Latest Drugwonks' Blog
Substandard Subcontinent.
On its Tuesday broadcast, the CBS Evening News reported on former Ranbaxy executive Dinesh Thakur, who “was asked by his boss to investigate allegations of fraud at the company” in 2004. He soon “uncovered disturbing problems with the data required by the FDA to prove the effectiveness of Ranbaxy drugs.” According to Thakur, the company had “gotten approvals from the FDA to sell drugs that were based on no data, or data that was fraudulent.” After presenting his finding to Ranbaxy executives in 2005, Thakur “says nothing was done,” so he “blew the whistle to the FDA.”
The CBS News website reports the FDA investigation uncovered a “persistent ... pattern” by Ranbaxy of submitting “untrue statements.” Auditors found that the applications of at least 15 new generic drugs contained over 1,600 data errors, leading the FDA to conclude the company’s products were “potentially unsafe and illegal to sell.” The investigation that was launched in the wake of “Thakur’s allegations led Ranbaxy to plead guilty to seven felonies.”
I’ve just returned from Kiev, Moscow, and Algiers where I spoke on pharmaceutical quality, bioequivalence, and generic interchangability. (And, yes, I did get a chance to tour around a little too.)
Two comments worth sharing.
* In Algiers, the head of the domestic generic drugs manufacturers, told me that the issues of generic quality and therapeutic substitution were “obsolete.” It was a laugh line – because that’s how the audience responded.
* In Moscow, at a meeting of federal and provincial healthcare officials, one comment (relative to patient choice vs. limited formulary options) was, “The only patients who give us trouble are those who want more expensive treatments.”
In Russia -- if you like your insurance, you can keep it. If you don't like it, you can keep it ... quiet.
Think of it as a healthcare safety nyet.
The themes for the Algerian Society of Pharmacy’s 22nd Journées Pharmaceutiques Nationales was health policy , intellectual property , self-medication and hospital pharmacy. A panel of national and international experts addressed the generic drugs and the pharmaceutical industry in Algeria.
According to Prof. P. J. Pitts , president of the U.S. Center for Medicine in the Public Interest, "We cannot replace quality with cost. Even a high quality generic does not always give the same therapeutic effect as the innovative product . The authorities should work with physicians and pharmacists to ensure that patients remain at the center of debate. The most expensive drug is the one that does not work. The most effective treatment is one that delivers good patient outcomes," he said.
The President of the National Council of the Order of Pharmacists , Dr. Lotfi Benbahmed, insisted on continuing education for pharmacists and also the establishment of a system to determine the traceability of drugs to determine responsibility.
"The door is open to counterfeiting and quackery. It is a great danger to public health if official medication is not controlled."
The complete article (in French) can be found here.
A small item from BioCentury that deserves more attention:
Drug companies will be able to provide copay assistance to consumers who purchase health insurance through the Affordable Care Act's exchanges. HHS Secretary Kathleen Sebelius announced the decision in a letter sent on Wednesday to Rep. Jim McDermott (D-Wash.), resolving a major uncertainty about the healthcare law. Under federal kickback laws, drug companies are not permitted to provide copay assistance directly to consumers insured by federal programs such as Medicare and Medicaid. According to Sebelius' letter, HHS does not consider qualified health plans purchased through federal or state exchanges to be federal health programs.
Washington, DC—HR Policy Association, representing the chief human resource officers of more than 350 of the largest private sector employers in the United States, announces the selection of Tevi Troy, former Deputy Secretary of the U.S. Department of Health and Human Services, to lead the development of a health care initiative of the HR Policy Foundation.
HR Policy Association member companies, all of whom are large employers, collectively spend more than $75 billion annually on health care in the U.S. and are in the process of assessing their company's current and future health care strategies in light of the growing instability of the American health care system. They are seeking to establish a leadership organization dedicated to developing a more sustainable health care delivery system for the employees, dependents and retirees of large employers.
Dr. Troy is currently a Senior Fellow at Hudson Institute, where he will remain an Adjunct Fellow, and a writer and consultant on health care and domestic policy. In 2007, he was unanimously confirmed by the U.S. Senate as the Deputy Secretary of the U.S. Department of Health and Human Services. He was the chief operating officer of the largest civilian department in the federal government, with a budget of $716 billion and over 67,000 employees. In that position, he oversaw all operations, including Medicare.
HR Policy Association CEO Jeffrey C. McGuiness said, “We are delighted to announce that Dr. Troy will be leading this critically important initiative. He brings not only a wealth of understanding and expertise about health care, policy and the government, but a strong managerial and operations background. Having successfully run the largest department in the government in terms of employees and budget, focused on all aspects of health care, Dr. Troy is uniquely qualified to help guide and lead this new organization.”
