Latest Drugwonks' Blog
Dear GO, CDER, and CBER staff:
We are pleased to announce an initiative to further our goal of ensuring that the public has access to quality pharmaceuticals. This initiative aims to deepen our reliance on trusted regulators outside of the United States who provide equivalent public safety and quality protection. This work is critically important and requires a dedicated FDA team to collaborate with our colleagues in European institutions and member states.
Managed jointly by GO, CDER, and CBER, this initiative will build upon our existing relationships with the European Medicines Agency (EMA) and member states of the European Union (EU), the European Commission (EC), and the European Parliament. It will complement the ongoing work of CDER, CBER, ORA, and OIP to enhance pharmaceutical quality through international collaboration, and also FDA’s work in implementing the FDA Safety and Innovation Act.
Dara Corrigan to Lead Initiative as Senior Counselor for Global Operations and Policy
Effective May 18, Dara Corrigan will lead this mutual reliance initiative. She will leave her position as director of FDA’s Europe Office, but remain in Brussels, in the role of senior counselor for global operations and policy. Dara will report directly to Howard Sklamberg, deputy commissioner for global operations and policy. She will provide strategic advice and counsel to the FDA Commissioner and other FDA senior executives. Don Prater, DVM, will serve as acting director, FDA Europe Office.
Dara brings a wealth of experience and knowledge of U.S. and EU laws and regulations that govern pharmaceutical products. Before serving as director of FDA’s Europe Office, she was FDA’s associate commissioner for regulatory affairs, overseeing one of FDA’s largest operating units and managing FDA’s inspection program. She also has held a variety of senior positions in HHS, and served as an attorney with the U.S. Department of Justice and at the law firm of Arnold & Porter.
CDER OCOMM’s Julie Zawisza and CDER OC’s Helen Saccone to Join Team
Dara will oversee a team that will be dedicated to mutual reliance activities and that will report to GO, CDER, and CBER. The team will include Julie Zawisza, who has served as director of CDER’s Office of Communications since 2008, and Helen Saccone, who has been a special assistant in the Office of Manufacturing and Product Quality (OMPQ) in CDER’s Office of Compliance since 2011.
Julie holds a master’s degree in international science, technology, and public policy from the George Washington University and has more than 14 years of FDA experience. Before working in CDER, she worked in communications at CBER and was the head of FDA’s press office in the Office of the Commissioner. Julie also has worked for health professional and industry associations in communications and advocacy roles, and as a medical technologist at major medical centers in Washington, D.C. and Ann Arbor, Michigan.
Helen Saccone, Pharm.D., has worked in FDA for six years. Before coming to FDA, she worked as senior manager for education at the American Pharmacists Association and as a pharmacist for the D.C. Department of Health, conducting pharmacy and hospital inspections, as well as providing technical assistance on D.C. regulations. She holds a doctoral degree in pharmacy from Rutgers University. The team also will draw upon the work of other experts in CDER, CBER, ORA, OIP, and OCC.
We are delighted that these seasoned and accomplished individuals have agreed to lead the charge, and we have every confidence that the program is in very capable hands going forward. We invite you to congratulate Dara, Julie, and Helen, and offer them your support.
Building on Existing Pharmaceutical Quality Efforts
We want to thank our FDA staff members who continue to work so diligently on improving pharmaceutical quality and safety for the American public. The initiative announced today builds on the Agency’s ongoing efforts to enhance collaboration between FDA centers and ORA, and to bolster our resources around drug quality.
We are very excited about this programmatic direction and its potential to leverage our relationships with our European partners and capitalize on our shared interests as regulators to strengthen mutual reliance and ensure pharmaceutical quality for the U.S. market.
In the coming months, you'll hear more about all of this as the team embarks on its first set of activities. A special town hall will be scheduled soon to give FDA staff an opportunity to ask questions about this initiative and how it fits in with the Agency’s pharmaceutical quality efforts.
