Working Together to Reduce the Devastating Effects of Opioid Misuse

By Robert M. Califf, M.D.

The public health crisis of opioid misuse, addiction and overdose is one of the most challenging issues the U.S. Food and Drug Administration has faced during my time as FDA commissioner.  Solving this issue is critical to our future.

The issues cut across every socioeconomic level and geographic boundary. It would be difficult to identify any community in America that has not been touched by friends, family members or colleagues suffering from addiction, and far too often, losing their lives to it. As I leave the agency as part of the presidential transition, I have reflected on what I have seen, how far the nation has come, and the important work that remains for both the public and private sectors.

Robert CaliffI’ve made it a point to see affected communities, first-hand, because interventions and national policy solutions work best when they are well informed by what communities actually need. Just last week, I visited Baltimore to better understand how our cities are being affected – in this case, by an inflow of illicit fentanyl, a synthetic opioid that is about 100 times more potent than many other prescription opioids, and can be deadly on its first use. I have also visited the neonatal intensive care unit, or “NICU” of a Tennessee hospital where babies were screaming and shaking in the pain of withdrawal because they were born with Neonatal Opioid Withdrawal Syndrome. I have met people in West Virginia who did back-breaking work in power plants or in coal mines; after suffering on-the-job injuries they were first afflicted with pain, then by addiction. They got prescription pain relief but, too often, it wasn’t accompanied by the proper support and counseling. In Kentucky, I spoke to spouses and families whose lives have been forever changed by addiction, even as the community rallied together to fight it. And, much closer to home, I have heard personal stories from FDA employees and providers in local health care facilities, whose families and friends are not immune.

We have taken a number of actions at the FDA over the past several years to help reduce the number of people who become addicted, or who ultimately overdose from prescription opioids. We’ve improved product labeling, pushed for prescriber education, and encouraged the development of abuse-deterrent formulations. In addition, we have approved new intranasal and auto-injector forms of naloxone — products to reverse opioid overdoses, which can be administered by laypersons and are, therefore, better available able to save lives.

I’m also proud of the partnerships we have formed with other federal Agencies and the work that has resulted from them. But the latest data, including data from the Centers for Disease Control and Prevention (CDC) remind us that while some progress is being made, there is more to do. For example, it is promising to see that the nationally estimated number of outpatient prescriptions dispensed for Schedule II opioids decreased by 10 percent in 2015 compared to the previous year, according to IMS Health. However, the CDC reports that while the rate of overdose deaths associated with prescription opioid use increased by just 4 percent instead of by 9 percent the previous year, deaths associated with heroin use have skyrocketed. Clearly, more work needs to be done.

As I prepare to turn over the awesome responsibility of FDA commissioner to the next Administration, I feel compelled to point out that public and private sector efforts in this area must be continued and strengthened. In particular, I want to call on the pharmaceutical companies that manufacture and sell these drugs to dig deeper into their expertise and resources to prioritize finding solutions to this public health problem. I have consistently been impressed that the motivation to cure disease and improve quality of life for patients is shared across the spectrum of federal agencies, public health workers, health care providers and scientists within the pharmaceutical industry. However, the financial incentives in the industry can lead to a focus on short-term profits instead of patient well-being.This is the time for both branded and generic drug companies  to go beyond marketing and distribution plans and instead commit their expertise and resources to  confronting  the devastating negative consequences of a class of drugs that brings much needed pain relief, when used appropriately.

Specifically, I urge us all to focus on the following priorities:

