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06/12/2017 03:08 PM | Robert Goldberg
Here's an oped from the Morning Consult by regenerative medicine/stem cell pioneer and visionary Robert Hariri and me. If America regains leadership in regenerative medicine it can spur better health and economic growth.
Regenerative Medicine Can Help Make America Great
ROBERT HARIRI AND ROBERT GOLDBERG | JUNE 12, 2017 | 05:00 AM
When President Donald Trump urged the biopharmaceutical industry to reduce the price of new medicines and to increase its manufacturing in the United States, many took it as a threat.
We believe it’s a call to action. America’s ingenuity in biomedical research is unsurpassed. However, our country is losing out to other nations in the fastest growing biotechnology sector, called regenerative medicine: harnessing the capacity of our cells to repair and restore health and sustain well-being.
Second place is not an option. The regenerative medicine market is growing about 21 percent a year and is expected to be worth over $350 billion by 2050. Today, the U.S. regenerative medicine sector is generating $3.6 billion in revenues and has produced 14,000 jobs. By 2050, the industry could create nearly a million new jobs nationwide.
Regenerative medicine will also reduce the cost of disease. Such therapies will replace drugs, devices, and surgery, saving lives, increasing productivity, and reducing the cost of care. This transformation will add trillions in value to our economy.
Finally, regenerative medicine will also make America more secure. Our nation still lacks the ability to quickly and cheaply mass produce vaccines, antidotes, and cell therapies to counter pandemics and bioterrorism. Our fighting forces need reliable sources of these countermeasures and deserve immediate access to treatments that give them back their lives. We shouldn’t outsource the safety and well-being of our nation and our Armed Forces to other countries.
To regain leadership in regenerative medicine, U.S. firms don’t need government loans, tax credits or massive de-regulation. Instead, it needs the opportunity to invest in reducing the time and cost of manufacturing cellular therapies. To the extent that regenerative medicine is curative it must be made available at vaccine like prices. At present, only a handful of people can afford such treatments.
China and Japan are now in forefront of reducing the cost of producing stem cells, tissue, and other products with restorative biological properties. As a result, they are attracting more capital and forming more new companies than the U.S.
In 2014 Japan became the first country in the world to adopt an expedited approval system specifically for regenerative medical products and to allow outsourced cell culturing. Two products were approved under the new system within a year of its adoption.
By contrast, the Food and Drug Administration regulates any use of manufactured stem cells as equally risky without regard to prior use, health benefit, or therapeutic potential. Indeed, many of the most common stem cell therapies — including bone marrow transplants and blood transfusions — would require 10 years of FDA review if they were brought to market today.
The problem isn’t over-regulation. It’s outdated regulation. Safety checks and benchmarks for cell manufacturing should be based on real world evidence of past applications. Regulation should focus on the specific potential side effects for each specific potential use. In this regard, we agree with incoming FDA Commissioner Scott Gottlieb, who has noted, “Expediting the development of these novel and transformative technologies like gene- and cell-based therapies doesn’t necessarily mean lowering the standard for approval, as I believe other countries have done. But it does mean having a framework that’s crafted to deal with the unique hypothetical risks that these products pose.”
In fact, the United States has the best regenerative medicine manufacturing technology in the world. But it is literally sitting unused in warehouses.
For example, under the Accelerated Manufacture of Pharmaceuticals program, private companies partnered with the Defense Advanced Research Projects Agency to develop mobile cell and tissue manufacturing plants that can be set up almost anywhere. The facilities can produce cells and tissues at a fraction of the current cost. These mobile factories make real-time production of vaccines and biologics for potential bioterrorist threats and pandemics possible. They are also low-cost, high-tech platforms for experimental evaluation of any type of regenerative medicine.
AMPs are operating in Indonesia, Singapore, China, and Japan where cell products — including vaccines — are being mass produced. Not a single AMP is being used in the United States because of outdated regulations.
To remove this regulatory obstacle, the Trump administration should establish a separate regenerative medicine pathway. This pathway, which could be developed by DARPA, FDA, and the Centers for Disease Control and Prevention, would develop regulatory standards for the safe manufacturing and testing of development of regenerative products to treat battlefield related traumas such as traumatic brain injury, life-threatening limb damage, and drug-resistant pathogens.
The focus on the conditions and circumstances unique to war or counter-terrorism is both appropriate and strategic. After World War II, Franklin Roosevelt directed that the scientific and entrepreneurial talents used to achieve ramp up war-time production of penicillin and blood plasma “be used in the days of peace ahead for the improvement of the national health, the creation of new enterprises bringing new jobs, and the betterment of the national standard of living.”
What was created exceeded that vision. The cooperative efforts to achieve mass production of penicillin and blood plasma inspired and supported the creation of industries that employ millions of people today.
Similarly, developing an affordable source of cell therapies to heal our fighting forces and protect the homeland will yield a wide array of affordable technologies and cures that will produce, in FDR’s words, a fuller and more fruitful employment and a fuller and more fruitful life. Simply put, by making the manufacture of regenerative medicine affordable can help make America great.
Robert Hariri is CEO of Celularity. Robert Goldberg is vice president of Center for Medicine in the Public Interest. Read More & Comment...
Regenerative Medicine Can Help Make America Great
ROBERT HARIRI AND ROBERT GOLDBERG | JUNE 12, 2017 | 05:00 AM
When President Donald Trump urged the biopharmaceutical industry to reduce the price of new medicines and to increase its manufacturing in the United States, many took it as a threat.
We believe it’s a call to action. America’s ingenuity in biomedical research is unsurpassed. However, our country is losing out to other nations in the fastest growing biotechnology sector, called regenerative medicine: harnessing the capacity of our cells to repair and restore health and sustain well-being.
Second place is not an option. The regenerative medicine market is growing about 21 percent a year and is expected to be worth over $350 billion by 2050. Today, the U.S. regenerative medicine sector is generating $3.6 billion in revenues and has produced 14,000 jobs. By 2050, the industry could create nearly a million new jobs nationwide.
Regenerative medicine will also reduce the cost of disease. Such therapies will replace drugs, devices, and surgery, saving lives, increasing productivity, and reducing the cost of care. This transformation will add trillions in value to our economy.
Finally, regenerative medicine will also make America more secure. Our nation still lacks the ability to quickly and cheaply mass produce vaccines, antidotes, and cell therapies to counter pandemics and bioterrorism. Our fighting forces need reliable sources of these countermeasures and deserve immediate access to treatments that give them back their lives. We shouldn’t outsource the safety and well-being of our nation and our Armed Forces to other countries.
To regain leadership in regenerative medicine, U.S. firms don’t need government loans, tax credits or massive de-regulation. Instead, it needs the opportunity to invest in reducing the time and cost of manufacturing cellular therapies. To the extent that regenerative medicine is curative it must be made available at vaccine like prices. At present, only a handful of people can afford such treatments.
China and Japan are now in forefront of reducing the cost of producing stem cells, tissue, and other products with restorative biological properties. As a result, they are attracting more capital and forming more new companies than the U.S.
In 2014 Japan became the first country in the world to adopt an expedited approval system specifically for regenerative medical products and to allow outsourced cell culturing. Two products were approved under the new system within a year of its adoption.
By contrast, the Food and Drug Administration regulates any use of manufactured stem cells as equally risky without regard to prior use, health benefit, or therapeutic potential. Indeed, many of the most common stem cell therapies — including bone marrow transplants and blood transfusions — would require 10 years of FDA review if they were brought to market today.
The problem isn’t over-regulation. It’s outdated regulation. Safety checks and benchmarks for cell manufacturing should be based on real world evidence of past applications. Regulation should focus on the specific potential side effects for each specific potential use. In this regard, we agree with incoming FDA Commissioner Scott Gottlieb, who has noted, “Expediting the development of these novel and transformative technologies like gene- and cell-based therapies doesn’t necessarily mean lowering the standard for approval, as I believe other countries have done. But it does mean having a framework that’s crafted to deal with the unique hypothetical risks that these products pose.”
In fact, the United States has the best regenerative medicine manufacturing technology in the world. But it is literally sitting unused in warehouses.
For example, under the Accelerated Manufacture of Pharmaceuticals program, private companies partnered with the Defense Advanced Research Projects Agency to develop mobile cell and tissue manufacturing plants that can be set up almost anywhere. The facilities can produce cells and tissues at a fraction of the current cost. These mobile factories make real-time production of vaccines and biologics for potential bioterrorist threats and pandemics possible. They are also low-cost, high-tech platforms for experimental evaluation of any type of regenerative medicine.
AMPs are operating in Indonesia, Singapore, China, and Japan where cell products — including vaccines — are being mass produced. Not a single AMP is being used in the United States because of outdated regulations.
To remove this regulatory obstacle, the Trump administration should establish a separate regenerative medicine pathway. This pathway, which could be developed by DARPA, FDA, and the Centers for Disease Control and Prevention, would develop regulatory standards for the safe manufacturing and testing of development of regenerative products to treat battlefield related traumas such as traumatic brain injury, life-threatening limb damage, and drug-resistant pathogens.
The focus on the conditions and circumstances unique to war or counter-terrorism is both appropriate and strategic. After World War II, Franklin Roosevelt directed that the scientific and entrepreneurial talents used to achieve ramp up war-time production of penicillin and blood plasma “be used in the days of peace ahead for the improvement of the national health, the creation of new enterprises bringing new jobs, and the betterment of the national standard of living.”
What was created exceeded that vision. The cooperative efforts to achieve mass production of penicillin and blood plasma inspired and supported the creation of industries that employ millions of people today.
Similarly, developing an affordable source of cell therapies to heal our fighting forces and protect the homeland will yield a wide array of affordable technologies and cures that will produce, in FDR’s words, a fuller and more fruitful employment and a fuller and more fruitful life. Simply put, by making the manufacture of regenerative medicine affordable can help make America great.
Robert Hariri is CEO of Celularity. Robert Goldberg is vice president of Center for Medicine in the Public Interest. Read More & Comment...
06/12/2017 06:46 AM | Peter Pitts
In March, the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) and the Drug Safety and Risk Management Advisory Committee (DSARM). voted 18-8 that Opana ER’s benefits do not outweigh its risks. And on June 8th, the other shoe dropped.
"After careful consideration, the agency is seeking removal based on its concern that the benefits of the drug may no longer outweigh its risks," the agency said in announcing the move. “This is the first time the agency has taken steps to remove a currently marketed opioid pain medication from sale due to the public health consequences of abuse."
The FDA said it was asking Endo to voluntarily cease marketing Opana ER. But it added that if the company refuses, the agency will "take steps to formally require its removal by withdrawing approval."
The FDA said its data indicate that the abuse of the drug has shifted from snorting to injection following reformulation in 2012, which was intended to help the pills resist physical and chemical manipulation. Subsequently, Opana ER was associated with a notorious outbreak of HIV and hepatitis C infection in rural Indiana two years ago, caused by needle-sharing among opioid addicts.