Howard Sklamberg, Deputy Commissioner for Global Regulatory Operations and Policy
Janet Woodcock, Director, Center for Drug Evaluation and Research
Karen Midthun, Director, Center for Biologics Evaluation and Research
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It’s not only “biosimilar” or “interchangeable” any more. The FDA (per a report in BioCentury) said the extent of data requirements for a biosimilar product will depend on the agency's confidence in the level of similarity to the reference product, according to draft guidance published Tuesday. Based on comparative analytical data, FDA will characterize its assessment of biosimilarity into one of four levels -- not similar, similar, highly similar or highly similar with a fingerprint-like similarity -- depending on the type, nature and extent of any structural and functional differences revealed. Additional pharmacologic studies would be required to show that the identified difference is "within an acceptable range to consider the proposed biosimilar product to be highly similar to the reference product." FDA said only products in the top two tiers would meet the statutory requirement for analytical similarity under the Biologics Price Competition and Innovation Act of 2009. Products in the top two tiers would then only require "targeted and selective animal and/or clinical studies to resolve residual uncertainties" to demonstrate biosimilarity. In addition, these data could be used to extrapolate clinical data for additional indications. Obvious implications here for the naming debate. Analytical studies and at least one clinical pharmacokinetic study intended to support a demonstration of biosimilarity must include an adequate comparison of the product directly with a U.S. licensed reference product. According to the draft, a sponsor may use a non-U.S. licensed comparator product in certain studies to support this comparison. The sponsor must provide adequate data to establish "an acceptable bridge" between the non-U.S. licensed comparator product and the U.S. licensed reference product. |
At the May 6th House Energy and Commerce Committee’s 21st Century Cures Initiative roundtable, participants were asked what steps Congress could take to expedite bringing new treatments and cures to patients.
Francis Collins, director of the NIH, said that what is needed is a “steady trajectory of support” so that scientists are willing to take risks. But what does that mean?
Collins said that over the past 10 years, the NIH has lost 20 percent of its purchasing power. His belief is that this loss has cost jobs and caused a lack of enthusiasm in our investigators, he said.
20%? That sounds like a statement worth investigating – because the NIH budget has grown significantly over the past decade.
“If we could have confidence of a stable trajectory for support, that would mean the world for an enterprise that is currently flagging,” he said. Not sure precisely what that means but, again, perhaps a study of how NIH is spending it’s current budget would help identify the strengths and weaknesses of its allocations – and the strategy behind them. After all, every dollar counts.
Janet Woodcock, director of the Food and Drug Administration's Center for Drug Evaluation and Research (CDER), said one issue affecting biomedical innovation is the current clinical trials system for drugs.
“The clinical trial system we have is not a system,” Woodcock said. “It takes years and it exhausts investigators.”
Woodcock said the FDA is starting to look at clinical trial networks that are already set up and funded. Testing a new drug in a clinical trial network is faster and “saves a lot of money,” she said.
Additionally, per Dr. Woodcock, since multiple new drugs are studied by the network, “you can do head-to-head comparisons of products.”
She also said there is a lot of innovation in drug manufacturing, and that the FDA will hold a meeting to pursue this avenue in a few weeks.
Another area that the FDA is focusing on is the Critical Path Initiative. Its goal is to bring innovative, high priority therapies to market quickly.
“There is a lot of research that needs to be done on things like biomarkers that would” speed the development of products, Woodcock said.
And, according to Margaret Anderson, executive director of FasterCures (an advocacy group aimed at improving the medical research system that is affiliated with the Milken Institute), “The appropriated dollars that go to the FDA are extremely valuable, and they are not enough.”
This past Sunday, I participated in a point/counterpoint in the pages of the Chicago Tribune with Dr. Kenneth Polonsky, Dean of Biological Sciences Division at Pritzker School of Medicine, and executive vice president, medical affairs, at the University of Chicago.
Dr. Polonsky’s perspective was, more or less, the same as Dr. Collins’, “more money equals more cures.” If only it was so simple. My view (IMHO) is somewhat more nuanced.
Here is Dr. Polonsky’s commentary.
And here’s mine:
Outside Opinion: Federal funds should go to medicine-makers
By Peter J. Pitts
Is more federal funding for the National Institutes of Health the best bang for the buck when it comes to using precious tax dollars to advance public health? No.
