FDA Working to Lift Barriers to Generic Drug Competition

By: Scott Gottlieb, M.D.

Too many patients are being priced out of the medicines they need. While FDA doesn’t have a direct role in drug pricing, we can take steps to help address this problem by facilitating increased competition in the market for prescription drugs through the approval of lower-cost, generic medicines.

Dr. Scott GottliebOver the last decade alone, competition from safe and effective generic drugs has saved the health care system about $1.67 trillion. When generics are dispensed at the pharmacy, the immediate savings to each of us are clear. We could see even greater cost savings if we helped more safe and effective generic drugs get to market sooner, after patent and statutory exclusivity periods have lapsed, by addressing some of the scientific and regulatory obstacles to generic competition across the full range of FDA-approved drugs. These barriers may delay and, in some cases, ultimately deny patient access to more affordable drugs.

That’s why we’re working on a Drug Competition Action Plan. As part of this effort, today, we’re announcing in the Federal Register our intent to hold a public meeting on July 18, 2017, to solicit input on places where FDA’s rules – including the standards and procedures related to generic drug approvals – are being used in ways that may create obstacles to generic access, instead of ensuring the vigorous competition Congress intended.

Innovation in pharmaceutical development is essential because it creates new and sometimes life-saving therapies. But access to lower-cost alternatives, once patent and exclusivity periods lapse, also is critical to the nation’s health.

We know that sometimes our regulatory rules might be “gamed” in ways that may delay generic drug approvals beyond the time frame the law intended, in order to reduce competition. We are actively looking at ways our rules are being used and, in some cases, misused.

One example of such gaming is the increasing unavailability of certain branded products for comparative testing. To perform the studies required to develop a generic alternative to a branded drug, a generic sponsor generally needs 1,500 to 3,000 doses of the originator drug. I understand that generic sponsors are willing to buy these products at fair market value; but, in some cases, branded companies may be using regulatory strategies or commercial techniques to deliberately try to block a generic company from getting access to testing samples.

This might occur, for example, when branded companies might use restrictions they place in their commercial contracts or their agreements with distributors to make it hard for intermediaries in the drug supply chain to sell the drugs to generic drug developers.

We also see problems accessing testing samples when branded products are subject to limited distribution – whether the company has voluntarily adopted limitations on distribution, or the limitations have been imposed as part of a Risk Evaluation and Mitigation Strategy, or REMS, a program that FDA implements to help ensure the safe use of certain drugs. I have been made aware that, in some of those cases, branded sponsors may use these limited distribution arrangements, whether or not they are REMS-related, as a basis for blocking generic firms from accessing the testing samples they need.

Besides limiting access to testing samples, some branded companies may be using the statutory default requirement to have a single shared REMS across both the branded and generic versions of a drug as a way to block generic entry. They might prolong negotiations with the generic firms over the implementation of these single shared systems, which could delay the entry of safe and effective generic drugs onto the market.

I want to take steps to address these concerns, to make sure that we are facilitating appropriate competition in circumstances where Congress intended. The forthcoming public meeting is intended to solicit public comment to inform us of circumstances where generic competition may be thwarted by these and other techniques.

As we solicit additional information, we also are going to be looking at policy and programmatic changes to address these issues. Some of these steps may be actions we can take by using our own authorities more forcefully. Other steps might involve our need to collaborate with sister agencies.

We’re also going to be looking hard at how best to coordinate with the Federal Trade Commission in identifying and publicizing practices that the FTC finds to be anti-competitive. FDA is not the FTC. It is the FTC’s responsibility to prevent anticompetitive business practices. But Congress set out certain laws that are meant to strike a careful balance between pharmaceutical innovation and access to lower cost generic products, and FDA has an important responsibility to enforce those laws in a manner that adheres to the balance struck by Congress.

We’ll be unveiling additional aspects of our larger Action Plan and providing updates, as these initial elements are implemented. I’m confident that these actions and the dedicated work of the outstanding staff in our generic drug program will help to address the issues patients are facing today when they’re priced out of buying the drugs they need. At the meeting on July 18 we want to hear from the public about ways our current rules may not be having their intended effects, and where current policies are falling short in ensuring the careful balance between new innovation and patient access.

Our goal is to broaden access to safe and effective generic drugs that can improve access to medicines and help consumers lower their health care costs. As in all of the things we do, we will steadfastly maintain FDA’s gold standard for rigorous, science-based regulation.

Over the past five years our generic drug program staff has evolved and grown remarkably, while implementing the first generic drug user fee program. The staff has demonstrated that they can rise to new challenges and they have my full support. Their hard work will serve as a strong foundation for the program as it moves forward. I want the policy framework they operate under to be as efficient, fair, and robust as the review program that they’re operating.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

FDA Science: Working at the Speed of Emerging Technologies

By Luciana Borio, M.D.

Let’s face it, we’ve all gotten used to nearly instant access to almost anything.

Today, with a tap of an app, we order a car ride, a book, or pizza for dinner. Need to navigate past traffic in downtown city streets? No problem. There’s an app for that, too.