"The abuse and manipulation of reformulated Opana ER by injection has resulted in a serious disease outbreak. When we determined that the product had dangerous unintended consequences, we made a decision to request its withdrawal from the market," said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, in a statement. "This action will protect the public from further potential for misuse and abuse of this product."
What can we learn from this action? First, that when a product’s risk/benefit profile is carefully monitored, aggressive action can be taken in a timely manner. But should we need an outbreak of HIV/AIDS and Hep-C to sound the alarm?
Kudos to the FDA for taking appropriate action to protect the public health – but we need more. Specifically we need the agency to work with sponsors o design more and better early warning mechanisms so that a problematic product can we recalled before dire consequences ensue. That means new and more immediate ways to collect, analyze, and share real-world evidence.
It’s time for apps to take center stage in the battle against opioid abuse.
Read More & Comment...
"After careful consideration, the agency is seeking removal based on its concern that the benefits of the drug may no longer outweigh its risks," the agency said in announcing the move. “This is the first time the agency has taken steps to remove a currently marketed opioid pain medication from sale due to the public health consequences of abuse."
The FDA said it was asking Endo to voluntarily cease marketing Opana ER. But it added that if the company refuses, the agency will "take steps to formally require its removal by withdrawing approval."
The FDA said its data indicate that the abuse of the drug has shifted from snorting to injection following reformulation in 2012, which was intended to help the pills resist physical and chemical manipulation. Subsequently, Opana ER was associated with a notorious outbreak of HIV and hepatitis C infection in rural Indiana two years ago, caused by needle-sharing among opioid addicts.
"The abuse and manipulation of reformulated Opana ER by injection has resulted in a serious disease outbreak. When we determined that the product had dangerous unintended consequences, we made a decision to request its withdrawal from the market," said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, in a statement. "This action will protect the public from further potential for misuse and abuse of this product."
What can we learn from this action? First, that when a product’s risk/benefit profile is carefully monitored, aggressive action can be taken in a timely manner. But should we need an outbreak of HIV/AIDS and Hep-C to sound the alarm?
Kudos to the FDA for taking appropriate action to protect the public health – but we need more. Specifically we need the agency to work with sponsors o design more and better early warning mechanisms so that a problematic product can we recalled before dire consequences ensue. That means new and more immediate ways to collect, analyze, and share real-world evidence.
It’s time for apps to take center stage in the battle against opioid abuse.
Read More & Comment...
06/08/2017 06:11 PM | Robert Goldberg
If it’s not obvious from the title “Orphan Drugs: Way Too Many, Way Too Expensive” the essence of Joseph Burns article in Managed Care Magazine is: isn’t is terrible that drug companies – who neglected rare and tropical disease for decades to make money – are now making money developing drugs for conditions they were criticized for ignoring and for which the Orphan Drug Act was created.
Burns article is based on the material and media accounts generated by a syndicate attacking rare disease groups and the Orphan Drug Act funded by Laura and John Arnold Foundation to the tune of $22.4 million. It is a network of left-leaning think tanks with a bias against the profitability of medical innovation, news outlets and patient advocacy organization that spread the anti-orphan message far and wide.
The Arnold funded think tanks provide the Arnold-funded news outlets with factoids and quotes attacking orphan drug development and patient groups. The Arnold funding patient organization then provides the rest of the syndicate with grass roots outlet for even more quotes and opportunities to spread the message. The advocacy group, Patients for Affordable Medicines, is run by David Mitchell who recently retired as a founder and principal of PR firm GMMB.
Mitchell knows a little bit about being a front organization or a pass through for political advocacy: GMMB earned $236.3 million from Hillary for America 2016 and moved over $314 million in Obama ad buys during the 2012 election cycle. It also runs a group called Waterfront Strategies that handles soft money, consulting and ad buys for a number of PACs.
Burns fails to tell his readers of Mitchell’s past and present work as a conduit. Instead, he depicts Mitchell as a selfless crusader against “drug companies (that) are manipulating the law that created the orphan drug status. Mitchell claims orphan drug development is mostly “salami slicing” strategies—companies dividing diseases into smaller and smaller categories based on genetic and biomarker differences so their products can achieve the coveted orphan drug status.”
“This gaming of the system to cut and recut for different orphan diseases means they get to use the same drug for multiple orphan drug designations,” says Mitchell. “That needs to stop.”
Neither Burns or Mitchell offer any proof that such practices are hurting patients. Instead, their beef with the fact that companies have the audacity to attempt ot make a profit.
Burns notes: “some commentators have said the trouble starts with the law’s prevalence-based definition of a rare disease as a condition that affects fewer than 200,000 individuals. Because drug companies can now price orphan drugs at between $100,000 to $200,000 per patient per year, they need only 5,000 to 10,000 patients to hit the blockbuster mark of $1 billion in annual sales.”
Well yeah, that’s what the Orphan Drug Act is supposed to do: Encourage the development of new medicines for groups of patients that do not benefit from existing therapies.
But Burns – like most critics past and present – claims “the law’s intended purpose of encouraging the development of drugs for rare diseases has been undermined in various ways.”
Rather than provide evidence of how the act has been undermined, Burns just asserts: companies “are using the 1983 Orphan Drug Act to secure lucrative incentives and gain monopoly control of rare disease markets where drugs often command astronomical price tags”
Burns assertions of gaming and astronomical prices are without substance:
For instance, he fails to note the retail price of the top selling 10 orphan drugs are a bargain relative to lives lost, health care spending saved and productivity gained.
Take Revlimid (used at various stages of multiple myeloma) as an example. The true per patient cost – net of rebates, discounts, and other concessions – is about $78K per patient. The median charge for a hospital stay is $82000.
Revlimid sales in 2014 were about $4.4 billion. But extrapolation of gains in life expectancy based on previous studies of the impact of advances in myeloma care on longevity suggests that each year the use of Revlimid and other novel treatments generate $22 billion in added value.
Further, many other orphan drugs NOT reviewed by Burns treat extremely small populations and require continuing evaluation and expensive production activities.
Of the orphan drugs approved since 2012, the average patient population has been under 2000. Nearly 80 percent of the new products or approvals were developed by small biotech companies that are losing money. If Burns and the critics he channels thinks that punishing companies after they turn a profit will not affect orphan drug development, they should prove it, not force dying patients into a twisted social experiment.
In addition to being upset about the handful of profitable orphan drugs, Burns claims that slicing and dicing (as he calls it) is an unfair way to make money. He notes: “Herceptin, originally approved as a breast cancer drug, has gained orphan designation for pancreatic and gastric cancers because those cancers can now also be classified as HER2-positive and HER2-negative.”
Burns cites an Arnold Foundation funded Kaiser Health News ‘study’ that highlights the number of orphan drug designations generated from existing medicines. It is not a study, it is simply the same list of orphan drug designations and approvals the FDA generates with KHN’s negative spin added as narrative.
It is true that there has been an increase in the discovery of markers for previously untreated tumors that are certainly fatal. And it is true that companies are conducting clinical trials or engaging in data mining to establish benefit in other subpopulations. KHN implies this is an immoral practice because profit is involved.
As the FDALawBlog points out, in some cases, a single orphan drug designation can result in multiple periods of orphan drug exclusivity. There appear to be a growing number of cases where FDA has granted multiple periods of orphan drug exclusivity based on the same original orphan drug designation, and where the drug’s indication evolves into something new, shedding and subsuming the previous indication statement.”
The obvious ‘solution’ to this situation is to allow companies faster approval for a broad number of tumors with biomarkers. FDA’s recent approval of Keytruda for all solid tumors with a specific mutation clears the path for this approach. Martin Makary (who Burns quotes) suggests this conditional path as an alternative to the multiple exclusivities. But the anti-orphan Arnold Foundation funded Jerry Avorn and Aaron Kesselheim has attacked the use of biomarkers as a watering down of science pushed by pharma funded patient groups. So my guess is that find a way to characterize THAT as profiteering. Indeed, Kesselheim is behind the Arnold-funded effort to eliminate biomarker-based disease treatment from Orphan Drug Act designations.
Burns and the anti-orphan movement suggest instead that orphan drug patent life should be shortened to allow for more generics. But that begs the question: as orphan drugs have gone generic, why haven’t the companies used their first to market exclusivity to engage in similar research? If it is just slicing and dicing, why wouldn’t a generic company want a line extension?
The answer is supplemental approvals of any type require time and money that innovator companies invest and generics don’t. The FDA does not simply tack on additional patent life. To obtain a period of orphan drug exclusivity for a drug that is otherwise the “same drug” as a previously approved drug (i.e., a drug containing the same active moiety and that is for the same orphan disease or condition), the sponsor must demonstrate that its product is clinically superior (by showing greater efficacy, greater safety, or by providing a major contribution to patient care) to the previously approved drug.”
If Burns and the “experts” he quotes wants to repurpose generic Gleevec or Humira for an orphan use and not charge for it, they should set up a company and do so.
Indeed, Burns and every other critic he cites in his repetition of how the ODA is used to make money ignores a very important point: “Generic competition is generally not thwarted because of the ability of an ANDA applicant to carve-out of its labeling (and thus avoid) a period of unexpired orphan drug exclusivity on the brand-name Reference Listed Drug.”
The FDA can approve a generic version of the drug product for one or more uses even if, in the future, an innovator company develops another use that garners orphan drug exclusivity.
Which means the generic version of the drug is on the market and can be used off-label.
But the anti-orphan critics attack off-label use as a slick, often illegal way, of increasing sales. So that leaves people with rare diseases with a longer wait for medicines that would cost more to make and must rely on generic companies to invest in new indications once innovator drugs go off patent.
I know people with rare diseases can’t live with that. I wonder if Joseph Burns and the anti-orphan movement can.
Read More & Comment...
06/08/2017 10:35 AM | Peter Pitts
The Joint Economic Committee (JEC) will hold a hearing on June 8th to explore the economic aspects of the opioid crisis.
According to the JEC website, “The opioid problem has various elements on the demand and the supply side that JEC witnesses, Professor Sir Angus Deaton, 2015 Nobel Prize laureate in economics, Ohio Attorney General Mike DeWine, Dr. Lisa Sacco, Congressional Research Service Crime Policy Analyst, and Dr. Richard G. Frank, Professor of Health Economics at Harvard will address in detail.” Mike DeWine? Really?
We’ll see.
I suspect that a key aspect of “opioid economics” that will get very little attention is the unwillingness of PBMs to pay for opioids of the abuse-deterrent variety. That’s simple economics. The reason that there are nearly a quarter of a billion generic, non-abuse opioid tablets prescribed annually (vs. about 5 million abuse-deterrent ones) is because they are inexpensive. But that is a failed metric. It’s benefited the bottom line of PBMs and created a national epidemic.
The same math explains why PBMs often implement barriers to the use of branded, on-label non-opioid medicines, relegating these treatments to second line options. 52% of patients diagnosed with osteoarthritis receive an opioid pain medicine as first line treatment as do 43% of patients diagnosed with fibromyalgia and 42% of patients with diabetic peripheral neuropathy even though there are FDA-approved, non-opioid medicines specifically designed and labeled to treat these conditions.
We’ll see.
