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

Clacker Balls and the Early Days of Federal Toy Safety

By: John P. Swann, Ph. D.

As many of us scramble to find the perfect toy for the children in our lives this holiday season, it’s interesting to note that at one time FDA could very well have been known as the Food Drug and Toy Administration.

John SwannThe 1966 Child Protection Act gave FDA authority to ban toys that had chemical, flammability, or radioactivity hazards and the 1969 Child Protection and Toy Safety Act further defined FDA’s responsibility for ensuring the safety of toys, which the agency pursued until the formation of the Consumer Product Safety Commission in 1973.

During FDA’s brief stint as toy regulator, the agency dealt with flammable dolls; infant and toddler playthings that posed serious puncture, laceration, and crushing risks; and the infamous lawn darts. To appreciate FDA’s role at the time, consider what happened with clacker balls. Their origin was unclear, but clacker balls were a veritable craze by January 1971, to the consternation of parents and school districts everywhere. Sold under a variety of other names such as Kerbonkers, Click-Clacks, and Bo-Los, they could vary somewhat in design but typically, they were plastic, wooden, or steel balls of about two-inches in diameter. The balls were attached at each end of a two-foot cord that had a ring or knot in the middle. By holding the cord in the middle and moving your hand up and down, you could cause the balls to strike each other at the top and bottom of an arc with great force and abundant noise. By the spring of 1971, over 100 manufacturers had sold millions of clacker balls, according to FDA’s Bureau of Product Safety, which oversaw such commodities. And it was not a uniquely American phenomenon. The village of Calcinatello in Italy held an international competition of clacker ball enthusiasts in August 1971. In lieu of a trophy the winner received a variety of local delicacies.

picture of clacker balls

Assorted clacker ball sets, including some that ruptured.

Many compared the sudden popularity of clacker balls with the Hula Hoop, but they posed considerably greater risk to the user, as FDA soon discovered. Though advertised to “teach skill and coordination” and to consist of “non-breakable plastic with strong cord,” some of those enthusiasts sustained serious eye and other injuries due to the design and action of the toy, prompting the Society for the Prevention of Blindness to raise an alarm.  The balls could rupture and spew fragments, or become wayward missiles through detachment from or fraying of the cord itself.

The 1969 Toy Safety Act had provided for the banning of toys that represented an electrical, mechanical, or thermal hazard, pending the agency’s publication of the hazardous nature of the item and, if applicable, means of eliminating the hazard. And the agency took that seriously, banning more than 300 individual toys in seven classes through 1971.

After learning  of several injuries to children and adults from clacker balls, FDA issued a public warning in February 1971 as it investigated these reports and studied the toy and its potential to hurt the user—or bystanders.

FDA Toy Review Committee

The recommendations of the Toy Safety Review Committee in the Bureau of Product Safety (pictured here), which included a pediatrician and two engineers, played a key role in FDA’s decisions to ban, further test, mandate product redesign, or create regulations to address the hazards.

With ongoing reports of clacker ball injuries, just two months later, in April, FDA published its intention to ban such toys unless they could meet detailed standards of safety that addressed the integrity of the balls, cords, and connections that held them together.  FDA’s notice stated that the manufacturer would have to carry out the prescribed tests on a proportional number of samples based on the size of the batch produced, maintain records of these results, and make them available to the agency upon request. FDA finalized this plan in November 1971, and all clacker balls marketed thereafter had to either abide by the new safety standards or be subject to the ban.

The rulemaking process rendered clacker balls a safer toy, and those that failed to follow the standards were seized. Over 300,000 sets were put into storage at the Port of Miami while the agency was developing its safety standards for the clacker balls (presumably because the manufacturer knew they wouldn’t pass the safety tests). After a manufacturer tried, unsuccessfully, to find a market for these in South America, a salvage dealer apparently purchased the lot late in 1972, but their subsequent history is unknown.

Ensuring safety was FDA’s goal – and later that of the CSPC. But the toy’s noise was quite another thing. The standards applied by the two agencies never addressed the click-clack-click-clack that tormented parents and others for all these years.

Enjoy the click-clack sound of clacker balls!

John P. Swann, Ph.D., is an FDA Historian

Academic Medical Centers and FDA – Working Together for the Future

By: Robert M. Califf, M.D.

