Congratulations to FDA’s Dr. Richard Pazdur, recipient of the AACR’s prestigious Distinguished Public Service Award

By: Stephen Ostroff, M.D.

In the past five years, FDA’s Center for Drug Evaluation and Research (CDER) has approved more than 40 novel cancer treatments, offering hope to many patients who previously had few or no treatment options. Among these products are new and cutting-edge targeted therapies—sometimes called “precision medicines”—tailored to treat patients based on their individual characteristics.

Acting FDA Commissioner, Stephen Ostroff, M.D.

Acting FDA Commissioner, Stephen Ostroff, M.D.

This achievement is a tribute to the dedicated CDER scientists and clinicians who support innovative development of cancer drugs, and evaluate the safety and effectiveness of new products for FDA approval. They are led by the dynamic and creative thinker, Dr. Richard Pazdur, a 16-year FDA veteran whose name has become synonymous with excellence in cancer drug research, development, evaluation and approval.

It is with great pride and admiration that I share with you today that the American Association for Cancer Research (AACR) has awarded its 2015 Distinguished Public Service Award to Dr. Pazdur. AACR selected Dr. Pazdur for this award based on his “extraordinary, steadfast leadership in scientific and regulatory affairs” and his “unwavering commitment to ensuring the development of safe and effective treatments for cancer patients.” The Association also noted that Dr. Pazdur’s “important work has been and continues to be nothing short of spectacular, and it is saving lives every day from this most feared disease that affects so many.”

Dr. Richard Pazdur (left) receives the 2015 Distinguished Public Service Award from AACR President Dr. Arteaga

Dr. Richard Pazdur (left) receives the 2015 Distinguished Public Service Award from AACR President Dr. Arteaga. Photo by © AACR/Todd Buchanan.

As director of the Office of Hematology and Oncology Products (OHOP) at FDA, Dr. Pazdur leads a staff of more than 150 oncologists, toxicologists, and other specialists dedicated to approving safe and effective drugs for cancer and blood-related conditions. Dr. Pazdur and his staff are committed to facilitating rapid development, review, and action on promising new treatments to combat these diseases and improve patient outcomes. Dr. Pazdur and the OHOP staff are also committed to outreach with the oncology community. In 2005, Dr. Pazdur established the Oncology Program, which coordinates oncology activities within FDA as well as with external stakeholders providing OHOP with a unique infrastructure within CDER to interact with professional societies and patient advocacy groups.

We are grateful for Dr. Pazdur’s sustained contributions and look forward to many more years of his leadership, and his adept and proficient manner in helping patients in need.

Stephen Ostroff, M.D., is Acting Commissioner of the U.S. Food and Drug Administration

FDA’s Keynote Address to the Annual Conference of the Food and Drug Law Institute

By Stephen Ostroff, M.D.

Today marks the start of my third week as Acting Commissioner of FDA and I “celebrated” by giving a keynote address to attendees at the annual conference of the Food and Drug Law Institute (FDLI). Few places offer a more appropriate stage for a newly designated leader of FDA. As our names suggest, our organizations have a lot in common.

Stephen OstroffFor decades, the FDA and FDLI have worked together to educate and inform the broad “food and drug” community about the latest developments in our field and FDA’s critical and complex role in promoting and protecting the public health.

It’s been an exciting, busy, and rewarding first three weeks since moving into my new office from the position of Chief Scientist. The FDLI annual meeting offered me the opportunity to highlight a number of FDA’s accomplishments over the last year. The credit for these achievements in no small measure goes to the immensely talented employees at FDA who are committed to assuring safe and nutritious foods, providing effective and high quality medical products, and reducing harm from tobacco products. Credit for these achievements also reflects the extraordinary leadership of my predecessor, Dr. Peggy Hamburg, over the last 6 years.

So today, I’m pleased and honored to present to this audience some of FDA’s accomplishments and challenges, and also to extend my sincere appreciation to FDA’s dedicated work force, who make my new job much easier. But much more importantly, our work force makes the lives of so many Americans safer and healthier. It is with great pride that I look forward to continuing to work with all of you in support of this noble goal.

Stephen Ostroff, M.D., is Acting Commissioner of the U.S. Food and Drug Administration

FDA and CMS Form Task Force on LDT Quality Requirements

By: Jeffrey Shuren, M.D., J.D. and Patrick H. Conway, MD, MSc

Health care providers and their patients expect that laboratory tests used in clinical management of patients should be consistent and of high quality.