Some may wonder: Why hasn’t rapid medical product development partaken of this need for speed that has reshaped other sectors of our economy? Well, in many ways, it has.

Innovation is happening extraordinarily fast in the biomedical sciences and at FDA. As FDA’s Acting Chief Scientist responsible for leading and coordinating FDA’s cross-cutting scientific and public health efforts, I see close up that years of scientific research, collaboration, and investment are paying off.

FDA Acting Chief Scientist Lu Borio

FDA Acting Chief Scientist Luciana Borio

When I testified at a congressional hearing recently, my colleague, Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, gave a tangible example of what I mean. He said it took his team about three months to begin clinical testing of a Zika vaccine candidate developed from scratch. In 2003, it took the same team 18 months to develop a candidate vaccine to address the SARS outbreak and begin clinical testing of that product.

And in just over two decades, a disease like multiple sclerosis has gone from being untreatable to one for which clinicians are nearly “flummoxed by the options,” according to a headline I saw recently.

There is a reason for this success. In the last several years, scientists have identified and begun using “safety-risk biomarkers.” Rather than those for efficacy, these biomarkers identify which patients are at highest risk for certain adverse events. They have opened up an array of therapeutic options for patients who might do just fine with some treatments that may not otherwise have been developed due to our previous inability to properly assess their risk.

None of these successes would be possible without our FDA product reviewers working at breakneck pace to guide these innovative development programs.

It’s not always fully understood that FDA scientists play an essential role in advancing many biomedical innovations. That’s why we invite the public to participate in a two-day Science Forum at FDA every other year to showcase the agency’s robust scientific research and the important work done by our 11,000 scientists.

Just as industry focuses on product development research and academia focuses on the scientific foundation, FDA research concentrates on creating test methods and developing knowledge of processes to ensure that our products are safe and effective or, with tobacco, at least with reduced harm.

I like to think that this year’s Science Forum was better than ever. Over two days, hundreds of participants were treated to 230 scientific posters and some 50 presentations by FDA scientists and others, organized under eight broad categories:

  1. Identification and Evaluation of New Biomarkers;
  2. FDA Response to Urgent Public Health Needs;
  3. Microbiome and Human Health;
  4. Advanced Manufacturing and 3D Printing;
  5. Omics Technologies at FDA;
  6. Patient and Consumer Engagement and Communication;
  7. Computational Modeling and Simulation at FDA; and,
  8. Current Progress in Nanotechnology Research at FDA.

Four poster sessions during the two days augmented the presentations that featured the authors of studies describing the methodology, challenges, and results of their research one-on-one with those at the forum. Among the meaty topics discussed were:

  • The emerging technology of additive manufacturing and medical devices, produced by 3D printing. Bioengineers at FDA’s Center for Devices and Radiological Health have positioned themselves at the forefront of knowledge and research about this cutting-edge manufacturing process, by looking into patient matching, imaging, and phantoms. With our proactive posture, FDA is paving the way for safe and effective innovation that will usher in life-saving advanced treatments for patients.
  • The growing use in medical products of nanomaterials – equal to about one-billionth of a meter – so small that they can’t be seen with a regular microscope. Silver nanoparticles are now used in wound dressing for their antimicrobial properties. And liposomal nanoparticles are used as drug carriers to reduce toxicity and increase circulation time in the blood. Characterizing these complex nanomaterials is challenging. FDA scientists highlighted their analytical methods for characterizing nanomaterials in over-the-counter FDA-regulated products. This will help us with assessing risk, developing industry guidelines for characterizing nanomaterials, postmarket surveillance, and determining shelf life of nanomaterials in consumer products.
  • In the area of food safety, FDA has contributed to enhancing antimicrobial resistance monitoring in a collaborative effort with USDA and the Centers for Disease Control and Prevention. And, genomics studies conducted by FDA scientists have demonstrated that we can use the emerging technology whole genome sequencing as an effective tool for predicting antimicrobial resistance of certain foodborne pathogens.

Not all of our essential research deals with cutting-edge technology. Scientists from FDA’s Center for Tobacco Products (CTP) shared their work on water pipe, or hookah, smoking. Water pipes, a centuries-old method of smoking, are becoming an increasingly common method of tobacco smoking in young adults. A rare and serious lung disease – water pipe-induced acute eosinophilic pneumonia – has been reported among these smokers. One of the forum’s posters described how CTP scientists identified the disease and made physicians aware of it.

And, as a sign of the times, mobile communications also were part of the poster sessions. Healthy Citizen @FDA will be a holistic, citizen-centric mobile platform for FDA to collaborate and communicate with citizens to improve public health outcomes and to receive timely FDA alerts.

Of course, events like these are equally valuable for what happens before and after the formal presentations. From the snippets of conversation I picked up in the hallways, FDA and outside scientists had plenty of opportunity to interact, share ideas, and even discuss potential collaborations.

Those who attended the 2017 Science Forum gained a deeper understanding of the cutting-edge science we do at FDA to protect and promote the public health. And those who missed the Forum have the option of watching the recorded presentations on FDA’s website. We look forward to future opportunities to share more of the exciting advances we’re making with our partners in the scientific community.