FDA and the nation’s academic medical centers (AMCs) have a rich history together. Many of us at FDA trained and worked at AMCs, and many of us will go back to AMCs when we leave FDA. AMCs are where much of the basic science of medicine is advanced, and where the fundamental concepts for many of the tools to test for and treat illnesses are initially developed. Increasing numbers of AMCs have regulatory science programs, FDA has memoranda of understanding with numerous AMCs, and we are pleased to host a number of fellows from AMCs annually. All of these intersections advance our shared goals of protecting and promoting public health while also helping to speed innovation. Together, we push the boundaries of the known and possible, and ensure that in doing so the health and safety of patients is the primary concern.

Robert CaliffMany of these intersections have been coincidental or ad hoc – people reaching out to each other as needed and as helpful.  To better understand our interactions, and to find ways to make those interactions more deliberate and strategic, I spent part of this fall on a college tour of sorts, visiting eight states across three time zones. I spent time at some of the nation’s leading AMCs which are increasingly becoming integrated economic and medical systems that play a key role in the development of solutions to health care challenges for the American public, and are therefore an essential partner for FDA.

During my meetings with professors, students, researchers, administrators, and academic partners, I saw many different ways in which people were engaged in remarkable science, policy analyses and discussions to advance the human condition. From university undergraduates to experienced researchers and clinicians, the men and women with whom I met share a commitment to ameliorating and curing disease for individual patients and promoting public health. Several themes and common challenges emerged from our discussions and laid the foundation for a positive course of action.

AMCs have evolved from “ivory tower” teaching hospitals with associated basic research labs to multi-billion dollar enterprises that own an array of entities in a common corporate structure. These entities, usually not for profit, include the traditional teaching hospitals and labs, as well as community hospitals, large and small physician practice groups, hospice, long-term care, extended living and social services organizations. In addition, AMCs are spinning off biotech startups and working directly with private corporations, state and federal partners, and entrepreneurs.

These AMCs are often part of larger complexes that cross state lines and international borders and they have the increasing ability to take on unprecedented health care. In the past they could claim to be separated from the responsibilities of health care delivery, population health and the success of the medical products industry as a key part of our economy. Now they are large employers, economic engines and the critical elements of strategies to develop new ideas and technologies for the future and they are accountable for the healthcare for most Americans.

An increasing proportion of large healthcare delivery systems include a medical school and other healthcare professions schools. And in many states major universities are partners or owners of such systems. This concentration of economic and intellectual talent, combined with the entrepreneurial spirit and stated mission of innovation, demand our attention and strategic thought.

Consider the Texas Medical Center (TMC) in Houston. With eight million patient interactions a year, TMC is the eighth largest business district in the United States; they deliver more than 25,000 babies a year and have $3 billion in construction projects underway. I met with researchers and academic leaders at TMC, and was introduced to a group of young entrepreneurs working in a medical tech incubator housed in what was once a Nabisco cookie factory, a facility funded by a mix of public, private, and corporate donors.

One area of focus everywhere I went is how to collect, manage, and use the unprecedented amount of data now accessible on the human genome, human behavior, how much people earn and spend, the environmental conditions, and other subjects. With information such as this at the societal and individual level, clinicians and health system leaders will ultimately be able to chart precise treatments for each person and evidence driven policies for populations. To be useful, we expect these data to accurately measure what they claim to measure and to be connected to the medical condition to which they claim to be connected.

And as much as possible, these datasets must be accessible and shared. To succeed, researchers at Southern Illinois University need to be able to combine their observations with data in Morgantown, Birmingham, New York, and Des Moines. The best minds must be brought to bear on the best data, no matter where those people happen to live or where the data happens to be stored. It can be tempting to wall-off data, protecting it as one does a garden. But just as the “walled garden” was a failed model for the internet in the 1990s, the walled garden is a failed model for the data needed for precision medicine to succeed.

FDA can be an important partner in this effort. Scientists, whether at FDA, in academic institutions across the nation, or in private industry, share the goal to protect and promote public health. Together we can ensure that researchers, patients, and health care providers can trust the data and ensure that as many people as possible have access to it. It is also true that even those of us with the best motivations are human. We make mistakes, get sloppy, and occasionally let things slide. That’s where FDA can play such an important role, by helping to maintain and hold everyone to a high standard while driving innovation forward.

