Rare Diseases in Children Pose Unique Challenges

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

Rare diseases – those that affect fewer than 200,000 people in the United States but collectively affect 30 million Americans – are often chronic, progressive, debilitating, and life-threatening. Because most are genetic in origin, they disproportionately affect children. The agency is strongly committed to advancing safe and effective therapies for these young patients.

Gayatri R. Rao, M.D., J.D., is Director of FDA's Office of Orphan Products DevelopmentIn recognition of International Rare Disease Day on February 28, 2014, we are focusing on pediatric rare diseases.

While developing products for any rare disease poses challenges, in part because of the small patient populations, developing products for children raises unique considerations.  Historically, pediatric care has involved the use of off-label therapies that are unstudied or under-studied in children. For example, pediatric drug dosing often involved adjusting adult doses based on a child’s decreased weight, without considering potential age-based differences in drug metabolism and toxicities. Similarly, many medical devices used in children have been adapted – in homes, clinics, and operating rooms – to solve problems quickly, with little time to consider the long term consequences of a device’s effect on a growing child’s physiology and development.

And while incentives currently exist to promote the development of products for pediatric rare diseases, development in this area continues to lag due to the compounded challenges associated with studying both a rare and pediatric population.

In recognition of these challenges, Congress directed FDA to issue a report and strategic plan focused on accelerating and encouraging the development of therapies for pediatric rare diseases. In response, FDA convened a series of public meetings from January 6 – 8, 2014 to discuss the many challenges in developing treatments for rare diseases, specifically for children with rare diseases, and how to overcome those challenges.  These meetings generated a great deal of interest in the rare disease and pediatric communities. Hundreds of people attended either in person or via webcast and represented a wide swath of these overlapping communities, including patients, academicians, researchers, clinicians, industry, and governmental agencies, many of whom were noted experts in their respective fields.

There were frank, robust and productive conversations on a wide range of topics. A few common themes emerged, especially the important role that patient advocacy groups, including parents of pediatric patients, play in furthering drug development, such as participating in the development of robust patient registries and natural history studies, and providing their perspectives on the risks and benefits of specific treatments. Another common theme was the need for strong collaborations between patients, researchers, industry, and government.

My office, the Office of Orphan Products Development (OOPD), is now coordinating a cross-agency effort with Center for Drugs Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), the Center for Devices and Radiological Health (CDRH), and the Office of Pediatric Therapeutics (OPT) to develop a report and strategic plan to encourage and accelerate the development of therapies for pediatric rare diseases. The goal of this report is to incorporate the valuable insights gained from these public meetings to inform and tailor ongoing and future agency initiatives to more effectively advance the development of such therapies.

OOPD, in collaboration with CDER, is also launching a web-based educational tool for rare disease patients, advocacy groups, researchers and industry on various FDA-related topics. Current topics include the essentials of interacting with FDA and expanded access to products under development. The goal is to continue to add to this educational resource over time. For the new educational tool, as well as additional information, visit the OOPD Educational Resources web page. In addition, FDA and the National Institutes of Health (NIH) will jointly celebrate Rare Disease Day with a one-day program at NIH Masur Auditorium highlighting various rare diseases programs, research activities, and initiatives. For more information about this event that is free and open to the public, and available via webcast, visit the OOPD web page.

The needs of rare disease patients and the pediatric population are complex and pose challenging issues. We are committed to working with the pediatric rare disease community to face those challenges head-on and to accelerate the development safe and effective therapies for these diseases.

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

Planning Healthy Changes to the Nutrition Facts Label

By: Margaret A. Hamburg, M.D.

When the Nutrition Facts Label was created in 1993, it was revolutionary. For the first time, consumers could read the nutrition information on a food package to know what was in it and that the information was held to government standards for consistency and accuracy. This rectangular box has since become one of the world’s most recognized graphics, with countries around the world adopting their own version.

Margaret Hamburg, M.D.To continue the spirit and purpose of the Nutrition Facts Label, we are proposing important changes to bring it fully into the 21st century. A lot has changed in the past 20 years. Much more is known about food consumption and nutrition, the health of our population and the dietary choices that can help keep us healthy or make us vulnerable to an array of chronic diseases.

