FDA Wants Your Perspective on Clinical Trial Demographic Data

By: Jonca Bull, M.D.

When designing clinical trials, it is essential to test the safety and effectiveness of medical products in the people they are meant to treat. Although FDA’s policies, guidances, and regulations reflect decades of agency efforts to foster the participation of diverse patient populations in clinical trials, more work is required.

Jonca Bull (2488 x 3738)FDA is seeking your comments on this important public health issue. On Tuesday, April 1, 2014, we’re holding a public hearing on the challenges of collecting and analyzing information on demographic subgroups—including sex, race, ethnicity and age—in clinical trials for FDA-regulated medical products.

We’re looking for ideas and viewpoints from our stakeholders—from clinical researchers, academia, industry, health care professionals and patient advocates. As director of FDA’s Office of Minority Health, I’m inviting you to attend this hearing in person or online, or to submit your comments before or after the hearing on issues that are vital to you.

Your perspectives will be critical as we develop our FDA action plan for improving public health across all demographic groups. The action plan will include recommendations on ways to enhance the collection and analysis of information about the sex, race, ethnicity, and age of clinical trial participants in applications that medical product developers submit for FDA review and approval. We are also seeking ideas and views about how to improve the communication of crucial information on medical products to patients, health care professionals and researchers.

Recently, in Section 907 of the Food and Drug Administration Safety and Innovation Act of 2012, Congress asked FDA to produce a report on this topic and to follow it up with an action plan. In the development of the report, FDA carefully examined 72 product applications approved in 2011.

We determined that the statutes, regulations and policies we have in place generally give drug developers a sound framework for providing information in their applications on the inclusion and analysis of these demographic groups. We also found that medical product developers generally are describing the demographic profiles of their clinical trial participants, and most applications submitted to FDA include analyses of these demographics.

However, we recognize that more can be done. So, as part of the process of developing FDA’s action plan, we’re holding this public hearing to get your views on these and related issues. We can’t do this without your help, so we hope you’ll join us at the hearing in person or online on Tuesday, April 1!

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

Women Scientists at FDA: A Legacy to be Proud Of

By: Suzanne Junod, Ph.D.

This is National Women’s History Month, a good time to reflect on FDA’s history of advancing women as scientists and health professionals. This tradition began with FDA’s predecessor in the late 19th and early 20th centuries, the Bureau of Chemistry in the Department of Agriculture. Several early female FDA scientists came out of the University of Pennsylvania, one of the first universities in the country to offer women chemistry degrees in the late 19th century.

Suzanne JunodHarvey Wiley, known as the Father of the 1906 Pure Food and Drugs Act and its “crusading chemist,” hired FDA’s first female laboratory chief. When his superiors found out that the “M. E. Pennington” he had selected to head a research laboratory was actually Mary Engles Pennington, he successfully argued that since she had received the top score on the Civil Service exam, he had no grounds on which to refuse her the position.  His argument carried the day.

Frances Kelsey, who had earned both an M.D. and a Ph.D. in pharmacology, was hired by FDA in 1960 as a medical officer. She came into the agency with top scientific credentials and a strong research background. In part, it was her experience with animal research that led her to question the effects of the drug thalidomide on fetal animals when that drug was submitted for FDA review. She had still not received a satisfactory answer to that question when the dangers of thalidomide became known and it was discovered to be a potent teratogen, an agent that can lead to birth defects. Thalidomide was never approved for marketing in the U.S.

FDA’s first women field inspectors, in contrast, were hired only after President Lyndon Johnson declared that the federal government would lead the way in implementing the 1964 Civil Rights Act. Imogene Gollinger, the first woman hired, had a degree from New York University and experience as a science teacher. She recognized that she was given the “opportunity of a lifetime” and happily reported to FDA wearing white gloves and a hat, which were immediately exchanged for standard-issue coveralls.

The concerns about women being able to keep up with the men proved to be misplaced. Gollinger was teased for buying a shopping cart to carry her heavy bag of inspector’s equipment, but she soon noticed men using them as well. While women willingly did the heavy and dirty field work, such as climbing into boxcars to obtain grain samples, they were increasingly drawn to investigative work involving piecing together data rather than simply gathering samples for analysis. For the female inspectors, compliance activities soon began to gain parity with traditional field sampling in FDA’s field operation.