Zero-sum thinking is an obsession of mine, but mostly in economics. -- P. J. O'Rourke Read More & Comment...
According to the JEC website, “The opioid problem has various elements on the demand and the supply side that JEC witnesses, Professor Sir Angus Deaton, 2015 Nobel Prize laureate in economics, Ohio Attorney General Mike DeWine, Dr. Lisa Sacco, Congressional Research Service Crime Policy Analyst, and Dr. Richard G. Frank, Professor of Health Economics at Harvard will address in detail.” Mike DeWine? Really?
We’ll see.
I suspect that a key aspect of “opioid economics” that will get very little attention is the unwillingness of PBMs to pay for opioids of the abuse-deterrent variety. That’s simple economics. The reason that there are nearly a quarter of a billion generic, non-abuse opioid tablets prescribed annually (vs. about 5 million abuse-deterrent ones) is because they are inexpensive. But that is a failed metric. It’s benefited the bottom line of PBMs and created a national epidemic.
The same math explains why PBMs often implement barriers to the use of branded, on-label non-opioid medicines, relegating these treatments to second line options. 52% of patients diagnosed with osteoarthritis receive an opioid pain medicine as first line treatment as do 43% of patients diagnosed with fibromyalgia and 42% of patients with diabetic peripheral neuropathy even though there are FDA-approved, non-opioid medicines specifically designed and labeled to treat these conditions.
We’ll see.
Zero-sum thinking is an obsession of mine, but mostly in economics. -- P. J. O'Rourke Read More & Comment...
06/04/2017 11:30 AM | Peter Pitts
To the Editor:
Per, "The Single-Payer Party? Democrats Shift Left on Health Care," (NYT, June 3, 2017) it seems somewhat ham-handed to have only one paragraph, deep inside the page 16 jump of a Page One article, mentioning the enormous cost and tax consequences of the California legislation -- and no mention at all of the proposal's impact on patient choice and resource rationing. That's not fake news -- but it certainly isn't all the news that's fit to print.
Peter J. Pitts
Read More & Comment...
Per, "The Single-Payer Party? Democrats Shift Left on Health Care," (NYT, June 3, 2017) it seems somewhat ham-handed to have only one paragraph, deep inside the page 16 jump of a Page One article, mentioning the enormous cost and tax consequences of the California legislation -- and no mention at all of the proposal's impact on patient choice and resource rationing. That's not fake news -- but it certainly isn't all the news that's fit to print.
Peter J. Pitts
Read More & Comment...
05/30/2017 08:11 AM | Peter Pitts
Per FDA Commissioner Scott Gottlieb, “As Commissioner, my highest initial priority is to take immediate steps to reduce the scope of the epidemic of opioid addiction. I believe the Food and Drug Administration continues to have an important role to play in addressing this crisis, particularly when it comes to reducing the number of new cases of addiction.”
One place to look for smart policy solutions is just north of the border, where medical experts and public health officials in Canada are also concerned about the abuse of prescription opioids. A study published by the Canadian Health Policy Institute (CHPI) estimates that if all prescription opioids in Canada were abuse deterrent formulations, societal costs could be substantially reduced.
“Mandating abuse deterrent formulations for prescription opioids could reduce societal costs by $140 million to $4 billion annually.”
The study estimated that the economic value of the health, social and productivity losses associated with the abuse of prescription opioids in Canada could have averaged as much as $4.3 billion per year during the four-year period from 2012 to 2015. The study also reviewed clinical research showing that existing abuse deterrent formulations ranged from 3.3% to 98.8% effective at reducing abuse rates of the tested products. The median effectiveness reducing abuse rates by between 45.1% and 64%.
The study concluded that if the federal government mandated abuse deterrent formulations for all prescription opioids, it would discourage non-medical use of these drugs, reducing associated societal costs by an estimated range of savings between $140 million and $4 billion annually.
Perhaps a cross-border partnership is in order to address this bi-lateral regulatory issue. Read More & Comment...
One place to look for smart policy solutions is just north of the border, where medical experts and public health officials in Canada are also concerned about the abuse of prescription opioids. A study published by the Canadian Health Policy Institute (CHPI) estimates that if all prescription opioids in Canada were abuse deterrent formulations, societal costs could be substantially reduced.
“Mandating abuse deterrent formulations for prescription opioids could reduce societal costs by $140 million to $4 billion annually.”
The study estimated that the economic value of the health, social and productivity losses associated with the abuse of prescription opioids in Canada could have averaged as much as $4.3 billion per year during the four-year period from 2012 to 2015. The study also reviewed clinical research showing that existing abuse deterrent formulations ranged from 3.3% to 98.8% effective at reducing abuse rates of the tested products. The median effectiveness reducing abuse rates by between 45.1% and 64%.
The study concluded that if the federal government mandated abuse deterrent formulations for all prescription opioids, it would discourage non-medical use of these drugs, reducing associated societal costs by an estimated range of savings between $140 million and $4 billion annually.
Perhaps a cross-border partnership is in order to address this bi-lateral regulatory issue. Read More & Comment...
05/25/2017 05:20 AM | Peter Pitts
As per a no-nonsense report in BioCentury, President Trump’s FY18 FDA budget request envisions cutting medical product safety funding by $17.8 million. The cuts would reduce the agency’s ability to ensure the safety of imported drugs and ingredients, and to conduct safety research the agency characterizes as “critical.”
FDA stated that the budget proposal would also curtail "proactive" activities to respond to global disease outbreaks.
The proposed cutbacks are a consequence of the administration’s proposal to transfer 100% of the responsibility for funding medical product reviews to user fees. Some FDA medical product safety and regulatory science activities cannot be funded with user fees. There is almost no chance that Congress will agree to the Trump administration’s plan to rip up the user fee reauthorization agreements that FDA and industry have negotiated. It is not clear whether FDA intends to implement the medical product safety oversight cuts outlined in the budget if Congress rejects the administration’s revamped user fees.
To compensate for proposed budget cuts, the proposal said FDA will "support at lower funding levels regulated product field exams, import entry review, investigations, sample analysis, and inspections for surveillance, compliance, and follow up activities, both domestically and abroad." The proposal added: "Risk assessments will be impacted along with sharing information with regulatory partners." The proposed $11 million cut to the Center for Drug Evaluation and Research (CDER) medical product safety budget would require the center to “reprioritize and refocus how it promotes and protects public health,” the document said.
The cuts would include "some contracts that promote drug safety and research studies, investments in innovation and research, and training and development opportunities for personnel,” it said. The document said FDA will seek “to minimize the impact of these reductions on FDA‘s core mission activities.” The medical product safety budget at the Center for Biologics Evaluation and Research (CBER) would be cut by $7.5 million. CBER would "reduce its applied scientific research, which supports the development of innovative products, in order to preserve critical regulatory oversight of its non-user fee programs that address blood components, tissues, and allergenic products." Spending on equipment upgrades and maintenance would be cut, as would "the number of research fellows hired to support the regulatory science program.”
The proposal noted that “research fellows bring innovative ideas, talents, and skills to FDA.” The budget proposal included reductions in CBER’s “work on the development of laboratory standards, including reference materials, assays, and methodologies that improve product quality and provide standards and guidance to address new technologies and emerging diseases.” If Trump’s budget is enacted, CBER would "reduce staff through attrition in its non-user fee activities that include the regulation of blood components, tissues, and allergenic products.”
CBER would be forced to “reprioritize how it provides advice to sponsors and reduce resources dedicated to the review of blood components for transfusion and allergenic extracts as well as the ability to provide advice to sponsors of tissues that do not require premarket review.”
As a result, CBER "may no longer be able to exceed its performance target to complete review and action on 90% of complete blood bank and source plasma Biologic License Application supplements within 12 months after submission date.” In addition, CBER would “limit proactive work to respond to infectious disease outbreaks globally, including limiting its active participation in international collaboration activities.”
More to come on this. Read More & Comment...
The proposed cutbacks are a consequence of the administration’s proposal to transfer 100% of the responsibility for funding medical product reviews to user fees. Some FDA medical product safety and regulatory science activities cannot be funded with user fees. There is almost no chance that Congress will agree to the Trump administration’s plan to rip up the user fee reauthorization agreements that FDA and industry have negotiated. It is not clear whether FDA intends to implement the medical product safety oversight cuts outlined in the budget if Congress rejects the administration’s revamped user fees.
To compensate for proposed budget cuts, the proposal said FDA will "support at lower funding levels regulated product field exams, import entry review, investigations, sample analysis, and inspections for surveillance, compliance, and follow up activities, both domestically and abroad." The proposal added: "Risk assessments will be impacted along with sharing information with regulatory partners." The proposed $11 million cut to the Center for Drug Evaluation and Research (CDER) medical product safety budget would require the center to “reprioritize and refocus how it promotes and protects public health,” the document said.
The cuts would include "some contracts that promote drug safety and research studies, investments in innovation and research, and training and development opportunities for personnel,” it said. The document said FDA will seek “to minimize the impact of these reductions on FDA‘s core mission activities.” The medical product safety budget at the Center for Biologics Evaluation and Research (CBER) would be cut by $7.5 million. CBER would "reduce its applied scientific research, which supports the development of innovative products, in order to preserve critical regulatory oversight of its non-user fee programs that address blood components, tissues, and allergenic products." Spending on equipment upgrades and maintenance would be cut, as would "the number of research fellows hired to support the regulatory science program.”
The proposal noted that “research fellows bring innovative ideas, talents, and skills to FDA.” The budget proposal included reductions in CBER’s “work on the development of laboratory standards, including reference materials, assays, and methodologies that improve product quality and provide standards and guidance to address new technologies and emerging diseases.” If Trump’s budget is enacted, CBER would "reduce staff through attrition in its non-user fee activities that include the regulation of blood components, tissues, and allergenic products.”
CBER would be forced to “reprioritize how it provides advice to sponsors and reduce resources dedicated to the review of blood components for transfusion and allergenic extracts as well as the ability to provide advice to sponsors of tissues that do not require premarket review.”
As a result, CBER "may no longer be able to exceed its performance target to complete review and action on 90% of complete blood bank and source plasma Biologic License Application supplements within 12 months after submission date.” In addition, CBER would “limit proactive work to respond to infectious disease outbreaks globally, including limiting its active participation in international collaboration activities.”
More to come on this. Read More & Comment...
05/20/2017 11:04 AM | Peter Pitts
In a recent Washington Post op-ed, Bill Schultz, the former deputy commissioner for policy of the Food and Drug Administration during the Clinton administration, incredulously offers that FDA policies developed 50 years ago are good enough for life in the 21st century (Trump’s new FDA commissioner has a huge decision to make). He’s wrong.
Time marches on and regulatory practices must evolve to better serve the public health. Nowhere is this more urgent than in making sure physicians and patients have unencumbered access to truthful accurate and non-misleading information about FDA-approved medicines –- both on and off-label. In a draft guidance, FDA notes that ‘‘good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment.’’ And, according to the House Energy & Commerce Committee’s 21st Century Cures Initiative, “… conversations between and among doctors, patients, researchers, and scientists in academia and industry should be facilitated. This includes the free flow of data, research, and results related to what a therapy or combination of therapies does or does not do well and in what types of patients.”
