We Moved Forward on Many Fronts This Year

By: Margaret A. Hamburg, M.D.

At the FDA, the agency that I’ve had the privilege to lead for the past five years, I am gratified to report that we have a lot to be proud of this year. In fact, this past year’s accomplishments on behalf of public health have been as substantial as any in FDA’s recent history.

Margaret Hamburg, M.D.We moved significantly forward, for example, in creating a system that will reduce foodborne illness, approving novel medical products in cutting-edge areas of science, and continuing to develop our new tobacco control program. We worked successfully with Congress and with regulated industry to reach agreement on a number of difficult issues, while continuing to use the law to the full extent possible to protect consumers and advance public health.

While there were many significant actions and events to recognize, below are some of the highlights of 2013.

In the foods area, there were many new actions this year that will have a long-standing impact on improving our food supply for consumers. Throughout the year we have been proposing new rules to reach the goals set forth by the FDA Food Safety Modernization Act (FSMA). These science-based standards will help ensure the safety of all foods produced for our market, whether they come from the U.S. or from other countries.

We also took important steps towards reducing artery-clogging trans fat in processed foods, and understanding the health impact of arsenic in rice. With a final rule that defines when baked goods, pastas and other foods can be considered free of gluten, people with celiac disease can have confidence in foods labeled “gluten free.” And we are studying whether adding caffeine to foods may have an effect on the health of young people and others.

There have likewise been many accomplishments in advancing the safety and effectiveness of medical products. We worked closely with Congress on the recently enacted Drug Quality and Security Act, which contains important provisions relating to the oversight of human drug compounding. The law also has provisions to help secure the drug supply chain so that we can better help protect consumers from the dangers of counterfeit, stolen, contaminated, or otherwise harmful drugs.

Using tools provided by last year’s landmark Food and Drug Administration Safety and Innovation Act (FDASIA), we are continuing to improve the speed and efficiency of medical product reviews, including those involving low-cost, high quality generic drugs and innovative new medical devices. The average number of days it takes for pre-market review of a new medical device has been reduced by about one-third since 2010. The percentage of pre-market approval applications that we approve has increased since then, after steadily decreasing each year since 2004.

We launched a powerful new tool to accelerate the development and review of “breakthrough therapies,” allowing FDA to expedite development of a drug or biologic (such as a vaccine) if preliminary clinical evidence indicates that it may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. This offers real opportunities to get promising drugs more quickly to patients who need them. In fact, using this new approach, FDA recently approved two advanced treatments for rare types of cancer and one for hepatitis C. We have also strengthened efforts to ensure product quality, increased protection of the drug supply chain, and reduced drug shortages.

We confronted the growing misuse of powerful opioid pain relievers by advising manufacturers on how to make these drugs harder to abuse with formulations that are more difficult to crush for inhalation or dissolve for injection. And we recommended that hydrocodone combination products be subject to stricter controls to help prevent abuse. 

We took an important step towards fighting the development of antibiotic-resistant bacteria by implementing a voluntary plan to phase out the use of antibiotics to enhance the growth of food-producing animals, and to move any remaining therapeutic uses of these drugs under the oversight of a licensed veterinarian. So-called “production” use is considered a contributing factor in the development of bacteria that are resistant to the antibiotics used in human medical treatment.

In many areas of our work we are supporting the emerging field of personalized medicine. Advances in sequencing the human genome and greater understanding of the underlying mechanisms of disease, combined with increasingly powerful computers and other technologies, are making it possible to tailor medical treatments to the specific characteristics, needs, and preferences of individual patients.

Many cancer drugs today are increasingly used with companion diagnostic tests that can help determine whether a patient will respond to the drug based on the genetic characteristics of the patient’s tumor. In May, FDA approved two drugs and companion diagnostic testing for the treatment of certain melanoma patients with particular genetic mutations.