In addition to raising the bar, standards can help products stand out in an increasingly crowded marketplace. In Cambridge, for example, I met a young innovator who said he was having trouble attracting venture capital to fund his idea in part because potential investors saw an unregulated marketplace into which competitors whose products sounded similar but with no proven positive effect, could begin marketing immediately and undercut him. Requiring FDA approval essentially freezes out fly-by-night companies more interested in quick profits than developing and disseminating technologies with evidence for benefits to individuals and populations.

Make no mistake, FDA has room to improve. During my trip I heard directly, without equivocation, how FDA could do a better job.  As someone who spent most of my career at an academic medical center, I understand those concerns up close and personal, and I also know that there is room for improvement on both sides.

That means I also know firsthand the challenges, and opportunities, presented by both AMCs and this important scientific regulatory agency. After my tour, I am more convinced than ever that FDA and the academic medical center enterprise need each other, must continue to communicate and engage with each other, and, where appropriate, must collaborate to advance their shared missions.

This is not a short-term project. This engagement must continue long after I leave FDA.

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

FDA’s Naloxone App Prize Competition Celebrates Innovation In Search of Technological Solutions to the Opioid Epidemic

By: Peter Lurie, M.D., M.P.H.

The epidemic of opioid dependence and abuse has had an impact upon communities both large and small across the United States. Since 1999, rates of overdose deaths involving opioids, whether prescription painkillers or street drugs like heroin, have nearly quadrupled. In 2015, 91 Americans died from an opioid overdose each day.

Dr. Peter LurieMany local, state, and federal agencies have worked to prevent these tragic deaths by expanding access to naloxone, a prescription medication that can rapidly reverse the effects of an opioid overdose. Supporting increased access to naloxone is also a key objective of the multifaceted Opioid Action Plan released by FDA earlier this year. In addition, FDA has sponsored two national meetings on the topic and in recent years has approved two naloxone products that facilitate use by laypeople.

These efforts and others by federal partners, state and local governments, and by community-based organizations have increased the availability of naloxone in many communities, enabling both first responders and laypeople like friends and families of drug users to carry this life-saving medication. From 1996, when a community-based organization first distributed naloxone, to mid-2014, these organizations are reported to have reversed over 26,000 overdoses.

For naloxone to reverse an opioid overdose, however, it must be administered as quickly as possible. That’s why the agency launched the Naloxone App Competition, an effort to develop innovative solutions to the problem of how to rapidly connect naloxone carriers to a person experiencing an opioid overdose.

Through this prize competition, FDA aimed to engage with creative communities outside the agency who may not have traditionally focused on public health issues. We invited computer scientists, researchers, health care providers, patient advocates, academics, and entrepreneurs to form teams and submit concepts for a crowd-sourced mobile phone app that could help accelerate delivery of naloxone to a person experiencing an overdose.

While we didn’t know what to expect from this first-of-its-kind competition for the agency, public health-focused innovators responded with enormous enthusiasm. Over 150 teams registered for the competition, and more than 100 individuals participated, either in-person or virtually, in a two-day code-a-thon hosted on the FDA’s White Oak campus. The teams were eager to learn more about the opioid epidemic and began to develop compelling concepts to bring technological solutions to bear on a real-world problem.

A total of 45 submissions were reviewed by our team of judges from FDA, the National Institute on Drug Abuse, and the Substance Abuse and Mental Health Services Administration. While we received many thoughtful and innovative submissions, a single winning team was selected to take home the cash prize of $40,000. We are pleased to announce that the winner of the 2016 FDA Naloxone App Competition is OD Help by Team Pwrdby, a small startup based in Venice, California.

OD Help’s concept is a simple, easy-to-use mobile app designed to connect potential opioid overdose victims with a crowd-sourced network of naloxone carriers. OD Help can easily be tailored for use in rural or urban areas by expanding or contracting the radius within which naloxone carriers are sought. An additional innovative feature of OD Help is the optional interface with a breathing monitor to detect when a victim’s breathing rate is dangerously low, a sign of an opioid overdose. Hence, if the victim is alone and unable to call for help, OD Help will detect the diminished breathing and alert a naloxone carrier of the potential overdose. Other features of OD Help include: only alerting people in one’s support network and allowing naloxone carriers to disable alerts when they are unable to respond. The app also provides instructions on how to correctly diagnose an overdose and administer naloxone and helps contact emergency medical services when help is required.