  1. Encouraging appropriate prescribing by healthcare practitioners. Too many people become addicted from unnecessary prescriptions for minor pain or injury. And even appropriately prescribed opioids can lead to addiction, so careful monitoring of patients prescribed these powerful drugs is needed. While there are situations where opioids are appropriate, there are also situations where other alternatives can be effective. Therefore, conversations between provider and patient about the pain treatment plan are imperative. If an opioid is appropriate, CDC guidelines and FDA labeling emphasize the need to start on the lowest dose and minimum time necessary, and carefully monitoring patients for signs of addiction and inadequate pain control.
  1. Considering the family as well as the patient. Pain treatment, and use of opioid drugs, will be more successful when the family is involved. It will result in fewer drugs diverted from the medicine chest, fewer babies born addicted to opioids and better treatment of pain. Women who use or abuse opioids, or who are in treatment for opioid addiction, should talk to their health care provider before considering pregnancy.
  1. Finding better ways to treat pain with new medications and with more holistic pain management. It’s time to put more resources into the development of non-opioid, non-addictive medications to help people who are in serious, debilitating pain. We need more research to define the most effective non-medication approaches to pain and how to deliver them in a complex and financially constrained healthcare system.
  1. Improving how companies, professional societies and academics communicate about their activities in this area. I urge companies to commit to transparent and appropriate company communications and to work with government and others in the community to do a better job in educating the medical professionals responsible for treating our nation’s pain, as part of the overarching effort to do everything possible to help prevent addiction. Professional societies and academic medical centers also need to continue their efforts at educating their members and examining their practices to find ways to improve. For example, the education of the next generation of physicians about how best to manage pain is critical.
  1. Finding new ways to curb diversion and misuse of opioids. In addition to our continuing efforts to help support the development of abuse-deterrent formulations, the FDA is exploring potential packaging, storage, delivery, and disposal solutions that companies and other stakeholders might consider that would prevent opioids from being diverted to those without a legitimate prescription for these powerful drugs. I implore companies to conduct research and offer their creative ideas and resources to innovate in this area.
  1. Increasing pragmatic research to better understand how to implement appropriate pain therapy in general and use of opioids in particular. Post-market requirements from FDA that mandate industry-funded studies and recent pragmatic research efforts by the Patient-Centered Outcomes Research Institute and the NIH and Department of Defense are expected to provide important data, but we need more robust evidence to better guide practice. Pain is a vexing issue that seems to fall between the cracks in research funding; we need to keep the pressure on funding entities to move pain to the forefront as a research issue.
  1. Treating addiction as a disease, not as criminal behavior. We have the tools to treat addiction and reverse overdose from opioids and are working to develop more of them. But there’s a lot we don’t know about the drivers for drug abuse, and scientific knowledge will help us make better decisions. This is one reason why we need companies with products on the market to monitor the safety of those drugs and make their data public. We have mandated post-market studies to define major questions about chronic use of opioids, and it is essential that industry fulfills these requirements.

I am proud to have been part of the effort that’s changing the tide on this epidemic, but the nation has a long way to go.Government, companies, healthcare systems and healthcare providers all have important roles to play. The most recent data reminds us it’s time to double down on these efforts. While I won’t have the good fortune of leading this fight in an official capacity, I’m proud of the work the FDA and others have done so far. I leave FDA’s efforts to the many leaders at the agency who have been working tirelessly on this issue — and will continue doing so — and look forward to supporting public and private efforts to bring this epidemic to an end.

Robert M. Califf, M.D., is Commissioner of the U.S. Food and Drug Administration

FDA’s Science-based Approach to Genome Edited Products

By Robert M. Califf M.D., and Ritu Nalubola, Ph.D.

Recent scientific advances now make it possible to more efficiently and precisely alter the genome of plants, animals, and microorganisms to produce desired traits. These genome editing technologies are relatively easy to use and can be applied broadly across the medical, food and environmental sectors, with potentially profound beneficial effects on human and animal health. However, there are also potential risks ranging from how the technology affects individual genomes to its potential environmental and ecosystem impacts. Additionally, genome editing has raised fundamental ethical questions about human and animal life.

Genome editing technologies can be used to introduce, remove, or substitute one or more specific nucleotides (letters in the DNA code) at a specific site in the organism’s genome, and is achieved with the use of protein-nucleotide complexes. Several classes of these complexes exist, the most recent discovery is known as CRISPR/Cas9.

Research is currently underway that would use these technologies to:

  • Treat HIV, cancer or rare diseases by genetically altering specific types of cells;
  • Control or alter organisms that carry infectious diseases (for example, mosquitoes that are vectors of viruses/parasites causing dengue fever, Zika or malaria; or mice that transmit bacteria causing Lyme disease);
  • Improve the health and welfare of food producing animals, (for example, hornless cattle, pigs resistant to African swine fever or porcine reproductive and respiratory virus); and
  • Alter specific traits of food plants or fungi (for example, non-browning mushrooms).

Accompanying the enthusiasm about these promising technologies are questions about whether FDA is prepared to ensure the safety of regulated products that use this technology. Providing appropriate and balanced regulatory oversight for applications involving an emerging technology is not a new or unique challenge for FDA, but the potential breadth of applications and the fundamental nature of altering the genome call for the participation of multiple constituencies in considering the most effective regulatory policies to address any potential risks.