Off-label communications is about getting the right medicine to the right patient in the right dose at the right time. Off-label communications advances both the practice of medicine and the safe and effective use of medicines. Read More & Comment...
Time marches on and regulatory practices must evolve to better serve the public health. Nowhere is this more urgent than in making sure physicians and patients have unencumbered access to truthful accurate and non-misleading information about FDA-approved medicines –- both on and off-label. In a draft guidance, FDA notes that ‘‘good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment.’’ And, according to the House Energy & Commerce Committee’s 21st Century Cures Initiative, “… conversations between and among doctors, patients, researchers, and scientists in academia and industry should be facilitated. This includes the free flow of data, research, and results related to what a therapy or combination of therapies does or does not do well and in what types of patients.”
Off-label communications is about getting the right medicine to the right patient in the right dose at the right time. Off-label communications advances both the practice of medicine and the safe and effective use of medicines. Read More & Comment...
05/09/2017 05:02 PM | Peter Pitts
It’s disappointing to say the least when our fine elected representatives place scoring transient political points in front of advancing the public health.
Such is always the case with the perennial non-starter issue of drug importation. What makes it even more dangerous this time is how it could delay swift and clean PDUFA approval.
Front and center is Senator Bernie Sanders. His two PDUFA amendments won’t lower drug prices or increase access for any Americans. But they would negatively impact safety and undercut intellectual property protection.
Let’s cut right to the chase. Generic drugs (85% + of all medicines volume in the US are LESS expensive than in Canada or any European country. Next, for the overwhelming number of Americans with private health insurance, the co-pays for their products are LESS expensive then buying them retail at either a brick-and-mortar of Internet Canadian pharmacy. Biologics? 85% of all biologics are administered in hospitals. Is Senator Sanders suggesting that American hospitals should import drugs that may or may not have been shipped under proper refrigeration conditions? FDA inspections speak otherwise.
So just what is Senator Sanders trying to accomplish? Certainly not a clean PDUFA – which is just what the doctor ordered for the FDA’s Gottlieb Era reforms -- including programs to help lower drig prices by expediting single sourcwe generic reviews.
He certainly doesn’t seem to be interested in safety concerns. Or counterfeits. Or cold-chain control. Or even that every study by the Congressional Budget Office reiterates over and over again that such schemes don’t save the American consumer any money.
But is sure is good for headlines. For shame. Read More & Comment...
Such is always the case with the perennial non-starter issue of drug importation. What makes it even more dangerous this time is how it could delay swift and clean PDUFA approval.
Front and center is Senator Bernie Sanders. His two PDUFA amendments won’t lower drug prices or increase access for any Americans. But they would negatively impact safety and undercut intellectual property protection.
Let’s cut right to the chase. Generic drugs (85% + of all medicines volume in the US are LESS expensive than in Canada or any European country. Next, for the overwhelming number of Americans with private health insurance, the co-pays for their products are LESS expensive then buying them retail at either a brick-and-mortar of Internet Canadian pharmacy. Biologics? 85% of all biologics are administered in hospitals. Is Senator Sanders suggesting that American hospitals should import drugs that may or may not have been shipped under proper refrigeration conditions? FDA inspections speak otherwise.
So just what is Senator Sanders trying to accomplish? Certainly not a clean PDUFA – which is just what the doctor ordered for the FDA’s Gottlieb Era reforms -- including programs to help lower drig prices by expediting single sourcwe generic reviews.
He certainly doesn’t seem to be interested in safety concerns. Or counterfeits. Or cold-chain control. Or even that every study by the Congressional Budget Office reiterates over and over again that such schemes don’t save the American consumer any money.
But is sure is good for headlines. For shame. Read More & Comment...
05/09/2017 01:54 PM | Peter Pitts
Via Medscape:
Safety Events Common in Newly Approved Drugs
Nearly one third of drugs newly approved by the US Food and Drug Administration (FDA) are affected by safety issues that were not known at the time of approval, a study has shown.
Biologic and psychiatric drugs, as well as those that received accelerated approval or were approved within 60 days of the statutory decision deadline, are the most vulnerable to postmarket safety events, Nicholas S. Downing, MD, from the Department of Medicine at Brigham and Women's Hospital in Boston, Massachusetts, and colleagues report. Their study was published online May 9 in JAMA.
The findings "are not surprising to those of us who have been following this for a while, but they do reflect a growing realization by the mainstream medical community that there are important differences between efficacy in randomized controlled trials and effectiveness once a drug hits the real world," Peter J. Pitts told Medscape Medical News. Pitts is a former FDA associate commissioner and current president of the Center for Medicine in the Public Interest, New York, New York. "It reinforces the basic truth that when you give people medicine, interesting things will happen — good and bad. Postmarket research is the continual search for understanding what these interesting things are in the real world," he added.
To determine the prevalence of postmarket safety events and the characteristics associated with the likelihood of their occurrence in newly approved drugs, the researchers used the Drugs@FDA database to identify all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010. They then separated the drugs on the basis on seven prespecified features: class (pharmaceutical, biologic), therapeutic area, priority review, accelerated approval, orphan product, near–regulatory deadline approval, and total review time.
Of 222 novel therapeutics identified, including 183 pharmaceuticals and 39 biologics, 71 (32%) were affected by a total of 123 postmarket safety events over a median 11.7 years of follow-up. The safety issues led to three drug withdrawals. The irritable bowel syndrome drugs valdecoxib and tegaserod were withdrawn in 2005 and 2007, respectively, as a result of adverse cardiovascular events. The psoriasis drug efalizumab was withdrawn in 2009 as a result of an observed increased risk for progressive multifocal leukoencephalopathy.
The approved drugs were also associated individually and class-wide with 61 incremental boxed warnings (43 drugs) and 59 safety communications (44 drugs).
Although safety events leading to market withdrawals were rare, "new boxed warnings, indicating that potentially life-threatening or preventable safety events had been observed in the postmarket period, and safety communications, which describe serious but non-life-threatening postmarket safety events, each occurred for approximately one-fifth of the novel therapeutics," the authors write.
The median time between drug approval and the first postmarket safety event was 4.2 years, and nearly one in three of the drugs had one or more safety events at 10 years, the authors write.
The researchers performed multivariate analyses looking at the relationship between each of the prespecified characteristics and postmarket safety events. They found an increased risk for safety issues among biologics compared with pharmaceuticals (incidence rate ratio [IRR], 1.93; 95% confidence interval [CI], 1.06 - 3.52; P = .03) and among drugs used to treat psychiatric conditions compared with cancer and hematologic therapeutics (IRR, 3.78; 95% CI, 1.77 - 8.06; P < .001). In addition, postmarket safety events were more prevalent among drugs that received accelerated approval (IRR, 2.20; 95% CI, 1.15 - 4.21; P = .02) and those approved near their regulatory deadline (IRR, 1.90; 95% CI, 1.19 - 3.05; P = .008).
Of interest, safety events were significantly less common among drugs with the shortest regulatory review times. This finding "conversely raises the possibility that some approval packages provide clearer evidence of safety, allowing for more rapid regulatory approval," the authors write. "An analysis of regulatory review documents from the European Medicines Agency indicated that safety risks that would ultimately prompt a postmarket safety event were not always evident in the premarket period, suggesting that additional premarket review might only delay approval without identifying therapeutics that pose a future safety concern."
"I agree with the authors' main point, which is that there are major gaps in our knowledge about the safety of drugs at the time that they are approved," Sean Hennessy, PharmD, PhD, told Medscape Medical News. Dr Hennessy is from the Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, and Department of Pharmacology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
"This isn't necessarily a bad thing, since requiring drug companies to perform the much larger studies that would need to be done to learn about rare adverse effects prior to approval would further increase the cost of drug development, which is already very expensive. Rather, we need to develop more robust systems to assess the safety of drugs after they are approved," Dr Hennessy explained.
Additional research is warranted to gain insight into the approval timeline and drug safety, the authors state. Further, they call for collaboration between stakeholders and the FDA "to develop and maintain an effective system for detecting postmarket safety events."
Stakeholder engagement is essential, Pitts told Medscape Medical News. "Although it's not taught in medical school, it's up to physicians and pharmacists to report adverse events, which is critical from a risk perspective and to mitigate potential problems with the use of approved medicines in everyday practice."
The good news, according to Pitts, is that "the FDA is taking this challenge to heart," by enhancing the capacity of its postmarket safety surveillance programs, and improving interactions with industry to achieve a better understanding of the performance of new drugs once they get into the market.The FDA's Sentinel Initiative, an integrated, national electronic monitoring system for active postmarket risk identification and analysis, is an important step in this direction, as is the sharing of premarket clinical trial data, the authors write. "[T]he integration of multiple data sources that include observations among large and diverse patient populations can facilitate the detection of postmarket safety events."
Previously, as reported by Medscape Medical News, the Government Accountability Office has questioned the sufficiency of the FDA's reporting of postmarket studies of approved drugs.
"I'm not as optimistic as the authors that the current system is working…. Sentinel, which I'm part of, is a great system, but has limited bandwidth. There aren't enough resources to use Sentinel as the only way to study the safety of every approved product, nor does FDA have the human resources to be primarily responsible for studying the safety of all products," Dr Hennessy explained.
"Industry needs to play a role. Unfortunately, FDA is limited by law in their ability to require companies to perform their own safety studies. Changing this would require an act of Congress," he added.
The authors acknowledge that even the most careful regulatory review and surveillance systems may not prevent all postmarket safety events. "[I]t may be impossible to detect other less common events until several years after approval, once the therapeutics are in broad use."
Dr Downing has disclosed no relevant financial relationships. One coauthor reports receiving personal fees from Cepton, OliverWyman, Roland Berger, McCann Health, Omnicom, Grey Healthcare, Saatchi & Saatchi, Sudler, TBWA, Havas, Agipharm, Mayoly Spindler, Teva, Menarini, Pierre Fabre, Merck, and AbbVie. One coauthor reports receiving a grant from the FDA; research agreements with Medtronic and Johnson & Johnson (Janssen) through Yale University; serving as chair of a cardiac scientific advisory board for UnitedHealth, being a founder of Hugo, being a participant and participant representative of the IBM Watson Health Life Sciences Board; and serving as an advisory board member of Element Science. One coauthor reports receiving grants from the FDA, Medtronic, Johnson & Johnson, the Centers for Medicare & Medicaid Services, Blue Cross Blue Shield Association, and the Laura and John Arnold Foundation. Mr Pitts serves as chief regulatory officer for Adherent Health Strategies. Dr Hennessy has disclosed no relevant financial relationships.
JAMA. 2017;317:1854-1863. Read More & Comment...
Safety Events Common in Newly Approved Drugs
Nearly one third of drugs newly approved by the US Food and Drug Administration (FDA) are affected by safety issues that were not known at the time of approval, a study has shown.