Jeffrey Shuren

Jeff Shuren, M.D., J.D.

Under FDA’s proposed framework for the oversight of laboratory developed tests (LDTs), outlined in draft guidance documents issued in October 2014, FDA would oversee the quality of these laboratory tests, alongside the Centers for Medicare and Medicaid Services (CMS), which regulate the laboratories themselves through the Clinical Laboratory Improvement Amendments (CLIA). We have heard stakeholder confusion about the roles of the two agencies in ensuring quality and concerns about potentially duplicative efforts. To coordinate efforts across the Department, FDA and CMS are establishing an interagency task force that will continue and expand on our collaboration related to the oversight of LDTs, which are tests intended for clinical use and designed, manufactured, and used within a single lab. The task force, comprised of leaders and subject matter experts from each agency, will work to address a range of issues, including those involving quality requirements for LDTs.

Patrick H. Conway, MD, MSc

Patrick H. Conway, MD, MSc

Under the proposed LDT framework, FDA would phase in enforcement of premarket review requirements and the quality system regulation for some LDTs. FDA’s oversight of LDTs will assure that the tests are both analytically valid (able to accurately detect analytes) and clinically valid (able to measure or detect the clinical condition for which the test is intended). FDA is currently reviewing public comments on the draft guidances that it received through an open public docket and a two-day public meeting. In response to public comments, FDA may modify the proposed framework when we issue final guidance.

CMS, under CLIA, oversees the labs’ processes, rather than the tests they develop. CLIA and its implementing regulations include requirements for establishing and maintaining quality laboratory operations and ensuring the lab is staffed by qualified personnel. These laws do not require premarket review of tests or any evidence that a test is clinically valid.

When FDA’s proposed framework is implemented, both FDA and CMS will play a role in ensuring that LDTs are high quality—CMS through CLIA by continuing to focus on laboratory operations including the testing process and FDA by enforcing compliance with the agency’s quality systems regulation pertaining to the design and manufacture of the laboratory tests.

Although the roles of the agencies are different, FDA and CMS share an interest in ensuring effective and efficient oversight of LDTs so laboratories can offer tests to the American public with confidence that they are accurate and provide clinically meaningful information without unnecessary or duplicative agency oversight.

The goals of the FDA/CMS Task Force on LDT Quality Requirements include:

  • identifying areas of similarity between the FDA quality system regulation and requirements under CLIA;
  • working together to clarify responsibilities for laboratories that fall under the purview of both agencies; and
  • leveraging joint resources to avoid duplication and maximize efficiency.

The task force is currently exploring areas where collaboration may realize greater oversight efficiency and produce the greatest benefit to patients, providers, and laboratories. The task force understands stakeholders’ concerns about differences in terminology used by FDA and CMS. We intend to clarify the terms used so that labs may better understand what is expected of them.

Our new task force is committed to its stakeholders and intends to provide education and outreach, including an upcoming webinar series, to address additional needs that are identified during this collaboration. We welcome any feedback and encourage you to contact us at LDTFramework@fda.hhs.gov.

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

Patrick H. Conway, MD, MSc, is Acting Principal Deputy Administrator CMS Chief Medical Officer

FDA Celebrates 30 Years of Advancing Health Equity

By: Jonca Bull, M.D.

April is Minority Health Month! I am proud to say that FDA’s Office of Minority Health (OMH), in collaboration with  the Department of Health and Human Service’s Office of Minority Health, is celebrating this year’s theme: “30 Years of Advancing Health Equity, The Heckler Report: A Force for Ending Health Disparities in America.” For us at FDA, this year also marks the 5th anniversary of OMH, which serves as the principal advisor to the Commissioner on minority health and health disparities.

Jonca BullThe Heckler Report was a major, ground breaking document that transformed HHS’s views and actions on minority health. For the first time in history, representatives from each agency convened to talk about minority health and, more importantly, put forth recommendations to achieve health equity. Findings illustrated huge disparities between African Americans and other minorities compared to the population at large for key health indicators, such as life expectancy and infant mortality. Key recommendations relevant to FDA’s mission centered around health information and education, cooperative efforts (inside and outside of the government), health professions development, data development, and developing a research agenda.

Let’s stroll down memory lane and recap FDA’s activities that resulted from the Heckler report.