Team Pwrdby was represented by the multi-disciplinary team of: Jared Sheehan, Dr. Talib Omer, Daniel Bouganim, Chris Rovin, Suresh Mohan, Ben Dukes, Andress Anantharaju, Oumayma Raimi, and Courtney Crockett. View the OD Help app video here: https://www.youtube.com/watch?v=wiiNvSLbUgo&feature=youtu.be.

FDA also congratulates Team MIT on their app concept, NalNow, which the judges recognized as a second high-performing submission. Team MIT receives an honorable mention as the team with the second-highest score in the Competition. Team MIT is represented by Dr. Hattie Chung, Grace Young, Sinchan Banerjee, Rodrigo Ipince and Emily Zhao. View the NalNow app video here:  http://bit.ly/nalnow_video. App developers interested in further developing their concepts are encouraged to seek support through NIDA’s Small Business Innovation Research grant program.

By enabling FDA to tap into the creativity, energy, and knowledge base of communities that do not regularly engage with the federal government, prize competitions expand the pool of smart, talented individuals committed to tackling the problems that face us as a society – and in this case that was a win for public health. We sincerely thank everyone who participated in the 2016 FDA Naloxone App Competition, and we congratulate Team Pwrdby on their winning concept, which has the potential to make a real difference in the fight against opioid overdose.

Peter Lurie, M.D., M.P.H., is FDA’s Associate Commissioner for Public Health Strategy and Analysis

Better Tool to Help Assess LASIK Patients

By: Malvina Eydelman, MD

LASIK (laser-assisted in situ keratomileusis) eye surgery is an alternative for patients who need glasses or contacts to see well. Some 600,000 to 800,000 patients undergo LASIK in the U.S. each year, and a very high number of those patients are satisfied with their surgical outcomes.

Malvina EydelmanHowever, some patients develop unwanted visual symptoms following surgery, symptoms that can have a significant impact on their daily lives. Patients who see starbursts, glare, ghosting, or halos—or those who experience severe dry eye—may have their daily lives change in negative ways.

While there are risks with all medical procedures – and the risks associated with LASIK are well known – FDA teamed up with the National Institutes of Health (NIH), and the Department of Defense (DoD) to more fully capture the patient experience with LASIK. Through the LQOLCP (LASIK Quality of Life Collaboration Project) and the Patient-Reported Outcomes with LASIK (PROWL) studies, we have developed a valid web-based questionnaire that can be used to assess LASIK patients before and after surgery. The questionnaire is available on FDA’s website.

The new scientifically validated questions can help assess patient expectations, symptoms, and satisfaction, and includes definitions of the visual symptoms and images depicting the range of the symptom to facilitate patients’ reporting. These questions can be used for a variety of purposes, such as being used by eye care providers to monitor symptoms before and after LASIK surgery. Additionally, manufacturers may wish to include such information in future LASIK product submissions along with other clinical and nonclinical evidence for FDA’s benefit-risk determination.

The LQOLCP focused on patient-reported outcomes (PROs)—which are reports of the status of a patient’s health condition that come directly from the patient, without interpretation of the patient’s response by a clinician or anyone else. Using well-developed PRO measures, everyone can better understand the impact that visual symptoms associated with LASIK treatment have on the patient’s life.

The newly-developed questions in the PROWL questionnaire can facilitate discussions between eye care providers and patients considering LASIK surgery. In the PROWL studies, patients were more than twice as likely to report their visual symptoms when filling out a questionnaire, than to tell them to their health care provider.

With this improved collection tool of patient experiences, the development of debilitating symptoms was uncommon. Less than 1 percent of study participants experienced difficulties performing their usual activities following LASIK surgery due to any one symptom in each of the PROWL studies. The PROWL questionnaire can be used in future research to more accurately estimate the prevalence of visual symptoms in LASIK patients and identify the predictors of visual symptoms and dissatisfaction.

By listening to the patient’s perspective during the development, evaluation, and use of medical devices, FDA and manufacturers can work together to better assure that LASIK devices marketed in the United States are safe, effective and meet the needs of the patients for whom they are intended. The patient perspective is so important to us that it is one of FDA’s Center for Devices and Radiological Health’s strategic priorities.