Today, women make up approximately 59 percent of FDA’s work force, all of whom are involved in protecting and promoting public health. This is a legacy to be proud of as we celebrate women’s history.

Suzanne Junod, Ph.D., is an Historian at FDA.

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Homing in Faster on Potentially Deadly Bacteria in Food

By: Nilda E. Villegas

Whether an outbreak of foodborne illnesses is caused by Listeria in cantaloupe, E.coli in salad or Salmonella in peanut butter, the faster the disease-causing bacteria are identified, the more illnesses can be averted.

Nilda VillegasLast year scientists based in FDA’s San Juan Laboratory were endowed with seed funding through a Health and Human Services HHSignite award to adapt traditional chemistry methods for the detection of foodborne pathogens. HHSignite (beta) is an internal competitive seed-funding opportunity to test new and unconventional ideas within HHS.

The team is being led by LCDR José Moreno of the U.S. Public Health Service, a microbiologist in FDA’s San Juan Laboratory. Working with Moreno on this project are Joseph Bloom, Ph.D., San Juan Laboratory science advisor, supervisory chemists Adalberto Cajigas and Héctor Espinet, science advisor Osvaldo Rosario, Ph.D., chemist Miguel A. Martínez, and staff fellow Fernando González, Ph.D.  FDA’s San Juan scientists were among 13 teams within HHS to receive such funding when Secretary Sebelius announced the finalists in June 2013.

San Juan Laboratory Team: Left to right in the back: Dr. Joseph Bloom, Dr. Osvaldo Rosario and Dr. Fernando González; standing in front Miguel A. Martínez and LCDR José Moreno.

San Juan Laboratory Team: Left to right in the back: Dr. Joseph Bloom, Dr. Osvaldo Rosario and Dr. Fernando González; standing in front Miguel A. Martínez and LCDR José Moreno.

Their proposal is to assess the utility and practicality of coupling CE-MS, which stands for Capillary Electrophoresis coupled with a Mass Spectrometer, that promises to be the workhorse of many analytical chemistry laboratories for use in identifying pathogenic microorganisms through the identification of specific proteins associated with pathogenicity by their fragmentation patterns. This essentially identifies specific “fingerprints” for disease-causing bacteria, such as E. coli, Salmonella, Listeria and Staphylococcus, in foods.

The research undertaken by Moreno and his team could result in faster screening methods for a wide array of pathogens as part of FDA’s food safety and food defense programs.

What’s next?

The San Juan team is continuing their research on this innovative screening tool to reduce testing times even more, and coordinating their efforts with their scientific colleagues in our Office of Regulatory Affairs and in our Center for Food Safety and Applied Nutrition on the mainland to protect the safety of the U.S. food supply.

Nilda E. Villegas is a Public Affairs Specialist in the San Juan District Office, part of FDA’s Office of Regulatory Affairs

FDA’s New Acting Chief Scientist Talks about His Office’s Vital Role

By: Stephen Ostroff, M.D.

This is a very exciting time to be stepping into the position of Acting Chief Scientist at FDA. A relative newcomer to the agency, I joined FDA’s Center for Food Safety and Applied Nutrition seven months ago as chief medical officer and senior public health advisor for the Office of Foods and Veterinary Medicine.

Stephen OstroffBut as the former deputy director of the National Center for Infectious Diseases at the Centers for Disease Control and Prevention and director of the Bureau of Epidemiology at the Pennsylvania Department of Health, I often worked with colleagues at FDA and have a solid appreciation for FDA’s public health mission and the pivotal role science plays in everything FDA does. So, I’m very enthusiastic about continuing the development of FDA’s scientific enterprise and positioning the Office of the Chief Scientist (OCS) to best support the agency’s scientific programs.

I’d like to take the opportunity over a series of blogs to discuss the important role that OCS plays in keeping our foods safe and nutritious and in getting essential therapies to the people who need them.

FDA has grown from a lone chemist in the U.S. Department of Agriculture in 1862 to an agency with a staff of 14,600 employees. More than 65% of them are scientific and technical staff, representing disciplines such as biologists, nurses, pharmacists, physicians, veterinarians, behavioral scientists, statisticians, epidemiologists, economists and engineers.