Health Information and Education 

FDA has developed numerous outreach activities to improve consumer education and access to health information by utilizing the best cultural and linguistic practices to reach diverse minority populations. Hosting symposiums and webinars, participating in conferences, exhibiting in health fairs, and creating consumer educational materials are just some of the activities FDA has carried out to raise awareness and educate the public. Most recently, OMH has created a social media presence on Twitter and Pinterest, and maintains an active listserve with a quarterly newsletter. One of our most successful outreach campaigns has been the “Heart Health Toolkit” for American Heart Month, which reached over 6,000 people in February.

Our most recent consumer outreach occurred on March 25th via a webinar on how the public can respond to requests for comments on regulatory proposals and public health issues by using FDA dockets.

Cooperative Efforts/Health Professions Development

OMH embraces the notion that protecting the public’s health cannot be done in isolation. We have focused on four areas to improve stakeholder relations:

  • Work with Industry to increase diversity in clinical trials;
  • Work with minority serving institutions and organizations to implement strategies and programs to improve regulatory science (specific to minorities);
  • Provide platforms for stakeholders to become informed and involved about our work; and,
  • Host and promote mentoring programs to encourage minorities to stay in scientific and academic careers.

Data Development and Research Agenda

We have a robust research agenda that focuses on advancing regulatory science related to eliminating health disparities. The agenda consists of various intramural and extramural grant programs, giving preference to minority-serving institutions. FDA also promotes and funds research that aims to increase the quantity, and improve the quality, of data on minorities, and to make these efforts transparent to the public.

In short: FDA has been and will continue to be committed to narrowing the health disparities gap. OMH will continue our legacy of creating culturally and linguistically tailored tools, materials, and resources for minority communities to increase their awareness and understanding of FDA’s mission and of the products that FDA regulates, increase their participation in clinical trials, and increase diversity in the workforce. This ensures better representation in the workforce, and most importantly: better health for all minorities!

More information about specific programs can be found on our website.

The Heckler Report can be found at: http://collections.nlm.nih.gov/catalog/nlm:nlmuid-8602912-mvset.

Jonca Bull, M.D., is Director of FDA’s Office of Minority Health

Reducing the number of unapproved drugs while working to prevent drug shortages: a job that calls for strong collaboration in FDA

By: CAPT Val Jensen and Cynthia Schnedar

Val Jensen

CAPT Valerie Jensen R.Ph., Associate Director of the Drug Shortage Staff, Center for Drug Evaluation and Research, FDA

Several of FDA’s recent drug approvals highlight how different parts of FDA work together to achieve the same goal: ensuring an adequate supply of FDA-approved drugs for U.S. consumers. Our drug shortages team partners with many groups within the agency to achieve this goal. One of these partnerships is with our unapproved prescription drugs staff.

Patients and doctors alike may be unaware that some prescription drugs are not FDA-approved, because versions of some of these products have been marketed for decades, often with little data to demonstrate whether these drugs are safe and effective. At FDA, one task of our unapproved prescription drugs team is to identify these products, and encourage companies to remove unapproved versions from the market, and begin the application process to obtain FDA approval.

A growing number of manufacturers have successfully obtained approval for formerly unapproved products. For example:

  • Bloxiverz (neostigmine methylsulfate injection), marketed by Éclat Pharmaceuticals and approved to reverse the effects of certain neuromuscular blocking agents after surgery, was approved in 2013, and,
  • Vasostrict (vasopressin), marketed by Par Sterile and approved to increase blood pressure in adults in vasodilatory shock whose blood pressure remains low despite administration of fluids and other efforts to raise it, was approved in 2014.
Cynthia Schnedar

Cynthia Schnedar, J.D., Director of the Office of Compliance at FDA’s Center for Drug Evaluation and Research

Such approvals highlight the strength of collaborations between FDA’s shortages staff, our unapproved drugs team, and the Office of New Drugs. These approvals are crucial for FDA: once a drug is approved, we know what ingredients are in the drug, how it is made, and that it has been shown to be safe and effective for its labeled use. Approval of formerly unapproved products also helps alleviate FDA’s concerns about a potential market disruption or shortage of these drugs, because the manufacturers of approved drugs have invested in a manufacturing process that helps to ensure the drug is produced the same way every single time, lowering the risk for shortage.

However, prescribers and their patients may sometimes think there is a shortage of product because once the manufacturer can produce an approved drug in sufficient quantities to meet market demand, the unapproved versions transition out of the market. To help allay such concerns, FDA’s unapproved drugs team works closely with the drug shortages staff to share information about the availability of the newly-approved product from the manufacturer, information that is then conveyed to patients and providers. This strong relationship between the different parts of the Agency facilitates adequate supply of safe and effective, FDA-approved drugs.