Robert Califf

Robert M. Califf, M.D., FDA Commissioner

Maintaining product-specific, risk-based regulation

Genome editing applications are relevant to three main FDA-regulated product classes. The specific regulatory approaches for each of these classes vary, reflecting differences in underlying statutory authorities. FDA is maintaining a product-focused, science-based regulatory policy, in accordance with specific legal standards applicable to each type of product and consistent with overarching U.S. Government policy principles.

Human medical products that apply gene editing to exert their therapeutic effect are regulated under our existing framework for biological products, which include gene therapy products. “Gene editing” here refers to non-heritable situations somatic cell gene therapy only, and not to heritable conditions (germ line gene therapy). The FY16 appropriations bill restricted use of federal funds “in research in which a human embryo is intentionally created or modified to include a heritable genetic modification.” FDA’s Center for Biologics Evaluation and Research (CBER) has a well-established program and policies in place to evaluate gene therapy products. Although different types of gene editing have potential clinical applications, currently only one type of gene editing, zinc finger nuclease- (ZFN) mediated, has been announced by their sponsors as being applied in clinical trials underway in the United States. Proposals for NIH-funded human gene therapy clinical trials are discussed and reviewed for scientific, clinical, and ethical issues by the NIH’s Recombinant DNA Advisory Committee (RAC). The RAC recently discussed (and did not find any objections to) the first clinical protocol to use CRISPR/Cas9-mediated gene editing. The potential for “off-target” effects such as insertions or deletions at unintended genetic loci has been identified by experts in the field as a key concern.

Similarly, FDA’s Center for Food Safety and Applied Nutrition and Center for Veterinary Medicine have in place programs to adequately address foods derived from plants produced using genome editing and animals produced using genome editing. In these two product areas, we are issuing documents to clarify our current thinking and seek scientific information. With respect to foods derived from plants produced using genome editing, FDA has a longstanding program for foods derived from new plant varieties, including those developed by recombinant DNA (rDNA) techniques. We are requesting information on whether human and animal foods derived from genome edited plants pose additional risks compared to those from traditionally bred plants. FDA’s decades of experience providing oversight of foods from new plant varieties, coupled with scientific evidence and data received, will help inform our thinking on risk considerations going forward.

When animals are produced using genome editing, FDA has determined that, unless otherwise excluded, the portion of an animal’s genome that has been intentionally altered, whether mediated by rDNA or modern genome editing technologies, is a drug because it is intended to alter the structure or function of the animal and, thus, subject to regulation under our provisions for new animal drugs. We have updated our existing guidance for genetically engineered animals to include genome editing within its scope, and are issuing it in draft form for public comment. We are also seeking input on whether certain types of genome editing in animals pose low or no significant risk, and we may modify our regulatory approach based on this input.

Our efforts to gather necessary scientific data aside, industry remains responsible for ensuring that its products meet all applicable requirements, including safety standards. FDA has historically made itself available to meet with developers and we encourage them to engage with us to help ensure they meet their statutory and regulatory obligations. And we will continue to provide technical advice and guidance for industry, as necessary.

Collaborating with Federal agencies

The White House Office of Science and Technology Policy (OSTP), FDA, the U.S. Environmental Protection Agency (EPA), and the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS) initiated an effort in 2015 to ensure public confidence in the regulatory system for biotechnology products and improve the transparency, predictability, coordination, and, ultimately, efficiency of that system. After reviewing public comment to a docket and holding three public meetings, the agencies produced A National Strategy for Modernizing the Regulatory System for Biotechnology Products, to help ensure that the federal regulatory system is prepared to assess future biotechnology products, issued in September; and, earlier this month, a 2017 Update to the Coordinated Framework for the Regulation of Biotechnology (CF Update), to clarify each agency’s role.

Ritu Nalubola

Ritu Nalubola, Ph.D., Senior Policy Advisor, FDA’s Office of Policy

APHIS is proposing to revise its regulation regarding genetically engineered organisms that may pose plant pest or noxious weed risks. As FDA, APHIS, and EPA formulate policies, there may be differences in approaches, reflecting differences in the scope of their authorities and the types of risks addressed. Under the CF Update, interagency coordination and cooperation will continue, including on appropriate terminology, identification of hazards, and approaches to addressing risks, within the constraints imposed by regulatory paradigms for different product areas.

FDA also has a longstanding collaborative relationship with the NIH office that oversees the RAC. FDA serves as a non-voting liaison on the committee, hears the discussions first-hand, and receives the written recommendations.  These recommendations may be considered during our overall review of investigational new drug applications (INDs) submitted to FDA.

