received the drug and 1,200 are still waiting.

Last November 21, Janssen issued a notice that the manufacturer, Ben Venue Laboratories of Bedford, Ohio, was stopping production indefinitely to attend to neglected maintenance of machinery. Janssen had an exclusive contract with Ben Venue to manufacture Doxil, although it knew or should have known that there had been a history of quality problems at the plant. That same company also recently suspended production of methotrexate because of “significant manufacturing and quality concerns.” When the current supplies are exhausted within the next two week, hundreds or even thousands of children may die of childhood leukemia, a disease that is largely curable.

I have had a successful run with Doxil since April 2010, with the exception of the one dose of Adriamycin last July, but now wait from month to month to see if I will get my Doxil infusion when I arrive at Mass. General after my 2 ½ hour drive from the Pioneer Valley. There may be some stores of the drug left because clinical trials using Doxil had to be cancelled and because patients have died or their diseases have progressed without the benefit of treatment with Doxil, but if I am able to get more than the 7 Doxil infusions earmarked for me, it will be difficult for me to rejoice while knowing that I benefit from the sacrifices of other women. When those stores have been exhausted, it’s back to Adriamycin or on the “the divil I don’t know.”

My story is one of too many. I am in touch with women across the country with ovarian cancer, and ache at the frustration and sadness I hear. These women, all of whom have metastatic cancer, know that there is a drug that promises a reprieve, quality time to spend with family or to work, to enjoy life, to pursue happiness. Science and industry created a successful drug, but industry let it disappear.

I speak you on behalf of all Massachusetts patients, indeed all Americans, affected by the drug shortages, not just for myself. Medicines, anesthesia drugs and nutritional supplements used for tube feeding, all of which have seen shortages in the past year, must be defined and treated differently from other manufactured goods. If an effective drug has been developed and placed in use, if people rely on it to achieve or maintain their health, how can the manufacturer

ethically or legally suspend production? There is no substitute for Doxil. We face debilitating chemo-induced fatigue, nausea, neuropathy, bowel obstructions and a cascade of worse side effects with the remaining end-of-the-line drugs. And for the most part, the other drugs that are used in Doxil’s absence are far more expensive than Doxil. Perhaps that is why pharmaceutical companies choose to devote their production capacity to the manufacture of new drugs: maximizing the bottom line fulfills their duty to shareholders, even if at the cost of consumer’s health, finances and happiness.

What can be done to make the drug manufacturing system more elastic and responsive to increased demand? Is not public health as much a legitimate goal for the business community as profits? If ever there were a cause which would provide definition and impetus to the Occupy Wall Street activists, this is one of the most stark and quantifiable, because people are dying. More important, the drug crisis affects the reputation of America, its values and its economic system. Massachusetts has historically served as the medical mecca for the world, but drug shortages undercut our reputation for both medical expertise and humanitarianism.

I have been fortunate: although I retired from the bar because of the unpredictability of treatments, cognitive deficits from chemotherapy and fatigue, I have found work as the director of a community cancer support center in the Pioneer Valley. Twice I have served as a consumer advocate on the ovarian cancer research program of the Congressionally Directed Medical Research Program of the Department of Defense. I also serve as consumer representative on Massachusetts General Hospital’s drug shortage task force. I have watched my children grow from 7 and 10 years old to 17 and 20. I am surfing along the tail end of the Bell curve. My cancer is stable as long as I continue on Doxil.

But I want to channel for you the frustration, the anger, the disappointment and the fear of others. I want you to imagine that you are in a locked room with your house on fire, and you have at hand a garden hose and a fire hose. Imagine how you would feel if someone were to take the fire hose away.

I appreciate the invitation to address you and applaud you for holding this inquiry. I hope that you will address this issue quickly and effectively.

First the Women, Then the Children

Although drug shortages ravage this country, to date only one drug, DOXIL, has become unavailable nationwide.  Until now.   Injectable Methotrexate, which is used to treat children's leukemia, is disappearing from the market.  Gardiner Harris reported in the New York Times on February 10, 2012 that supplies could run out in the next few weeks.  ABC News echoed that report. (see below) Both observed that acute lymphoblastic leukemia (ALL),  one of the cancers we have learned largely to cure, could again become deadly for children as it was more than 60 years ago before the discovery and use of methotrexate as a treatment. (Developing a cure for ALL is a key story in the excellent book, Emperor of All Maladies, A Biography of Cancer by Siddhartha Mukherjee.  See review here.)

Methotrexate is, in part,  the victim of the Ben Venue Laboratories debacle which also caused the DOXIL shortage.  However, unlike DOXIL, which only Ben Venue manufactured, four other companies, APP, Hospira, Sandoz and Mylan, manufactured injectable methotrexate .  Like Ben Venue, Sandoz stopped manufacturing methotrexate due to quality control problems and issued a recall.  However, that was in 2010 and Sandoz has not brought the drug back to market.  The other manufacturers have experienced increased demand or "manufacturing delays" and now are facing shortages.