Advances in science and technology are also seen in the creation of new medical devices. For example, 3-D printing - the making of a three-dimensional solid object from a digital model – was once considered the wave of the future. But in February, FDA cleared for marketing a device created by 3-D printing – a plate used in a surgical repair of the skull that is built specifically for the individual patient.

While we have worked hard to get therapies to patients, we are at the same time using the tools available to us to remove unsafe and dangerous products from the market. In November, we used new enforcement tools provided by the food-safety law to act quickly in the face of a potential danger to public health presented by certain OxyElite Pro products. These supplements had been linked to dozens of cases of acute liver failure and hepatitis. After FDA took action, the manufacturer agreed to recall and destroy the supplements.

Finally, we made significant progress in implementing the letter and spirit of the Family Smoking Prevention and Tobacco Control Act. We have signed contracts with numerous state and local authorities to enforce the ban on the sale of tobacco to children and teens; conducted close to 240,000 inspections; and written more than 12,100 warning letters to retailers. And, in the first quarter of 2014 we will launch a public education campaign aimed at reducing the number of young people who use tobacco products.

All of us take great pride in the skill and vigor with which we overcame the year’s challenges and new demands. And so, as the year draws to a close, I extend my gratitude to the employees at the FDA who work tirelessly on behalf of the American public year in and year out. To all of our stakeholders, my heartfelt wishes for a joyous holiday season and a safe and healthy 2014.

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

Driving Innovation Is a Key Part of Our Mission

By: Margaret A. Hamburg, M.D.

Ensuring the safety of the food supply and the safety and effectiveness of drugs, devices and biologics has always been at the core of FDA’s responsibility to protect the public health – and always will be.

Margaret Hamburg, M.D.But what is often lost or neglected in discussions about FDA’s vigilance on behalf of consumer and patient safety is how this kind of oversight and regulation, when done right, can be a key driver of innovation throughout society. Whether it involves the development of some remarkable new drug or oversight of a particular product, the addition of rigorous regulatory science from FDA helps to safeguard the safety and effectiveness of innovative new products; ensures that these scientific achievements quickly reach their full potential; and builds a pathway for ongoing innovation. That’s why we continue to adapt and change regulatory policies in response to – and in anticipation of – scientific opportunities so that they can best be harnessed to improve health and medical care.

There are many recent examples of this thoughtful approach to innovative products. For instance, we have put in place a new breakthrough pathway to market for promising drugs that may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. Using this new approach, we have already approved two treatments for rare types of cancer and one for hepatitis C. And there may be considerably more in the weeks and months ahead because many companies have expressed interest. So far we have received 119 requests for designation and granted 35.

In a very different realm, another example is mobile medical apps. We took a measured and sensible approach that promotes innovation when we finalized guidance related to these devices earlier this year. Although many mobile apps pertain to health, CDRH intends to focus its oversight on a very small subset of those mobile apps that are medical devices. We have called that subset “mobile medical apps” and we are approaching their regulatory oversight within a risk-based framework. We believe this approach will promote innovation while protecting patient safety by focusing on those mobile apps that pose greater risk to patients.

As explained in the final mobile medical application guidance, our regulation of software as a medical device – and a mobile app is software – is based on risk and functionality, and that functionality should be treated the same regardless of the platform on which it is used. For example, an electrocardiography device – an ECG machine – that measures heart rhythms to help doctors diagnose patients is still an ECG machine regardless of whether it is the size of a bread box or the size of a smartphone. The risks it poses to patients and the importance of assuring for practitioners and patients that it is safe and effective are essentially the same.

And, just a few weeks ago, we authorized for marketing four innovative gene-sequencing devices. Two of these products comprise a system that allows laboratories to develop clinical tests that can look at a person’s genetic makeup and detect abnormalities that could be responsible for illness. FDA realized the innumerable uses of these systems from the outset, and rather than focusing on specific diseases or areas of the genome, we took a tool-based regulatory approach. We assessed whether the devices overall measure what they are intended to measure accurately, reliably and precisely so that there can be greater confidence in the test results. These types of genome sequencers represent a significant step forward in the ability to generate genomic information that may ultimately improve patient care.