Scientific engagement and horizon-scanning

Being ready to evaluate innovative emerging technologies is a top FDA regulatory science priority. FDA is co-sponsoring two studies, conducted by the National Academies of Sciences, Engineering, and Medicine (NASEM). Both are expected to be completed this year. FDA is also conducting its own horizon-scanning through its Emerging Sciences Working Group, an FDA-wide science-based forum, and opened a public docket to receive input on emerging technologies.

Working with international partners

Scientific advances do not adhere to national boundaries and therefore it is critical that we understand the evolving views of our international counterparts. Given the leadership role of the United States in biomedical and biological sciences, we cannot afford to fall behind in this exciting scientific frontier. As expected, international regulatory agencies, too, are currently working in this area. FDA’s CBER is an active member of the International Pharmaceutical Regulators’ Forum (and its Gene Therapy working group), which provides a forum for members to identify and exchange information on issues of mutual concern and undertake targeted regulatory cooperation activities.

Going forward

FDA is committed to fulfilling its mission to safeguard public health, while encouraging innovation and competitiveness. The actions we have taken to date, including release of the CF Update, National Strategy, and FDA’s documents – are steps in a series of ongoing activities. We will continue to collaborate with our federal and international partners, and actively communicate with stakeholders to help ensure confidence in FDA’s regulatory system. However, oversight provided by FDA is one aspect of broader governance necessary for safe and responsible research and development of genome editing applications. Moreover, the expansive scope of intentional genomic alterations using modern genome editing technologies has triggered debate on fundamental ethical and social issues, which will continue to influence public opinion and acceptance of genome editing applications. Even as FDA implements necessary steps for effective regulation to ensure the safety of products, the role of broader, inclusive public discussion involving multiple constituencies (e.g., scientists, developers, bioethicists, and public interest and community groups) to address the larger societal considerations should not be overlooked.

Robert M. Califf, M.D., is Commissioner of the Food and Drug Administration

Ritu Nalubola, Ph.D., is a Senior Policy Advisor in FDA’s Office of Policy

 

Managing Medical Device Cybersecurity in the Postmarket: At the Crossroads of Cyber-safety and Advancing Technology

By:  Suzanne B. Schwartz, M.D., M.B.A.

Protecting medical devices from ever-shifting cybersecurity threats requires an all-out, lifecycle approach that begins with early product development and extends throughout the product’s lifespan.

Today, we’re pleased to announce that industry now has advice from FDA across this product continuum with the release of a final guidance on the postmarket management of medical device cybersecurity. It joins an earlier final guidance on medical device premarket cybersecurity issued in October 2014.

suzanne-schwartz-new-dec-2016To understand why such guidance is so important for patients, caregivers and the medical device community, we need to take a step back and look at how cybersecurity fits into the medical device ecosystem.

In today’s world of medical devices that are connected to a hospital’s network or even a patient’s own Internet service at home, we see significant technological advances in patient care and, at the same time, an increase in the risk of cybersecurity breaches that could affect a device’s performance and functionality.

The best way to combat these threats is for manufacturers to consider cybersecurity throughout the total product lifecycle of a device. In other words, manufacturers should build in cybersecurity controls when they design and develop the device to assure proper device performance in the face of cyber threats, and then they should continuously monitor and address cybersecurity concerns once the device is on the market and being used by patients.

Today’s postmarket guidance recognizes today’s reality – cybersecurity threats are real, ever-present,  and continuously changing. In fact, hospital networks experience constant attempts of intrusion and attack, which can pose a threat to patient safety. And as hackers become more sophisticated, these cybersecurity risks will evolve.

With this guidance, we now have an outline of steps the FDA recommends manufacturers take to remain vigilant and continually address the cybersecurity risks of marketed medical devices. Central to these recommendations is FDA’s belief that medical device manufacturers should implement a structured and comprehensive program to manage cybersecurity risks. This means manufacturers  should, among other things:

  • Have a way to monitor and detect cybersecurity vulnerabilities in their devices
  • Understand, assess and detect the level of risk a vulnerability poses to patient safety
  • Establish a process for working with cybersecurity researchers and other stakeholders to receive information about potential vulnerabilities (known as a “coordinated vulnerability disclosure policy”)
  • Deploy mitigations (e.g., software patches) to address cybersecurity issues early, before they can be exploited and cause harm

This approach enables manufacturers to focus on continuous quality improvement, which is essential to ensuring the safety and effectiveness of medical devices at all stages in the device’s lifecycle.