Luciana Borio, M.D., is FDA’s Acting Chief Scientist

Fostering Medical Innovation: A Plan for Digital Health Devices

By: Scott Gottlieb, M.D.

It is incumbent upon FDA to ensure that we have the right policies in place to promote and encourage safe and effective innovation that can benefit consumers, and adopt regulatory approaches to enable the efficient development of these technologies. By taking an efficient, risk-based approach to our regulation, FDA can promote health through the creation of more new and beneficial medical technologies. We can also help reduce the development costs for these innovations by making sure that our own policies and tools are modern and efficient, giving entrepreneurs more opportunities to develop products that can benefit people’s lives.

Dr. Scott GottliebTo this end, FDA will soon be putting forward a broad initiative that is focused on fostering new innovation across our medical product centers. I will have more to say on many elements of this initiative soon. However, today I want to focus on one critical aspect of this innovation initiative: A new Digital Health Innovation Plan that is focused on fostering innovation at the intersection of medicine and digital health technology. This plan will include a novel, post-market approach to how we intend to regulate these digital medical devices.

According to one estimate, last year there were 165,000 health-related apps available for Apple or Android smartphones. Forecasts predict that such apps would be downloaded 1.7 billion times by 2017. From mobile apps and fitness trackers to clinical decision support software, innovative digital technologies have the power to transform health care in important ways, such as:

  • Empowering consumers to make more and better decisions every day about their own health, monitor and manage chronic health conditions, or connect with medical professionals, using  consumer-directed apps and other technologies to  help people  live healthier lifestyles through fitness, nutrition, and wellness monitoring;
  • Enabling better and more efficient clinical practice and decision making through decision support software and technologies to assist in making diagnoses and developing treatment options; managing, storing, and sharing health records; and managing schedules and workflow;
  • Helping to address public health crises, such as the opioid epidemic that is devastating many American communities. In fact, FDA conducted a prize competition to encourage the development of a mobile app to help connect opioid users experiencing an overdose with nearby carriers of the prescription drug naloxone for emergency treatment.

For these and other digital technologies to take hold and reach their fullest potential, it is critical that FDA be forward-leaning in making sure that we have implemented the right policies and regulatory tools, and communicated them clearly, to encourage safe and effective innovation. In this rapidly changing environment, ambiguity regarding how FDA will approach a new technology can lead innovators to invest their time and resources in other ventures. To encourage innovation, FDA should carry out its mission to protect and promote the public health through policies that are clear enough for developers to apply them on their own, without having to seek out, on a case-by-case basis, FDA’s position on every individual technological change or iterative software development.

Congress has already taken a major step to advance these goals in the 21st Century Cures Act. Expanding upon policies advanced by FDA’s Center for Devices and Radiological Health (CDRH), the Act revised FDA’s governing statute to, among other things, make clear that certain digital health technologies—such as clinical administrative support software and mobile apps that are intended only for maintaining or encouraging a healthy lifestyle—generally fall outside the scope of FDA regulation. Such technologies tend to pose low risk to patients but can provide great value to the health care system. FDA, led by CDRH, is working to implement the digital health provisions of the 21st Century Cures Act and, in the coming months, will be publishing guidance to further clarify what falls outside the scope of FDA regulation and to explain how the new statutory provisions affect pre-existing FDA policies.

FDA will provide guidance to clarify our position on products that contain multiple software functions, where some fall outside the scope of FDA regulation, but others do not. In addition, FDA will provide new guidance on other technologies that, although not addressed in the 21st Century Cures Act, present low enough risks that FDA does not intend to subject them to certain pre-market regulatory requirements. Greater certainty regarding what types of digital health technology is subject to regulation and regarding FDA’s compliance policies will not only help foster innovation, but also will help the agency to devote more resources to higher risk priorities.

In addition to these efforts, we are also announcing today a new initiative that FDA is undertaking. This fall, as part of a comprehensive approach to the regulation of digital health tools and in collaboration with our customers, FDA will pilot an entirely new approach toward regulating this technology. This will be the cornerstone to a more efficient, risk-based regulatory framework for overseeing these medical technologies.

While the pilot program is still being developed, we are considering whether and how, under current authorities, we can create a third party certification program under which lower risk digital health products could be marketed without FDA premarket review and higher risk products could be marketed with a streamlined FDA premarket review. Certification could be used to assess, for example, whether a company consistently and reliably engages in high quality software design and testing (validation) and ongoing maintenance of its software products. Employing a unique pre-certification program for software as a medical device (SaMD) could reduce the time and cost of market entry for digital health technologies.

In addition, post-market collection of real-world data might be able to be used to support new and evolving product functions. For example, product developers could leverage real-world data gathered through the National Evaluation System for health Technology (NEST) to expedite market entry and subsequent expansion of indications more efficiently. NEST will be a federated virtual system for evidence generation composed of strategic alliances among data sources including registries, electronic health records, payer claims, and other sources. The Medical Device Innovation Consortium (MDIC), a 501(c)(3) public-private partnership, is serving as an independent coordinating center that operates NEST. In the coming weeks, MDIC will announce the establishment of a Governing Committee for the NEST Coordinating Center comprised of stakeholder representatives of the ecosystem, such as patients, health care professionals, health care organizations, payers, industry, and government. Although FDA does not own or operate NEST, we have been establishing strategic alliances among data sources to accelerate NEST’s launch with the initial version of a fully operational system anticipated by the end of 2019.

