Latest Drugwonks' Blog

The FDA gets it exactly right -- and the key word is "evolving."

FDA issues final guidance on the evaluation and labeling of abuse-deterrent opioids

The U.S. Food and Drug Administration today issued a final guidance to assist industry in developing opioid drug products with potentially abuse-deterrent properties.

Opioid drugs provide significant benefit for patients when used properly; however opioids also carry a risk of misuse, abuse and death. To combat opioid misuse and abuse, the FDA is encouraging manufacturers to develop abuse-deterrent drugs that work correctly when taken as prescribed, but, for example, may be formulated in such a way that deters misuse and abuse, including making it difficult to snort or inject the drug for a more intense high. While drugs with abuse-deterrent properties are not “abuse-proof,” the FDA sees this guidance as an important step toward balancing appropriate access to opioids for patients with pain with the importance of reducing opioid misuse and abuse.

The document “Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling” explains the FDA’s current thinking about the studies that should be conducted to demonstrate that a given formulation has abuse-deterrent properties. It also makes recommendations about how those studies should be performed and evaluated, and discusses what labeling claims may be approved based on the results of those studies.

“The science of abuse-deterrent medication is rapidly evolving, and the FDA is eager to engage with manufacturers to help make these medications available to patients who need them,” said FDA Commissioner Margaret A. Hamburg, M.D. “We feel this is a key part of combating opioid abuse. We have to work hard with industry to support the development of new formulations that are difficult to abuse but are effective and available when needed.”

The science of abuse-deterrent technology is still relatively new and evolving. The final guidance is intended to assist drug makers who wish to develop opioid drug products with potentially abuse-deterrent properties. The FDA is working with many drug makers to support advancements in this area and help drug makers navigate the regulatory path to market as quickly as possible. In working with industry, the FDA will take a flexible, adaptive approach to the evaluation and labeling of potentially abuse-deterrent products.

“Development of abuse-deterrent products is a priority for the FDA, and we hope this guidance will lead to more approved drugs with meaningful abuse-deterrent properties,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “While abuse-deterrent formulations do not make an opioid impossible to abuse and cannot wholly prevent overdose and death, they are an important part of the effort to reduce opioid misuse and abuse.”

While this final guidance does not address generic opioid products, the agency understands the importance of available generic options to ensure appropriate access to effective opioid drugs for patients who need them. The FDA is committed to supporting the development and use of generic drugs that have abuse-deterrent properties and is working on draft guidance in this area.

To help support the safe use of all opioid products, the FDA is working in many other ways to help prescribers and patients make the best possible choices about how to use these powerful drugs. The agency’s goal is to find the balance between appropriate access to opioids for patients with pain and the need to reduce opioid misuse and abuse.

Senator David Vitter (R, LA) is, once again, trying to fool his colleagues (and the American public) about drug importation. Let’s go, once again, into the abyss and set the facts straight.

Brand-name pharmaceuticals found abroad tend to be significantly cheaper than they are in the States, largely because foreign governments impose stringent price controls on most drug sales.

Advocates claim that “re-importation” will allow American patients to benefit from this price disparity.

But “re-importation” doesn’t actually describe what will happen if foreign drug importation is legalized. Using the term is an act of linguistic misdirection — or outright chicanery, if you’ve got a cynical streak. It’s not “re-importation,” it’s importation. This isn’t about medicines that have ever been inside US borders.

Nor is this about denigrating the Canadian medicines regulatory system -- it’s about reality.

Importing drugs from Canada is exceedingly dangerous for a number of reasons. For starters, many Internet pharmacies based up North are stocked with drugs from the European Union. And while many wouldn’t hesitate to take medicines purchased from countries like France and Great Britain, there’s plenty of risk involved.

The EU currently operates under a system of “parallel trade,” which allows products to be freely imported between member countries. This means that any drugs exported from the U.K. to Canada could have originated in an EU country with significantly less rigorous safety regulations, like Greece, Portugal, Latvia, or Malta.

Just last year, EU officials seized over 34 million fake pills in just two months. And in May, Irish drug enforcers confiscated over 1.7 million pounds of counterfeit and illegal drug packages. So if American customers start buying drugs over the Internet from Canadian pharmacies, they could easily wind up with tainted medicines of unknown European origin.