Read more information about the LASIK Quality of Life Collaboration Project.

Malvina Eydelman, M.D., is the Director of the Division of Ophthalmic, and Ear, Nose, and Throat Devices, Office of Device Evaluation, at FDA’s Center for Devices and Radiological Health

21st Century Cures Act: Making Progress on Shared Goals for Patients

By: Robert M. Califf, M.D.

Today, President Obama signed into law the 21st Century Cures Act, which, I am pleased to report, builds on FDA’s ongoing efforts to advance medical product innovation and ensure that patients get access to treatments as quickly as possible, with continued assurance from high quality evidence that they are safe and effective.

Robert CaliffCures will greatly improve FDA’s ability to hire and retain scientific experts. One of our ongoing challenges has been recruiting and retaining the experts we need in specialized areas to allow us to get our work done and meet our growing responsibilities. This is an especially important need given the tremendous advances in biological sciences, engineering, information technology and data science. Preventive, diagnostic and therapeutic strategies will become more complex with much greater potential for benefit and in some cases greater risk if used without adequate evidence to exclude risks that exceed potential benefits.

This new law rightly recognizes that patients should play an essential role in the development of drugs and devices to diagnose and treat their disease, since patients are in a unique position to provide essential insights about what it is like to live with and fight their disease. That’s been our perspective as well, and it’s why FDA has continued to advance the science of patient input through our patient-focused drug development program and our partner with patients program for medical devices. As it is, Cures will enhance these ongoing efforts to better incorporate the patient’s voice into FDA’s decision-making.

Cures will also support our efforts to modernize and improve efficiency in clinical trial design. This has been an important FDA priority for decades, but exciting new approaches are now available, and we need to develop a common understanding of which designs should be used for which clinical issues. In cancer, for example, we’re already weighing the use of common control trials, which share a control arm, involve multiple different drugs for the same indication, and may even involve different companies. One of the benefits of using a common control arm is that the overall number of patients who need to be recruited and enrolled decreases, thereby optimizing clinical trial resources and potentially shortening the time it takes to get a new study off the ground

Even without the benefit of Cures, patients have been well-served by FDA’s program efficiencies, emphasis on early meetings, and use of expedited pathway programs to speed approval and delivery of new drugs and devices to patients. Rather than passively processing product applications, FDA works to advise companies and inventors from the earliest stages of the development process on the kinds of medical products needed, how to do the necessary research, and how to viably and effectively translate from concept to product. This not only means that important new products will be developed as efficiently as possible but also that medicines and devices with no chance of success are identified much earlier so that money isn’t wasted on futile development. These programs have been embraced by developers of medical products in this country, and they are making a real and positive difference.

In the United States, the FDA uses expedited programs (fast track, priority review, accelerated approval, and breakthrough therapy) for drugs and biologics more than comparable drug and biologic regulators in other countries use theirs and as a result FDA is the first to approve a majority of novel drugs compared to our foreign counterparts.

For devices, this past year was the first full year of operation for FDA’s expedited access pathway (EAP) program, which helps speed the development and availability of certain medical devices that demonstrate the potential to address unmet medical needs for life-threatening or irreversibly-debilitating diseases or conditions. So far, we have granted 24 devices access to this program. Cures builds on EAP by creating the breakthrough device pathway.

The law establishes other new programs as well. For instance, the Limited Population pathway will help streamline the development programs for certain antibacterials and antifungals intended to treat targeted groups of patients suffering from serious or life-threatening infections where unmet need exists due to lack of available therapies. Approvals of these antimicrobials are expected to rely on data primarily targeting these limited populations. The statement “Limited Population” will appear prominently next to the drug’s name in labeling, which will provide notice to healthcare providers that the drug is indicated for use in a limited and specific population of patients. The limited population statement, additional labeling statements describing the data, and FDA review of promotional materials, will help assure these drugs are used narrowly to treat these serious and life-threatening infections while additional evidence is generated to assess safety and effectiveness for broader use.