Applying this firm-based approach, rather than the traditional product-based approach, combined with leveraging real-world evidence, would create market incentives for greater investment in and growth of the digital health technology industry. Such processes could enable developers to deploy new or updated software more rapidly and would help FDA to better focus our resources.

Through these and other steps, FDA will help innovators navigate a new, modern regulatory process so that promising, safe and effective developments in digital health can advance more quickly and responsibly, and Americans can reap the full benefits from these innovations. These efforts are just one part of a much broader initiative that FDA is currently undertaking to advance policies that promote the development of safe and effective medical technologies that can help consumers improve their health. Our goal is to make sure that FDA has the most modern and efficient regulatory approaches when it comes to evaluating new, beneficial technologies.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

How Creative FDA Regulation Led to First-in-the-World Approval of a Cutting-Edge Heart Valve

By: Jeffrey Shuren, M.D., J.D., and Bram Zuckerman, M.D.

Jeffrey Shuren

Jeffrey Shuren, M.D., J.D., Director of FDA’s Center for Devices and Radiological Health

Nearly six years ago FDA approved an artificial transcatheter heart valve (THV) to treat patients having severe symptoms and life-threatening heart problems such as fainting, chest pain, heart failure, irregular heart rhythms, or cardiac arrest, because one of the valves in their heart (the aortic valve) was no longer working properly and they were too sick for surgery.

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of these patients.  But the U.S. wasn’t the trendsetter – in fact, it was the 42nd country to approve the first TAVR device, the Edwards Sapien THV.

Since that approval, FDA has sharpened its focus on patient access to innovative medical devices. On June 5th, 2017, FDA became the first regulatory body in the world to approve the most recent iteration of the Sapien valve, the Sapien 3, to treat high-risk patients whose surgically-placed aortic or mitral bioprosthetic valves were old and worn out. The Sapien 3 is intended to slip into these valves using a so-called “valve-in-valve” option, a procedure that can be done without open heart surgery through a patient’s blood vessel or a small cut in the chest.

Sapien 3

SAPIEN 3 Heart Valve Device

To narrow the gap from 42nd to first required creativity and commitment. The FDA Heart Valve Review Team first streamlined FDA’s expectations for nonclinical testing – something that had been a huge rate-limiting factor for translating innovative TAVR devices from bench to bedside. We became more consistent, predictable, and transparent about our expectations, which helped significantly reduce the total time to initiating clinical studies. And we worked closely with the industry on creative clinical trial designs and the use of other sources of clinical evidence that could demonstrate that the device is safe and effective when used in the intended patient population.

Bram Zuckerman

Bram Zuckerman, M.D., FDA’s Director, Division of Cardiovascular Devices, Center for Devices and Radiological Health

This latest approval is the most recent example of our increasing use of real-world evidence, made possible in this case by the Transcatheter Valve Therapy (TVT) Registry, a partnership of the American College of Cardiology and the Society of Thoracic Surgeons. The TVT registry collects clinical data on the performance of transcatheter valve replacement procedures performed in the U.S. once a product goes to market – including both on-label and off-label uses – making it possible, under certain circumstances, to accumulate more data faster, without the need for costly and time-consuming formal clinical trials.

Some 100,000 patients have received TAVR since FDA’s first approval in 2011, including more than 600 patients for what were then off-label, valve-in-valve uses. FDA relied on real-world evidence to evaluate the benefits and risks of this off-label use — such as the safety of the procedure, the function of the valve, and the improvement of patient symptoms – to approve the new indication for Sapien 3. This is a promising approach for the expansion of indications for other devices, provided robust registries are available.  FDA is working to broaden and improve the opportunities to leverage real-world evidence for many types of devices through the establishment of the National Evaluation System for health Technology, or NEST, which will integrate data from clinical registries, electronic health records, and medical billing claims to gather more comprehensive evidence of medical device safety and effectiveness.

CDRH Sapien 3 Reviewers

John C. Laschinger, M.D., Medical Officer, and Changfu Wu, Ph.D., Lead Reviewer, Members of FDA’s Structural Heart Devices Branch

And we’re not stopping here. U.S. medical device companies have long been accustomed to going overseas to conduct early feasibility studies (including first-in-human studies) for new heart valve devices, securing marketing authorization in other countries, and then returning to the U.S. for pivotal clinical trials before FDA approval. We’re trying to break that model with a new program that encourages early feasibility studies for new medical devices in the United States. These studies allow for early clinical evaluation of devices to provide proof of principle and initial clinical safety data, and may be appropriate early in device development when clinical experience is necessary because nonclinical testing methods are not available or adequate to provide the information needed to advance the developmental process.

Many heart valve device companies have already responded. Rather than traveling to other countries, they’re staying put in the U.S. for their early feasibility studies, saving on travel costs, enjoying more convenient communications with the investigators, and benefiting from early interactions with FDA.