The changes that we’re proposing reflect that knowledge, based on an extensive examination of the latest public health trends and research on nutrition and disease, including obesity. There is a lot of information on FDA.gov about our plans, but I’d like to hit the highlights:

  • “Added sugars” would be listed on the label along with the current “Sugars” declaration (which includes both naturally occurring and added sugar). This alone is huge: The average American takes in many calories every day in sugars added during food production. Experts call these “empty calories” that often take the place of foods rich in nutrients.
  • Speaking of nutrients, listing the amount of Vitamin D and potassium – which many of us don’t get enough of – would be required. They would join calcium and iron as nutrients important to public health.
  • People generally eat differently today than they did 20 years ago. The serving size requirements would be updated to more accurately reflect what we’re actually eating. By law, serving sizes must be based on what people actually eat, not on what people “should” be eating.
  • Certain packages that are typically eaten in one sitting would be required to be labeled as a single serving, which would mean you would know how many calories and nutrients you are consuming for the whole package. For example, a 20-ounce soft drink would be one serving under the proposal, not more. Certain larger packages that could be consumed in one sitting or in multiple sittings would be required to be labeled per serving and per package.
  • While continuing to require “Total Fat,” “Saturated Fat,” and “Trans Fat” on the label, “Calories from Fat” would be removed because research shows the type of fat is more important than the amount.
  • The format would be modernized. Calories and serving sizes would be displayed more prominently in larger, bold type. The %DV (daily value) would be moved to the left, so that you can immediately put a nutrient in the context of your daily dietary needs.

I’ve been asked if we’re proposing these changes because an increasing number of people in this country, including children, are obese and at risk of serious diseases tied to food consumption.

The answer is both no – and yes.

No, because the Nutrition Facts Label is for everyone. FDA does not regulate diets, but we can make sure that you know exactly what you’re eating. Having more information can enable you to make an educated decision about the foods you eat and serve your family.

Yes, because we know that too many people’s health is being compromised by the food they eat. This includes those at risk for serious disease like cardiovascular disease, hypertension, strokes, diabetes, and obesity and all of us to wanting to have healthy diets can tell at a glance what is in a particular food.

As a consumer myself, I would find a Nutrition Facts Label that reflects the current science very helpful when making food choices for myself and my family. These changes should make it easier than ever to judge a food by its label.

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

Honoring African American History by Increasing Access to Information Protecting and Promoting Your Health

By: Walter Harris

African-American History Month offers the opportunity to reflect on the contributions of African Americans in various ways, both in our local communities and on a national scale. 

Walter HarrisWe should also use this month of observance to note the public health disparities that continue in underrepresented and underserved communities.  Current CDC health statistics highlight poorer health outcomes for the African American, American Indian and Alaska Native, Asian American, Hispanic American, Native Hawaiian, and Pacific Islander communities. 

FDA’s Office of Minority Health (OMH), established in 2010 as a mandate of the Affordable Care Act, works to reduce racial and ethnic health disparities and to support achieving the highest standard of health for all.  A key effort to advance this mission is to promote effective communication and the dissemination of information to the public, particularly underserved, vulnerable populations. 

FDA’s website has a wealth of resources to help minority communities use safe medicines, foods, and other products the Agency regulates.  Whether you are a patient, student, health professional or caregiver, reading in English or Spanish, our website has resources to help you stay informed and stay healthy. 

We are continually working to improve user experience on FDA.gov.  We recently launched the mobile version, as our increasingly mobile stakeholders and workforce require creative approaches to keep our data and systems accessible on mobile platforms. We are also working to significantly improve the search capabilities on the website, as well as maintaining Section 508 compliance to ensure that www.FDA.gov content is accessible to people with disabilities. OMH also works to improve and strengthen the research and evaluation of subgroup demographic data associations with race and ethnicity, particularly how data is represented in clinical trial participation, safety and effectiveness data.  As a participant in FDA’s Data Standards Council, OMH helps to coordinate the evaluation, development, maintenance, and adoption of health and regulatory data standards for race and ethnicity to ensure that common data standards are used throughout the agency. 