Dr. Troy has extensive White House and Capitol Hill experience. During the George W. Bush Administration, he served as Deputy Assistant and then Acting Assistant to the President for Domestic Policy and was the White House’s lead adviser on health care, labor, education, transportation, immigration, crime, veterans and welfare. Dr. Troy also served as the Policy Director for U.S. Senator John Ashcroft and as Senior Domestic Policy Adviser and Domestic Policy Director for the U.S. House Policy Committee.
In addition to his senior level government work and health care expertise, Dr. Troy is also an author and presidential historian. He is a frequent television and radio analyst, and has appeared on CNN, CNBC, FOX News, FOX Business, and The Jim Lehrer Show, among other outlets. He is currently on tour for his latest book, What Jefferson Read, Ike Watched, and Obama Tweeted: 200 Years of Popular Culture in the White House and is the author of Intellectuals and the American Presidency: Philosophers, Jesters, or Technicians? (Lanham: Rowman & Littlefield, 2002). He has written over 100 articles, for The Wall Street Journal, The Washington Post, Forbes, The New Republic, Commentary, Reason, Investor’s Business Daily, National Review, Washingtonian, The Weekly Standard, and other publications. Dr. Troy has a B.S. in Industrial and Labor Relations from Cornell University and an M.A and Ph.D. in American Civilization from the University of Texas at Austin.
I'm in town to give a presentation on the importance of API and excipient quality, the urgency of advancing pharmacovigilance, and the evolution of both regulatory innovation and international regulatory fraternity.
The local english-language newspaper is The Moscow Times. It's what you get at the hotel. And amidst all the stories on NSA wire-tapping was an editorial that nearly made my heart stop. The title, "Dispelling the Smoke Screen." Here's the opening paragraph:
"The statement that smoking is harmful to your health is only a theory, not a medical fact."
Don't believe me? Read the article and then exhale. And then get angry.
This in a nation where non-communicable diseases (most notably alchohol and heart disease) are major killers. 50% of Russians smoke cigarettes.
I intend to discuss this article during my presentation.
Outrageous!
Check out Pfizer’s new “Value of Medicines: How Medicines Have Changed Our World” position papers. They’re actually concise and to the point (unlike many of the policy papers we see these days).
At the moment there are three to choose from:
* The Value of Statins
* The Value of Oncology Medicines
* The Value of Adherence
They can all be found here.
According to the website, “Papers will soon be available demonstrating value in a variety of areas including Vaccines, Diabetes, Rare Diseases, Atrial Fibrillation-Stroke, Pain, Renal Cell Carcinoma, Smoking Cessation, Breast Cancer, and more. Stay tuned!”
Kudos to Ian & Company for a job well done.
According to Friedrich Hayek, socialists are wrong because they disregard the fact that modern civilization naturally evolved and was not planned. Hayek refers to this fundamental error as “the fatal conceit.”
And on CNBC it’s what Larry Kudlow used to describe ObamaCare during a debate on the roll-out of the Affordable Care Act– the fatal conceit. The panel consisted of Jonathan Gruber (MIT professor and a designer of the ACA), Matt Welch (editor of Reason Magazine), and me.
Here are two clips to enjoy:
“ObamaCare already a huge turkey”
“Previous system of healthcare archaic”
Are we on a slippery slope to a single payer system? If we are, you can kiss investment goodbye, along with innovation, and any hopes for the future of personalized medicine. Is this a system that was designed to fail?
You be the judge.
We shall not grow wiser before we learn that much we have done was very foolish
-- Friedrich Hayek
Factory Closing Means One Less Producer
Nick Mulcahy, MedScape
The already small number of producers of generic cancer drugs in the United States just got smaller.
Ben Venue Laboratories, a major manufacturer of generic chemotherapy injectables, announced the closure of its plant, in Bedford, Ohio, earlier this month, citing problems with both the facility and projected revenues. It will effectively depart the US market by the end of the year.
The loss is a significant blow to the recovery of the US marketplace for generic cancer drugs, said Erin Fox, PharmD, director of the drug information service at the University of Utah Hospitals and Clinics in Salt Lake City. Dr. Fox has been monitoring drug shortages in the United States since 2001.
"I really feel like it's a big step back," she told Medscape Medical News in an interview.
Our supply chain is that much more fragile.
The US market for generic cancer chemotherapy injectables has improved since the "crisis" of 2011, she said. But the loss of Ben Venue, which a company Web site touts as "one of the largest sterile injectable facilities in the world," is important. "Our supply chain is that much more fragile with the closing," said Dr. Fox.