These steps – along with our other reforms – will ensure that cutting-edge treatments get to U.S. patients as quickly as possible.

Jeffrey Shuren, M.D., J.D., is FDA’s Director of the Center for Devices and Radiological Health

Bram Zuckerman, M.D., is FDA’s Director, Division of Cardiovascular Devices, Center for Devices and Radiological Health

#IAmHHS: Fighting Misleading Prescription Drug Ad Claims

By: Mike Sauers

These days, you can hardly turn a magazine page, watch a TV show or sit in the lobby of your doctor’s office without seeing advertising and promotions for prescription drugs. They’re everywhere you go. And they tend to be impressive and reassuring. But are they accurate?

A big part of my career at the Department of Health and Human Services has been about helping to make sure those ads are truthful and not misleading.

At the FDA, I’m staff supervisor of the Office of Prescription Drug Promotion’s (OPDP) Advertising and Promotion Policy Staff, which helps develop policies for advertising and promotion of prescription drugs across the United States. In my job, I help make sure that drug companies’ communications of information about their prescription drugs to consumers and healthcare professionals are truthful and not misleading. In my role, I also help to make sure our stakeholders in the pharmaceutical industry understand the rules of the road.

I started my career as a drug representative in Philadelphia, promoting a pharmaceutical company’s drugs. It was a good job in a great industry.

But to be 100 percent honest, it was not personally fulfilling and I decided to pursue public service. I went back to school, earned a master in public policy from Georgetown Public Policy Institute (now McCourt School of Public Policy), and then joined HHS as a budget analyst in the Office of the Secretary through the Presidential Management Fellows Program. Working in the Office of the Secretary gave me the chance to see many of the incredible programs that HHS operates to help improve the lives of Americans on a daily basis.

After my fellowship ended, I decided to continue my HHS career at FDA by focusing on a subject area I knew very well: prescription drug advertising.

I became a regulatory review officer in OPDP and looked at specific ads aimed at doctors or consumers to make sure the claims were truthful and not misleading.

That work prepared me to move into my current role in OPDP where I lead the group that helps develop industry-wide policies for all prescription drug advertising and promotion. One of the highlights of my government service was co-creating the Bad Ad Program, an initiative designed to educate health care providers about misleading prescription drug promotion and to make it easier for them to report this activity to the agency.

It’s an awesome responsibility and very challenging, but I truly believe I am making a difference by helping to ensure that advertisements provide accurate and truthful information about the effectiveness and potential risks of prescription drugs.

You just can’t quantify the type of job satisfaction that comes from knowing that every day you come to work, you have the opportunity to make an impact.

I’m Mike Sauers. I work for the FDA and I am HHS.

Mike Sauers is a staff supervisor in FDA’s Office of Prescription Drug Promotion, Center for Drug Evaluation and Research

Mike is one of more than 79,000 people who make HHS run every day. You can share his story and see others on Twitter and Facebook using #IAmHHS.

In cancer treatment, there’s more than one way to measure patient benefit

By: Richard Pazdur, M.D.

We all want a cure for cancer. But the reality is that advances in cancer treatment rarely come in one big discovery, but rather with the continued step-by-step progress in developing new therapies. Currently, a few cancers—such as childhood leukemia and testicular cancer—can be cured. There are many ways of evaluating cancer therapies, including an improvement in overall survival, stabilizing the disease, and reducing tumor burden and tumor-related symptoms. Over the years, we have discussed with many patients facing serious and life-threatening diseases how to evaluate cancer treatments. The patients have told us there is a need for flexibility in our evaluation process.

Dr. Richard PazdurBefore a new drug is approved, FDA evaluates clinical trials in which the drug is tested in patients. We hope that the study will show a result, or endpoint, that helps us understand if the drug is safe and effective. When evaluating drugs that treat life-threatening illnesses like cancer, the risk-benefit analysis may involve weighing relatively higher risks against relatively smaller benefits.

The gold standard for determining benefit from a new cancer drug traditionally has been a randomized controlled study that demonstrates an improvement in overall survival, or OS. This is a measure of how much longer patients live who take the drug compared with patients who take another drug. An overall survival endpoint clearly demonstrates the drug’s value in extending a patient’s life.

But achieving an improvement in overall survival may not always be possible. Some cancers grow very slowly, so it might take many years for a trial to evaluate whether a potential new drug helps people live longer. Many oncology drugs target specific mutations in the tumor and there may be a limited number of patients with the mutation. Because of the small number of patients, randomized studies evaluating OS may not be possible. Also, many patients in the trial may be taking additional therapies at the time their disease progresses. This may make it difficult to accurately assess the new drug’s effect on overall survival.

When emerging data shows that a new drug demonstrates substantial benefit compared to available drugs, it may not be possible to conduct a randomized trial with certain endpoints comparing the new drug to a standard therapy with modest benefit. This is known as loss of equipoise.