FDA requires this breadth and depth of expertise to ensure that science informs the decisions we make about the safety and effectiveness of drugs, biologics, and medical devices, the safety of foods and cosmetics, and the regulation of tobacco products, particularly as those products become increasingly complex. Only then can the public be confident that these products are rigorously reviewed and assessed before and after they go to market.

Transformative changes in society and technology over the past several decades have created numerous opportunities to improve public health. They’ve also created challenges affecting FDA-regulated products and the way FDA conducts its operations.

For example, globalization is bringing an increasing volume of foods and drugs to our shores, often produced in countries that may not have our high standards of regulatory oversight. New areas of science and rapidly evolving technologies are showing real promise in our ability to prevent and cure some of today’s biggest killers, such as diabetes, cancer, and Alzheimer’s.

To meet these challenges, we are “advancing regulatory science.” In other words, we are developing the new tools, methods and approaches that will be needed for a globalized regulatory environment and for translating new discoveries into innovative medical treatments. But advancing regulatory science research and training requires multidisciplinary and interdisciplinary collaboration within FDA and with our partners in academia, industry, other government agencies and with patient advocates. OCS works to meet these goals by strengthening FDA’s scientific infrastructure, forging a common vision, and working with our stakeholders to identify critical regulatory science and innovation needs.

In my future blogs, I will discuss examples of the exceptional work underway in the different OCS components—the National Center for Toxicological Research (NCTR), the Office of Counterterrorism and Emerging Threats, the Office of Minority Health, the Office of Regulatory Science and Innovation, the Office of Scientific Integrity, the Office of Scientific Professional Development, and the Office of Women’s Health. I can think of no more exciting place to be than at the core of FDA’s pioneering regulatory science culture.

Stephen Ostroff, M.D., is FDA’s Acting Chief Scientist

Sentinel: Harnessing the Power of Databases to Evaluate Medical Products

By: Michael D. Nguyen, MD

Clinical trials are designed to evaluate the safety and effectiveness of medications. But the number of participants in clinical trials represents only a fraction of the number of people who will ultimately use the product after FDA approves it. Occasionally, rare and unexpected health problems (which we call “adverse events”) become apparent only after a medical product is on the market and many more people use it. That’s why it’s so important for FDA to continue to monitor the safety of medical products, a practice called surveillance.

Michael NguyenMost safety surveillance systems are passive: They rely on health care professionals and consumers to notice and report adverse events. Although these passive systems remain essential, they have certain limitations. For example, health care professionals and consumers might not recognize that the product is the cause of an adverse effect and not report it to FDA. Or, they might report a suspected adverse event that’s not truly the cause of a problem the consumer experiences.

Now imagine if we could actively search more than 100 million health insurance records to uncover possible adverse events, rather than relying on doctors and patients to report them. Such a system would enable us to get continuous feedback on the use of medicines under real-world conditions – feedback that might help us to discover unexpected patient reactions or unexpected drug interactions.

FDA scientists have partnered with the Harvard Pilgrim Healthcare Institute to create such a surveillance system, called Sentinel. Within Sentinel, FDA has supported the development of software that analyzes information from health insurance and health record databases to search for evidence that certain products are linked to specific adverse effects. Although these data are protected behind tight firewalls and remain under the control of the original health insurance plans that created them, the software makes it possible to analyze the information without disclosing identifying information in order to strictly maintain patient privacy.

FDA and Harvard Pilgrim Healthcare Institute are using this surveillance system to determine whether a certain type of immune therapy is associated with heart attacks or strokes, and to better define the true rate of acute lung injury after transfusions of certain blood components.

More recently, FDA completed its first study using the Sentinel system, which evaluated the safety of the two current vaccines (RotaTeq and Rotarix) that prevent rotavirus infection (the leading cause of severe diarrhea and dehydration in infants). The new study revealed that these rotavirus vaccines slightly raise the risk of a rare bowel problem (intussusception) that previously caused a prior rotavirus vaccine (Rotashield ) to be voluntarily withdrawn from the market by its manufacturer. But the Sentinel study showed that the newer vaccines have a much lower rate of this bowel problem and are safer, with the benefits outweighing the risks, including the risk of intussusception, associated with vaccination.

The Sentinel rotavirus vaccine and immune therapy studies are examples of how FDA scientists are harnessing the power of big electronic databases to ensure the safety of the medical products we use every day.