FDA’s Office of Information Management and Technology is engaged in various ways to improve the availability of data for consumers, researchers, developers, and industry.  More than 80 resources are currently indexed publicly, many updated daily, including adverse drug events, reports involving medical devices, searchable listings of over-the-counter tests cleared or approved by the FDA, and a database of accredited mammography facilities. 

Our goal is to increase the transparency of FDA data to the public through the openFDA initiative, which is being run by the newly-established Office of Informatics and Technology Innovation. We plan to provide access to multiple high-value structured data sets to consumers, including the mobile app and software developer community, starting in Summer 2014.

FDA believes that access to this data will further the Agency’s regulatory mission and, most importantly, will help inform minority and underserved populations – as well as  the general population – on ways to improve their health. In support of this goal, we must break many of the traditional technology infrastructure barriers by implementing cloud technologies to better support the exponential growth of data we are managing. We are also leveraging this ingenuity to address, for example, analyzing and sharing large amounts of information such as applying Next Generation Sequencing for generating, analyzing, reviewing, and sharing genetic information.

I encourage all of us to commemorate this month by not only reflecting on the drive and inspirational spirit of past and present African Americans, but to also taking the time to think of how we can apply that same drive and spirit to our mission of protecting and promoting public health. 

Walter Harris is Deputy Commissioner for Operations and Acting Chief Information Officer, Food and Drug Administration

Visiting India: The Importance of Biomedical Research and Quality

By: Margaret A. Hamburg, M.D.

As my busy and productive trip to India drew to a close, I had the opportunity for one final meeting and one last memory with a group of some of the country’s most extraordinary women. The occasion was a Women’s Roundtable in Mumbai, organized by the Confederation of Indian Industry (CII). It brought together a diverse collection of female industry and academic leaders in India for a thought-provoking discussion and a wonderful chance to share perspectives with these accomplished women.

Commissioner Hamburg and members of the Women's Roundtable in Mumbai

Commissioner Margaret A. Hamburg, M.D. and members of Women’s Roundtable in Mumbai, India.

We covered a wide range of important and timely topics and could have gone on for much longer had time allowed. We discussed the many challenges that professional women often face in today’s workplace including efforts to achieve work-life balance and the importance of educating, motivating, mentoring and empowering women at every stage of both their professional and personal development. We also focused on a number of pressing issues in biomedical research, clinical trials and the regulatory framework for food and drugs.

What was most striking about this remarkable group of women is the commitment each has made not only to support one another in their diverse professional endeavors, but also to work to improve the lives of people living in India and around the world.

Two themes emerged during our discussion: the importance of biomedical research in India, specifically clinical trial design and enrollment; and the importance of quality and the role these prominent leaders in the pharmaceutical and food production sectors can play in communicating why quality matters.

The group expressed concern about the status of the clinical trial system in India. Many Indians have been wary of the way clinical trials have been conducted and how trial participants are chosen and informed. India has been in the midst of a significant re-examination of its clinical trial infrastructure and the legal, regulatory, ethical and scientific required for future research.

Certainly, we understand the importance of a vibrant, reliable and transparent clinical trials system. The information FDA receives and reviews from clinical trials conducted in the U.S. and abroad is an essential part of the agency’s decision-making for all new and existing drugs. Without it, we would not have important information such as how a drug works, whether it is reasonably safe for patients, and how the human body metabolizes the drug. Additionally, clinical trials may represent a vital mechanism to access an investigational drug for patients living with serious and life-threatening diseases.

Over the years, the FDA has worked closely with academia, industry and the advocacy community to improve transparency around the design and conduct of the clinical trials used to generate data for medical product review and approval. The agency has been working with the health care and research community to improve a clinical trial subject’s understanding of what it means to participate in a clinical trial, as well as the specifics of the trial in which they are considering enrollment.