Endpoints other than overall survival can shorten the duration of clinical trials so that drugs can be available sooner to patients. These alternative endpoints include progression-free survival—a measurement of how long a drug may have prevented the cancer from getting worse—and overall response rate—an evaluation of the portion of patients in the trial whose tumor size was reduced by a treatment.

Thousands of patients who previously had few therapeutic options available have already benefited from cancer therapies that were approved based on alternative endpoints, including those with renal cell carcinoma, Merkel cell carcinoma, medullary thyroid cancer, gastrointestinal stromal tumor, metastatic basal cell carcinoma, pancreatic neuroendocrine tumor, multiple myeloma, chronic myelogenous leukemia, chronic lymphocytic leukemia, and certain types of lung cancer.

We’ve held many advisory committee meetings and have heard directly from patients who believe that delaying the growth of cancer or reducing the cancer’s size are of benefit to them, since these endpoints may relate to reduced symptoms and the ability to carry on with many daily activities.

Patients have benefited, too, from the Breakthrough Therapy Designation, which was established in the FDA Safety & Innovation Act of 2012 to expedite the development and review of transformative therapies that show great promise in early clinical trials, compared to available therapy. Drugs that are designated as breakthrough therapies receive more intensive FDA consultation throughout their development period and may also qualify for other expedited development programs such as fast track and priority review. Many oncology drugs have breakthrough therapy designations, and this designation enables FDA to expedite the review of therapies that may meet patient’s needs.

There is still much more to learn about what patients need and expect from their cancer drugs. Our patient-focused drug development program has sponsored daylong meetings with patients and caregivers to discuss their views on a specific disease. A patient at our breast cancer meeting said: “As long as I can live my life and continue to work full-time, that is my goal.”

Based on these and other patient interactions, we are actively investigating ways to incorporate the patient’s experience and quality of life in benefit-risk assessments of new cancer treatments.

It’s also important to recognize that the drug approval process does not end with the drug’s approval. This is just the beginning. By looking at real-world use of the drug in the broader patient population, we may learn more about new uses for the drug, previously unknown side effects, and how different subsets of patients may respond. This information may be added to the drug labeling and can help inform our future regulatory decisions.

Our ultimate goal is to approve products that make a meaningful difference for patients and their loved ones living with the devastating effects of their disease.

Richard Pazdur, M.D., is FDA’s Director, Oncology Center of Excellence

A Year Later, FDA Is Better and Stronger in Protecting Consumers from Unsafe Foods

By: William Correll and Douglas Stearn

We have made dramatic changes in our response to complex, potentially high-risk food safety situations that may be difficult to address quickly.

Bill Correll

William Correll is the director of the Office of Compliance in FDA’s Center for Food Safety and Applied Nutrition

Almost a year ago, we heard concerns that FDA was not doing enough to ensure that companies promptly and effectively initiate recalls of potentially dangerous food products in those rare instances in which a firm is not responding appropriately. FDA has always been committed to protecting the U.S. food supply, which is among the safest in the world, but we recognized the need to strengthen certain compliance and enforcement strategies in cases made more complex by factors that include the nature of the product, the scope of available evidence, and the company’s response.

And so, we took to heart issues raised by the Office of the Inspector General at the Department of Health and Human Services and have used them as a catalyst for change.

Doug Stearn

Douglas Stearn is the director of the Office of Enforcement and Import Operations in FDA’s Office of Regulatory Affairs

Not just change, but a culture change. At the heart of this change was the creation of SCORE, which stands for Strategic Coordinated Oversight of Recall Execution. We are the co-chairs of this group of senior leaders that gets involved in the most challenging food safety situations, working with field staff and district offices to evaluate the range of available options and deciding quickly what action to take. For example, SCORE can drive agency action if the company is not acting aggressively enough to recall their products, and can push for use of administrative or judicial remedies.

We now have FDA compliance, enforcement, and field leaders at the table, reviewing cases every week or more often, as needed. Science and medical officers are engaged in the conversation, as are field investigators, and lawyers.

What is the right action? What should FDA be doing? What should the company be doing? These are real time, high-level decisions, with the result being that field investigators are now empowered to immediately engage senior leaders in overcoming obstacles to the rapid removal from the marketplace of foods that are, or could be, contaminated. The process of raising a food safety issue up within the agency has thus been streamlined to put FDA leaders and field staff on the same page right away.

Among the thousands of product recalls that FDA oversees each year, SCORE has played a critical role in addressing the most significant risks to the public. SCORE’s involvement has ensured that multiple recalls involving high-risk products have been initiated, has improved tactical planning, and sped the use of enforcement tools when necessary.

In the past year, SCORE has been involved in cases that included lead contamination of dietary supplements, Salmonella contamination of powdered milk, E.coli O157:H7 in soy nut butter, and Listeria monocytogenes in hummus, soft cheese and smoked fish. In addition to facilitating recalls and import alerts for the detention of products entering the United States, SCORE initiated or expedited the process for suspending the registration of two food facilities, actions that block the facilities’ ability to distribute food.

The creation of SCORE is not the only change we’ve made. There is a new recall audit plan to assess the adequacy of a company’s recall efforts and more than two dozen procedural and policy changes that have either happened or are in the works. These include an expansion of public notification of recalls that may affect the most vulnerable consumers, including the very young and elderly.