It’s also important to note that drugs from anywhere in Europe aren’t even legal for sale in Canada. So, when politicians say we can get “the same drugs” that Canadians get, they’re just plain wrong.

Even more worrisome is outright fraud — many “Canadian” pharmacies are actually headquartered somewhere else.

A 2005 investigation by the Food and Drug Administration looked at 4,000 drug shipments coming into the United States. Almost half of them claimed to be from Canada. Of those, a full 85 percent were actually from countries such as India, Vanuatu, and Costa Rica.

As part of another investigation, FDA officials bought three popular drugs from two Internet pharmacies claiming to be “located in, and operated out of, Canada.” Both websites had Canadian flags on their websites. Yet neither the pharmacies nor the drugs were actually from Canada.

As an FDA official told Congress, “We determined there is no evidence that the dispensers of the drugs or the drugs themselves are Canadian. The registrants, technical contacts, and billing contacts for both web sites have addresses in China. The reordering website for both purchases and its registrant, technical contact, and billing contact have addresses in Belize. The drugs were shipped from Texas, with a customer service and return address in Florida.”

And in laboratory analysis, every pill failed basic purity and potency tests.

The on-the-ground reality of s tate and local importation schemes have been dismal and politically embarrassing. Remember Illinois' high profile "I-Save-RX" program? Over 19 months of operation, a grand total of 3,689 Illinois residents used the program—which equals approximately .02 percent of the population.

And what of Minnesota's RxConnect? According to its latest statistics, Minnesota RxConnect fills about 138 prescriptions a month. That's for the whole state. Minnesota population: 5,167,101.

Remember Springfield, Massachusetts and “the New Boston Tea Party?” Well the city of Springfield has been out of the “drugs from Canada business” since August 2006.

And, speaking of tea parties, according to a story in the Boston Globe, “Four years after Mayor Thomas M. Menino bucked federal regulators and made Boston the biggest city in the nation to offer low-cost Canadian prescription drugs to employees and retirees, the program has fizzled, never having attracted more than a few dozen participants.”

The Canadian supplier for the program, Winnipeg-based Total Care Pharmacy, sent a letter to city officials saying the firm was terminating its agreement because there were so few participants. In 2006, Boston saved $4,300 on a total of 73 prescriptions. When Total Care decided to end its relationship with the city, only 16 Boston retirees were still participating.

And such programs won't do any better on a national basis. A study by the non-partisan federal Congressional Budget Office showed that importation would reduce our nation's spending on prescription medicines a whopping 0.1 percent—and that's not including the tens of millions of dollars the FDA would need to oversee drug safety for the dozen or so nations generally mentioned in foreign drug importation schemes.

 Calling foreign drug importation “re-importation” is a clever way to sell the idea to the American people. But the term simply doesn’t fit with the facts. In reality, Americans would end up jeopardizing their health by purchasing unsafe drugs made in foreign countries – while not saving money.

Think again, Senator Vitter.

Lost in the Reeds

  • 03.31.2015

Senator Jack Reed (D, RI) wants to repeal the Non-Interference Clause. He thinks it will lower the government’s prescription drug bill. He’s wrong. Let’s look at the record.

While Medicare as a whole is a fiscal basket case -- due to run out of money in 2024 -- Part D has been the very model of a well functioning federal program since its implementation.

The Congressional Budget Office (CBO) found that, between 2004 and 2013, Part D will cost an extraordinary 45 percent below what was initially estimated. Premiums for the program, meanwhile, are roughly half of the government’s original projections. Part D enrollees pay, on average, $30 a month -- a rate that has remained essentially unchanged for years.

It’s no wonder that beneficiaries are so pleased with the program. In fact, 96 percent of those enrolled in Part D say that their coverage works well.

These unprecedented results are largely due to Part D’s market-based structure. Beneficiaries are free to choose from a slate of private drug coverage plans, forcing insurers to compete to offer the best options to American seniors. It’s hardly surprising that the program has led to low prices and satisfied customers.

Through their own negotiations with drugmakers, private insurance plans that operate under Part D have already had great success in keeping pharmaceutical prices down. In fact, the CBO has observed that Part D plans have “secured rebates somewhat larger than the average rebates observed in commercial health plans.”