Because the information we learn from clinical trials has the potential to benefit people living around the world – and the trials may be conducted in a wide range of countries – it is important that government officials, industry, the research community and patient organizations work together to ensure appropriate human subject protections, rigorous clinical trial design, and needed health care. We look forward to continuing our discussions with government, industry and academia on these important topics.

Quality was a recurring theme during my visit to India. I was pleased that the women who participated in the roundtable were as committed to quality as I am.  As leaders in their industries and academic institutions, these women are uniquely positioned to help reinforce the message that quality matters and to educate the next generation of leaders in their respective industries and organizations about the importance of building quality into everything they do. And I was delighted that the group appreciated how smart regulation can help shape, support, and strengthen the product development and manufacturing processes that can help ensure continuous quality. In the words of moderator Swati Piramal, one of the highest ranking and most eminent leaders in Indian Pharma today, “good regulators make good companies.” And that combination can lead to better, safer and higher quality products – which benefits the health of people in both our nations and around the world.

Margaret A. Hamburg, M.D., is Commissioner of Food and Drugs

FDA’s First-Ever NSE Orders for Marketed Tobacco Products

By: Ann Simoneau, J.D.

Ensuring compliance with the law is critical to FDA’s mission to protect public health. As part of that mission, FDA is committed to making sure that all tobacco products that are sold and distributed to the public meet the requirements of the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act).

Ann SimoneauIn support of this commitment, we recently announced that four tobacco products now on the market – Sutra Bidis Red, Sutra Bidis Menthol, Sutra Bidis Red Cone, and Sutra Bidis Menthol Cone – do not meet the criteria in the law to remain on the market. These products entered the market during a grace period set up in the Tobacco Control Act. However, after a thorough review of the submitted applications, FDA determined that Jash International, the manufacturer of the four new products, did not provide sufficient evidence to demonstrate that they are “substantially equivalent” to eligible products that were previously marketed (otherwise known as predicate products). Specifically, the company did not identify eligible predicate tobacco products and was unresponsive to multiple requests for information that was necessary for FDA to determine whether the new products raised different questions of public health. This marks the first time that we have used our authority under the Tobacco Control Act to stop the continued sale and distribution of currently marketed tobacco products because they were not found “substantially equivalent” – and it is not an action we take lightly.

New tobacco products that FDA determines to be “Not Substantially Equivalent” (NSE) to predicate products can no longer be legally imported, sold, or distributed in interstate commerce, and failure to comply may result in FDA initiating enforcement action—such as seizures or injunctions – without further notice.

We have released a draft guidance document that explains the enforcement policy the agency intends to follow with respect to tobacco products that entered the market during the grace period and later receive NSE orders. The draft guidance is available for public comment and details our current thinking on this topic, including:

  • Products determined to be NSE cannot be sold or distributed in interstate commerce and may be subject to seizure at any time;
  • Companies that continue to sell and distribute these products in the United States may be subject to enforcement actions by FDA;
  • FDA does not intend to take enforcement action at the retail level for 30 days after an NSE order is issued, understanding that retailers may have existing inventories of NSE products in specific retail locations as of today; and
  • Retailers are encouraged to contact their supplier or manufacturer to discuss possible options for the NSE products in their current inventory.

We have also developed a new webpage, entitled Misbranded and Adulterated NSE Tobacco Products, to inform the public and companies in the distribution chain about products that have been on the market but are now considered misbranded and adulterated due to the failure of the manufacturer to satisfy the requirements for an SE marketing order. The webpage will be updated whenever any currently marketed products receive an NSE order.

Today’s announcement is an important step for the FDA as we continue to review new product applications, make science-based decisions, and take enforcement actions to ensure the protection of the nation’s public health.

Ann Simoneau is the Director of the Office of Compliance and Enforcement at FDA’s Center for Tobacco Products

Regulatory Science Supports FDA’s Regulatory Mission

By: Carolyn A. Wilson, Ph.D.