Most companies readily initiate a voluntary recall when faced with evidence that their product is unsafe. But when there is an obstacle, we are determined to overcome it, using all of the tools we have available. We’ve always taken our job seriously and we’ve shown over the past year that we will use every opportunity to do it better.

William Correll is the director of the Office of Compliance in FDA’s Center for Food Safety and Applied Nutrition

Douglas Stearn is the director of the Office of Enforcement and Import Operations in FDA’s Office of Regulatory Affairs

FDA Commissioner Asks Staff for ‘More Forceful Steps’ to Stem the Opioid Crisis

By: Scott Gottlieb, M.D.

As Commissioner, my highest initial priority is to take immediate steps to reduce the scope of the epidemic of opioid addiction. I believe the Food and Drug Administration continues to have an important role to play in addressing this crisis, particularly when it comes to reducing the number of new cases of addiction.

Dr. Scott GottliebToday, I sent an email to all of my colleagues at FDA, sharing with them the first steps I plan to take to better achieve this public health goal. With this, my first post to the FDA Voice blog, I also wanted to share my plans with you.

I believe it is within the scope of FDA’s regulatory tools – and our societal obligations – to take whatever steps we can, under our existing legal authorities, to ensure that exposure to opioids is occurring under only appropriate clinical circumstances, and for appropriate patients.

Patients must be prescribed opioids only for durations of treatment that closely match their clinical circumstances and that don’t expose them unnecessarily to prolonged use, which increases the risk of opioid addiction. Moreover, as FDA does in other contexts in our regulatory portfolio, we need to consider the broader public health implications of opioid use. We need to consider both the individual and the societal consequences.

While there has been a lot of good work done by FDA to date, and many people are working hard on this problem, I have asked my FDA colleagues to see what additional, more forceful steps we might take.

As a first step, I am establishing an Opioid Policy Steering Committee that will bring together some of the agency’s most senior career leaders to explore and develop additional tools or strategies FDA can use to confront this crisis.

I have asked the Steering Committee to consider three important questions. However, the Committee will have a broad mandate to consider whatever additional questions FDA should be seeking to answer. The Committee will solicit input, and engage the public. I want the Committee to go in whatever direction the scientific and public health considerations leads, as FDA works to further its mandate to confront the crisis of opioid addiction.

The initial questions I have tasked the Steering Committee to answer are:

  1. Are there circumstances under which FDA should require some form of mandatory education for health care professionals, to make certain that prescribing doctors are properly informed about appropriate prescribing recommendations, understand how to identify the risk of abuse in individual patients, and know how to get addicted patients into treatment?
  2. Should FDA take additional steps, under our risk management authorities, to make sure that the number of opioid doses that an individual patient can be prescribed is more closely tailored to the medical indication? For example, only a few situations require a 30-day supply. In those cases, we want to make sure patients have what they need. But there are plenty of situations where the best prescription is a two- or three-day course of treatment. So, are there things FDA can do to make sure that the dispensing of opioids more consistently reflects the clinical circumstances? This might require FDA to work more closely with provider groups to develop standards for prescribing opioids in different clinical settings.
  3. Is FDA using the proper policy framework to adequately consider the risk of abuse and misuse as part of the drug review process for the approval of these medicines? Are we doing enough when we evaluate new opioid drugs for market authorization, and do we need additional policies in this area?

These are just some of the questions I will be asking this new Steering Committee to consider right away, given the scope of the emergency we face. In the coming days, I’ll continue to work closely with the senior leadership of FDA. I want to know what other important ideas my colleagues at FDA may have, so that we can lean even further into this problem, using our full authorities to work toward reducing the scope of this epidemic.

Despite the efforts of FDA and many other public health agencies, the scope of the epidemic continues to grow, and the human and economic costs are staggering. According to data from CDC and SAMHSA, nearly 2 million Americans abused or were dependent on prescription opioids in 2014, and more than 1,000 people are treated in emergency departments each day due to misusing prescription opioids.

Opioid overdose deaths involving prescription opioids have quadrupled since 1999. In 2015, opioids were involved in the deaths of 33,091 people in the United States. Most of these deaths – more than 22,000 (about 62 people per day) – involved prescription opioids.

We know that the majority of people who eventually become addicted to opioids are exposed first to prescription opioids. One recent study found that in a sample of heroin users in treatment for opioid addiction, 75% of those who began abusing opioids in the 2000s started with prescription opioid products.

This March, a study published in CDC’s Morbidity and Mortality Weekly Report, found that opioid-naïve patients who fill a prescription for a one-day supply of opioids face a 6% risk of continuing their use of opioids for more than one year. This study also found that the longer a person’s first exposure to opioids, the greater the risk that he or she will continue using opioids after one, or even three years. For example, when a person’s first exposure to opioids increases from one day to 30 days, that person’s likelihood of continuing to use opioids after one year increases from 6% to about 35%.