Biologic and psychiatric drugs, as well as those that received accelerated approval or were approved within 60 days of the statutory decision deadline, are the most vulnerable to postmarket safety events, Nicholas S. Downing, MD, from the Department of Medicine at Brigham and Women's Hospital in Boston, Massachusetts, and colleagues report. Their study was published online May 9 in JAMA.
The findings "are not surprising to those of us who have been following this for a while, but they do reflect a growing realization by the mainstream medical community that there are important differences between efficacy in randomized controlled trials and effectiveness once a drug hits the real world," Peter J. Pitts told Medscape Medical News. Pitts is a former FDA associate commissioner and current president of the Center for Medicine in the Public Interest, New York, New York. "It reinforces the basic truth that when you give people medicine, interesting things will happen — good and bad. Postmarket research is the continual search for understanding what these interesting things are in the real world," he added.
To determine the prevalence of postmarket safety events and the characteristics associated with the likelihood of their occurrence in newly approved drugs, the researchers used the Drugs@FDA database to identify all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010. They then separated the drugs on the basis on seven prespecified features: class (pharmaceutical, biologic), therapeutic area, priority review, accelerated approval, orphan product, near–regulatory deadline approval, and total review time.
Of 222 novel therapeutics identified, including 183 pharmaceuticals and 39 biologics, 71 (32%) were affected by a total of 123 postmarket safety events over a median 11.7 years of follow-up. The safety issues led to three drug withdrawals. The irritable bowel syndrome drugs valdecoxib and tegaserod were withdrawn in 2005 and 2007, respectively, as a result of adverse cardiovascular events. The psoriasis drug efalizumab was withdrawn in 2009 as a result of an observed increased risk for progressive multifocal leukoencephalopathy.
The approved drugs were also associated individually and class-wide with 61 incremental boxed warnings (43 drugs) and 59 safety communications (44 drugs).
Although safety events leading to market withdrawals were rare, "new boxed warnings, indicating that potentially life-threatening or preventable safety events had been observed in the postmarket period, and safety communications, which describe serious but non-life-threatening postmarket safety events, each occurred for approximately one-fifth of the novel therapeutics," the authors write.
The median time between drug approval and the first postmarket safety event was 4.2 years, and nearly one in three of the drugs had one or more safety events at 10 years, the authors write.
The researchers performed multivariate analyses looking at the relationship between each of the prespecified characteristics and postmarket safety events. They found an increased risk for safety issues among biologics compared with pharmaceuticals (incidence rate ratio [IRR], 1.93; 95% confidence interval [CI], 1.06 - 3.52; P = .03) and among drugs used to treat psychiatric conditions compared with cancer and hematologic therapeutics (IRR, 3.78; 95% CI, 1.77 - 8.06; P < .001). In addition, postmarket safety events were more prevalent among drugs that received accelerated approval (IRR, 2.20; 95% CI, 1.15 - 4.21; P = .02) and those approved near their regulatory deadline (IRR, 1.90; 95% CI, 1.19 - 3.05; P = .008).
Of interest, safety events were significantly less common among drugs with the shortest regulatory review times. This finding "conversely raises the possibility that some approval packages provide clearer evidence of safety, allowing for more rapid regulatory approval," the authors write. "An analysis of regulatory review documents from the European Medicines Agency indicated that safety risks that would ultimately prompt a postmarket safety event were not always evident in the premarket period, suggesting that additional premarket review might only delay approval without identifying therapeutics that pose a future safety concern."
"I agree with the authors' main point, which is that there are major gaps in our knowledge about the safety of drugs at the time that they are approved," Sean Hennessy, PharmD, PhD, told Medscape Medical News. Dr Hennessy is from the Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, and Department of Pharmacology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
"This isn't necessarily a bad thing, since requiring drug companies to perform the much larger studies that would need to be done to learn about rare adverse effects prior to approval would further increase the cost of drug development, which is already very expensive. Rather, we need to develop more robust systems to assess the safety of drugs after they are approved," Dr Hennessy explained.
Additional research is warranted to gain insight into the approval timeline and drug safety, the authors state. Further, they call for collaboration between stakeholders and the FDA "to develop and maintain an effective system for detecting postmarket safety events."
Stakeholder engagement is essential, Pitts told Medscape Medical News. "Although it's not taught in medical school, it's up to physicians and pharmacists to report adverse events, which is critical from a risk perspective and to mitigate potential problems with the use of approved medicines in everyday practice."
The good news, according to Pitts, is that "the FDA is taking this challenge to heart," by enhancing the capacity of its postmarket safety surveillance programs, and improving interactions with industry to achieve a better understanding of the performance of new drugs once they get into the market.The FDA's Sentinel Initiative, an integrated, national electronic monitoring system for active postmarket risk identification and analysis, is an important step in this direction, as is the sharing of premarket clinical trial data, the authors write. "[T]he integration of multiple data sources that include observations among large and diverse patient populations can facilitate the detection of postmarket safety events."
Previously, as reported by Medscape Medical News, the Government Accountability Office has questioned the sufficiency of the FDA's reporting of postmarket studies of approved drugs.
"I'm not as optimistic as the authors that the current system is working…. Sentinel, which I'm part of, is a great system, but has limited bandwidth. There aren't enough resources to use Sentinel as the only way to study the safety of every approved product, nor does FDA have the human resources to be primarily responsible for studying the safety of all products," Dr Hennessy explained.
"Industry needs to play a role. Unfortunately, FDA is limited by law in their ability to require companies to perform their own safety studies. Changing this would require an act of Congress," he added.
The authors acknowledge that even the most careful regulatory review and surveillance systems may not prevent all postmarket safety events. "[I]t may be impossible to detect other less common events until several years after approval, once the therapeutics are in broad use."
Dr Downing has disclosed no relevant financial relationships. One coauthor reports receiving personal fees from Cepton, OliverWyman, Roland Berger, McCann Health, Omnicom, Grey Healthcare, Saatchi & Saatchi, Sudler, TBWA, Havas, Agipharm, Mayoly Spindler, Teva, Menarini, Pierre Fabre, Merck, and AbbVie. One coauthor reports receiving a grant from the FDA; research agreements with Medtronic and Johnson & Johnson (Janssen) through Yale University; serving as chair of a cardiac scientific advisory board for UnitedHealth, being a founder of Hugo, being a participant and participant representative of the IBM Watson Health Life Sciences Board; and serving as an advisory board member of Element Science. One coauthor reports receiving grants from the FDA, Medtronic, Johnson & Johnson, the Centers for Medicare & Medicaid Services, Blue Cross Blue Shield Association, and the Laura and John Arnold Foundation. Mr Pitts serves as chief regulatory officer for Adherent Health Strategies. Dr Hennessy has disclosed no relevant financial relationships.
JAMA. 2017;317:1854-1863. Read More & Comment...
05/09/2017 12:26 PM | Robert Goldberg
The policy shop of BCBS has released a report about drug costs that is deliberately deceptive and misleading. It focuses only on the contribution of innovative drugs to total drug spending, ignoring other facts that underscore the important role new medicines play in reducing the rate of health care spending and hiding the rebates they, along with PBMs pocket.
The report claims that “since 2010 prescription drug spending has increased 10 percent annually for Blue Cross and Blue Shield (BCBS)members since 2010, an overall rise of 73 percent.This upward trend is due to a small fraction of emerging, patented drugs with rapid uptake and large year-over-year price increases that are more than offsetting the continued growth in utilization of lower-cost generic drugs. These higher costs are being incurred by consumers and payers alike; while consumer out-of-pocket costs have risen just three percent annually for prescription drugs in total, they have risen 18 percent annually for patented drugs.”
You might wonder how it is possible for consumer out of pocket costs to rise 3 percent annually if the increase in patented drug spending has increased 18 percent? Is it because health plans are sucking up the difference in cost for our sake? A closer look at the findings suggests answers.
1 BCBS compared apples – the average increase in out of pocket costs – which includes the increase in the use of generic drugs – to oranges, namely the pre-rebate increase in spending on drugs for Hepatitis C, autoimmune diseases and cancer for less than 1 percent of chronically ill patients. Indeed, the BCBS ‘study’ acknowledges that the drug spending data they use is pre-rebate. But let’s stick with sticker prices for now and ask: how does the increase in the use of a small number of new medicines affect drug spending and total health expenditures.
2 It turns out that employer-sponsored health plans are spending LESS on brand or innovator drugs as a percent of total health care spending. And total drug spending is about the same as it was in 2007:
Sources: Health Care Cost and Utilization Reports for 2010-2015
3. Since 2007, brand drugs as a percent of total drug spending has DECLINED
Sources: Health Care Cost and Utilization Reports for 2010-2015
4. If brand spending is down and total drug spending as a percent of all health expenditures are flat, why is cost sharing for drugs going up by 3 percent a year?
BCBS notes: “Utilization is down for all brand drugs, but the unit price has increased by an average of 17 percent each year, leading to a total increase in spending of 10 percent.”
In other words, health plans are charging the retail, not the rebated price, in determining copays and coinsurance even as brand drug spending as a percent of total Rx dollars has declined. Indeed, the spread between the rebated and retail price has been increasing.
Source: IMS Data
What's more, these rebates are not used to reduce the out of pocket costs of patients And plans use the retail price to fatten their margins with rebates AND the out of pocket spending of consumers. Reports about rebate revenues are hard to come by. However, an NAIC report suggests that rebates industry-wide are at least $30 billion which is more than the total underwriting gain of all health insurers.
The BCBS policy report hides the fact that drug spending as a percent of total health care spending is flat. It hides the fact that it is using rebates and retail prices to pad the bottom line. And it is using innovator drug prices as scapegoats.
A final thought: The Healthcare Cost Institute reports show that the utilization of all inpatient and outpatient services has declined since 2007 even as the use of both new and generic medicines has increased. And yet health plans have rarely considered or acknowledged that the use of prescription drugs reduces the reliance on more expensive forms of care.
Read More & Comment...
The report claims that “since 2010 prescription drug spending has increased 10 percent annually for Blue Cross and Blue Shield (BCBS)members since 2010, an overall rise of 73 percent.This upward trend is due to a small fraction of emerging, patented drugs with rapid uptake and large year-over-year price increases that are more than offsetting the continued growth in utilization of lower-cost generic drugs. These higher costs are being incurred by consumers and payers alike; while consumer out-of-pocket costs have risen just three percent annually for prescription drugs in total, they have risen 18 percent annually for patented drugs.”
You might wonder how it is possible for consumer out of pocket costs to rise 3 percent annually if the increase in patented drug spending has increased 18 percent? Is it because health plans are sucking up the difference in cost for our sake? A closer look at the findings suggests answers.
1 BCBS compared apples – the average increase in out of pocket costs – which includes the increase in the use of generic drugs – to oranges, namely the pre-rebate increase in spending on drugs for Hepatitis C, autoimmune diseases and cancer for less than 1 percent of chronically ill patients. Indeed, the BCBS ‘study’ acknowledges that the drug spending data they use is pre-rebate. But let’s stick with sticker prices for now and ask: how does the increase in the use of a small number of new medicines affect drug spending and total health expenditures.