You might only think of FDA as a regulatory agency that oversees medical and food products. But FDA scientists, including those in the Center for Biologics Evaluation and Research (CBER), also perform research. In this first of two blog posts, I will describe how regulatory science, as it is called, helps to turn innovative medical research done at FDA and other places into life-saving or life-enhancing biological products.

Carolyn WilsonMost of the discoveries made at CBER support the development of new or improved vaccines, blood and blood products, and tissue, gene and cell therapies. This research also helps CBER make very informed decisions about new products and policies. That’s because many of the same CBER scientists whose research puts them at the cutting edge of science also review potential new products, inspect commercial facilities that make products, and help develop new policies and guidance documents for industry. In the past year, discoveries that CBER scientists have published in research journals have contributed significantly to public health by addressing issues that affect the safety and effectiveness of vaccines, gene therapy, and a treatment for a serious blood disorder.  

For example, scientists in the Office of Vaccines Research and Review (OVRR) took a big step in solving the mystery of why the rates of pertussis (whooping cough) in the United States have been increasing since the 1980s – despite widespread use of a pertussis vaccine. OVRR scientists showed in baboons that even though the vaccine can prevent symptoms of pertussis, animals receiving it still had the bacteria that cause the disease in their airways for up to six weeks.

These animals were then able to spread the bacteria to other animals. This suggests that while the vaccine protects children from getting pertussis symptoms, vaccinated children can still spread the bacteria through coughing to other children for several weeks – especially if those children aren’t vaccinated. This information is important because it can help scientists and public health officials design new vaccines and strategies to reduce the rate of pertussis in the US.

Statisticians and epidemiologists at CBER also make critical contributions to regulatory science. Serious adverse medical events sometimes occur in patients treated with licensed products (i.e., vaccines). When physicians or consumers report such events to the FDA, epidemiologists at the agency work to determine whether these events are actually caused by the licensed product or are just a coincidence. For example, epidemiologists and statisticians in the Office of Biostatistics and Epidemiology (OBE) studied whether getting the vaccine for 2009 H1N1 influenza (the so-called “swine flu”) several years ago increased the risk of developing a nerve disease called Guillain-Barré Syndrome (GBS). GBS can sometimes occur after infections or vaccinations, causing weakness in the arms and legs and reducing reflexes. The concern about the 2009 vaccine was based on the occurrence of GBS over 30 years ago among some people who received the vaccine against a related strain of H1N1 virus in 1976. CBER’s epidemiologists asked whether the more recent vaccine used to protect against the 2009 H1N1 virus also increases this risk. To answer this question, OBE researchers reviewed the medical records of 23 million individuals who received the 2009 H1N1 influenza vaccine during the 2009-2010 influenza outbreak. Their statistical analysis showed that the risk of death or hospitalization from H1N1 infection was about 500 times greater than the risk of developing GBS from the vaccine. 

Studies like these are very important because they help FDA regulators and public health officials to determine whether potential adverse effects are actually linked to the use of a particular product. In this case, confirming the safety of the vaccine was an important public health measure because it reassured the public that this vaccine was safe to take. 

In my next blog post I’ll be discussing important contributions CBER scientists recently made to gene therapy and the treatment of a blood disease called hemophilia. 

Carolyn A. Wilson, Ph.D., is Associate Director for Research at FDA’s Center for Biologics Evaluation and Research.

FDA Is Committed to Determining Sex Differences in How Drugs Work

By: RADM (Ret.) Sandra L. Kweder, M.D., F.A.C.P. 

There’s a lot happening these days with regard to the personalization of medicine and how drugs work differently in people, particularly in men versus women. FDA has a long history in understanding and analyzing these effects. 

Sandra KwederWe’ve issued guidance to the pharmaceutical industry explaining in detail our expectations about analyzing clinical data for sex-related differences as well as differences according to other demographic groupings. Those assessments, depending on the drug, may start with routine animal studies, in case a difference is evident by sex, but become most important when drugs begin to be tested in humans to see if data signal potential differences that require follow-up. 