The NIH budget is about $30 billion. But what does that buy? Where do discoveries that advance public health really come from? Some do come from NIH-funded research — but not nearly the majority. The engine of innovation is the biopharmaceutical industry, which spends in excess of $50 billion annually on research and development. It's not a competition; the NIH and industry complement each other's efforts. But context matters.
The NIH focuses on basic research, the study of fundamental aspects of phenomena without specific applications. The biopharmaceutical industry addresses most of its R&D toward clinical research, science focused on the actual development of new medicines. The NIH provides grants to academic institutions. Industry employs the scientists who do the work and, increasingly, funds academic research.
But there's a problem. While universities love NIH dollars, they are less enamored of industry resources. Why? One reason is that NIH funding counts toward achieving tenure, while similar dollars from biopharmaceutical companies do not. Durbin's legislation would disincentivize more industry-academic partnerships. More government spending is not always the mother of invention.
As the Prairie State's great Sen. Everett Dirksen once (allegedly) quipped, "A billion here, a billion there, and pretty soon you're talking about real money." Some $10 billion annually could be allocated elsewhere to achieve broader access to newer, more targeted therapeutic medicines (and $5 billion could go toward the NIH's good work, hardly a paltry sum). The Food and Drug Administration should be No. 1 on the list to get more money.
The FDA regulates more than 25 percent of the U.S. economy, yet operates on an annual budget of $4.7 billion (about $2 billion generated by industry user fees). The budget's federal funding portion is about one-tenth the NIH's. Why hasn't Durbin proposed additional tax dollars for the FDA's programs on advancing regulatory science, expedited review pathways or more ready access to experimental medicines for desperately ill patients? The FDA doesn't even need $10 billion a year for 10 years to become our nation's leading force in health care innovation. Some $1 billion a year would do the job quite nicely. As to the remaining $9 billion, the line forms to the left.
Alas, headlines for hyped and misleading "NIH-funded cures" are far sexier than those for "more money for drug regulation." They may not be inversely important, but they are equally urgent in advancing 21st-century American health care.
China is adopting a free market solution to drug shortages.
China will scrap caps on retail prices for low-cost medicine and is moving toward free-market pricing for pharmaceuticals, after price controls led to drug quality problems and shortages in the country.
The Wall Street Journal reports that Chinese leaders want health care to be more accessible and affordable, but there have been unintended consequences in attempting to ensure the lowest prices on drugs. For instance, many pharmaceutical companies registered to sell the thyroid medication Tapazole have halted production in recent years after pricing restrictions squeezed out profits, experts say, creating a shortage.
The lesson for US lawmakers is clear – artificially low prices are the major cause drug shortages.
Perhaps its time for our lawmakers to revisit the legislative solution proposed in Senator Orrin Hatch’s Patient Access to Drugs in Shortage Act. There are three key codicils:
1. Price Stability
The Hatch bill would change the Medicare reimbursement rate for generic injectable products with 4 or fewer active manufacturers from ASP + 6% to Wholesale Acquisition Cost in order to achieve market price stability.
2. Medicaid/340B Rebate Exemption
The bill exempts generic injectable products with 4 or fewer active manufacturers from Medicaid rebates and 340B discounts in order to achieve market price stability.
3. Extended Exclusivity
Manufacturers who hold an approved application for a drug that would mitigate a shortage can extend by 5 years any period of exclusivity, even if the drug is eventually moved from drug shortage designation.
It’s embarrassing that the world’s leading free market economy (that’s us) hasn’t learned the Econ 101 lessons our friends in China are now implementing to solve the problem of drug shortages.
HEP, HEP, Hooray!
CDER Director, Dr. Janet Woodcock. responding to criticism about the high price of breakthrough drugs, said that the agency is working towards approving more effective treatments for diseases like cancer and hepatitis. Reacting to controversy around the price of the breakthrough Hepatitis C drug Sovaldi, Dr. Woodcock discussed the potential decrease in societal costs and increase in patients' quality of life.
"I think we have to in some ways think about this as a transition period," she said during a panel discussion about the breakthrough designation. "We may have to put a big down payment down now to get something really good."