What’s more, the CBO has said time and again that doing away with the non-interference clause “would have a negligible effect on federal spending.” In a report from 2009, they reiterated this view, explaining that such a reform would “have little, if any, effect on [drug] prices.”

In fact, allowing the feds to negotiate drug prices under Part D would likely have a negative effect on the program. The CBO predicts that, when HHS forces pharmaceutical firms to lower the cost of a particular drug, this tactic brings with it “the threat of not allowing that drug to be prescribed.”

Senator Reed is lost in the wilderness.

Many nations in the developing world look to Brazil’s drug licensing agency, the National Agency of Sanitary Vigilance (ANVISA), as a model to emulate. Last week, the outgoing president of ANVISA, Jaime Oliveira, said ANVISA should decrease the time it takes to analyze the registration of new products and spend more time monitoring “what is on the pharmacy counter.”

Per Oliveria, ANVISA should dedicate more time going into drugstores and supermarkets to check whether the products it has already approved are being manufactured and sold according to appropriate quality standards.

This makes ANVISA the latest big nation regulatory agency to recognize the growing urgency in quality management and post-marketing surveillance. As more and more regulatory bodies (including the EMA and the USFDA) refocus their attentions on bioequivalence, API and excipient sourcing, and cGMPs, Mr. Oliveria’s statement reinforces the urgency and importance of both pre-market scrutiny and real world integrity. 

Abuse Deterrent Opioids: Don't Fix the Blame, Fix the Problem

By: Peter J. Pitts

Mark Twain quipped, “For every complex problem there is usually a simple answer – and it is usually wrong.” Welcome to the debate over opioid pain medications. What those seeking to solve the problem with one-shot solutions have ignored is that pain in America is a medical problem of enormous proportion.

One-hundred million Americans are now living with chronic pain. That’s a third of the U.S. population. Ten million of those have pain so severe that it disables them. Pain costs the U.S. economy roughly $600 billion dollars a year in lost productivity and healthcare costs. And lawsuits, recalls, and police action won’t change those dire statistics.

The vast majority of people who use opioids do so legally and safely. A subset of approximately 4% uses these medications illegally. In fact, from 2010 to 2011, the number of Americans misusing and abusing opioid medications declined from 4.6% to 4.2%.

One reason is the development of abuse deterrent opioid medications. According to the Journal of Pain, in a real-world study, abuse by snorting, smoking, and injecting prescription opioids declined by 66% after the reformulation of the drug with abuse deterrent properties. The New England Journal of Medicine has reported that, “the selection of OxyContin as a primary drug of abuse decreased from 35.6% of respondents before the release of the abuse deterrent formulation to just 12.8% twenty-one months later.”

“Abuse deterrent formulations” are opioids with physical and chemical properties that prevent chewing, crushing, grating, grinding or extracting, or contain another substance that reduces or defeats the euphoria that those susceptible to substance abuse disorders experience. The new law requires insurance companies to provide the same coverage for the new abuse deterrent formulations as non-abuse deterrents, and they are not permitted to shift any additional cost of these medications to patients. It makes doctors better able to prescribe these medications without pushback from insurance companies.

Abuse deterrent formulations are not the only solution, but they are a good step forward toward balancing the legitimate needs of pain patients with the need to reduce medication abuse. Other efforts must also include more robust education of both medical professionals and consumers to keep the medication out of the hands of potential abusers in the first place. Government statistics show that 78.5% of those who abuse prescription pain medication did not obtain the drugs from a doctor themselves.

“While the science of abuse deterrence is still evolving, the development of opioids that are harder to abuse is helpful in addressing the public health crisis of prescription drug abuse in the U.S.,” said Janet Woodcock, M.D., Director of the FDA’s Center for Drug Evaluation and Research. “Preventing prescription opioid abuse is a top public health priority for the FDA, and encouraging the development of opioids with abuse-deterrent properties is just one component of a broader approach to reducing abuse and misuse, and will better enable the agency to balance addressing this problem with ensuring that patients have access to appropriate treatments for pain.

Abuse deterrence is a worthy goal and will evolve when all the players work together in a more regular and synchronistic fashion. As the Japanese proverb goes, “Don’t fix the blame, fix the problem.”