Cures also creates a new program for  the development of regenerative medicine products, an important and exciting new field that deserves this special focus. The program designates drugs as regenerative advanced therapies and takes appropriate actions to improve the efficiency of development and to enhance the exchange of information among FDA, researchers and developers. An especially important element of this program is the creation of a research network and a public-private partnership to assist developers in generating definitive evidence about whether their proposed therapies indeed provide clinical benefits that are hoped for.

Looking ahead, much still needs to be done to spur product development. There have yet to be successful therapies identified for certain diseases, such as Alzheimer’s disease, where underlying scientific knowledge is still lacking.  In addition, we are only at the early stage in building a national evidence generation system based on registries, claims data, and electronic health records that will be a rich source of post-market data and an avenue for conducting more efficient research. Last week we published a consensus of FDA leadership on the use of real world evidence in the New England Journal of Medicine, focusing on the misperception that randomized trials and real world data are incompatible.  In fact, the use of randomization within the context of clinical practice will constitute a major advance in evidence generation and we are actively encouraging proposals with this combination of randomized trials conducted in real world practice. Cures provides support for continued exploration of the use of real world evidence in the regulatory context.

The law also addresses drug firms providing healthcare economic information to payers and formulary committees. This complex area will require careful delineation of principles to guide information exchange to enable these entities to appropriately assess the value of drugs.

With Cures, great progress has been made towards our shared goal of advancing regulatory science so that we can continue to speed the discovery, development, and delivery of medical products to prevent and cure disease and improve health while sustaining the evidence framework that enables assurance to the public of the safety and effectiveness of medical products. We are excited about the major advances in NIH funding, and welcome the increasing focus on rigorous translational science and data sharing reflected in the bill. Furthermore the funding of opioid addiction treatment and mental health services is a major positive element for our country and consistent with tremendous needs that we recognize.

FDA now stands ready to work with Congress, our sister federal agencies and the medical products ecosystem to implement these important provisions as we continue to work on behalf of all Americans to protect and promote public health and promote innovation in this exciting time.

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

Faster Information from FDA Means Improved Drug Safety for Patients

Mary E. Kremzner, PharmD, MPH, CAPT, U.S. Public Health Service

FDA is now making it easier and faster for health care professionals and patients to get the most up-to-date drug safety information on the more than 18,000 drugs available on our website. Our improved Drug Safety Labeling Changes Program enables FDA to post the latest safety information about a medicine almost at the same time we approve a change, as opposed to once a month.

Mary KremznerWhen your physician or other health care professional prescribes your medicine using their e-prescribing system, the new safety information now displays much faster than with our previous system. Here’s how – within days of FDA approval of new drug safety information for a drug product, the information is entered into the safety labeling changes database. Health IT vendors that provide clinical and drug information support for hospitals and pharmacies are then alerted to integrate the safety labeling changes data into their systems. So instead of waiting weeks for the monthly release of all safety labeling updates, this information is now accessible in days. From my point of view as a practicing pharmacist, the improved connection between new safety information and safety alerts on the pharmacy computer system builds more confidence into each prescription I fill for my patients.

For each FDA-approved drug, we provide detailed prescribing information, known as product “labeling.” Labeling helps those who prescribe medications understand key information about the drug, such as how much to prescribe, how often a patient should take a drug, which conditions the medicine treats, and what safety precautions should be followed for patients taking the drug.

Safety information can change multiple times over the lifetime of a drug as FDA learns about new risks, interactions with other medications and side effects. After we become aware of new safety information, changes to the drug product labeling may be required.

The public can access this information as well, now in a searchable database. Just key in the drug name and get a comprehensive listing of the labeling changes related to safety for that product.

Our new program is a game-changer for health care professionals seeking to provide the best quality care for their patients. FDA continues to pursue and provide innovative ways to rapidly access important information that protects and advances public health.

Mary E. Kremzner, PharmD, MPH, CAPT, U.S. Public Health Service, is the Director, Division of Drug Information, in FDA’s Center for Drug Evaluation and Research

The Mutual Reliance Initiative: A New Path for Pharmaceutical Inspections in Europe and Beyond

By: Dara Corrigan, J.D.

Dara CorriganFor FDA professionals focused on drug quality and safety, the rapid increase in imported drugs from nations where we devote limited inspection resources is of great concern. One way to address this concern would be to create an expanded inspectorate, one where investigators and inspectors from FDA and trusted partners, such as those in the European Union, would work together, rely on each other’s inspections, avoid duplicating inspections, and conduct more inspections in areas where the increase in drug manufacturing has greatly increased, like in China and India.