She highlighted the cost to society and burden on patients in dealing with the side effects and morbidity of having Hepatitis C. "I really do believe we need to drive toward curing, but you have to have a transition period, she said. "We are driving toward a cure with hepatitis."
Woodcock further advocated getting these drugs on the market so they could be combined with other products to drive toward cures. "In cancer, I think we have to recognized this is version 1.0, but we're going to get there," she said. "And to get there we can't hold back. We can see that cure."
The battle for the heart and soul of 21st century health care is the battle over innovation. And nothing short of victory is acceptable. To borrow an over-used adjective from the world of global climate change, we must protect “sustainable” innovation.
Representative Anna Eshoo (D, CA) and the late Senator Edward Kennedy worked long and hard to write, lobby for, and pass the Biologics Price Competition and Innovation Act.
Unlike many of her congressional colleagues, Representative Eshoo has the creds to ask some tough questions of the FDA. She’s also smart enough to know the right questions to ask.
Unlike some of her fellow members who are swinging their political heft, trying to lobby the FDA on science-based questions, Ms. Eshoo is asking for clarification on the timing of a decision.
That is an appropriate and important question.
Representative Eshoo, in a letter to FDA Commissioner Hamburg asks (among other things) that the agency …
“Share with me the FDA’s timeline for the release of the draft guidance on naming and interchangeability.”
That’s a fair question from a member of Congress who deserves a prompt answer.
Observe due measure, for right timing is in all things the most important factor.
Hesiod
I’ve just returned from Riyadh, Saudi Arabia where both the Saudi FDA and the Ministry of Health are embroiled in the current MERS (coronavirus ) crisis.
It’s already cost the Minister of Health his job and many citizens are questioning the ability of the government to protect their wellbeing. It’s also an international news story that does not reflect well on the Kingdom.
Another reason to reexamine the state of overall health preparedness – and not only in Saudi Arabia.
A good place to start is with a serious conversation on 21st century pharmacovigilance. Let’s start with definitions.
According to the WHO, “Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.”
Okay as far as it goes. But this is a very 20th century perspective. Perhaps a more progressive view comes from our regulatory cousins at the MHRA, “Assessing the risks and benefits of medicines in order to determine what action, if any, is necessary to improve their safe use.”
The significant difference is that most regulatory officials still view PV through the lens of adverse events. The MHRA definition, however, broadens the conversation to include safe use. That’s 21st century pharmacovigilance.
What does this have to do with the coronavirus?
It speaks to the need of public health officials to be both the guardians of the public health as well as the watchmen. And that takes more than vigilance – it takes resources. It also takes a village – a public health village – comprised not just of public officials, but physicians, nurses, pharmacists, hospitalists, patients, and caregivers.
And it’s got to be more than MedWatch.
How much sooner could the coronavirus been identified and dealt with if the Saudi Ministry of Health had a more robust mechanism for post-market surveillance that went beyond adverse events?
But it’s not just the Saudis.
The FDA is establishing an Office of Pharmaceutical Quality to improve the agency’s scrutiny of brand-name, generic and over-the-counter drugs, CDER Director, Dr. Janet Woodcock said at the Bloomberg health-care summit. The FDA is talking with the industry to develop data that may signal which manufacturing plants are straying from standards and need inspection, she said.
The agency now collects such information only during inspections. The thrust of the effort would be to head off potential concerns before the agency wields penalties such as banning products from troubled factories. “We want to use leading indicators. These people aren’t in trouble yet but they could be.”
Forewarned is Forearmed.
Yet another reason to stop calling it "compassionate use" and start calling it by it's proper name -- "expanded access."
The Wall Street Journal reports …
The FDA Says It’s More Compassionate Than You Think
Even as drug makers and desperate patients increasingly battle over access to experimental medicines for life-threatening conditions, Food and Drug Administration officials argue the agency is doing its part to make things right.
In the wake of some recent high-profile cases that made television news and prompted social media outcries, the FDA has released data showing that nearly every request it gets for “compassionate use”’ is approved.