Both women and men participate in drug studies. (As early as 2001, a report from the U.S. Government Accountability Office showed women were included in all drug trials at a statistically significant level, and women were the majority of participants in trials supporting half of the applications analyzed.) We also consider separately the effects of drugs on men and women to determine whether sex differences exist and whether we need more information to assess variations, if they exist at all. 

We take action if variations are suspected or found. For instance, last year FDA updated the dosing recommendation for sleep medications, such as those containing zolpidem (Ambien and other brands), lowering the recommended starting dose for women to 5 mg (from 10 mg). We did this because women were found to be especially susceptible to zolpidem’s side effects, largely because it is cleared from the body more slowly in women than in men. Moreover, new information became available to FDA last year about how sensitive to blood levels one important side effect of zolpidem is – that of driving impairment. New methods of studying the relationship between drug levels and certain driving tests were key to this understanding. We learned that even when individuals with certain blood levels of zolpidem don’t report feeling drowsy, their driving skills can still be affected. This is true of men and women, but because of women’s slower clearance of the drug from their system they are more likely to be at risk the morning after taking zolpidem. 

This zolpidem case highlights how biologic differences can sometimes play out in individuals’ responses to medications. Some differences in how drugs affect men versus women can relate to variations in metabolism and rates of absorption, and sometimes even because a particular illness has different characteristics in men and women. So we expect our reviewers and pharmaceutical companies to routinely look for sex differences in their new drug applications. Despite looking, it is rare for us to find that drugs differ based on sex alone.

Many drug labels already comment on dose considerations or side effect profiles related to age, health problems, or sex. Some drugs are only approved for one sex. For example, Lotronex (alosetron), a drug used to treat irritable bowel syndrome (IBS), is only approved for women because clinical trial data showed the drug is not effective in men. And Giazo (balsalazide) is used to to treat mildly to moderately active ulcerative colitis in males age 18 and older because it was shown to be ineffective in female patients. 

FDA also monitors all human drugs on the market via our surveillance programs. When findings suggest safety issues we think are important, we work with companies to put that information in labeling (if it is not already present), and sometimes we require companies to do additional studies. If you, as a patient, have any concerns about your specific medication or dose, you should talk to your health care professional. A drug can act differently in people not just because of their sex, but also due to factors such as weight and other medications taken. 

Our staff, including those in our longstanding Office of Women’s Health, are dedicated to protecting and advancing women’s health through policy, science, and outreach. We’ll continue to advocate for the inclusion of women in clinical trials and for analyses of how their bodies process medications. Our recent zolpidem decision is an example of how science evolves – and shows the importance of using new information to review previous decisions when needed. This is an exciting area of science. 

Sandra L. Kweder, M.D., is the Deputy Director of the Office of New Drugs at FDA’s Center for Drug Evaluation and Research 

Quality: A Recurring Theme During My Visit to India

By: Margaret A. Hamburg, M.D.

As one of the Seven Wonders of the World, the Taj Mahal is not only one of India’s most sacred symbols, but one of the finest, most carefully designed architectural structures in the world. As I studied the details of the marble and embedded precious stones of the mausoleum during a recent visit to the city of Agra, I could not help but reflect on the care, craftsmanship and quality of the work that took just over two decades to complete. It was evident as I walked along with hundreds of other visitors in socked feet that those responsible for building the Taj and those that are preserving the centuries old structure are committed to extraordinary quality.

Commissioner Hamburg with A Didar Singh

FDA Commissioner Margaret A. Hamburg, M.D., and A Didar Singh of the Federation of Indian Chambers of Commerce and Industries.

This vision of quality and care remained with me when I met with executives from pharmaceutical and food exporting companies operating in India. The roundtable meetings, organized by the Federation of Indian Chambers of Commerce and Industries, were an opportunity for me to learn about two of the largest business sectors in India and to hear from business leaders about the challenges they are facing as a result of globalization.