What explains the drug shortages?  I have written about this topic before here and here, suggesting it is the profit motive of the pharmaceutical companies.  However, two recent articles, one in the New England Journal of Medicine and the other in the Huffington Post, seem to suggest that demand of the pharmaceuticals is affected by how much money oncologists earn from chemotherapy drugs. The NEJM article explains (after identifying manufacturer profit as the first cause of the shortages):

The second economic cause of shortages is that oncologists have less incentive to administer generics than brand-name drugs. Unlike other drugs, chemotherapeutics are bought and sold in the doctor's office — a practice that originated 40 years ago, when only oncologists would handle such toxic substances and the drugs were relatively cheap. A business model evolved in which oncologists bought low and sold high to support their practice and maximize financial margins. Oncologists buy drugs from wholesalers, mark them up, and sell them to patients (or insurers) in the office. Since medical oncology is a cognitive specialty lacking associated procedures, without drug sales, oncologists' salaries would be lower than geriatricians'. In recent decades, oncology-drug prices have skyrocketed, and today more than half the revenue of an oncology office may come from chemotherapy sales, which boost oncologists' salaries and support expanding hospital cancer centers.

Ultimately the change in the Medicare law is blamed again for the shortages because neither oncologists nor drug manufacturers make sufficient profit from these generic injectables.  However, this explanation remains at odds with the ASPE Report of Health and Human Services,  as I discussed more thoroughly here, that manufacturers are influenced less by price than by the practice of avoiding inventory surplus.

No matter the specific cause, as I have said before, it is all about making sure that those companies that have a significant amount of money continue to do so.  The pharmaceutical industry is the third most profitable industry (running almost at a dead heat with number 2, the internet industry).  In the name of profits, first the women will die (thanks to the DOXIL shortage) and then the children (thanks to the Methotrexate shortage).  When will it stop?

If you want to help, please sign this petition to the very rich Johnson & Johnson demanding that DOXIL be returned to the marketplace immediately.
 http://www.change.org/petitions/janssen-products-lp-bring-back-doxil-to-the-market-immediately

#BoycottJohnson&JohnsonGotDoxil?

People with cancer are dying due to drug shortages.  It was to be expected and indeed was reported this week as a result of a survey of oncologists by a for profit research company with ties to the drug industry.  The survey results revealed that 40% of the oncologists  said deaths were hastened by the drug shortages.  "[L]egislative action is too late for some patients, the survey results suggest."

The worst shortage this past year was the worldwide shortage of Doxil due to serious quality control problems at the manufacturing facility.  Johnson & Johnson, through its company, Janssen Products LP, owns the patent to Doxil.  J&J decided in 2010 to use only one contract manufacturer for worldwide production of Doxil.  That manufacturer, Ben Venue Laboratories, has had known quality control problems in its manufacturing but to save a buck, J&J stood by Ben Venue.  By the summer of 2011 regulators from the FDA and European Medicines Agency (EMA) had identified enough problems at Ben Venue that the manufacturer shut down production lines to address the problems.  Ben Venue stopped manufacturing Doxil and the patients who needed it, mostly women with ovarian cancer but also patients with Kaposi's sarcoma and multiple myeloma, were left high and dry.  J&J tried to pretend the drug would be back soon and set up a waiting list for patients already on the drug, but doses trickled out. Eventually in late December 2011, J&J had to acknowledge Doxil would not be available until "November or December 2012, at the earliest". (A Message From Our President 12/23/11).

On its Facebook page, J&J claims : "Caring for the world, one person at a time, inspires and unites the people of Johnson & Johnson."  Really??  How much do you care about our mothers, sisters, grandmothers, aunts and nieces that are dying because you did not want to spend the money to have a backup plan to manufacture Doxil? This drug shortage is deadly.  Johnson & Johnson must be held accountable.

We have seen the power of the internet for change, not only in the Middle East, but here in this country. In recent weeks mass outrage on the internet has lead to the demise of (1) antipiracy bills, (2) the antigay campaign to remove Ellen Degeneres as J.C. Penney's spokesperson (#StandUpForEllen) (3) Susan G Komen's withdrawal of grants to Planned Parenthood and (4) Bank of America's fee for debit cards.  I propose that we express our outrage at the drug shortages, which are driven by the same Wall Street greed for the almighty dollar, by organizing against Johnson & Johnson on the internet.  We need to take to Facebook, Twitter and our emails, engage organizations such as Change.org, Care2petitionsite and credoaction.com and get the message out to Boycott J&J for their role in producing a life threatening drug shortage.  We need graphics, cartoons and a lot of social media communication about the issue so that action is finally taken to save people's lives and stop the greedy pharmaceutical industry.

Who is with me?