Each of the new medical products we approve and usher to the market involves a balancing of risks and benefits, which is based on study and evaluation of hard data and the best available science. It is a huge responsibility that FDA is charged with, nowhere more so than when dealing with unfolding technologies that offer enormous potential – but that also may present real risks for people and their health.

We know there will be new and continuing challenges that arise with additional technological developments and advancements in science and medicine. This is why FDA’s regulatory role in these emerging areas continues to develop as well, sometimes even as the technologies themselves are taking shape

But our goal remains constant – to protect the public health through smart regulation that helps to enhance innovation and ensure that new medical technologies have real value to the people who will use them, and that they are used effectively and safely to address their needs.

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

Personalized Medicine: The Future is Now

By Margaret A. Hamburg, M.D.

Margaret Hamburg, M.D.The difference between science and science fiction is a line that seems ever harder to distinguish, thanks in part to a host of astonishing advances in medical science that are helping to create a new age of promise and possibility for patients.

Today cancer drugs are increasingly twinned with a diagnostic device that can determine whether a patient will respond to the drug based on their tumor’s genetic characteristics; medical imaging can be used to identify the best implantable device to treat a specific patient with clogged coronary arteries; and progress in regenerative medicine and stem cell therapy using a patient’s own cells could lead to the replacement or regeneration of their missing or damaged tissues. Given these trends, the future of medicine is rapidly approaching the promising level of care and cure once imagined by Hollywood in futuristic dramas like Star Trek.

But these examples are not science fiction. They are very real achievements that demonstrate the era of “personalized medicine” where advances in the science of drug development, the study of genes and their functions, the availability of increasingly powerful computers and other technologies, combined with our greater understanding of the complexity of disease, makes it possible to tailor treatments to the needs of an individual patient. We now know that patients with similar symptoms may have different diseases with different causes. Individual patients who may appear to have the same disease may respond differently (or not at all) to treatments of that disease.

FDA has been playing a critical role in the growth of this new era for a number of years. Even before I became FDA Commissioner the agency was creating the organizational infrastructure and putting in place the regulatory processes and policies needed to meet the challenges of regulating these complex products and coordinating their review and oversight. It has been my pleasure to serve at FDA during this next exciting period and to help ensure that the agency continues to prioritize this evolution by anticipating, responding to, and encouraging scientific advancements.

I am very pleased to be able to present a new report by FDA as part of our ongoing efforts in this field. Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development describes many of the exciting developments and looming advances in personalized medicine, lays out the historical progress in this field, and examines FDA’s regulatory role: from ensuring the availability of safe and effective diagnostic devices, to addressing the challenges of aligning a drug with a diagnostic device, to post-market surveillance.

Outside collaboration and information sharing is essential for this field to flourish. On Tuesday, the American Association for Cancer Research and AdvaMedDX held a fruitful daylong conversation on personalized medicine to treat cancer. I was one of the speakers, participating in a conversation with Dr. Francis Collins, the head of the National Institutes of Health. Our discussion focused in part on current status of drug and diagnostic co-development and the challenges and potential of whole genome sequencing, where data can be collected on a patient’s entire genetic makeup at a reasonable cost in a reasonable amount of time.

FDA is committed to fostering these cooperative efforts, as it will require the full force of government, private industry, academia and other concerned stakeholders to maximize our efforts and fully realize the promise of personalized medicine. Our new report outlines that commitment, and helps chart the way forward so that more people can live long and prosper.

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

FDA Uses Web Tool to Better the Odds for Food Safety

By: Ted Elkin

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

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

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

How does FDA-iRISK work?

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

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

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

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

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

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

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

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

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

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

Looking Back and Looking Ahead: FDASIA’s One Year Anniversary

By: Margaret A. Hamburg, M.D. 

One year ago today President Obama signed into law the Food and Drug Administration Safety and Innovation Act, bipartisan legislation reauthorizing user fee programs for innovator drugs and medical devices and establishing two new user fee programs for generic drugs and biosimilar biological products. 