Peter J. Pitts, a former FDA Associate Commissioner, is President of the Center for Medicine in the Public Interest.

From the pages of The Hill

Biosimilar drugs need clarification

In a recent op-ed piece on The Hill’s Congress Blog (“More must be done to improve access to biosimilar drugs,” March 19), Ike Bannon erroneously argues that the use of unique international non-proprietary names (INN) for biosimilar medicines would slow the entry of this new class of drugs into the U.S. market. On the contrary, names that clearly differentiate biosimilars from one another and the original biologic medicine will enhance transparency and build physician confidence in this class of medicine, without which robust utilization is not possible.

Biologic drugs are extremely complex medicines. As such, unlike traditional chemical drugs, it is all but impossible for biosimilar drugs to be identical to the approved biologic they are meant to resemble. The naming of these drugs is an important patient safety issue because the INN is used in the surveillance of drugs on the market to quickly identify which drug may be responsible for an adverse event. If biosimilars use the same INN as their reference biologics, it would be more difficult for regulators to recognize exactly which product is causing a problem.

As the Food and Drug Administration (FDA) finalizes its naming policy, the agency must learn from real-world global biosimilar experiences to understand how different a biosimilar can be from the original biologic. These differences will make it resoundingly clear that FDA must finalize its policy in favor of unique names.

Case in point: A poster presentation at the European Crohn’s and Colitis Organization titled “Biosimilar but not the same” offered timely and real-world data on the differences between originator biologics and their biosimilars. The study examined the clinical impact of both the innovator product (Remicade) and its European Medicines Agency-approved biosimilar (Inflectra). The findings show the rates of surgery in Remicade and Inflectra groups were significantly different. Specifically, 80 percent of the Inflectra group required hospital readmission versus 5 percent of the Remicade group. The conclusion of the study is not ambiguous: “Our results suggest that biosimilars may not be as efficacious as the reference medicine.”

Biosimilar approvals are based on similarity — but in the real world, success will be measured by patient outcomes. Biosimilars are here to stay and it is not surprising that physicians will have more confidence in them if they know exactly what drug they are prescribing. Distinguishable names provide that transparency and a necessary safeguard to maximize safety and credibility. It’s really that simple.

From Peter Pitts, president of the Center for Medicine in the Public Interest, New York, N.Y.

Some interesting new regulatory tea leaves in the debate over biosimilar nomenclature.

According to the USP, if Sandoz’s biosimilar (Zarxio – or filgrastim-sndz) meets the filgrastim monograph, it should carry the same nonproprietary name as Neupogen. But the FDA says it’s already determined the monograph does not apply. According to Dr. John Jenkins, director of FDA's Office of New Drugs the naming of this particular drug does not necessarily mean this will become the general policy for naming biosimilars. 

An important point to remember is that the USP is not responsible for testing and enforcement of its standards, including comparing products to existing monographs. That’s an FDA responsibility.

While the FDA agrees that the USP has a role “regarding the nonproprietary names of drugs in certain circumstances,” they  do not believe that the nonproprietary names FDA assigns for drugs and biologics are temporary until the USP reached a decision.

On March 18 (just under two weeks after the FDA approved Zarxio) USP issued a statement to the effect that it had “just begun a dialog with FDA regarding Zarxio and it is too early to comment further.”

So watch the regualtory fur fly and keep those tea leaves steeping.

This week, an article entitled “Why Are Cancer Drugs So Expensive in the United States, and What Are the Solutions?” written by Dr. Hagop Kantarjian and Dr. S. Vincent Rajkumar was published on the Mayo Clinic Proceedings website. 

Dr. Kantarjian and Dr. Rajkumar use a combination of misstatements and unsupported claims in demonstrating that they are more concerned with protecting the profits of health insurers than they are with the lives and well-being of their patients.

To learn more go to

First Big Pharma was advised to adopt free or differential pricing to developing nations – now the mask is off and it’s all about middle-income countries after all. But wasn’t this entirely predictable, that companies would be criticized for doing what the activists had asked for in the first place?

In healthcare, as in life – no good deed goes unpunished.