"A significant portion of the ability of the market to meet demand is now gone," said William Greene, PharmD, chief pharmaceutical officer at St. Jude Children's Research Hospital in Memphis, Tennessee, who also spoke to Medscape Medical News about the Ben Venue closure.
"We are reaching a scary situation," said Sara Butler, PharmD, oncology clinical pharmacy supervisor at Barnes-Jewish Hospital in St. Louis, Missouri, about the loss of manufacturing capacity in an interview.
Another expert said that the impact of the plant closure is unclear.
"There's not enough transparency [from product distributors about the factory origins of generic drugs] to know exactly what [Ben Venue is] producing at this point," said Jeffrey Ward, MD, from the Swedish Medical Center in Seattle, who is chair of the Clinical Practice Committee of the American Society of Clinical Oncology (ASCO). "That's almost scarier than knowing what the impact is," he told Medscape Medical News.
Set Back of 4 to 6 Years
Before the news of the Ben Venue closing, Dr. Fox believed that the problem would see a significant improvement in ongoing and active shortages in about 2 years. Now, that time period doubles or triples. "I think it does set us back 4 to 6 years," she said.
Dr. Fox's speculative timeline was revealed earlier this week in the trade publication The Cancer Letter.
Ben Venue, which specializes in making injectable drugs, has been a major player in the US market for generic chemotherapy, Dr. Fox explained. There is no new manufacturer to take Ben Venue's place. "Nobody's jumping on board right now," she said.
We really need another supplier.
In the US cancer generics market, there are 3 "workhorse companies" that provide most of the generic chemotherapy injectables, said Dr. Fox. These are Hospira, Teva, and Bedford Laboratories, which is a distributor of Ben Venue products and products of other third parties. (Bedford and Ben Venue are both owned by Boehringer Ingelheim.) Pfizer is also in the market. Given this small circle, the loss of Ben Venue's manufacturing is significant, she believes. "We really need another supplier [of generic oncology products]," she said.
However, she emphasized that the situation is not as bad as it was 2 years ago. "People are not going without treatment, as in 2011."
A different opinion comes from Dr. Butler, who said that at Barnes-Jewish Hospital, there are still times when staff have to tell cancer patients that "we don't have certain drugs." She believes the situation has become "much worse in the last 2 years."
New Data on Chemotherapy Shortages
Currently, there are 31 cancer drugs actively in short supply, which is down from nearly 40 in 2011, according to Dr. Fox.
Also, there were only 4 chemotherapies that newly went into shortage in 2013, compared with 26 new chemotherapy shortages in 2011, according to data from a presentation that Dr. Fox made this week at a conference of hospital executives in Atlanta.
However, chemotherapies in short supply are just a small part of the overall drug shortage picture in the United States, Dr. Fox pointed out.
Notably, Ben Venue played a role in the cancer drug shortage crisis of 2011, Dr. Fox believes.
The production facility closed that year after a series of customer complaints about products and inspections from the US Food and Drug Administration (FDA) and other agencies. Subsequently, 2 very important mainstays of cancer treatment — doxorubicin and methotrexate — went into extremely short supply, said Dr. Fox. It turned out that Ben Venue was a producer of both drugs.
The marketplace eventually reacted, with some help from the FDA, and both dire shortages were alleviated.
Among other events, the FDA approved APP Pharmaceuticals as the manufacturer of a preservative-free form of methotrexate, and allowed an Indian manufacturer, Sun Pharma Global, to export generic doxorubicin to the United States.
After the 2011 closing, the Ben Venue plant resumed "limited" production in 2012. By that time, the drastic impact of the initial closure on the marketplace had passed, said Dr. Fox. "All of that pain has been dealt with in one way or another," she explained, adding that it holds true today, even with the news of the plant closure.
Immediate Problems
The closure nonetheless creates immediate clinical problems. For instance, Ben Venue and its sibling company, Bedford Laboratories, have been the sole US suppliers of thiotepa, Dr. Fox pointed out. The FDA is now allowing thiotepa, which is used in stem cell transplants and other settings, to be imported from Italy. "But that's very inconvenient for people; there's almost a month's delay," she said.
Dr. Greene said that procuring thiotepa from abroad is "exceedingly expensive and time consuming," and that St. Jude's is now looking for alternative drugs for chemotherapy regimens involving thiotepa. He is also concerned that daunorubicin, which is used in the treatment of leukemias, will fall into short supply because, now, only Teva will be producing the drug.