Margaret Hamburg, M.D.Coming at a time of continuing budget restraints, this steady and reliable source of funding is essential to support and maintain FDA’s staff of experts who review the thousands of product submissions we receive every year, and do so in a timely and thoughtful manner. Over the years, our user fee programs have ensured a predictable, consistent, and streamlined premarket program for industry and helped speed patient access to new safe and effective products. 

One of our major undertakings since last July has been putting in place the infrastructure for a new generic drug user fee program that will expedite the availability of low-cost, high quality generic drugs. The program has already achieved several significant milestones, including reducing the backlog of generic drug applications, enhancing review efficiencies, and streamlining hiring. Likewise, reauthorization of the medical device user fee program has helped to expedite the availability of innovative new products to market, and the program has already seen a decrease in the application backlog for device submissions. 

But user fees are by no means the only focus of the 140-page law. Additionally, FDASIA includes provisions to strengthen the drug supply chain, enhance engagement with FDA stakeholders, address the problem of drug shortages, and promote innovation. 

Since last July, FDA continues to meet its FDASIA milestones, and is on track to implement more provisions very soon. Consider some of our more significant accomplishments. In the area of innovation, we launched the new breakthrough therapy designation for drugs that may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases and published guidance on the use of this and all of our expedited programs. In the area of engagement, we initiated the Patient-Focused Drug Development Program. The objective of this five-year effort is to more systematically obtain the patient’s perspective on a disease and its impact on patients’ daily lives, the types of treatment benefit that matter most to patients, and the adequacy of the available therapies for the disease. We have already held patient meetings on three major diseases and another is scheduled in September. 

Also, FDASIA is helping FDA take important steps to address the challenges posed by an increasingly global drug supply chain in which nearly 40 percent of finished drugs are imported and nearly 80 percent of active ingredients come from overseas sources. FDA has been able to halt food and devices from distribution if an inspector believes they are adulterated or misbranded, but the agency lacked this authority for drugs. FDASIA has extended the agency’s administrative detention authority to include drugs as well, and the agency is taking steps to implement this authority. In addition, earlier this year the agency pushed for higher penalties for counterfeiting and intentionally adulterating drugs before the federal sentencing commission – and succeeded. These are the first of several provisions that we must implement under Title VII, the section of FDASIA that strengthens FDA’s authorities over the drug supply chain. Later this week I hope many of you will join me at a public meeting to discuss how we might implement some of the other portions of this important section. 

To help the public keep track of our progress on these and other provisions, we’ve established a FDASIA web portal that includes a link to our three year implementation plan, which we intend to update on a monthly basis. 

Implementing FDASIA is a massive undertaking, requiring detailed planning to integrate these tasks with the rest of our workload. FDA is committed to implementing the requirements of FDASIA in a way that provides lasting improvements to public health, and we will meet these objectives as quickly as resources allow. 

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

Cancer Care in the U.S. – Looking Back, Looking Forward

By: Richard Pazdur, M.D.

2012. A milestone in my professional career marking the 30th anniversary since I finished my medical oncology fellowship and started practicing in the field. Oncology is a much different place today than in the late 1970’s when I was an oncology fellow in Chicago and when I took my first faculty position at Wayne State University in Detroit in 1982.  In 1988, I assumed a faculty position at The University of Texas M.D. Anderson Cancer Center and left Houston in 1999 to join FDA.

I remember a time when the only drug we had to treat advanced kidney cancer was the hormone, Megace… a time when the only drug to treatment metastatic colorectal cancer was 5-fluorouracil… a time when the only drugs to treat chronic myelogenous leukemia (CML) were hydroxyurea and Busulfan… a time when adjuvant therapy in breast cancer was just beginning to be investigated.