No Drugs for You! Growing Indifference to the Drug Shortage

For over a year, this country has been plagued by drug shortages.  The Senate and House have held hearings but there appears to be no movement toward any action in passing even the minimalist bills pending in each chamber which would merely require notice to FDA from drug manufacturers six months before drug shortages are expected. Indeed there appears to be little publicity about the problem even as it affects problems other than cancer such as ADHD (see also here) and severe vitamin deficiencies.  Contrast this lack of interest in drug shortages with the overwhelming interest and coverage of the antipiracy laws last week as certain websites went down in protest of what they claimed (erroneously) was censorship.  Young people, in particular, were gripped by what they thought might be the loss of access to the internet and free content on the internet.  Almost a quarter of young people thought the antipiracy bills were the top news story of the week of January 17, 2012.

Perhaps young people do not think much about drug shortages because they are less likely to get sick or have any personal experience with the shortages unless they take Adderal or have a family member with cancer.  But the shortages continue and are spreading to other countries such as Australia, affecting availability of chemotherapy, antibiotics and anesthetics there, and Canada.  Indeed 2011 was a record year for shortages in the United States affecting 267 drugs, according to the University of Utah.  And still nothing is being done.  We strutiously proceed and hope that, like the weird weather we are experiencing, it will not last and definitely will not hurt us in the long run.

Janssen released a new batch of Doxil in mid January because of number of people, like me, fell off the waiting list as we were treated with other medications.  Some of my friends got a reprieve as a result and got much needed doses of Doxil.  I am in remission according to my doctor although for how long is uncertain.  Given the lack of interest in the shortages or any other significant issue by the public or Congress, who seem to be mobilized only by the hysteria surrounding the alleged threat of loss of the internet (see here), it is hard for those of us directly affected by the shortages to keep the issue alive, particularly when we are struggling to keep ourselves alive.

A little help here?

To the Senate: Don't Take Money from the Elderly; Follow the Real Money!

TODAY IS A GUEST POST FROM ONE OF MY "SISTERS" WITH OVCA. IT IS A LETTER TO THE SENATE FINANCE COMMITTEE WHICH HELD A HEARING A FEW WEEKS AGO ON THE DRUG SHORTAGES. THOSE WHO TESTIFIED WERE CLEARLY HANDPICKED TO SUPPORT THE VIEWPOINT THAT THE MEDICARE PLAN B CAP IS CAUSING THE SHORTAGES, A VIEW WITH WHICH ECONOMISTS FROM HHS DISAGREE. SEE MY POST HERE


To: Senate Committee on Finance
Editorial and Document Section
Room SD-219, Dirksen Senate Office Building
Washington, DC 20510-6200

Re: Senate Finance Committee Hearing “Drug Shortages: Why They Happen and What They Mean”, December 7, 2011

I wish to submit this statement for the record of the hearing on the shortages of critical drugs. I have been a biomedical researcher for my entire adult life. For eight years I was a scientist at the National Institutes of Health in Bethesda Maryland and for twenty years I have been a professor of biological sciences at St. John’s University in New York City. A year and a half ago I was diagnosed with ovarian cancer. I would be taking Doxil, one of the most powerful of the chemotherapies for this type of cancer, if it were available but unfortunately Johnson and Johnson has stopped manufacturing it, forcing me to turn to less effective drugs with worse side effects.

In a free market another manufacturer could step in to take advantage of the unavailability of Doxil and other life-saving drugs that are in short supply. For several reasons there is no longer a free market in these drugs. In the case of Doxil, Johnson and Johnson sought and won extended patent protection under the Orphan Drug Act. They have the exclusive right to manufacture Doxil until 2014 but they aren’t making it, thus endangering the lives of the over 7,000 people who were depending on it and bringing to a halt many of the 30 clinical trials that require it.

Most of the drugs in short supply are generics with low profit margins, while the most expensive drugs rarely have these “production problems”. According to an article in March in Business Week , the operating margins of Johnson and Johnson have grown considerably, from 17.7 percent in 1990 to 26.8 percent in 2010, and they have 28 billion dollars in cash. One might think this would be enough to fix production problems and resume saving lives.

However according to a recent article in the NY Times  many drug companies are having difficulty finding ways to profitably invest their hoards of cash. Instead of investing in research or improving their production facilities they are laying off scientists and using their cash to buy back their stock. This inflates the earnings per share of the stock by simply reducing the number of shares. Coincidentally, executive compensation is often pegged to increases in earnings per share. Since 2006 Johnson and Johnson has bought back 23.5 billion dollars worth of its own stock while laying off over 10% of its workforce .

As a taxpayer and a scientist I have contributed to the development of the basic science and drug discovery necessary to the continuing profitability of the drug companies. I do not believe they should have the right to maintain patent protection on critically needed drugs that they cannot or will not provide. There has been a total lack of transparency from Johnson and Johnson on this situation. They are endangering lives and yet they do not seem to be accountable.

The ovarian cancer patients who have been abandoned by Johnson and Johnson are America’s mothers, sisters and daughters. Most of us know someone with this disease. Our president’s mother died of it. How can they just shut off the supplies of life-saving drugs? The consolidation of the drug companies has resulted in powerful monopolies that increasingly do not serve the public interest

Signed,
[NAME REMOVED FOR PRIVACY REASONS]

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

 Doxil.com

UPDATED DECEMBER 13, 2011

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.