2 It turns out that employer-sponsored health plans are spending LESS on brand or innovator drugs as a percent of total health care spending. And total drug spending is about the same as it was in 2007:
Sources: Health Care Cost and Utilization Reports for 2010-2015
3. Since 2007, brand drugs as a percent of total drug spending has DECLINED
Sources: Health Care Cost and Utilization Reports for 2010-2015
4. If brand spending is down and total drug spending as a percent of all health expenditures are flat, why is cost sharing for drugs going up by 3 percent a year?
BCBS notes: “Utilization is down for all brand drugs, but the unit price has increased by an average of 17 percent each year, leading to a total increase in spending of 10 percent.”
In other words, health plans are charging the retail, not the rebated price, in determining copays and coinsurance even as brand drug spending as a percent of total Rx dollars has declined. Indeed, the spread between the rebated and retail price has been increasing.
Source: IMS Data
What's more, these rebates are not used to reduce the out of pocket costs of patients And plans use the retail price to fatten their margins with rebates AND the out of pocket spending of consumers. Reports about rebate revenues are hard to come by. However, an NAIC report suggests that rebates industry-wide are at least $30 billion which is more than the total underwriting gain of all health insurers.
The BCBS policy report hides the fact that drug spending as a percent of total health care spending is flat. It hides the fact that it is using rebates and retail prices to pad the bottom line. And it is using innovator drug prices as scapegoats.
A final thought: The Healthcare Cost Institute reports show that the utilization of all inpatient and outpatient services has declined since 2007 even as the use of both new and generic medicines has increased. And yet health plans have rarely considered or acknowledged that the use of prescription drugs reduces the reliance on more expensive forms of care.
Read More & Comment...
05/06/2017 02:31 PM | Peter Pitts
In the wake of the unraveling scandal surrounding the agency’s television viewing habits, CDRH spokesperson Teng Kay has denied allegations they have been instructed by “unconfirmed alien contact” to reclassify TV remotes as Class II Medical devices. In a related story, Acting FDA Commissioner Rupert Murdoch has issued a list of “breakthrough therapy” entertainment for recommended viewing. The list is said to include: ANDA and the King of Siam, Complete Response Letters from Iwo Jima, and Fahrenheit 453. All programming has been deemed truthful, accurate, and non-misleading by the Shkreli Institute for Ethical Studies. Read More & Comment...
05/05/2017 02:58 PM | Peter Pitts
ICER’s new report, to no one’s great surprise, has found abuse-deterrent opioids provide neither financial nor societal benefits.
GIGO. Garbage In. Garbage Out.
For example:
The ICER analysis specifically does not include diversion – even though the majority of the problem arises from this community.
ICER also changed its model at the last minute to be include all abuse-deterrent formulations (ADFs) and not just Oxycontin -- despite preliminary results that showed that, over 5 years, OxyContin ADF prevented 4,300 cases of abuse, >12,000 abuse years, saved $300 million in medical costs against $387 million in incremental pharmacy costs. These results alone are within the realm of cost effectiveness: $20,500 per abuser avoided, $7100 per abuse year avoided for the most successful ADO introduced into the market.
Societal costs are not included despite ICER’s promise they would be.
Heroin switching is included, despite the fact that it is an incident cohort. Per ICER, “We did not include the effects of increasing heroin use that might result from opioid abusers being switched to ADF opioid, as we are considering only incident and not prevalent opioid abuse in the model.” Hm.
ADF benefit is reduced by 25% because of the author of the original paper (Rossiter) conducted a sensitivity analysis to see how such a reduction would effect the model.
ICER is calling for ADFs to be “cost-neutral.” But how is this possible since the overwhelming cause of the problem are inexpensive, non-ADF generics?
What the ICER report ignores entirely is that one of the factors driving abuse and addiction is the inappropriate use of generic opioids for conditions that have non-opioid, on-label options. (52 percent of patients diagnosed with osteoarthritis receive an opioid pain medicine as first line treatment as do 43 percent of patients diagnosed with fibromyalgia and 42 percent of patients with diabetic peripheral neuropathy.)
Payers often implement barriers to the use of branded, on-label non-opioid medicines, relegating these treatments to second line options – along with new abuse-deterrent opioid formulations. The result is a gateway to abuse and addiction. An unintended consequence of the ICER analysis will be more of this inappropriate behavior.
According to Harvard health economist David Cutler, Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost. But, as Aldous Huxley reminds us, ““Most human beings have an almost infinite capacity for taking things for granted.”
Abuse-deterrent opioids are precision medicines. They are not for everyone. As Dr. Charles Inturrisi, professor of pharmacology at the Weill Cornell Medical College, said at a 2013 Center for Medicine in the Public Interest Capitol Hill conference on opioids, “Personalized medicine can reduce the non-responder rate because you can focus in on individuals who are highly associated with being responders and you can eliminate the trial and error inefficiencies that inflate healthcare cost.”
One of the consequences of the ICER report is that it will deter investment in more and more creative abuse deterrent programs. The phrase, “strangling the baby in the crib” comes to mind.
Remember – ICER is the organization that found the new class of Hepatitis C therapeutics failing their cost/benefit litmus test -- another example of this organization being on the wrong side of history. Alas, it’s totally understandable considering that, on September 3, 2016, Dan Ollendorf (ICER Chief Scientific Officer) told the Pink Sheet, “It’s difficult to really understand how these [abuse deterrent opioids] are going to be of benefit if the non abuse-deterrent formulations are still out there.”
Talk about Confirmation Bias!
Read More & Comment...
GIGO. Garbage In. Garbage Out.
For example:
The ICER analysis specifically does not include diversion – even though the majority of the problem arises from this community.
ICER also changed its model at the last minute to be include all abuse-deterrent formulations (ADFs) and not just Oxycontin -- despite preliminary results that showed that, over 5 years, OxyContin ADF prevented 4,300 cases of abuse, >12,000 abuse years, saved $300 million in medical costs against $387 million in incremental pharmacy costs. These results alone are within the realm of cost effectiveness: $20,500 per abuser avoided, $7100 per abuse year avoided for the most successful ADO introduced into the market.
Societal costs are not included despite ICER’s promise they would be.
Heroin switching is included, despite the fact that it is an incident cohort. Per ICER, “We did not include the effects of increasing heroin use that might result from opioid abusers being switched to ADF opioid, as we are considering only incident and not prevalent opioid abuse in the model.” Hm.
ADF benefit is reduced by 25% because of the author of the original paper (Rossiter) conducted a sensitivity analysis to see how such a reduction would effect the model.
ICER is calling for ADFs to be “cost-neutral.” But how is this possible since the overwhelming cause of the problem are inexpensive, non-ADF generics?
What the ICER report ignores entirely is that one of the factors driving abuse and addiction is the inappropriate use of generic opioids for conditions that have non-opioid, on-label options. (52 percent of patients diagnosed with osteoarthritis receive an opioid pain medicine as first line treatment as do 43 percent of patients diagnosed with fibromyalgia and 42 percent of patients with diabetic peripheral neuropathy.)
Payers often implement barriers to the use of branded, on-label non-opioid medicines, relegating these treatments to second line options – along with new abuse-deterrent opioid formulations. The result is a gateway to abuse and addiction. An unintended consequence of the ICER analysis will be more of this inappropriate behavior.
According to Harvard health economist David Cutler, Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost. But, as Aldous Huxley reminds us, ““Most human beings have an almost infinite capacity for taking things for granted.”
Abuse-deterrent opioids are precision medicines. They are not for everyone. As Dr. Charles Inturrisi, professor of pharmacology at the Weill Cornell Medical College, said at a 2013 Center for Medicine in the Public Interest Capitol Hill conference on opioids, “Personalized medicine can reduce the non-responder rate because you can focus in on individuals who are highly associated with being responders and you can eliminate the trial and error inefficiencies that inflate healthcare cost.”
One of the consequences of the ICER report is that it will deter investment in more and more creative abuse deterrent programs. The phrase, “strangling the baby in the crib” comes to mind.
Remember – ICER is the organization that found the new class of Hepatitis C therapeutics failing their cost/benefit litmus test -- another example of this organization being on the wrong side of history. Alas, it’s totally understandable considering that, on September 3, 2016, Dan Ollendorf (ICER Chief Scientific Officer) told the Pink Sheet, “It’s difficult to really understand how these [abuse deterrent opioids] are going to be of benefit if the non abuse-deterrent formulations are still out there.”
Talk about Confirmation Bias!
Read More & Comment...
05/05/2017 07:06 AM | Peter Pitts
The QuintilesIMS Institute has issued a very interesting new report, “Medicines Use and Spending in the US: A Review of 2016 and Outlook to 2021.” It’s a must-read for many reasons – not the least of which is its plethora of data. Many items to peruse and digest.
Here are four of the reports conclusions – as an appetizer …
* The outlook for spending has been revised downward as expectations for new products and price increases have moderated.
* Invoice price growth for protected brands is projected to be between 7-10% down from 8-11% in the prior outlook.
* Net price growth for protected brands is forecast to be 2-5% through 2021.
* The impact of losses of exclusivity are expected to be 50% greater in the next five years, including the impact of biosimilar introductions.
With the caveat that statistics are like swimwear (what they show you is interesting but what they conceal is essential), have a look and draw your own conclusions. Read More & Comment...
Here are four of the reports conclusions – as an appetizer …
* The outlook for spending has been revised downward as expectations for new products and price increases have moderated.
* Invoice price growth for protected brands is projected to be between 7-10% down from 8-11% in the prior outlook.
* Net price growth for protected brands is forecast to be 2-5% through 2021.
* The impact of losses of exclusivity are expected to be 50% greater in the next five years, including the impact of biosimilar introductions.
With the caveat that statistics are like swimwear (what they show you is interesting but what they conceal is essential), have a look and draw your own conclusions. Read More & Comment...
05/04/2017 05:03 PM | Peter Pitts
Representative Morgan Griffith (R/VA) has introduced HR 1703, the Medical Product Communications Act. It’s legislation that would take a lot of the ambiguity out of the FDA’s biggest conundrum – regulatory clarity on the sharing of truthful accurate, and non-misleading off-label information.
As Mr. Griffith writes in a Dear Colleague letter, “Doctors should have the most up-to-date information when caring for their patients and, when done responsibly and in an appropriate context, manufacturers should be able to provide it.”
Amen.
For more detail on the issue, have a look at this new article from the Therapeutic Innovation and Regulatory Science (the official journal of the Drug Information Association), “Using Off-Label Communications to Responsibly Advance the Public Health.” Read More & Comment...
As Mr. Griffith writes in a Dear Colleague letter, “Doctors should have the most up-to-date information when caring for their patients and, when done responsibly and in an appropriate context, manufacturers should be able to provide it.”
Amen.
For more detail on the issue, have a look at this new article from the Therapeutic Innovation and Regulatory Science (the official journal of the Drug Information Association), “Using Off-Label Communications to Responsibly Advance the Public Health.” Read More & Comment...
05/03/2017 07:58 AM | Peter Pitts
When it comes to 21st century pharmacovigilance, sometimes it’s important to look … backwards. According to the 10th century Arab physician, Ibn Sina, “The time of action must be observed, so that essence and accident are not confused.”
