Vaccines: A Critical Tool in Protecting and Promoting Public Health

By: Karen Midthun, M.D.

Vaccines are a critical tool in protecting and promoting the public health in the U.S. and around the world. The risks from childhood diseases like measles, mumps and polio have been greatly reduced, or in the case of polio, eliminated in the U.S. Vaccines are one of the great public health success stories of the 20th century.

Dr. Karen MidthunFDA is responsible for ensuring the safety and effectiveness of vaccines available for use in the U.S. Our lifecycle evaluation begins during the development stages and continues through approval and after the vaccines are on the market. As part of the Department of Health and Human Services, FDA is but one agency that plays an important role in developing and implementing the Department’s National Vaccine Plan. The plan outlines five goals:

  • Develop new and improved vaccines;
  • Enhance the vaccine safety system;
  • Support communications to enhance informed vaccine decision-making;
  • Ensure a stable supply of, access to, and better use of recommended vaccines in the United States;
  • Increase global prevention of death and disease through safe and effective vaccination.

A report on the work of FDA and its sister agencies in addressing these five goals – the State of the National Vaccine Plan – was recently issued by the Department’s National Vaccine Program Office. The report gives consumers, health care professionals and other stakeholders a look into the ongoing efforts of the various agencies, and how those efforts align with the plan’s vision of enhancing all aspects of vaccines and vaccination.

We at FDA are very proud of the work we do to ensure the safety, effectiveness, and availability of vaccines for the United States. The activities highlighted in the report offer a glimpse into this important work being done at FDA and across the Department – work that lies at the heart of our public health mission.

Dr. Karen Midthun is the director of FDA’s Center for Biologics Evaluation and Research

What’s new in the FDA’s 2015 budget?

By: William Tootle

A few days ago, President Obama released his Fiscal Year 2015 Budget Message to Congress, which included a high-level summary of his proposed funding for the FDA. Today the White House is out with the full budget, complete with all of the nitty gritty details.

William TootleAlthough these budgetary times are difficult, the FDA received some good financial news. The president is requesting a $4.7 billion budget for FDA, an 8.1 percent increase over the 2014 budget that Congress passed earlier this year.

For ease in discussing a budget of such scope, we typically group budgetary line items into a few large categories. This year our categories are medical product safety (which also includes our premarket review activities) and food safety (which also includes cosmetics).

Most of the $61 million increase for medical product safety comes from increases that were written into the statute when Congress authorized each of the five-year user fee programs.

One new line item in the budget is $25 million to strengthen oversight of the pharmacy compounding industry. In 2012 there was a fungal meningitis outbreak that killed 64 people and infected over 750 others in 20 states. This outbreak was shown to be the result of compounded drugs – the combination of two or more drugs to create a custom medication – that were created in unsafe conditions. To better protect the American people, FDA stepped up activities within available resources and Congress passed the Drug Quality and Security Act, giving us new responsibilities and authorities, but without commensurate resources. The President’s proposed 2015 budget doesn’t provide FDA with a $25 million increase to cover the agency’s pharmacy compounding activities. The money is coming from trims “on the margin” to other portions of our medical product programs.

The food safety portion of the budget includes $263 million in increased funding — including $253 million to implement the landmark Food Safety Modernization Act or FSMA. That 2011 law provided FDA with the authorities and mandates to build a modern domestic and imported food safety system designed to prevent rather than react to food-borne illness. Every year, contaminated food sickens about 48 million Americans and kills about 3,000.

FDA estimated in 2012 that it would need $400 million to $450 million to implement FSMA. Since then, the agency has received $78 million and issued proposed rules for all seven of the foundational provisions of FSMA.

Most of the $253 million proposed for FY 2015 would come from new user fees for imported foods, imposed on the industry. It’s worth noting that with current resources, we will still be able to issue the rules, but we won’t be able to effectively implement them and improve food safety without new resources to retrain inspectors, provide guidance and technical assistance to industry, partner with state agencies and build the modern import safety system Congress mandated.