FDA is aware of another access-related issue as well when unapproved drugs are approved. If a single manufacturer is the sole maker of a newly-approved product, the price of the drug may be higher than what patients and prescribers paid for the unapproved drug. FDA welcomes manufacturers’ sensitivity to pricing of these newly approved versions. However, FDA is charged by Congress to ensure that drugs are safe, effective and properly labeled and does not factor costs into its drug approvals or safety related decisions. While approved drugs may cost more, patients are assured a safe and effective product.

FDA encourages companies to apply for approval of generic versions of newly-approved drugs since this would be anticipated to foster competition and promote price reductions. For example, neostigmine, a formerly unapproved drug, now has two approved manufacturers. FDA expects to receive more applications for approvals in the future.

Making safe and effective medicines available to patients is our number one goal. While working to bring FDA-approved drugs to market frequently involves exceptional challenges and complications, we believe that in the long run, our efforts enhance public health for all Americans.

CAPT Valerie Jensen R.Ph., is Associate Director of the Drug Shortage Staff, Center for Drug Evaluation and Research, FDA

Cynthia Schnedar, J.D., is Director of the Office of Compliance, Center for Drug Evaluation and Research, FDA

From New Jersey to New Delhi, a global focus on quality

By: Howard Sklamberg and Cynthia Schnedar

As we walked through the bustling, ancient city streets of Old Delhi last week, teeming with tourists and shop keepers selling spices and saris, we were struck by how resplendent this country is, and just how much it offers the world.

Howard Sklamberg

Howard Sklamberg, J.D., FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

This is certainly true about prescription drugs. India is a significant exporter of generic drugs to the United States. The American people benefit tremendously from generic drugs, as more and more generic medications reduce costs for patients, and the American healthcare system. The rise of India’s pharmaceutical star is one of the reasons why our trip to India is so important.

While here, we have had a chance to meet with our regulatory counterparts in the Indian government, as well as the drug manufacturers that are either based here, or who have facilities in the country. Needless to say, we are learning a great deal.

It’s no secret there have been challenges associated with the quality of generic drugs coming out of some facilities in India. Some people have asked us here if the FDA is “singling out” India for increased inspections. We simply reply that increased exports to the U.S. result in increased inspection, no matter where you are in the world. FDA inspections ensure that when a firm wants to export drugs to the United States, the drugs meet FDA standards and will be of the quality patients and consumers want and deserve.

Cynthia Schnedar

Cynthia Schnedar, J.D., Director of the Office of Compliance at FDA’s Center for Drug Evaluation and Research

And we’ve been happy to hear that this focus on quality is, in fact, a shared goal, held by both the Indian — and India-based — regulators and pharmaceutical manufacturers with whom we’ve met. They understand what we mean when we tell them the FDA is interested in helping to build a global network of quality; that it doesn’t matter whether a drug is made in Hoboken or Hyderabad, if it is intended for use in the United States, the drug, and the way and under what conditions it’s produced, will be reviewed using the same standards and levels of scrutiny.

That scrutiny, by the way, doesn’t always have to have negative results. The inspections associated with drug production have been a central discussion point on this trip, and we’ve brought news that has been well-received, especially by the drug industry. We shared our proposed plan to create a new approach to facility inspections, one that will not only note problems, but will also allow our inspectors to document where a firm’s quality management system exceeds what would be required to meet regulatory compliance. To put it simply: the inspections can yield also carrots, and not just sticks.

Meeting in India

Last week, FDA’s Howard Sklamberg and Cynthia Schnedar participated in a panel discussion on drug quality with drug associations in India

So what are the carrots? These findings could be used to influence the frequency of our inspection of a particular facility, and possibly even support regulatory flexibility around post-approval manufacturing changes. These kinds of decisions would be anchored by data that proves that the risks of manufacturing problems in a certain facility are minimal.

We have often said we cannot inspect our way to absolute drug quality. Many of our discussions on this trip have focused on the importance of firms enhancing their own “quality cultures.” And, to that end, we know there are initiatives we can take to help them succeed. For example, we will be piloting a new questionnaire that could be used to further standardize inspections, with the goal of uniformly harvesting the kind of data that supports accurate measures of quality. We believe that by improving the inspection process in this way, future “metrics” that define quality will be understood and aspired to by manufacturers — no matter where they are in the world.