In addition, it is paramount for manufacturers and stakeholders across the entire ecosystem to consider applying the National Institute of Standards and Technology’s (NIST) core principles for improving critical infrastructure cybersecurity: to identify, protect, detect, respond and recover. It is only through application of these guiding principles, executed alongside best practices such as coordinated vulnerability disclosure, that will allow us all to navigate this uncharted territory of evolving risks to device security.

This is clearly not the end of what FDA will do to address cybersecurity. We will continue to work with all medical device cybersecurity stakeholders to monitor, identify and address threats, and intend to adjust our guidance or issue new guidance, as needed.

Digital connections power great innovation—and medical device cybersecurity must keep pace with that innovation. The same innovations and features that improve health care can increase cybersecurity risks. This is why we need all stakeholders in the medical device ecosystem to collaborate to simultaneously address innovation and cybersecurity. We’ve made great strides but we know that cybersecurity threats are capable of evolving at the same pace as innovation, and therefore, more work must be done.

Learn More

For more information about medical device cybersecurity, visit the FDA’s Center for Devices and Radiological Health web page.

Suzanne B. Schwartz, M.D., M.B.A., is FDA’s Associate Director for Science and Strategic Partnerships, at the Center for Devices and Radiological Health

FDA Working to Keep the U.S. Blood Supply Safe from Zika and other Emerging Threats

By: Peter Marks, M.D., Ph.D., and Luciana Borio, M.D.

En Español

Each day in the United States, thousands of people receive transfusions of blood or blood products as part of their medical treatment. Although such transfusions can save lives, like most medical treatments they may also carry some risks. Among the most concerning risks is the chance that a patient might get an infection from a transfusion. Some of these risks, like hepatitis and HIV, have been known for some time. Others, like the Zika virus, have emerged more recently.

One of FDA’s top priorities is to help assure that the blood supply is safe for all those who need these potentially life-saving products. This mission is accomplished through close collaboration with other government agencies, such as the Centers for Disease Control and Prevention, and non-governmental partners, such as blood collection establishments and screening test developers.

These coordinated efforts are crucial because blood safety relies on a combination of factors, including understanding the epidemiology of infectious disease transmission and the testing that can be done to detect it.

Our experience with other infectious agents has positioned us well to address Zika virus. We have worked closely with the CDC since the outbreak began to emerge. We have also been in continual contact with blood collection establishments, screening test manufacturers, and local health authorities.

When it became apparent early in 2016 that Zika virus could pose a risk to the blood supply in the United States, FDA issued recommendations to reduce the risk of its transmission through blood transfusions by deferring those donors at risk of being infected with Zika virus as well as by screening donated blood in certain areas. Given the large amount of scientific data that is emerging and the rapid spread of the outbreak in the Western hemisphere, FDA understands that it may need to revisit and update this guidance soon to maintain the safety of the blood supply.

As part of the overall response, FDA also collaborated with the HHS Office of the Assistant Secretary for Health to ensure that safe blood was available to those needing a transfusion in Puerto Rico and other areas at risk before a blood screening test for Zika virus became available. The Agency also worked with manufacturers to help speed the development of screening tests to detect Zika virus at the earliest point in time after infection. We also worked with the Biomedical Advanced Research and Development Agency to help facilitate the evaluation of these tests and other measures.

Helped by these and other ongoing collaborations with federal and non-federal partners, FDA is able to pursue its mission of protecting and promoting your health.

Peter Marks, M.D., Ph.D., is Director of FDA’s Center for Biologics Evaluation and Research
Luciana Borio, M.D., is FDA’s Acting Chief Scientist

FDA Working to Keep Patients Well Informed

By: Steve L. Morin R.N., B.S.N.

Steve Morin_2823My job in the Food and Drug Administration’s Office of Health and Constituent Affairs (OHCA) is to serve our nation’s patients in two ways: by listening to their concerns regarding FDA’s policy and decision-making and advocating for them in our agency;  and by informing many patients and patient organizations about FDA’s mission and its work to advance the development, evaluation and approval of new therapeutic products.

This dialogue was formalized and greatly expanded in 2012 when, after a series of listening sessions with many patient advocacy organizations, OHCA created the Patient Network.

Specifically designed for patients, caregivers, patient advocates and disease-specific patient advocacy organizations and the communities that advocate on their behalf, this program serves two goals. It facilitates patient engagement with FDA policy and decision makers, and it educates its audience about the process that brings new medications – both prescription and over-the-counter ­– and medical devices from a concept to the marketplace.

Our Patient Network covers a range of FDA-specific topics and conducts numerous activities that are of interest to patients and patient advocates. One of these activities were webinars with information about upcoming public meetings hosted by FDA.