The budget contains one final broad category of note, promoting the development of products that can be used to prevent or protect the public from bioterrorism. These medical countermeasures promote readiness against deliberate and naturally occurring public health threats. The FY 2015 budget includes $25 million for this initiative, the same as in FY 2014.

The FDA delivers significant results that help Americans every day in many different ways. FDA’s drug approval system continues to lead the world in both quality and speed. The agency approved 27 drugs that are entirely new to medicine in 2013, including advances in the treatment of rare forms of cancer and a virtual cure for Hepatitis C. The FDA approved a new flu vaccine, and a bird flu vaccine to be reserved in case of an outbreak. In addition to new drug approvals, the FDA has reduced the time it takes to review new medical devices. And the agency is promoting greater safety of cosmetic products. Finally, the FDA has made progress in carrying out new tobacco control legislation.

Americans rely on the FDA to keep their food and medical products safe and effective. The Fiscal Year 2015 budget contains the blueprint for how the FDA plans to accomplish this mission. We invite you to follow this link to peruse the details of the FDA budget of greatest interest to you.

William Tootle is Director of FDA’s Office of Budget

Supporting Innovative Research Through Regulatory Science

By: Carolyn A. Wilson, Ph.D.

In my last blog post I discussed aspects of regulatory science, that is, how scientists in FDA’s Center for Biologics Evaluation and Research (CBER) help to turn innovative medical research into life-saving or life-enhancing biological products. I also described how FDA scientists help determine if potential health problems are linked to the use of a particular medical product. In this post, I’ll discuss two more studies that made important contributions to public health.

Carolyn WilsonSometimes CBER research changes the way scientists look at a problem so their research is more efficient. For example, in the field of gene therapy, a strain of the common cold virus called an adenovirus, is used as a vector – delivering therapeutic genes to treat both inherited and non-inherited conditions. However, success of this therapeutic approach has been hampered in part by the finding that an immune response to the adenovirus may prevent efficient delivery of the therapeutic genes to their targets, such as cancer cells. The problem appeared to be that once inside the body, the adenovirus attaches a blood clotting protein called FX to itself and binds to liver cells. As a result the vector doesn’t reach the desired target cells where it would deliver the therapeutic gene.

Some scientists thought that altering the virus so it couldn’t bind FX would let it avoid the liver, making it a more efficient vector. However, scientists in the Office of Cellular, Tissue and Gene Therapies (OCTGT) discovered that adenovirus commandeers the FX protein to use as a shield to evade attack by the immune system. So removing it would likely enable the immune system to attack and disable the adenovirus and block treatment. This new knowledge that the adenovirus needs FX to disguise itself from the immune system will help guide researchers to design gene therapy vectors that survive in the bloodstream and reach their desired target cells.

Another group of scientists, in the Office of Blood Research and Review (OBRR), has contributed to our understanding of why African Americans are significantly more likely than whites to produce antibodies against a drug used to treat hemophilia A. People with hemophilia A carry a mutation in the gene for the protein Factor VIII (FVIII) – a protein that plays an essential role in clotting and preventing blood loss. This mutation either eliminates or greatly reduces the amount of Factor VIII in the blood. Fortunately, there is a therapeutic form of FVIII made through biotechnology that is used to replace faulty or missing, natural FVIII. But unfortunately, some African Americans with hemophilia A make antibodies against therapeutic FVIII. These antibodies attack it and disrupt treatment. The FDA scientists discovered certain genetic variations in the gene for Factor VIII made by these individuals that appear to be responsible for this immune system attack. The discovery is an important step in developing ways to predict which patients will develop antibodies against this complication. And that is an important step toward developing a personalized-medicine approach to hemophilia A by custom-designing medical responses to this life-threatening disease.

The examples I’ve given of CBER research here and in my previous blog are just a small sample of the important knowledge our scientists are creating that supports efforts of medical researchers striving to develop products that improve public health nationally and globally.  In 2013, CBER scientists published their research findings in over 200 journals and books.

I’ll be back to update you on more exciting research from CBER during 2014.

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

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