The term refers to an FDA program in which individuals who are seriously sick and lack options are able to gain access to a medicine being developed, even though they are not enrolled in a clinical trial. For this to happen, a patient’s physician must first receive permission from the drug maker testing the medicine. From there, the physician must seek what amounts to a blessing from the FDA.
In recent years, the FDA has been very agreeable. In the fiscal year ended last October, the agency approved 863 requests, or 99 percent of all cases reviewed, according to FDA data. And one-third of those were approved on an emergency basis. In fact, the agency has approved 99 percent of all requests since October 2009. On average, 932 requests were endorsed annually since then.
“I think the numbers speak well for the program,” says Richard Klein, director of the patient liaison program in the FDA Office of Health and Constituent Affairs.
In reality, though, the process is not working as some patients would hope. Drug makers sometimes deny requests for compassionate use because they want to stick with strict trial criteria needed to win FDA marketing approval for their medicines. An unexpected patient reaction, for instance, might jeopardize a drug’s chance of success. In some instances, a company claims not to have sufficient supplies to handle a large number of requests.
This is what happened recently when a small biotech company called Chimerix denied a Virginia family. Their 7-year-old son, a cancer survivor, developed a viral infection after a bone marrow transplant and they hoped he would benefit from an antiviral drug Chimerix is developing. But repeated rejections became a publicity debacle as criticism was directed at the company and the FDA program as well.
The FDA said it intervened by working with Chimerix to design a pilot study to include the boy. That pilot study is now underway, according to a Chimerix spokesman. But an FDA spokeswoman says this was not the first time the FDA took such a step. Meanwhile, the FDA’s Klein says the agency is developing a new draft guidance, or blueprint, for handling expanded access cases.
“The agency only provides the pathway,” he says. “If a company is not willing to entertain a request [for compassionate use], then it doesn’t come to us. Most of the time, we only know about the applications where companies are willing to make drugs available. The numbers we have don’t include the times when companies say no. And there’s not a lot of data to say what the outcomes of these situations are.”
Maybe not. But perhaps FDA officials should find a way to require drug makers to report their compassionate use decisions – approvals and rejections – so the public can see the extent to which the program is having its intended effect.
According to Robert Jamison, PhD, professor of anesthesia and psychiatry at Harvard Medical School and pain psychologist with Brigham and Women’s Hospital, mobile medicine is helping chronic pain patients cope with and manage their condition thanks to new smartphone apps, which can track patients from a distance and monitor pain, mood, physical activity, drug side effects, and treatment compliance.
Per Jamison, smartphone apps are helping the shrinking ranks of pain specialists treat and monitor rapidly increasing populations of chronic pain sufferers. “Today the ratio is one pain specialist for every 10,000 patients, but mobile technology allows for easy time-effective coverage of patients at a low cost, offering significant opportunities to improve access to health care, contain costs, and improve clinical outcomes,” he explained.
At the American Pain Society annual meeting, Jamison presented results of his research on smartphone apps, developed at Brigham and Women’s, for monitoring pain patients. He found that internet-based cognitive behavioral therapy could significantly decrease pain levels, improve function, and decrease costs compared to standard care.
“Online networks, for example, can promote communication, distraction, information sharing, self expression and social support,” Jamison said. “We also believe online networks decrease feelings of withdrawn behavior and instill a greater willingness to return for treatment.”
Jamison added that electronic diaries maintained by patients are more effective than paper diaries for evaluating pain levels, daily activities, treatment compliance and mood.
Jamison said that while few studies have been conducted on text messaging as a pain management tool, texting has proven to be effective for managing patients with diabetes, hypertension, asthma, smoking cessation and weight loss.
In his ongoing research, Jamison is studying 60 patients with chronic cancer and non-cancer pain who use a pain management smartphone app. “We hypothesized that the pain management smartphone app will help providers track patients and reduce emergency department visits and hospitalizations by 50 percent,” said Jamison.
A key feature of the pain management app is daily pain tracking in which patients are asked five questions about their pain, activity interference, sleep, mood, and overall status on a sliding scale of 1 to 10, and compare these with baseline ratings. Should pain ratings significantly increase from baseline or reach 9 or 10, the patient gets an immediate response that the pain specialist has been contacted.