For example on March 31, 2014, OHCA was pleased to host the first-of-its-kind “LiveChat” with the diabetes community. This online discussion gave patients an opportunity to interact with FDA experts and to better understand a recently released draft guidance dealing with the studies and criteria that FDA recommends be used when submitting premarket notifications (510(k)s) for blood glucose meters.

On September 10, 2014, our Third Annual Patient Network Meeting titled “Under the Microscope: Pediatric Product Development” brought together more than 100 patients, patient advocates, representatives of academia and industry, and FDA leaders. The participants discussed pediatric product development and the ways patient advocates can participate in it.

And on September 17, 2014, our Patient Network webpages were upgraded. The “For Patients” section on FDA’s website is presented in a clear manner with easy-to-use formats. Also, a “For Patients” button is located on our homepage.

We have continued to pursue our goals of informing the public and engaging with patients by building upon the patient-centered webpages and enhancing activities that express our desire to be helpful and transparent. This is our philosophy that has helped the Patient Network evolve to what you see today.

As the Patient Network program continues to grow, I hope to expand it to have more interactive webinars like the “LiveChat” that address specific concerns  of the patient communities. Also, we will continue to make it possible for patients to learn from FDA experts who approve medical products.

The FDA realizes that listening to the “patient voice” and conducting our dialogue is important, and it continues to develop its model for patient involvement through the Patient-Focused Drug Development Meetings and other OHCA sponsored meetings and webinars. We hope patients and those who care for them will join us in that effort, and make it still more helpful in protecting and promoting the public health.

Steve L. Morin, R.N., B.S.N., is a Commander of the United States Public Health Service and the Manager of the Patient Network in FDA’s Office of Health and Constituent Affairs

FDA Uses Web Tool to Better the Odds for Food Safety

By: Ted Elkin

When most people hear the words, “Monte Carlo,” they may think about high-stakes gambling.

We, however, think about reducing the risk in food safety through the use of FDA-iRISK, an innovative Web-based food safety modeling tool developed by the Food and Drug Administration and our partners.

Launched in October 2012, FDA-iRISK uses mathematical logic and Monte Carlo simulation (a computer program named for the gambling mecca) to integrate data and generate results that compare and rank risks of the contamination of foods by various hazards.  Unlike a traditional risk assessment of a single food and a single contaminant, FDA-iRISK allows users to compare multiple hazards – microbial or chemical – in multiple foods.

How does FDA-iRISK work?

Through extensive outreach to and collaboration with partners, we developed built-in templates and other features that allow the user to create real-world (or hypothetical) food safety scenarios.

The user provides the data for seven elements: the food(s), the hazard(s), the population of concern (for instance, elderly or immune-compromised), the production or processing system being used for the food, the consumption patterns, the dose response (what level of exposure will have a health impact), and how the health effects are to be calculated.

This allows the user flexibility, for instance, to look at the impact of potential interventions at various stages of the food production system as well as the populations affected.  And it’s easy to use.

Of particular benefit to the user is FDA-iRISK’s ability to generate reports that measure the health impact of an intervention in terms of the widely used public health metric, DALYs (“Disability-Adjusted Life Years,” meaning years of healthy life lost to illness or death).  This measure lets us know the “bang for the buck” of a particular intervention.

FDA-iRISK is quickly gaining acceptance and use in the food safety community.  As of the middle of May, almost 500 users had established accounts with FDA-iRISK and they came from every continent. Because it is web-based, FDA-iRISK is available to anyone in the world who sets up an account, and it is free to use.

Therefore, the knowledge and sharing power of FDA-iRISK is exponential.  As more users use it and generate reports that are then available to the other users, a more consistent, well documented, systematic, structured and quantitative picture of risk in the food supply will emerge, as well as scenarios for reducing risk.

“Information provided by iRisk can aid in developing global scientific exchanges aimed at maintaining and developing agricultural markets around the world,” according to Jamilah (Fagbene) Cassagnol, an international trade specialist at the U.S. Department of Agriculture.

FDA-iRisk is supported by an exceptional project team. FDA staff members Sherri Dennis, Yuhuan Chen, David Oryang, Regis Pouillot, Karin Hoelzer and Susan Cahill developed the tool in collaboration with Risk Sciences International, RTI International and the Institute of Food Technologists.

Ultimately, for food safety, Monte Carlo shouldn’t mean taking a gamble.  Rather, it’s all about using a quantified, standardized and transparent methodology to better understand what interventions and controls will reduce the risk and improve our public health.