To meet this challenge, FDA has responded with the Mutual Reliance Initiative (MRI). The concept is simple. EU country inspectors inspect in their respective countries, FDA inspects the manufacturing facilities in the U.S., and the EU and FDA would rely upon each other. This would avoid duplication, lower costs, and enable the regulators to devote more resources to other parts of the world where there is greater risk. The savings would be considerable – over the last 5 years, about 40 percent of FDA’s drug inspections were performed in the EU.

The Mutual Reliance Initiative

There is a history to U.S.-EU collaboration. In 1998, in an annex to a U.S.-EU trade agreement, the U.S. and the EU agreed to recognize each other’s good manufacturing practice drug inspections. However, the agreement was never fully implemented.

Since 1998, FDA has expanded its reach beyond U.S. borders by opening foreign offices in China, Europe, India, and Latin America. We conduct more foreign inspections now and have gathered more than 15 years of experience in collaborating with the EU.

Equally important was the 2012 passage of the Food and Drug Administration Safety and Innovation Act. Congress recognized that FDA cannot and should not monitor the world’s drug inventory by itself and authorized FDA to accept the findings of a foreign inspector when its drug inspectorate is capable of conducting inspections that meet U.S. standards.

Working With The EU Inspectorates

The MRI was launched in May 2014. As part of MRI, FDA and EU assembled dedicated teams to assess the risk and benefits of entering into a mutual recognition agreement. FDA was invited to observe the EU’s Joint Audit Programme, in which two EU nations audit the inspectorate – the regulatory authority – of another member. FDA first observed the audit of Sweden’s inspectorate by auditors from the United Kingdom and Norway. Since then, FDA has observed an additional 12 audits of drug inspectorates across the EU with more audit observations planned through 2017.

This unprecedented access allows FDA observers to gather firsthand knowledge of the laws that govern EU GMP drug inspections and how inspectorates manage the drug inventory within their respective borders. Also, interacting with auditors across the EU provides a unique opportunity to understand the regulatory framework in the EU. With 28 member states (27 after Britain leaves the EU), there can be differences FDA must understand.

And to clarify, the so-called “Brexit” has no impact on FDA’s relationship with our United Kingdom counterparts at this time. Once the UK finalizes its departure from the EU, FDA and the UK will reexamine existing commitments and, if necessary, renegotiate any existing agreements. According to reports, it is likely going to take the UK and EU two years to finalize the terms of the Brexit.

MRI is one of the key components of the pharmaceutical sector covered in the Transatlantic Trade and Investment Partnerships (T-TIP) but could also take another path if the initiative progresses more quickly than the trade negotiations.

The observation and analysis of the drug inspectorates in the EU has only been possible because of the extraordinary devotion and collaboration across FDA. Observers of the audits have included subject matter experts, management, and investigators from the Center for Biologics Evaluation and Research, the Center for Drug Evaluation and Research, the Office of Regulatory Affairs and the Office of Global Regulatory Operations and Policy. These same FDA employees, and others, guided FDA successfully through the EU’s audit of FDA in September 2015 when the EU visited three district offices, the main campus, and a drug laboratory as part of its assessment. The EU team applied the same criteria that it applies within the EU when it audits its own member states.

Looking Forward

What is next? We hope to sign an agreement with the EU soon and are working to complete assessments of the capability of the drug manufacturing inspectorates of two to four countries within the EU.

These first steps with the EU will lead toward our goal of an expanded inspectorate, containing investigators and inspectors from FDA and from across the EU. These collaborations will enhance our ability to evaluate risk, produce better data, and minimize public health risk globally. Indeed, the need to engage globally in different ways is imperative. With MRI, we are moving boldly forward in that direction.

Dara Corrigan, J.D., is FDA’s Associate Commissioner for Global Regulatory Policy

Why FDA Is Making Data Extracted from Reports of Adverse Events for Foods and Cosmetics Available to the Public

By: Susan Mayne, Ph.D., and Katherine Vierk, M.P.H.

Transparency in the actions we take as an agency, and our reasons for taking them, is an important value for FDA in its mission to protect public health.