CEO meeting in India

Last week, FDA’s Howard Sklamberg and Cynthia Schnedar met with pharmaceutical CEOs in India to discuss drug quality

Of course, enforcement has been, and will continue to be, an important part of our program to ensure drug quality. Enforcement is a particularly appropriate tool when a firm does not submit accurate data to us. FDA relies on information to do its job, and faulty information means that we cannot ensure the quality of the drugs that the firm produces.

It is already clear to us, after speaking with regulators and industry leaders here, that India intends to be part of that global community that is committed to producing the highest quality of drugs possible. Through workshops and joint inspections, we continue to work with the Indian government to raise awareness and understanding of our inspections processes. And to the industry leaders we have met with here, we have pledged to continue to collect their feedback on how we might be able to help them improve regarding quality issues, and to incentivize them to do so.

India has a significant spot in the constellation of drug-producing nations. As one Indian official so eloquently said to us, we have “a galaxy” in common. And, we are happy to add, that the brightest star in that galaxy may just be our shared commitment to a global system of drug quality.

Howard Sklamberg is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

Cynthia Schnedar, J.D., is Director of the Office of Compliance at FDA’s Center for Drug Evaluation and Research

FDA Continues to Lead in Precision Medicine

By: Janet Woodcock, M.D.

Everyone knows that different people don’t respond the same way to medications, and that “one size does not fit all.” FDA has been pushing for targeted drug therapies, sometimes called “personalized medicines” or “precision medicines,” for a long time.

Janet WoodcockTargeted therapies make use of blood tests, images of the body, or other technologies to measure individual factors called “biomarkers.” These biomarkers can then be used to determine who is most likely to benefit from a treatment, who is at higher risk of a side effect, or who needs a different dose. Targeting therapy can improve drug safety, and make sure that only people likely to have a good response get put on a drug.

Targeted therapies have gained public attention since President Obama announced a Precision Medicine Initiative in his most recent State of the Union address. This initiative will reinforce our work at FDA, where development of targeted drug therapies has been a priority since the 1990s. In 1998, FDA approved the targeted therapy, Herceptin (trastuzumab), offering new hope for many patients with breast cancer. High levels of a biomarker, known as “HER-2,” identified breast tumors that were more likely to be susceptible to this drug.

Since the approval of Herceptin, the development of targeted therapies has grown rapidly. FDA’s Center for Drug Evaluation and Research (CDER) approved 30 targeted therapies since 2012, including Kalydeco (ivacaftor), a targeted drug for cystic fibrosis. In 2014 alone, eight of the 41 novel drugs approved were targeted, including:

  1. Lynparza (olaparib) for the treatment of advanced ovarian cancer.
  2. Blincyto (blinatumomab) for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL).
  3. Harvoni (ledipasvir and sofosbuvir) to treat patients with chronic hepatitis C infection.
  4. Viekira Pak (ombitasvir, paritaprevir, dasabuvir and ritonavir) for the treatment of chronic hepatitis C infection.
  5. Cardelga (eliglustat) for the long-term treatment of Gaucher disease type 1.
  6. Beleodaq (belinostat) for the treatment of peripheral T-cell lymphoma.
  7. Zykadia (ceritinib) to treat patients with non-small cell lung cancer (NSCLC).
  8. Vimizim (elosulfase alpha) for the treatment of Mucopolysaccharidosis Type IV (Morquio Syndrome).

Since the 1990s, FDA has also been working on personalized drug dosing. People differ in how they eliminate a drug—some eliminate it much more slowly than most other people and are susceptible to overdosing, and others eliminate it much faster, and may not get any effect. There are biomarkers to identify people who have these unusual results, and CDER has been actively working for more than 15 years to put these findings into drug labels, so that each patient gets the correct dose, particularly for highly toxic or critically important drugs.

Personalized drug safety has also gotten attention. Often, one person experiences a serious side effect that does not affect thousands of others. Science is beginning to unlock the reasons for these rare toxicities, and the labels of some medicines advise screening people to make sure they are not at high risk for a severe side effect. This can make drugs much safer.

CDER has been recognized with awards from the Personalized Medicine Coalition and the Personalized Medicine World Conference for its longstanding work in this area.

CDER uses a lot of flexibility when reviewing applications for targeted drugs. Targeting people with a good chance of response means fewer people are eligible for a drug. CDER has adapted to the resulting small development programs. For example, among the targeted therapies approved in recent years, almost 60 percent were approved on the basis of one main clinical trial along with supporting evidence. In addition, 90 percent used one or more of FDA’s expedited programs such as Breakthrough, Fast Track, Priority Review and Accelerated Approval.