Ted Elkin is Director, Office of Analytics and Outreach, at FDA’s Center for Food Safety and Applied Nutrition.

“Breakthrough” Designation … Another Powerful Tool in FDA’s Toolbox for Expediting the Development and Review of Promising New Drugs for Serious Conditions

By: Janet Woodcock, M.D.

Janet Woodcock, M.D. is the Director of FDA’s Center for Drug Evaluation and Research

In fiscal year 2012, FDA approved 35 novel new drugs, also known as “new molecular entities.” Among these new products were drugs to treat patients with unmet medical needs, such as a groundbreaking treatment for a form of cystic fibrosis, the first FDA-approved human cord blood product for hematopoietic reconstitution, used to help patients with blood forming disorders, and the first drug to treat advanced basal cell carcinoma (a form of the most common skin cancer).

To enable our ongoing efforts to bring innovative drug products to the public as efficiently as possible, FDA relies heavily on several expedited development and review tools such as fast track designation, the accelerated approval pathway and priority review designation. For instance, 56 percent of the novel drugs approved by the Center for Drug Evaluation and Research in calendar year 2012 used some combination of these tools to speed promising therapies to patients with serious conditions. And any given drug may have received multiple expedited program designations. (See a brief summary of how each of these tools helps FDA shorten the development and review of promising new therapies.)

In July 2012, a provision in the new law called the Food and Drug Administration Safety and Innovation Act, or FDASIA for short, gave FDA another powerful expedited development tool, known as the “breakthrough therapy” designation. This new designation is now helping FDA assist drug developers expedite the development of new drugs with preliminary clinical evidence that indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. Although the designation is not yet even a year old, FDA has received 62 requests to grant this new designation to products under development. We have been very active on this subject, meeting with companies and discussing ways to expedite the drug development process for drugs that show striking early results. We have already granted the breakthrough designation to 20 potential innovative new drugs that have shown encouraging early clinical results.

Drug developers should have a clear understanding of all of FDA’s expedited development and review tools. To help industry better understand each tool, including when the tools can be used and the features of each, we have just published an industry draft guidance titled Expedited Programs for Serious Conditions — Drugs and BiologicsAmong other important information, the draft guidance describes FDA’s policies and the threshold criteria for each expedited program, defines and discusses important concepts, including serious condition, unmet medical need, and available therapy, and provides some general considerations for products utilizing an expedited program, such as manufacturing and product quality, nonclinical considerations, and clinical inspection considerations.

The breakthrough therapy designation gives us another tool in our “toolbox” to help expedite the development and review of new drugs to treat patients with serious medical conditions and little or no treatment options. We’ll continue to use the new breakthrough therapy designation and our existing tools to help make our expedited programs even more effective.

We’ve said it before — and I believe it’s worth repeating — our decision-making on whether to approve a drug always involves an evaluation of many factors, such as the seriousness of the disease.  However, ultimately any drug approved must show that its benefits outweigh its risks and regardless of which expedited development or review program or programs are used, FDA does not compromise its safety or efficacy standards in exchange for rapid approval. Like all drugs we approve, those approved after having been designated as breakthrough therapies will meet our usual rigorous standards for safety and effectiveness.

Janet Woodcock, M.D. is the Director of FDA’s Center for Drug Evaluation and Research

Setting the Bar High for FDA

By: Margaret A. Hamburg, M.D.

Rick Pazdur receiving ASCO Public Service Award

Rick Pazdur, accompanied by Margaret Hamburg, receiving ASCO Public Service Award

To say that Rick Pazdur faces enormous challenges in his job is an understatement. To say that he faces each day with energy, insight and resolve still falls short of the mark.

It’s my privilege to tell you that the American Society of Clinical Oncology (ASCO) has awarded Dr. Pazdur with its prestigious Public Service Award for his dedication to improving the lives of people living with cancer.

As director of the Office of Hematology and Oncology Products (OHOP) at FDA, Dr. Pazdur leads a staff of more than 130 oncologists, toxicologists and other specialists.

Their mission is making safe and effective drugs for cancer and hematologic (blood-related) conditions available to the patients who need them. The office is committed to facilitating rapid development, review and action on promising new treatments for these diseases.