Michael D. Nguyen, MD, is the Acting Director of the Division of Epidemiology in FDA’s Center for Biologics Evaluation and Research

Mexico and the U.S.: Progress on Food Safety Partnerships

By: Michael R. Taylor

En Español

Spring may be on the way, but it’s still winter weather in most areas of the country. If you are enjoying fresh avocados, berries or grapes, there is a good chance they came from Mexico. In fact, about two-thirds of the fresh produce imported into the United States comes from our neighbor to the south.

Food safety meeting attendees, Tubac, Arizona

Food Safety Meeting attendees, from left to right:
Samir Assar, Director, Produce Safety Staff
Bonnie Fernandez-Fenaroli, Executive Director, Center for Produce Safety – UC Davis
Lance Jungmeyer, President, Fresh Produce Association of the Americas
Hugo Fragoso Sanchez, General Director of Food Safety for Food, Agriculture and Fisheries, SENASICA
Walter Ram, Vice President of Food Safety, The Giumarra Companies
Mike Taylor, Deputy Commissioner for Foods and Veterinary Medicine

Ensuring the safety of imported produce is a major focus of FDA’s food safety strategy. That is why I am in Tubac, Arizona to meet with Mexican government officials and producers of fresh fruits and vegetables from both sides of the border. The meeting is sponsored by the Fresh Produce Association of the Americas and the Center for Produce Safety in Davis, California – two organizations that take food safety very seriously.

There’s no substitute for face-to-face meetings like this to move the needle forward on food safety. Under the Food Safety Modernization Act (FSMA), FDA is developing standards for produce safety that, when implemented, will raise the food safety bar for produce sold in the U.S., whether grown here or in other countries. However, we also have to focus on how the new standards can be effectively and efficiently implemented. How will government and industry – both in the U.S. and abroad – operate under the new requirements? How can we take best advantage of our collective efforts to understand and prevent foodborne hazards and verify that applicable standards have been met? That, after all, is where the rubber meets the road.

We don’t have all the answers yet, but we do know we can’t do it alone. I’m joined in Tubac by Samir Assar, who heads FDA’s Produce Safety Team, Dominic Veneziano, who directs our import operations; and Bruce Ross, deputy director of FDA’s Latin America office. And we are sharing the podium with Hugo Fragoso Sanchez from SENASICA and Mario Alanis Garza from COFEPRIS – the two Mexican agencies with which we have long worked closely on food safety.

Historically, our government-to-government collaboration has come mostly in response to outbreaks, import alerts and other incidents. Now, we are focused on work we can do together to better understand potential foodborne hazards and take risk-based steps to prevent or minimize them. This means building partnerships to implement FSMA in the United States and at our common border, as well as collaborating with Mexico to support its food safety modernization initiatives.

Food safety partnerships – at the U.S.-Mexico border and across the food system – must, of course, extend well beyond government. The food safety practices of growers and processors, coupled with private sector supply-chain management, are what make food safe. Government establishes the common base of standards and provides a measure of public accountability for food safety, but verification that standards are being met is a joint public-private effort.

So, we are taking advantage of the Tubac meeting to talk to members of the produce industry about how public and private verification efforts can mesh. Our goal is simple: We want to provide the high levels of assurance about the safety of produce and other food that FSMA calls for and consumers expect. And, in a world of finite resources, we can do that only by relying, where possible, on others to complement our own efforts, and by avoiding duplication.

The next step in building our partnership with Mexico is a three-day meeting in late March with our SENASICA and COFEPRIS colleagues that we will be hosting at our Silver Spring, MD, headquarters. That discussion will build on past collaborative efforts on training, laboratory coordination, risk assessment and outbreak response, but it will be looking ahead to how we can build partnerships for the prevention of food safety problems. After the meeting, we will also be engaging our private stakeholders – industry, consumers, and academia – in this dialogue.

“Partnership” is an easy word to say, but making it real is hard work. We have to learn, continuously, about and from each other; and we have to deal with hard issues in order to expand and align our capacities, share data and information across both public and public-private lines, and build the trust that is the basis for mutual reliance. Some of this will be hard, but we wouldn’t be in Tubac if we didn’t think it were possible – and if we didn’t know active partnership is essential to achieving the food safety goals we all share.

We’ll keep you posted on our progress.

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

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.