It is still hard to develop targeted therapies for many diseases, because there isn’t enough scientific understanding of why the disease occurs and what biomarkers would be useful. For many common illnesses, much more research is needed to reveal the individual differences that would enable development of targeted therapies.

We still have much work to do. However, we are pleased to see substantial progress and look forward to continuing our efforts to advance biomarkers, which will help bring additional important new therapies to patients in need.

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

In India, With Our Sleeves Rolled Up

By: Howard Sklamberg and Michael Taylor

Howard Sklamberg

Howard Sklamberg

These facts surprise many people, but roughly 80 percent of active pharmaceutical ingredients, 40 percent of finished drugs, 80 percent of seafood, 50 percent of fresh fruit and 20 percent of fresh vegetables come from outside of the U.S.

Each year, the FDA has to assess millions of products grown, harvested, processed, manufactured and shipped from outside of the U.S. And one of the most impressive examples of how this globalization of production, consumption and trade has altered the regulatory landscape is India.

India is quickly becoming a significant player in the global marketplace, representing an important source of FDA‐regulated products. With a diverse population, highly skilled work force, and favorable economic conditions, India has become an increasingly attractive location for companies to operate.

Michael Taylor

Michael Taylor

And with that, Indian regulators have become important strategic partners for FDA. Today, we regularly engage with them on everything from sharing information on clinical trials to collaboratively addressing product safety issues that may harm American consumers.

When Commissioner Hamburg visited the country last year, she remarked that the “rapid globalization of commerce has posed significant challenges to ensuring consumer safety as the number of suppliers entering the U.S. has increased.” On her visit she signed a milestone Statement of Intent between our two countries  seeking to “collectively work together to improve the lines of communication between our agencies and work diligently to ensure that the products being exported from India are safe and of high quality.”

We are eager to continue the work she started. And improving the lines of communication of which she spoke is the purpose  of our working visit to India. Before the trip we discussed with our teams what we expect from our journey. Our top goal is to listen and learn. We want to understand what challenges the Indian government is facing with regard to drug and food safety. We want to hear from both American companies operating in India, as well as Indian manufacturers. And we want to discuss with our Indian counterparts a number of significant changes in the American regulatory system that affect our relationship.

FDA’s Howard Sklamberg, Deputy Commissioner for Global Regulatory Operations & Policy, and Cynthia Schnedar, Director, Office of Compliance at CDER, meet with Dr. G.N. Singh, Drugs Controller General of India.

FDA’s Howard Sklamberg, Deputy Commissioner for Global Regulatory Operations & Policy, and Cynthia Schnedar, Director, Office of Compliance at CDER, meet with Dr. G.N. Singh, Drugs Controller General of India. Get this and other photos from FDA’s trip to India on Flickr.

It is no secret that relationship has been challenged in the recent past by lapses of quality at a handful of pharmaceutical firms. And while our first regulatory responsibility is to protect the American patient and consumer, we are also very willing to collaborate with Indian regulators and other stakeholders to ensure the achievement of highest standards of safety and quality, something we feel only benefits both nations.

We have harvested some of the fruits of this cooperation already. A significant example of collaboration between the U.S. and India occurred in 2012, when a Salmonella outbreak was traced to a manufacturer in India. An FDA inspection confirmed that the tuna product implicated in the outbreak came from the suspect facility, and the Indian government revoked the manufacturer’s license.

In yet another case, FDA’s India office worked with other United States government agencies to inform industry and Indian regulators about issues associated with an import alert for Basmati rice from India. The FDA office shared laboratory procedures for testing of pesticides.

More recently, in November of 2014, as a continuation of FDA’s efforts to strengthen the quality, safety and integrity of imported drugs, the FDA India Office, in collaboration with our Center for Drug Evaluation and Research’s Office of Compliance and the Office of Regulatory Affairs, held four workshops in India.  The workshops were held in partnership with European Directorate for the Quality of Medicines and Drug Information Association and involved the Indian Drug Manufacturers Association, Parenteral Drug Association and Organization of Pharmaceutical Producers of India. Over 560 participants from the pharmaceutical industry attended the four two-day workshops.

We are confident our trip will yield more examples of such fruitful collaboration, moving the regulatory relationship between two of the world’s largest democracies to the next stage, from the intention to work together, to the ability to work together to solve the complex globalization issues facing both nations.

Howard Sklamberg is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

Michael R. Taylor is FDA’s Deputy Commissioner for Foods and Veterinary Medicine

FDA Advances Medical Product Innovation

By: Margaret A. Hamburg, M.D.