Dr. Pazdur sets the bar high. His demand for excellence in his staff as well as in the treatments they review is unparalleled. Ultimately, Dr .Pazdur and his staff must decide whether or not an investigational drug can be tested in a clinical trial and, after testing, be approved for more widespread use. Sometimes, after careful investigation, they conclude that a drug has not been proven effective enough to outweigh the potential risks. These are the types of challenges and the tough decisions that Dr. Pazdur faces on a daily basis. A man of personal integrity with great compassion for those who are ill, he nonetheless is  often the recipient of criticism from patients, advocacy groups, drug companies and others. I have heard him say ruefully, but with characteristic humor, that you can’t win in this job—that if he approves a drug, he’s accused of lowering standards.  And if he doesn’t, he is insensitive to the plight of patients with cancer. Nothing could be farther from the truth.

Since his arrival at FDA in 1999, Dr. Pazdur has worked tirelessly to speed the development and availability of drugs that treat serious diseases, especially when the drugs are the first available treatment or have advantages over existing therapies. He has made a special effort to reach out to patient and advocacy groups, professional associations and foreign regulatory agencies. In 2012, nearly 40 percent of the new molecular entities approved in the Center for Drug Evaluation and Research were to treat cancer, often when few therapeutic options previously existed.

Members of Dr. Pazdur’s staff speak with warmth and enthusiasm of his dedication to cancer patients and his unflagging efforts to streamline the drug approval process. They call him not just a manager, but “a visionary,” and “one of the most unique people I know.” I quite agree.

To one of the most dedicated and accomplished people I know: It’s a pleasure to work at your side, Dr. Pazdur. Congratulations for this well-deserved honor.

Margaret A. Hamburg, M.D. is Commissioner of the Food and Drug Administration

We’re Working to Offset Ameridose Impact

By Margaret A. Hamburg, M.D.

Drug shortages are two words that no one wants to hear—not patients, not health care professionals, and not me.

Margaret Hamburg, M.D.FDA has been working hard to prevent and mitigate drug shortages. In 2011, the number of medications in short supply hit 251. Addressing drug shortages must be a top priority for us at FDA because these are medications that people need to stay healthy, to treat their illnesses, and even, in some cases, to stay alive.

This year, we’ve taken significant steps to expand our efforts and to engage in new ways with industry. Between Jan. 1 and Sept. 30, 2012, FDA worked with drug manufacturers to help avert the shortage of 145 drugs. Many critical medicines used to treat cancer and conditions such as attention deficit hyperactivity disorder (ADHD) are no longer in short supply.

However, drug shortages are still a serious problem, one that may be temporarily impacted by Ameridose LLC’s voluntary recall of all of its unexpired products. Ameridose, located in Westborough, Mass., is managed by some of the same people as the New England Compounding Center—which produced the drug that is implicated in the deadly, multi-state outbreak of fungal meningitis. An inspection of Ameridose was initiated as part of FDA’s ongoing investigation of the outbreak.

FDA recommended that Ameridose recall its sterile drugs because we could not be assured of the sterility of those products. However, this recall may affect supplies of certain life-saving drugs for some health care systems. FDA has identified a number of Ameridose products—including drugs used during surgery and to treat medical conditions that include congestive heart failure—that were on the current drug shortages list before the recall.

We also know that the supply of other drugs may be affected by the Ameridose recall. That’s why FDA is taking proactive steps to minimize the impact this recall may have on current drug shortages, and to prevent other shortages from occurring.

For recalled medications on the current drug shortages list, FDA is taking the same actions it has used successfully to mitigate other shortages.

  • FDA is working with manufacturers of these drugs, requesting that they ramp up production if they are willing and able to do so.
  • For any manufacturers of these drugs that may be experiencing manufacturing or quality problems, FDA is offering assistance to enable them to produce shortage drug products that are safe and high quality.
  •  As with shortages of any critical products, FDA will expedite the reviews of any pending applications that could help with addressing the shortages.
  • FDA is identifying any additional manufacturers willing to initiate or increase production.
  • If manufacturers of critical drugs are not able to meet U.S. patient needs, FDA will explore overseas companies that are willing and able to import foreign drugs to address the shortage. In these instances, FDA evaluates the imported drug to ensure that it is of adequate quality and that the drug does not pose undue risks for U.S. patients.

Since the beginning of the year, the number of advance notifications to FDA of potential shortages has greatly increased. If we know that a problem is on the horizon, we’re able to proactively work with industry, organizations, patients and stakeholders to address it. We have doubled the number of staff members who work in drug shortage prevention and response.

We at FDA are committed to doing everything we can, using all available tools, to prevent or mitigate drug shortages and help keep critically needed products on the market.

Margaret A. Hamburg, M.D., is Commissioner of the U.S. Food and Drug Administration.