At the United Arab Emirates’ Sixth National Pharmacovigilance Conference” held last month in Dubai, specific recommendations (known as “the Dubai Declaration”) were released by the Ministry of Health and Prevention (MoHP).
According to Dr. Amin Hussain Al Amiri (MoHP- Assistant Undersecretary for Public Health Policy & Licensing Sector, the Declaration will be submitted to the regional Gulf Health Council for Cooperation Council States and the 22-member Arab League with the hope that this “would benefit the Arab World.”
The complete list of recommendations can be found here.
A few stand out from the rest, specifically:
1- Build trust in the critical role of testing medicines following registration and testing random sample from the field.
2- Enhance of pharmacovigilance education programs among HCPs in the region.
3- Include pharmacovigilance education in the academic curricula of medical and scientific schools and making it among the basics of education.
4- ADRs reporting must become a “culture of HCPs” who must not be embarrassed in doing so.
5- Enhance health education to raise public awareness on expected ADRs.
6- Reported ADRs to be categorized and separated according to originator medicine, generic, and the biological view of the difference in chemical compositions.
7- Focus on the educational role of pharmacovigilance officers among the various healthcare establishments in the region.
When it comes to the quality of medicines, remember the words of Dr. Janet Woodcock, (CDER Director, USFDA), “The spark that ignited the flame was when we asked ourselves, Do we know enough about the quality of drugs that are sold in the United States? And the answer was … no.”
We would all do well to learn not just from the past – but from other parts of the world. The West doesn’t have a monopoly on good ideas.
Read More & Comment...
At the United Arab Emirates’ Sixth National Pharmacovigilance Conference” held last month in Dubai, specific recommendations (known as “the Dubai Declaration”) were released by the Ministry of Health and Prevention (MoHP).
According to Dr. Amin Hussain Al Amiri (MoHP- Assistant Undersecretary for Public Health Policy & Licensing Sector, the Declaration will be submitted to the regional Gulf Health Council for Cooperation Council States and the 22-member Arab League with the hope that this “would benefit the Arab World.”
The complete list of recommendations can be found here.
A few stand out from the rest, specifically:
1- Build trust in the critical role of testing medicines following registration and testing random sample from the field.
2- Enhance of pharmacovigilance education programs among HCPs in the region.
3- Include pharmacovigilance education in the academic curricula of medical and scientific schools and making it among the basics of education.
4- ADRs reporting must become a “culture of HCPs” who must not be embarrassed in doing so.
5- Enhance health education to raise public awareness on expected ADRs.
6- Reported ADRs to be categorized and separated according to originator medicine, generic, and the biological view of the difference in chemical compositions.
7- Focus on the educational role of pharmacovigilance officers among the various healthcare establishments in the region.
When it comes to the quality of medicines, remember the words of Dr. Janet Woodcock, (CDER Director, USFDA), “The spark that ignited the flame was when we asked ourselves, Do we know enough about the quality of drugs that are sold in the United States? And the answer was … no.”
We would all do well to learn not just from the past – but from other parts of the world. The West doesn’t have a monopoly on good ideas.
Read More & Comment...
04/27/2017 10:18 AM | Robert Goldberg
Today (we hope) the Senate HELP Committee will vote to confirm Dr. Scott Gottlieb as the next FDA commissioner.
Three things stand out about his nomination:
1. Dr. Gottlieb has garnered the support of a wide range of patient organizations and medical associations. The same coalition supported Dr. Rob Califf’s nomination in 2016.
2. The same groups and individuals who oppose Dr. Califf’s nomination are opposing Scott. Apart from the Senators who opposed both individuals to demonstrate frustration with the FDA’s response to the opioid addiction problem, the critics are the self-important and self-serving hacks from Public Citizen along with smug academics whose names I will not repeat.
3. Both Dr. Gottlieb and Dr. Califf are deeply committed to changing the paradigm of FDA approval by working with talented individuals inside the agency.
Dr. Gottlieb’s nomination reflects a bi-partisan consensus about the role of the FDA that originated with President Obama and the nomination of Dr. Peggy Hamburg: When it comes to evaluating the risk and benefit of innovations that determine not only whether we live or die but how we live and die, patients and their loved ones have as much of say on the basis for approval and regulation as any expert.
Dr. Gottlieb will carry on that tradition. His opponents want to destroy that tradition. Hope vs. hate. Remember that the next time you see a hateful, angry tweet about the next FDA commissioner.
Read More & Comment...
Three things stand out about his nomination:
1. Dr. Gottlieb has garnered the support of a wide range of patient organizations and medical associations. The same coalition supported Dr. Rob Califf’s nomination in 2016.
2. The same groups and individuals who oppose Dr. Califf’s nomination are opposing Scott. Apart from the Senators who opposed both individuals to demonstrate frustration with the FDA’s response to the opioid addiction problem, the critics are the self-important and self-serving hacks from Public Citizen along with smug academics whose names I will not repeat.
3. Both Dr. Gottlieb and Dr. Califf are deeply committed to changing the paradigm of FDA approval by working with talented individuals inside the agency.
Dr. Gottlieb’s nomination reflects a bi-partisan consensus about the role of the FDA that originated with President Obama and the nomination of Dr. Peggy Hamburg: When it comes to evaluating the risk and benefit of innovations that determine not only whether we live or die but how we live and die, patients and their loved ones have as much of say on the basis for approval and regulation as any expert.
Dr. Gottlieb will carry on that tradition. His opponents want to destroy that tradition. Hope vs. hate. Remember that the next time you see a hateful, angry tweet about the next FDA commissioner.
Read More & Comment...
04/21/2017 12:25 PM | Peter Pitts
From the pages of Investor’s Business Daily …
Making Drug Manufacturing Great Again
President Trump wants to lower drug prices and reinvigorate domestic pharmaceutical manufacturing. Bravo. But standing in the way is the inside-the-Beltway gospel that preaches that regulators love ambiguity.
As a former FDA associate commissioner, I can affirm that's true. Vagueness gives the agency almost unlimited authority to do whatever it wants.
But, when it comes to the FDA, it's predictability in pursuit of the public health that's important. And nowhere is this truer or more timely than when it comes to the oversight of drug manufacturing.
Drug manufacturing isn't sexy to the general public and rarely makes headlines — unless something goes wrong. Recalls make headlines. Adherence to current good manufacturing practices (GMPs) do not.
A few years ago I had the chance to visit Pfizer's Kalamazoo production facility. What impressed me more than the gee-whiz production aspects of the facility (of which there were plenty) was the dedication of the people who work there — top to bottom.
It actually reminded me a lot of the FDA. Long-term employees dedicated to serving the public health through dedication to quality. And they all took it very personally. Just like at the FDA, the Pfizer folks were on personal missions of quality. There was a lot of pride on display.
Mr. President — there hasn't been an exodus of pharma manufacturing to foreign shores. In fact, when I visited the Kalamazoo facility they were exporting (among other things) the active pharmaceutical ingredient (or API, the actual drug substance) for methyl prednisolone (a corticosteroid long off patent) to both China and India.
A U.S. manufacturing facility of an innovative biopharmaceutical company that exports drugs to China and India for profit? What's wrong with this picture? Well, as it turns out, it's what's right — innovation through manufacturing prowess, organic chemistry smarts and green technology. Better. Faster. Cheaper.
Pharma's always bragging about its ever-growing investment in R&D. But when was the last time you heard about investments in domestic manufacturing? Probably never.
And when was the last time you read about enhanced drug safety through good manufacturing processes and cooperation between industry and the FDA? Not recently. That's a shame because they're both important stories.
The president's nomination of Dr. Scott Gottlieb to be the next FDA commissioner likely portends a more holistic view of drug regulation. I served with Scott for two years at the agency. Not only is he a voice for greater regulatory predictability, he's also a silo-buster.
Having previously served as deputy commissioner, he understands the need for greater interdepartmental cooperation. In other words, it's not just about better utilization of expedited review pathways or better use of real-world data, or enhanced post-market surveillance, or more robust off-label communications. It's about making the process work for patients.
But manufacturing is all about process. Modernized pharmaceutical manufacturing isn't only about ensuring and enhancing quality for finished medicines, it's also about making America's pharmaceutical factories globally competitive players in the production of API (like Pfizer's plant in Kalamazoo) and excipients (the ingredients other than the API that are included in the manufacturing process or are contained in a finished pharmaceutical product.)
And the more complicated the drug, the more complicated the active pharmaceuticals and other ingredients. American know-how and dedication to GMPs present a wonderful opportunity for our domestic facilities to thrive. Quality manufacturing is our unique proposition vis-a-vis less expensive operations overseas.
FDA regulation of medicine manufacturing is also a crucial piece of the solution to preventing future drug shortages. According to a 2012 report from the House Committee on Oversight and Government Reform, by hastily ramping up manufacturing enforcement actions, the FDA "effectively shut down 30% of the total manufacturing capacity at four of the country's largest producers of generic injectable medications."
Resolving this problem will require the FDA to work with manufacturers to find practical, science-based solutions to quality-control issues that neither compromise safety nor slow down production. Regulatory discretion is often the better part of valor.
Enforcement of savvy manufacturing quality control is crucial, but an equally important (and often ignored) aspect of the FDA's mission is to advance America's pharmaceutical production acumen by being both regulator of and partner with industry.
That's a winning combination: the best and the brightest from industry and government together with the best production capabilities in the world. The keys to the kingdom are on the table.
Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest. Read More & Comment...
Making Drug Manufacturing Great Again
President Trump wants to lower drug prices and reinvigorate domestic pharmaceutical manufacturing. Bravo. But standing in the way is the inside-the-Beltway gospel that preaches that regulators love ambiguity.
As a former FDA associate commissioner, I can affirm that's true. Vagueness gives the agency almost unlimited authority to do whatever it wants.
But, when it comes to the FDA, it's predictability in pursuit of the public health that's important. And nowhere is this truer or more timely than when it comes to the oversight of drug manufacturing.
Drug manufacturing isn't sexy to the general public and rarely makes headlines — unless something goes wrong. Recalls make headlines. Adherence to current good manufacturing practices (GMPs) do not.
A few years ago I had the chance to visit Pfizer's Kalamazoo production facility. What impressed me more than the gee-whiz production aspects of the facility (of which there were plenty) was the dedication of the people who work there — top to bottom.
It actually reminded me a lot of the FDA. Long-term employees dedicated to serving the public health through dedication to quality. And they all took it very personally. Just like at the FDA, the Pfizer folks were on personal missions of quality. There was a lot of pride on display.
Mr. President — there hasn't been an exodus of pharma manufacturing to foreign shores. In fact, when I visited the Kalamazoo facility they were exporting (among other things) the active pharmaceutical ingredient (or API, the actual drug substance) for methyl prednisolone (a corticosteroid long off patent) to both China and India.
A U.S. manufacturing facility of an innovative biopharmaceutical company that exports drugs to China and India for profit? What's wrong with this picture? Well, as it turns out, it's what's right — innovation through manufacturing prowess, organic chemistry smarts and green technology. Better. Faster. Cheaper.