One of the challenges cited by the pharmaceutical leaders is approval times for abbreviated new drug applications – the applications filed for generic drugs. I am happy to report that the FDA is working quickly to fulfil one of our commitments under the Generic Drug User Fee Act (GDUFA) – reducing the backlog of generic drug applications that were pending when the new user fee program went into effect on Oct. 2, 2012.  As of the end of January 2014, our Center for Drug Evaluation and Research had taken a formal action on 45 percent of backlogged generic drug applications. In December 2013 alone, the center completed 174 actions, including 30 full approvals for generic drugs.

GDUFA also requires that we step up our number of foreign inspections and gives us the funding to do so. Companies participating in both the pharmaceutical and drug roundtables said they were challenged by our heightened inspectional activities. I told them that every company supplying the U.S. market has the responsibility of ensuring that their products are safe, effective and of high-quality.

In my talks with regulators and companies here in India I have placed a great deal of emphasis on why quality matters. As I explained, quality is linked to product safety and without a direct focus on quality, the potential for patient harm increases significantly.

In recent years the FDA has identified significant lapses in quality by some companies operating in the U.S. and around the world. As a result, American consumers have had to endure greater risk of illnesses, recalls, and warnings about the products many of them rely on each day. This is unacceptable. Consumers should be confident that the products they are using are safe and high quality and when companies sacrifice quality, putting consumers at risk, they must be held accountable.

Regulatory agencies around the world share my vision for ensuring that consumers, patients and healthcare providers in all of our nations have access to high quality products. I am pleased that, as a global leader in the pharmaceutical and foods sectors, India will continue partnering with us to ensure that the companies exporting products to the U.S. are adhering to established quality standards.

On the home front, we at the FDA will also continue to increase our focus on quality. One way we are doing this is through the creation of a new Office of Pharmaceutical Quality that will create one voice for drug quality at the FDA and improve our oversight of quality throughout the lifecycle of a pharmaceutical product.

All companies must understand that quality is the basis for the public’s trust and confidence in their products and maintaining high quality standards is part of the cost of doing business.

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

 

Visiting India: Sharing a Vision for Strengthening Food and Medical Product Safety

By: Margaret A. Hamburg, M.D.

Fresh mangos, bananas and other native fruits add a pop of color and provide the backdrop while we ride along the busy streets of Delhi. While en route to the first of several meetings I held with Indian regulators, I can’t help but marvel at the vibrant buzz of India’s capital and the progress that has been made since I traveled here years ago as a young woman. Since that time, the rapid globalization of commerce has posed significant challenges to ensuring consumer safety as the number of products and suppliers entering the U.S. has increased. India now represents the 3rd largest trade partner, 2nd largest supplier of over-the-counter and prescription drugs, and 8th largest supplier of food to the United States.

Margaret Hamburg and officials in India

(L-to-R) Arun Panda, Joint Secretary, Ministry of Health and Family Welfare; Shri Keshav Desiraju, Secretary, Ministry of Health and Family Welfare; Shri Ghulam Nabi Azad, Minister, Ministry of Health and Family Welfare; Dr. Margaret A. Hamburg, M.D., Commissioner of the U.S. Food and Drug Administration; Dr. Altaf Lal, Director of U.S. FDA’s India Office; Nancy Powell, U.S. Ambassador to India.

On Monday, I began my first official visit to the country as Commissioner of the FDA. I met with officials from the Indian government who oversee the country’s health-related matters as well as those responsible for overseeing the export of foods to the U.S. and more than 200 countries around the world. These meetings provided the opportunity for me to discuss our shared vision for strengthening the quality of the foods and medical products exported from India to the United States. Ultimately this vision is intended to enhance consumer confidence in these products both at home and abroad.

As two of the largest democracies in the world, our countries have enjoyed an enduring partnership and commitment to collaborate on initiatives designed to enhance both our economies and the lives of the people in our respective countries.

Ensuring that the products distributed in the United States meet our requirements for product safety and quality is among my top priorities as Commissioner. Unfortunately the many Indian companies that understand good manufacturing and quality processes have been overshadowed by recent lapses in quality at a handful of pharmaceutical firms.

While the FDA will take appropriate action against any company that doesn’t meet our requirements, we are also willing to work with them to address their issues. All consumers deserve access to safe and affordable drugs and should not have to sacrifice quality to get that.