Merck and the Medicines Patent Pool (MPP) signed a licensing agreement last for pediatric formulations of raltegravir, one of the few HIV drugs approved for children younger than three. Using the new license, drug manufacturers can make cheaper versions of raltegravir because they do not have to pay royalties to Merck.

The MPP was founded in 2010 by UNITAID, a UN-backed initiative aiming to use innovative financing to increase access to HIV, tuberculosis and malaria medicines in developing nations. The pool lets drug manufacturers in developing countries produce and sell low-cost HIV treatments through voluntary licensing and patent pooling.

Good news right? Not for some. Critics have told SciDev.Net (hardly a pharma-friendly media outlet) that it is "a false solution to a real problem.”

Intellectual property “expert” Othoman Mellouk is critical of the agreement. Mellouk, who works at the International Treatment Preparedness Coalition, a well-known anti-IP organization, says he thinks the agreement looks like a PR exercise that will not deliver improved access to medicines where they are most needed.

"The MPP mechanism ensures originator companies are in control and determine the parameters of agreements,” says Mellouk. He then adds that voluntary licenses such as those agreed through MPP actually undermine a country's negotiation power and ability to use TRIPS flexibilities.

He notes that the 92 licensed nations are mostly low-income countries with little pharmaceutical industry, meaning it would be easy for monopolies on drug production to form. He points out that middle-income nations including China and India - which have more competitive pharmaceutical industries - are excluded.

"The MPP mechanism ensures originator companies are in control and determine the parameters of agreements.” Owners of intellectual property, per Mr. Mellouk, shouldn’t be in charge of their … intellectual property.

The bottom line is that he’s living in a fantasyland where working with the globally applauded Medicines Patent Pool is not just a bad idea – but a nefarious scheme. Note to Mr. Mellouk – Wake up. The reality of global healthcare isn’t good versus evil but about allies working together to improve patient care. Alas, that is not a potent fund raising message for his (and like-minded) organizations, but it’s good news for patients in the developing world.

Martina Penazzato, pediatric advisor for the WHO's HIV department, is more positive about the agreement: "What we need for children with HIV is better drugs, better formulations, and we need to have them developed much more quickly."


Departing FDA Commissioner Peggy Hamburg isn’t going to take “blame the FDA” as an excuse any more.


According to a report in BioCentury, Senator Lamar Alexander (R/TN) is leading the Senate down a narrower, slower path to 21st Century Cures legislation than the House is taking. Speaking at a hearing to launch legislation intended as a companion to the House Energy & Commerce Committee’s 21st Century Cures initiative, Alexander asked FDA Commissioner Margaret Hamburg to identify two or three top priorities for legislation and said he didn’t want to “waste time” discussing a large number of ideas. The focus on a slim bill is a stark contrast to the 393-page discussion draft of 21st Century Cures legislation released by the Energy & Commerce Committee.

Responding to Alexander’s request for top legislative priorities, Hamburg called for greater investment in “regulatory science to develop the knowledge, tools and strategies that allow us to assess in an efficient way the safety, efficacy and performance of medical products.”
Taking aim at a white paper Alexander and Senator Richard Burr (R/NC) released in January outlining the committee's goals for legislation to promote medical innovation, Hamburg argued against assuming that "FDA regulation is the principal obstacle to the development of innovative treatments, and that FDA’s authorities and procedures should be fundamentally reconsidered." She also cautioned "against solutions that seek to lower the safety and effectiveness standards for approval of the medical products on which Americans rely."

Like Gogol says, "It is no use to blame the looking glass if your face is awry."

“Blame the FDA” is a simplistic view of a complex problem. Unfortunately, it’s a sure-fire media sound-bite and it removes all responsibility for correcting many important problems from everyone else. How convenient. It’s time to grow up.

The reality is that FDA is at the center of the “21st century cures” innovation ecosystem. So rather than continuing to listen to the facile and ignorant drumbeat of “FDA as the problem,” emanating from certain quarters, groups ranging from the pharmaceutical industry, to patients groups, forward-thinking members of Congress, academia, and healthcare practitioners are beginning to realize (some faster than others) that FDA is a crucial partner – indeed a senior partner in advancing the public health.

Blame the FDA? The fault, dear Brutus …

PDUFA VI anyone?


Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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