Pharma's always bragging about its ever-growing investment in R&D. But when was the last time you heard about investments in domestic manufacturing? Probably never.
And when was the last time you read about enhanced drug safety through good manufacturing processes and cooperation between industry and the FDA? Not recently. That's a shame because they're both important stories.
The president's nomination of Dr. Scott Gottlieb to be the next FDA commissioner likely portends a more holistic view of drug regulation. I served with Scott for two years at the agency. Not only is he a voice for greater regulatory predictability, he's also a silo-buster.
Having previously served as deputy commissioner, he understands the need for greater interdepartmental cooperation. In other words, it's not just about better utilization of expedited review pathways or better use of real-world data, or enhanced post-market surveillance, or more robust off-label communications. It's about making the process work for patients.
But manufacturing is all about process. Modernized pharmaceutical manufacturing isn't only about ensuring and enhancing quality for finished medicines, it's also about making America's pharmaceutical factories globally competitive players in the production of API (like Pfizer's plant in Kalamazoo) and excipients (the ingredients other than the API that are included in the manufacturing process or are contained in a finished pharmaceutical product.)
And the more complicated the drug, the more complicated the active pharmaceuticals and other ingredients. American know-how and dedication to GMPs present a wonderful opportunity for our domestic facilities to thrive. Quality manufacturing is our unique proposition vis-a-vis less expensive operations overseas.
FDA regulation of medicine manufacturing is also a crucial piece of the solution to preventing future drug shortages. According to a 2012 report from the House Committee on Oversight and Government Reform, by hastily ramping up manufacturing enforcement actions, the FDA "effectively shut down 30% of the total manufacturing capacity at four of the country's largest producers of generic injectable medications."
Resolving this problem will require the FDA to work with manufacturers to find practical, science-based solutions to quality-control issues that neither compromise safety nor slow down production. Regulatory discretion is often the better part of valor.
Enforcement of savvy manufacturing quality control is crucial, but an equally important (and often ignored) aspect of the FDA's mission is to advance America's pharmaceutical production acumen by being both regulator of and partner with industry.
That's a winning combination: the best and the brightest from industry and government together with the best production capabilities in the world. The keys to the kingdom are on the table.
Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest. Read More & Comment...
04/17/2017 08:19 AM | Peter Pitts
House Judiciary Committee Chairman, Rep. Bob Goodlatte (R/VA.) wants drug side-effect ads that are run by lawyers to include a warning that patients should talk with their doctors before adjusting medication, the Wall Street Journal reports. Along with the American Medical Association and some drug companies, he contends the ads are to blame for patients suffering harm or even dying after dropping treatment.
Read More & Comment...
Read More & Comment...
04/14/2017 04:54 PM | Peter Pitts
House, Senate Health Committee Leaders Release Discussion Draft of FDA User Fees Reauthorization
WASHINGTON, DC – The leaders of the Senate and House health committees today released a discussion draft of bipartisan legislation reauthorizing the Food and Drug Administration user fee agreements.
The Food and Drug Administration (FDA) Reauthorization Act of 2017 renews FDA's authority to collect user fees from the makers of prescription brand drugs, medical devices, generic drugs and biosimilars, and several vital programs at the FDA. The 2012 prescription drug user fee amendments (PDUFA), medical device user fee amendments (MDUFA), generic drug user fee amendments (GDUFA), and biosimilar user fee amendments (BsUFA) all must be updated and reauthorized by Congress before the current user fee agreements expire on September 30.
If the agreements are not reauthorized before the August work period, the agency will be forced to send layoff notices to more than 5,000 FDA employees. A delay in reauthorizing these agreements would delay the reviews of critical drugs and devices.
“We are fully committed to a timely reauthorization of the agreements and are well on our way,” said Energy and Commerce Committee Chairman Greg Walden (R-OR). “This represents another opportunity to help expedite the review and approval of new cures and treatments for patients, and we must prioritize it. As this process proceeds, I look forward to continued discussions with my colleagues in the House on other member priorities that could strengthen this important legislation.”
"The swift reauthorization of these user fee agreements is critical to making sure FDA has the resources and personnel it needs to ensure timely review and approval of safe and effective medical treatments,” said Energy and Commerce Committee Ranking Member Frank Pallone, Jr. (D-NJ). “These carefully negotiated agreements encourage innovation, improve our regulatory review process, and provide certainty to both patients and industry. I look forward to working with my colleagues to move this legislation through Congress and to the President's desk.”
“If we do not move quickly to reauthorize these agreements, in late July, the FDA will be forced to begin sending layoff notices to more than 5,000 employees to notify them that they may lose their job in 60 days,” said Senate Health, Education, Labor and Pensions Committee Chairman Lamar Alexander (R-TN). “The sooner we reauthorize the agreements, the better – to give patients, reviewers, and companies certainty. In addition to harming patients and families that rely on medical innovation, a delay in reauthorizing the user fees would threaten biomedical industry jobs and America’s global leadership in biomedical innovation.”
“I’m encouraged by our bipartisan work to reauthorize these agreements to advance safe, effective, and innovative medical products,” said Senate Health, Education, Labor and Pensions Committee Ranking Member Patty Murray (D-WA). “Patients and families nationwide are relying on us to ensure FDA can continue its vital work without interruption. I hope that we can continue to put partisanship aside and advance this important legislation.”
The FDA Reauthorization Act of 2017:
Updates and reauthorizes the user fee programs, which, in Fiscal Year 2016, accounted for 70 percent of the brand drug review budget, 36 percent of the medical device review budget, 75 percent of the generic drug review budget, and 29 percent of the biosimilar review budget.
Reflects the recommendations sent by FDA to Congress in January, which were based on over a year of negotiations and discussions with industry, Congress, patients, and other stakeholders.
Implements the four user fee agreements authorized by FDARA, which support the goals of the 21st Century Cures act and advance key bipartisan priorities:
Prescription Drug User Fee Amendments (PDUFA VI): Enhances patient-focused drug development, supports biomarker development and qualification, dedicates staff to assist in the development and review of rare disease drugs, sets clear timelines and improves guidance for drug and device combination products, and evaluates ways to modernize the clinical trial process.
Medical Device User Fee Amendments (MDUFA IV): Enhances the patient voice in the device development process, supports the collection of real world evidence on the safety and effectiveness of devices, and improves the review process for “de novo” devices—low- to moderate-risk devices that are the first of their kind.
Generic Drug User Fee Amendments (GDUFA II): Improves the fee structure to support small businesses, provides goal dates for all outstanding generic applications, and establishes priority review timelines.
Biosimilar User Fee Amendments (BsUFA II): Continues to build the biosimilars program, and supports guidance for product developers.
CLICK HERE for the text of the discussion draft, HERE for a section-by-section summary of the discussion draft, and HERE for a one-pager. Health committee leaders ask that stakeholders who wish to comment on the contents of this draft please submit to FDAuserfees2017@help.senate.gov by April 28th. Read More & Comment...
WASHINGTON, DC – The leaders of the Senate and House health committees today released a discussion draft of bipartisan legislation reauthorizing the Food and Drug Administration user fee agreements.
The Food and Drug Administration (FDA) Reauthorization Act of 2017 renews FDA's authority to collect user fees from the makers of prescription brand drugs, medical devices, generic drugs and biosimilars, and several vital programs at the FDA. The 2012 prescription drug user fee amendments (PDUFA), medical device user fee amendments (MDUFA), generic drug user fee amendments (GDUFA), and biosimilar user fee amendments (BsUFA) all must be updated and reauthorized by Congress before the current user fee agreements expire on September 30.
If the agreements are not reauthorized before the August work period, the agency will be forced to send layoff notices to more than 5,000 FDA employees. A delay in reauthorizing these agreements would delay the reviews of critical drugs and devices.
“We are fully committed to a timely reauthorization of the agreements and are well on our way,” said Energy and Commerce Committee Chairman Greg Walden (R-OR). “This represents another opportunity to help expedite the review and approval of new cures and treatments for patients, and we must prioritize it. As this process proceeds, I look forward to continued discussions with my colleagues in the House on other member priorities that could strengthen this important legislation.”
"The swift reauthorization of these user fee agreements is critical to making sure FDA has the resources and personnel it needs to ensure timely review and approval of safe and effective medical treatments,” said Energy and Commerce Committee Ranking Member Frank Pallone, Jr. (D-NJ). “These carefully negotiated agreements encourage innovation, improve our regulatory review process, and provide certainty to both patients and industry. I look forward to working with my colleagues to move this legislation through Congress and to the President's desk.”
“If we do not move quickly to reauthorize these agreements, in late July, the FDA will be forced to begin sending layoff notices to more than 5,000 employees to notify them that they may lose their job in 60 days,” said Senate Health, Education, Labor and Pensions Committee Chairman Lamar Alexander (R-TN). “The sooner we reauthorize the agreements, the better – to give patients, reviewers, and companies certainty. In addition to harming patients and families that rely on medical innovation, a delay in reauthorizing the user fees would threaten biomedical industry jobs and America’s global leadership in biomedical innovation.”
“I’m encouraged by our bipartisan work to reauthorize these agreements to advance safe, effective, and innovative medical products,” said Senate Health, Education, Labor and Pensions Committee Ranking Member Patty Murray (D-WA). “Patients and families nationwide are relying on us to ensure FDA can continue its vital work without interruption. I hope that we can continue to put partisanship aside and advance this important legislation.”
The FDA Reauthorization Act of 2017:
Updates and reauthorizes the user fee programs, which, in Fiscal Year 2016, accounted for 70 percent of the brand drug review budget, 36 percent of the medical device review budget, 75 percent of the generic drug review budget, and 29 percent of the biosimilar review budget.
Reflects the recommendations sent by FDA to Congress in January, which were based on over a year of negotiations and discussions with industry, Congress, patients, and other stakeholders.
Implements the four user fee agreements authorized by FDARA, which support the goals of the 21st Century Cures act and advance key bipartisan priorities:
Prescription Drug User Fee Amendments (PDUFA VI): Enhances patient-focused drug development, supports biomarker development and qualification, dedicates staff to assist in the development and review of rare disease drugs, sets clear timelines and improves guidance for drug and device combination products, and evaluates ways to modernize the clinical trial process.
Medical Device User Fee Amendments (MDUFA IV): Enhances the patient voice in the device development process, supports the collection of real world evidence on the safety and effectiveness of devices, and improves the review process for “de novo” devices—low- to moderate-risk devices that are the first of their kind.
Generic Drug User Fee Amendments (GDUFA II): Improves the fee structure to support small businesses, provides goal dates for all outstanding generic applications, and establishes priority review timelines.
Biosimilar User Fee Amendments (BsUFA II): Continues to build the biosimilars program, and supports guidance for product developers.
CLICK HERE for the text of the discussion draft, HERE for a section-by-section summary of the discussion draft, and HERE for a one-pager. Health committee leaders ask that stakeholders who wish to comment on the contents of this draft please submit to FDAuserfees2017@help.senate.gov by April 28th. Read More & Comment...
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