Officials at India’s Ministry of Health and Family Welfare share this goal. In the spirit of continued collaboration and a commitment to quality, our agencies signed the first-ever Statement of Intent. Our organizations plan 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.

While the Statement of Intent is an important milestone, I am proud to report that FDA’s Office in India has already been working closely with India’s drug regulators to reinforce the importance of producing quality products for patients. Drug and food regulators in India have participated in FDA-hosted workshops and observed FDA inspections of manufacturing facilities and clinical sites with operations in India.

During my visit I am eager to learn more about the industries that produce products for the United States and to meet with business leaders where I will reinforce our expectations that they meet our requirements for ensuring that consumers here and around the world have access to safe and high-quality products.

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

Why FDA Supports a Flexible Approach to Drug Development

By: Margaret A. Hamburg, M.D.

We all know that just as every person is different, so too is every disease and every drug.

Margaret Hamburg, M.D.And so we weren’t surprised by the results of a new study published in the Journal of the American Medical Association. The study found that FDA used a range of clinical trial evidence when approving 188 novel therapeutic drugs for 208 indications (uses) between 2005 and 2012. These results are entirely consistent with our regulatory mandate. We believe varying approaches to clinical studies to support drug approval is good news, not bad.

Data to support the approvals studied were based on a median of two pivotal trials per indication. A pivotal trial presents the most important data used by FDA to decide whether to approve a drug.

But when the authors looked more closely, they found that more than a third of these drugs were approved on the basis of a single pivotal clinical trial, while still other trials involved only small groups of patients for shorter durations. Of the approvals studied, the new drug was compared with existing drugs on the market only about 40 percent of the time.

The authors concluded that, based on these results, the ways in which FDA arrived at those approvals “vary widely in their thoroughness.” Or, in the words of one study author, “Not all FDA approvals are created equally.” Although I don’t think it was actually the author’s intent, a number of commentators framed this as criticism. But I would be more troubled if FDA used a rigid, “one size fits all” approach.

People with serious or life-threatening illnesses, particularly those who lack good alternatives, have told us repeatedly that they are willing to make some trade-offs in order to gain access.

And, of course, “thoroughness,” such as whether a clinical trial is large enough, is in the eyes of the beholder. There is no reason to expect drugs to be tested on similar numbers of patients, regardless of the disease.

Variation in approach to clinical studies demonstrates FDA’s innovative and flexible approach to drug development and approvals. Such an approach was specifically adopted by Congress in the Food and Drug Administration Modernization Act in 1997 and, most recently, in the Food and Drug Administration Safety and Innovation Act in 2012.

The FDA of today works with sponsors of new drugs to design a development and review pathway for each drug that best reflects the disease and patients it is intended to treat, the drug itself, and other treatment options. Some of the factors that enter into our calculus include whether the drug treats a rare or serious disease or addresses an unmet need and any previous knowledge we might have about the drug.

Thus, for example, FDA approved Imbruvica (ibrutinib), a treatment for mantle cell lymphoma, last year based on an “open-label, single-arm trial,” which means that every patient received the treatment and both patients and researchers knew they were receiving it. The results were compared to how well the 111 participating patients had responded to previous treatment for their disease.

And Elelyso (taliglucerase alfa) – for Gaucher disease – was an orphan drug approved in 2012 based on two trials with 56 patients.

In contrast, some trials require large numbers of patients to demonstrate a drug’s effects. This is often the case in studies in patients with a chronic condition such as cardiovascular disease, where larger populations are studied to capture treatment effects.

No matter what clinical trial design is chosen, the Agency always applies the same statutory approval standards of safety and efficacy to all drugs seeking to be marketed in the United States.

Increased flexibility does not mean abandoning standards, and it certainly does not mean abandoning science. Just the opposite. We need to employ the best science in ways that will increase efficiency, productivity and our shared ability to find creative solutions to the challenges that confront us.

At the end of the day, that is just smart regulation – ensuring that patients can more rapidly have access to the best that science has to offer.

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