On March 10, I had the pleasure of appearing with my colleague Dr. Francis Collins before the Senate Committee on Health, Education, Labor and Pensions to testify at a hearing on the subject of “Continuing America’s Leadership in Medical Innovation for Patients.” I thought the broader public health community would be interested in my oral testimony, and so I am sharing it here:

Margaret Hamburg, M.D.“Thank you, Mr. Chairman and Members of the Committee. I’m very pleased to be here today to discuss our shared goal of speeding innovative treatments to patients. FDA looks forward to working with you on this important effort.

As you have noted, this will be my last appearance before the Committee, as I am stepping down, but I want to thank you for your support over the years, and our constructive engagement with this committee to advance FDA’s public health mission.

I came to the Agency at a time of considerable uncertainty and change in the biomedical product industry; a time when dramatic advances in science and technology, some that my colleague Dr. Collins just outlined, demanded new models and approaches.

In turn, we took a very serious look at our role in advancing biomedical product innovation to ensure that we would be a gateway, not a barrier, to the delivery of better, safer and more effective treatments and cures.

In fact, this has been a high priority for me throughout my tenure and I’m very pleased, as Sen. Murray noted, last year, we approved the most new drugs in almost 20 years, and more orphan drugs than ever before. Forty-one percent of these new approvals were first-in-class products, resulting in a breathtaking array of truly innovative new therapies for patients.

Today, FDA approves drugs faster on average than all other advanced nations: 40 days faster than Japan; 70 days faster than Canada; and 174 days faster than Europe. And FDA has made substantial improvements in the efficiency of medical device reviews as well.

Moreover, we’ve accomplished this while remaining the gold standard around the world for safety and effectiveness.

Yet despite these successes, too many diseases still await treatments and cures.  Serious public health needs, such as treatments for Alzheimer’s disease, are not being met. And rising R&D expenditures are not matched by a proportionate discovery of new treatments.

In this context, I want to address concerns raised by some that FDA regulation is the principal obstacle to the development of innovative treatments, and suggestions that FDA’s authorities and procedures must be fundamentally restructured.

As a physician, I know that if you incorrectly diagnose a patient’s condition, the treatment that you’ll prescribe is unlikely to work. Unless we correctly diagnose why cures are still lacking for many diseases, we’re unlikely to find the solutions that will actually deliver those cures so let me give you three examples of misconceptions.

First is the incorrect but commonly repeated assertion that FDA’s approval of new drugs lags behind other countries. The reality is starkly different: over 75% of the new drugs approved by Japan, EU, Canada, Australia Switzerland and FDA from 2004 to 2013 were approved first by FDA, according to a recent report by the British-based Centre for Innovation in Regulatory Science. The result is that Americans are far more likely to get first access to a new medicine before patients abroad.

Second, FDA is said to be rigid and inflexible in its approach to requesting and using data for approval of a new drug. In fact, FDA’s clinical trial requirements have been steadily increasing in flexibility:

  • 45% of new drugs are approved based on a surrogate endpoint;
  • one-third are approved on the basis of a single clinical trial;
  • Last year, we used expedited approval processes for more drugs than ever before – about 66%.

And thanks in part to the new authority that you gave us in FDASIA, 74 drugs had received the new “breakthrough” designation.

My final example is the concern that investment in biotechnology has dropped precipitously in the United States, and that the FDA is to blame. But in the words of The National Venture Capital Association (NVCA), “Biotechnology investment dollars rose 29 percent in 2014 to $6.0 billion . . , placing it as the second largest investment sector for the year in terms of dollars invested.”  And Jonathan Leff, a leading biotechnology investor affiliated with NVCA, said that one of the two reasons for the increased investment in biotechnology is the improved regulatory climate in recent years at FDA.

I cite these examples to suggest not that the world of biomedical research and product development is all fine, but to urge that we start with the right diagnosis. We do not want solutions based on inaccurate diagnoses.

I caution against solutions that seek to lower the safety and effectiveness standards for approval of the medical products on which Americans rely. Remember that the great leaps forward in evidence-based medicine of the last 50 years have come in part because of the high standards for product approval that Congress put in place after a series of disasters involving unsafe and ineffective medical products. Those standards have also boosted the confidence that Americans place in medical products and that the world places in the American biomedical product industry.

Together, we can build on the progress that has been made in recent years, to further advance biomedical science and improve the lives of patients. And there are some areas from the FDA perspective that I believe we can all agree need to be improved.