Susan Mayne

Susan Mayne, Ph.D., is Director of the FDA’s Center for Food Safety and Applied Nutrition

That is why we are, for the first time, making public the data that FDA’s Center for Food Safety and Applied Nutrition (CFSAN) receives about adverse events related to foods, including conventional foods and dietary supplements, and cosmetics regulated by FDA. This is information that was once only available through Freedom of Information Act (FOIA) requests, but will now be easily available to researchers, consumers, and health professionals.

This first posting of data from CFSAN’s Adverse Event Reporting System (CAERS) includes data from reports submitted by consumers, medical professionals and industry from 2004 through September 2016. The term “adverse event” is an umbrella term for a number of poor outcomes, including bad reactions, illnesses or deaths. We plan to update this information quarterly to ensure that the public has the most current information available.

Katherine Vierk

Katherine Vierk, M.P.H., is the Director of the Division of Public Health Informatics and Analytics at FDA’s Center for Food Safety and Applied Nutrition

The goal of CAERS is to provide indications, or “signals” of potential hazards. FDA uses these adverse event reports to monitor the safety of foods, including conventional foods and dietary supplements, and cosmetics. This information can, and has, led to investigations of specific products, targeted inspections and product testing, import alerts, warning letters, and enforcement actions.

Examples of how adverse event data has been used to support multiple actions by FDA include recalls of HydroxyCut and OxyElite Pro dietary supplements, and investigations of cosmetic products, such as EOS lip balm and Brazilian BlowOut hair smoothing treatment.

A few caveats about CAERS: The data from the reports is what was reported to the agency. FDA has not necessarily determined that the events reported were actually caused by the product in question. And there often are gaps in the information provided, which should ideally include the product name, symptoms, outcome, consumer’s sex and age, and the date the adverse event was experienced.

Going forward, FDA intends to modernize the system to make reporting adverse events as user-friendly as possible. You can expect to hear more about that in about a year. But in the meantime we didn’t want to delay giving the public access to data we have. The CAERS data will be posted on fda.gov and is also available through OpenFDA, launched in 2014 to make it easier to access the agency’s publicly available information.

We’re hoping that this increased transparency will result in more detailed and complete reports that will help us to more rapidly identify red flags about a possible safety issue with products we regulate. Anyone can report a safety or quality issue with an FDA-regulated food (conventional foods and dietary supplements) and cosmetics. To do so, visit fda.gov.

Susan Mayne, Ph.D., is the Director of FDA’s Center for Food Safety and Applied Nutrition

Katherine Vierk, M.P.H., is the Director of the Division of Public Health Informatics and Analytics at FDA’s Center for Food Safety and Applied Nutrition

Combination Products Review Program: Progress and Potential

By: Nina L. Hunter, Ph.D., and Robert M. Califf, M.D.

Nina Hunter

Nina L. Hunter, Ph.D., FDA’s Associate Director for Science Policy in the Office of Medical Products and Tobacco

About a year ago, we shared with you our Combination Product Review, Intercenter Consult Process Study Report, which was developed by FDA’s Office of Planning. The report’s findings were derived from focus group studies with reviewers from FDA’s different Centers and included input from industry. Since then, we have built on foundational policies and processes to address many of the issues identified in the report.

The team has made tremendous progress toward the goal of modernizing the combination products review program by improving coordination, ensuring consistency, enhancing clarity, and providing transparency within the Agency as well as with all stakeholders. We are excited to share our progress with you now. The table below summarizes some key achievements from the past year, including publication of draft guidances, a variety of new processes, and a look at future goals.

Robert Califf

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

As technologies advance across multiple fields, the distinctions that previously allowed combination products to be neatly categorized by FDA’s medical product centers are blurring or even vanishing.

Combination products account for a growing proportion of products submitted for review, and FDA will continue to pursue new approaches to collaboration that ensure safe, effective and innovative medical products are made available to patients as quickly as possible. Continued collaboration with you, our stakeholders, will be critical as together we continue to make progress in this important area.

We are still listening and have much more work to do!

Combination Products Review Table

This table summarizes key Combination Product Review Program achievements from the past year. Click on table for PDF version.

The PDF version of the table is also located here: combination-products-review-program

Nina L. Hunter, Ph.D., is FDA’s Associate Director for Science Policy in the Office of Medical Products and Tobacco

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