Today is a very different picture. Since 2005 FDA has approved seven drugs for advanced kidney cancer. Oncologists now have multiple options for the treatment of metastatic colon cancer, including the combinations of Camptosar (irinotecan), Xeloda (capecitabine), Eloxatin (oxaliplatin), Avastin (bevacizumab), Erbitux (cetuximab), and Vectibix (panitumumab). Patients with CML have been greatly helped with the introduction of tyrosine kinase inhibitors. Adjuvant therapy, both for breast and colorectal cancers, now has an established role in medical oncology practice and we have moved the early use of anti-cancer drugs a step further into the neoadjuvant setting in breast cancer.

There have been many advances during this 30-year period, including the development of curative therapies in childhood malignancies and great strides in supportive care products. I did not intend to prioritize these advances and I apologize for missing the one you feel most important.

“Cancer” is a multitude of diseases and our current classification of cancer based on organ location (“breast cancer”, “colon cancer”, lung cancer”) will be transformed based on the “molecular fingerprints” of an individual’s tumor. The increased understanding of cancer biology will have profound positive implications for all stakeholders with the development of drugs with greater efficacy and less toxicity.  

The future therapeutic advances in oncology will be based on our enhanced understanding of the biology of cancers. The identification of specific mutations in the BRAF gene in melanoma and mutations in BCR/ABL genes led to the development of therapeutic breakthroughs in melanomas and CML, respectively. Herceptin (trastuzumab) for the treatment of HER-2 positive breast cancer and the anti-CD-20 antibody, Rituxan (rituximab), to treat B-cell lymphomas are examples of using enhanced understanding of cancer biology to discover and develop targeted therapies.  In 2011, FDA approved two drugs – Xalkori (crizotinib) and Zelboraf (vemurafenib) – with concurrent approvals of in vitro diagnostic tests for patient selection providing a clear regulatory pathway for co-development of a drug and a diagnostic test. This year we also saw the approval of Jakafi (ruxolitinib), the first drug approved for myelofibrosis, whose development was based on our understanding of the JAK 1 and 2 pathways in the disease.

In a two-part appearance on Biocentury TV starting Sunday, January 29, I discuss what I see as the changing landscape of oncology (check your local listings). One point I discuss is the need for companies to take a more strategic approach to cancer drug development and to begin thinking of their business as a “disease” company vs. a “drug” company. Successful drug development will only occur with an in-depth understanding of basic disease mechanisms. This “disease orientation” will require greater collaboration between pharmaceutical sponsors, the academic community, government agencies, and patient groups.

The following week (February 5), three reviewers from FDA’s oncology office join me for a roundtable discussion about what they see as the future of oncology and what they encounter as practicing oncologists.

I have been fortunate to work with a talented team of oncologists, pharmacists, toxicologists, nurses, safety and public health experts to evaluate cancer drugs. Our staff understands that there are many diverse opinions in the oncology community regarding approval of oncology drugs. The balance between the immediate needs of an individual patient and the assurance of a drug’s safety and efficacy for approval will always exist. When appropriate, we have permitted the use of single patient INDs, exemptions to existing protocols, and expanded access programs to allow patient access to promising, yet unapproved, drugs.

To expedite drug development and our review of applications, FDA has approved oncology drugs on the basis of a single trial and used a variety of clinical trial endpoints — including overall survival (the time a patient lives before death), progression-free survival (the time a patient lives without their cancer progressing), and response rates (tumor size reduction). FDA has taken advantage of regulatory initiatives for serious and life-threatening diseases, such as fast-track, priority review, and accelerated approval.

When aspiring physicians ask me what it takes to become a medical oncologist I tell them – you must be an optimistic person. It’s demonstrated in the care of patients and a vision for the future of cancer care. Thirty years from now, our success won’t be measured by the number of cancer drugs approved, but by the number of patients living and functioning longer and feeling better.

This year also marks my 30th wedding anniversary to an oncology nurse who I met while we were mixing a chemotherapy drug in Chicago. My wife Mary would clobber me if I didn’t acknowledge the role of the dedicated oncology nurses who kept us all in line—past, present, and future.

Richard Pazdur, M.D., is the Director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research