First, patients are uniquely positioned to inform medical product development. Treatments can better meet their needs if we can capture science-based, disease-specific patient input to incorporate in the development and review process.

Second, more attention needs to be given to the development of “biomarkers” and surrogate endpoints. These can help scientists identify and target successful medical treatments and shorten drug development times as Dr. Collins was noting in his remarks.

FDA has accepted hundreds of biomarkers and surrogates, such as blood pressure changes, blood sugar reduction, and tumor shrinkage. Yet biomarkers are still lacking for many diseases, such as Alzheimer’s. The biggest obstacle is that scientists do not sufficiently understand the causes of Alzheimer’s and other diseases to identify drug targets or identify which patients will benefit from certain drugs. To solve this problem we must support the establishment of strong public-private partnerships, bringing the best minds together to develop the science that we need.

Third, evidence from clinical experience (called “real world evidence” or “big data” by some) provides a vital tool to monitor medical products in use in the marketplace. FDA’s Sentinel Initiative, with more than 170 million lives, is one of the largest uses of this type of information in healthcare and proving vital for monitoring safety and emerging safety concerns. The science of using evidence from clinical experience to establish product effectiveness is still in its infancy. Real progress demands that we develop the methodologies needed to harness its promise.

And fourth, FDA and industry agree that the Agency must be able to attract and retain talented scientists to review cutting-edge products. We look forward to working with you to improve our ability to hire and retain these experts.

So let me close by underscoring that speeding innovation while maintaining standards for safety and efficacy serves patients well, supports the needs of our health care system, and has enabled the medical product industry in this country to thrive. And so I thank you for your support for our efforts at FDA and the work you are going to be doing going forward to advance that work and the work of all our colleagues in the biomedical research community so we can deliver on the promise of science for patients.”

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

Rare Diseases at FDA: A Successful Year for Orphan Products

By: Gayatri R. Rao, M.D., J.D.

2014 was a strong year for rare disease product development at FDA. It was also a year of significant firsts.

Dr. Gayatri RaoIn recognition of Rare Disease Day, February 28th, we want to reflect on the progress we have made thus far as we renew our commitment to rare disease patients. A rare disease is generally defined as a disease which affects fewer than 200,000 Americans a year. At FDA, the commitment to increase access to diagnostics and treatments to change the day-to-day reality of those living with rare diseases began over 30 years ago with the passage of the Orphan Drug Act.That commitment has steadily increased since then.

In 2014, we received our highest number to date of new requests for orphan drug designation. We received over 440 requests while just 7 years ago, we received less than half of that. We designated and approved more orphan drugs in 2014 than we had in previous years – nearly 300 drugs were designated and 48 were approved, including both novel and repurposed drugs. In 2014, 41% of all novel new drugs approved by the Center for Drug Evaluation and Research were for the treatment of rare diseases. Many of these orphan drug approvals were new and innovative, including Sylvant, to treat Castleman’s disease, which results in excessive lymph node growth, and Impavido, to treat forms of the tropical disease, leishmaniasis.

2014 was also a year of firsts for rare disease product development:

There were firsts in device development. For example, the Center for Biologics Evaluation and Research approved its first device through the Humanitarian Device Exemption (HDE) pathway. This device, CliniMACS CD34 Reagent System, helps to mitigate potentially serious immune reactions associated with stem cell transplantation in patients with acute myeloid leukemia.

FDA produced in 2014 its first agency-wide blueprint to accelerate the development of therapies for pediatric rare diseases – a report and strategic plan outlining how to address issues for developing products for this population.

2014 saw the issuance of the first rare pediatric disease priority review voucher for the treatment of mucopolysaccharidosis type IVA (Morquio A syndrome), a rare lysosomal storage disease which affects about 1000 patients in the United States and can lead to debilitating and life-threatening abnormalities of bones, joints and the heart.

In recognition of Rare Disease Day 2015, the international rare disease community is coming together to pay tribute to the millions of individuals impacted by rare diseases all over the world. Through the solidarity and commitment of many stakeholders – patients and families, healthcare professionals, researchers, companies, and policy makers – the awareness of the daily challenges that are unique to each rare disease and the efforts to create solutions has risen exponentially in the past several decades. As members of the rare disease community, we are proud of our collective accomplishments but remain acutely aware of how much more there is still to be done. Given how 2015 is already shaping up, we expect that by working together, we will continue to make great strides in developing much needed products for the millions of patients living with rare diseases.

Gayatri R. Rao, M.D., J.D., is FDA’s Director for The Office of Orphan Products Development