“The pain management smartphone app can deliver non-pharmacological, cognitive behavioral treatment as well as prompt patients to stay active, comply with therapy, and develop pain coping skills,” Jamison reported. He added that the smartphone data can be summarized and transmitted every day into the patient’s electronic medical record.
Jamison noted that the average response rate to text messages to pain patients is 70 to 90 percent and that high responders show improved pain levels.
PITTS: America’s pain and opioid problem
Millions risk overdose death as they seek relief from suffering
Former Canadian Prime Minister Pierre Trudeau once said, "There's no place for the state in the bedrooms of the nation." What's the appropriate place for the state in our nation's pharmacies and medicine chests — particularly regarding for opioid pain medications?
Earlier this month, the Food and Drug Administration (FDA) took a big step in making sure that the number of opioid drug-related deaths doesn't continue spiraling out of control by approving a drug called Evzio. A take-home, one-time-use autoinjector, Evzio is the first drug of its kind. It releases a narcotic antagonist called naloxone to reverse the effects of an opioid overdose until emergency medical help arrives.
Fast-tracking drugs like Evzio, which will help dramatically reduce the number of opioid-overdose deaths, is just one part of a complex solution. Improved provider and patient education is crucial. Caregivers need to know how to properly prescribe based on an individual's pain-management needs, and patients need to know how to properly follow their treatment plans. If not, addiction will continue consuming lives.
Opioids work by targeting the same receptors in the brain as heroin, resulting in feelings of euphoria. The numbers speak for themselves: People are hooked.
According to the National Institute on Drug Abuse, 5.1 million people reported abusing prescription painkillers. Teenagers account for a large share of the rising prevalence of opioid abuse — they report abuse or dependence problems at six times the rate of folks 50 and older. Eight percent of high school seniors report using Vicodin nonmedically. Curtailing the frequency of opioid-related abuse — and at an early age — must remain a priority.
It's not just a user problem. It's a provider problem, too.
In the United States, the use of opioids as first-line treatment for chronic pain conditions doesn't follow either label indications or guideline recommendations. Fifty-two 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 pain medicines, relegating these treatments to second-line options. The result is a gateway to abuse and addiction.
How do we fight the twin dangers of opioid misuse and addiction?
In her statement on opioid abuse last month, FDA Commissioner Margaret Hamburg explained that the FDA will continue to work collaboratively with "state and local governments, public health experts, health care professionals, addiction experts, researchers, industry and patient organizations" to help reduce the risks of opioid misuse, abuse, addiction and overdose.
The first step is providing physicians with extensive clinical guidelines and educational opportunities for prescribing opioids. For example, continuing medical education classes are offered by the Substance Abuse and Mental Health Services Administration to make sure that physicians are up to date on the importance of creating individualized patient treatment plans.
Last year, the FDA announced labeling changes and post-market study requirements for opioids in an attempt to begin more accurately prescribing and treating patients requiring opioid pain medications. Labeling changes mark one important step in highlighting the value of physician-to-patient communication and individualized patient pain-management programs.
In addition to providing patients with materials on proper use of opioid medications, patients should also be educated about proper drug disposal. The National Survey on Drug Use and Health found that painkillers used for nonmedical reasons were obtained from friends or family members 70 percent of the time.
Prescription-drug monitoring programs offer another solution. The programs are state databases that make sure patients are filling prescriptions belonging only to them, are taking the right dosages, and are not receiving prescriptions from multiple physicians.
Continued research into drugs that can reverse the symptoms of opioid overdose and ensuring patients have access to naloxone agents such as Evzio will also reduce the occurrence of overdose-related deaths. Mitigating the occurrence of opioid overdose could also save our health care system upward of $70 billion per year.
The FDA took a big step this month in approving a take-home drug that temporarily reverses the effects of opioid overdose. However, the battle over misuse, addiction and overdose is far from over. Health care providers and policymakers need to continue working toward a solution — or the line between the orange bottle in the medicine cabinet and the syringe in a back alley will become increasingly blurred.
Peter Pitts, a former Food and Drug Administration associate commissioner, is president of the Center for Medicine in the Public Interest.
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.