Working together, we need to do all we can to get ahead of this crisis. That’s why we’ll also be soliciting public input, through various forums, on what additional steps FDA should consider. I look forward to working closely with my FDA colleagues as we quickly move forward, capitalizing on good work that has already been done, and expanding those efforts in novel directions. I will keep you updated on our work as we continue to confront this epidemic.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

FSMA Collaborative Training Forum: ‘Educate Before and While We Regulate’

By: Donald Kautter Jr. and Stephen Hughes

“We will educate before and while we regulate.”

That’s been a mantra for FDA as the rules that implement the FDA Food Safety Modernization Act (FSMA) have taken shape. Making sure that food producers understand the new requirements and have the knowledge they need to meet them is key to the success of this effort to prevent illnesses caused by domestic and imported foods.

However, FDA recognized early on that one size won’t fit all when it comes to training and that a variety of training options and delivery formats would be necessary to meet needs shaped by product, region, size, and other factors.

Enter the FSMA Collaborative Training Forum, convened in partnership by FDA and the U.S. Department of Agriculture. The forum is made up of the agencies, centers, associations, universities and others funded by FDA and USDA through cooperative agreements and grants to develop and deliver FSMA training. Communication between them is important to minimize overlap and improve coordination and efficiency.

The forum held its first meetings in April. Participants laid the groundwork for a vibrant collaboration that will support diverse food producers who are preparing to meet the FSMA standards.

photo of various produceThe diversity of the food producers is matched by the diverse community of training providers. The forum includes representatives of the public-private alliances funded primarily by FDA as a resource for industry: the Produce Safety, Food Safety Preventive Controls and Sprout Safety Alliances. It also includes the National Coordination Center (NCC) and four Regional Centers that were created in a partnership between FDA and USDA’s National Institute of Food and Agriculture to provide training opportunities for farmers, small food processors, and small produce merchant wholesalers.

In addition, the National Farmers Union Foundation and the University of Arkansas-Fayetteville, which entered into cooperative agreements with FDA to develop training curricula and delivery for local and tribal food producers, respectively, are among the training providers. The National Association of State Departments of Agriculture, which is engaged in a cooperative agreement with FDA to plan implementation of the produce safety rule, is also a member of the forum.

Last, but not least, there’s the Joint Institute for Food Safety and Applied Nutrition (JIFSAN), a partnership between the FDA and the University of Maryland that is focused on increasing global knowledge of effective food safety practices.

These first meetings focused on the new produce safety standards, which set science and risk-based requirements for the production of fruits and vegetables. All of these training programs are up and running, although they’re at different stages of development. But no matter where they are in this journey, they’re working together. The NCC, for example, has been coordinating with regional centers monthly and, through forum discussions, is now including those working with local and tribal food producers.

Everyone wants to measure success and to determine that they’re reaching the right audiences. Examining metrics and coordinating data will be a priority going forward so that all training providers have the same sense of what’s working and what isn’t.

Group members shared their experiences and knowledge in these first meetings. For example, a common experience has been that growers don’t use online training as much as other food producers. Lack of access to the internet or insufficient bandwidth to run the programs are the issues for some. We’ll reshape how the training is offered based on feedback as more data are collected.

This is just the beginning. There are plans to work with forum participants to post resource materials in a way that’s accessible to food producers around the world.

This is a great example of good governance – working in partnership and communicating across organizational boundaries to support those who will do the important work of strengthening our food safety system. The forum will meet every few months to help ensure that training programs meet the needs of those who must understand the new FSMA standards, no matter their size, nature, or location.

Donald Kautter Jr. is a Consumer Safety Officer in FDA’s Division of Plant Products and Beverages.

Stephen Hughes is a Team Leader in FDA’s Produce Safety Network.

They are the FDA co-leads of the FSMA Collaborative Training Forum, and partner closely with USDA to facilitate the forum.

‘Radiating Shoe Sales’

By: Vanessa Burrows

Since the discovery of X-rays in the late 19th century, the technology has enhanced health care in a variety of ways. Like many cutting-edge scientific developments, however, it also has inspired uses of uncertain therapeutic value. That was the case with the shoe-fitting fluoroscope, the subject of the latest episode of FDA’s history video series.

Vanessa Burrons

Vanessa Burrows, FDA Historian, next to a shoe-fitting fluoroscope

Marketed as a scientific method for optimizing shoe fit, the fluoroscope appeared in shoe stores nationwide from the 1920s to the 1960s. But the machines not only didn’t do what they promised, they also exposed children, their parents, and store clerks to unhealthy doses of radiation.

In the late 1940s, scientists and regulators began to raise serious concerns about the dangerous levels of radiation. Over the next two decades, individual states gradually took action to either ban or restrict the use of the device.

By the 1970s, concerns grew about radiation emitted from common appliances, such as televisions and microwave ovens. And in 1971, FDA was given authority to regulate radiation-emitting devices. The agency continues this oversight, working to protect consumers from harmful novelty devices like the shoe-fitting fluoroscope. FDA also sets standards for medical imaging, surgical and therapeutic equipment, security systems, and consumer products – all for the protection of the health of American consumers.

We hope you enjoy your visit to FDA’s HistoryVault.

Vanessa Burrows is an FDA Historian