The Ben Venue plant has also been the world's sole manufacturer of Doxil, the branded version of doxorubicin hydrochloride liposome injection, which is owned by Johnson & Johnson. The product could disappear from the market for a time until a new manufacturer is found, as reported this week by Medscape Medical News.
Currently, Doxil is being evaluated in a number of clinical trials. Its potential disappearance from the marketplace puts the viability of these trials at risk because a generic substitution, which would be acceptable for patients in the clinic, is not possible in a research setting, ASCO's Dr. Ward pointed out.
The Murky World of Generics Manufacturing
Dr. Ward said he was surprised to learn that a branded drug, Doxil, owned by a major drug company, Janssen/Johnson & Johnson, was made by a generics manufacturer. But the cancer generics market is full of surprises and unknowns, he noted.
Take the example of Bedford Laboratories, which began as a division of Ben Venue in 1993. Both entities have been properties of Boehringer Ingelheim since 1997.
Unlike Ben Venue, Bedford will remain in business.
That's good news, because Bedford is the leading provider of cancer generic sterile injectables in the United States, with 30% of the market, according to an analysis led by Janet Woodcock, MD, head of the pharmaceuticals division at the FDA, and published earlier this year (Clin Pharmacol Ther. 2013;93:170-176).
But currently, Bedford is "out of stock" of a long list of sterile injectables, including many oncology products. The list, posted October 1 on the company Web site, includes Adriamycin, cytarabine, dacarbazine, etoposide, gemcitabine, methotrexate, paclitaxel, and vinblastine.
Some of these are very important products, said Dr. Ward. For instance, gemcitabine is part of the standard of care in pancreatic cancer.
"What you don't know from that list is how many of these drugs were manufactured by Ben Venue and how many come from elsewhere," he explained.
The company product announcement says these out-of-stock injectable drugs could be available "pending production as capacity permits."
"Bedford will continue to distribute products manufactured by Ben Venue Laboratories until that inventory is depleted," a company spokesperson said in an email to Medscape Medical News.
Generally, "there is not much transparency in this market," observed Dr. Ward.
He explained that producers of generic sterile injectables in the United States are regulated in terms of original licensure and the design of manufacturing processes. "But the FDA does not know who is having problems with a factory or profitability," he said, referring to the 2 reasons cited by Ben Venue for leaving the US market.
Generics companies can also switch their manufacturing from a drug that is not profitable to one that is, which can play havoc with the market availability of agents, said Dr. Ward.
He noted that the generics market, which includes chemotherapy injectables, is inherently volatile because profit margins are thin. Once on the market, "generics get very cheap very quickly," he said. Any variable that increases costs cuts into these already thin profits. This is exacerbated by that fact that the Centers for Medicare & Medicaid Services only updates the stated average sales price every 6 months, forcing companies to wait long periods for an approved adjustment in price. As a result, companies can feel a need to start and stop the production of certain products.
St Jude's Dr. Greene agrees that the generics market is a murky business in which many manufacturing and related planning details are not disclosed. "We just know when something is gone," he noted. The FDA Safety and Innovation Act, enacted in 2012, requires that drug manufacturers to notify the FDA as soon as they anticipate interruptions in drug production, and 6 months in advance if a product is to be discontinued. Although the law "improves the situation," Dr. Greene said, it has shortcomings.
Dr. Ward observed that the generics manufacturers managed to retain a number of loopholes in the law, which weaken its sentinel nature.
Seven companies supply 90% of the generic injectables market, said Dr. Fox. However, not all 7 make oncology products. Who manufacturers what product at what time is not publicly available information, and must be discerned through data detective work, she said.
The whole model is problematic, said Dr. Ward. "We have left it to business to ensure our drug supply."
Medical errors are a real problem. I won’t deny that.
It was bad enough when the often-quoted Institute of Medicine figure that 98,000 deaths per year in the US are caused by medical errors was in vogue, but now a paper in the Journal of Patient Safety states that adverse medical events result in 210,000 to 400,000 deaths per year and 10 to 20 times those numbers of serious harms.
Since the paper disparages the medical profession, it has received a lot of media attention.
Most articles about it simply regurgitate the dismal estimates without any real attempt to dig into the paper’s methods.
Let’s take a closer look.
As is true of many papers, the abstract is a bit sketchy when describing how the paper arrived at its conclusion.
The full text of the paper reveals the author found four studies that looked at what are described as preventable adverse events in US hospitals within the last seven years. All four used the Global Trigger Tool which involves the screening of records for adverse events by nurses or pharmacists and a secondary review by physicians.
Based on opinions by “experts,” the author made a key, but erroneous, assumption that all adverse events are preventable.
Read the full blog here.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
