Crafting better drug labeling to ensure safer use of opioids

By: Margaret A. Hamburg, M.D.

One of the FDA’s primary public health missions is ensuring that healthcare providers and their patients have all the information they need to help decide whether a medication is safe and appropriate to use.

Margaret Hamburg, M.D.Communicating the full risks and benefits of a drug becomes all the more important for those medications that are potentially deadly if used incorrectly. Extended-release long-acting(ER/LA) opioids fall into that category, and can sometimes cause serious harm, like addiction, even when used properly.

These medications, which include drugs such as morphine, oxycodone, and fentanyl, can improve the quality of life for many people who must live every day with pain. But ER/LA opioids often also contain a large amount of the active ingredient, sometimes in sufficient quantity to be lethal, and they are a prime target of drug abusers.

As part of FDA’s efforts to address the serious risks of ER/LA opioids, we looked more closely at the product labeling, known by many as the package insert, to determine whether this essential tool for conveying information about a drug should be revised to encourage safer use.

We closely reviewed medical literature and evaluated public input. We then came to the conclusion that if we improved what the labeling says about proper patient selection and the risks from these drugs, we might be able to reduce the frequency of bad outcomes.

And so today I’m pleased to announce new, proposed labeling changes for ER/LA opioid pain relievers, as well as new postmarket requirements that will include additional studies and clinical trials to better assess certain significant questions about the risks and safety practices of these drugs. The goal is to achieve safer and more appropriate use of these potent pain relievers.

These labeling changes better describe the risks associated with the ER/LA opioid medications and clarify the population for whom the benefits of these products outweigh their risks.

Rather than stating that these medications are indicated “for the relief of moderate to severe pain in patients requiring continuous, around-the clock opioid treatment for an extended period of time,” once final, the updated label will clarify that these products are indicated for “management of pain severe enough to require daily, around the clock, long-term opioid treatment and for which alternative treatment options are inadequate.”

And in the section of the label regarding limitations of use, we have added language plainly stating just how risky these drugs are — even at recommended doses.

In addition, we are requiring changes to the boxed warning for these products to give greater emphasis and prominence to the risk of Neonatal Opioid Withdrawal Syndrome that may occur in newborns due to prolonged opioid exposure during gestation.

We know that the way a patient characterizes pain is always going to be subjective: “moderate” pain for one patient may be “severe” pain to another. And we recognize that there are some women who have an appropriate need for opioids during their pregnancy.

The goal of all of these labeling changes is to help physicians work with their patients to determine whether these potent pain relievers are the most appropriate treatment for their specific situation and if so, to help them in managing their use.

While our intent is to encourage safer and more appropriate use of these products, simply changing the labeling won’t make an impact if these changes are not understood and integrated into practice by healthcare providers. So I am urging prescribers to spend some time going over this new labeling, when final, reflecting on what the language means to their practice, and communicating what they’ve learned to their patients.

The fact is, improving the safe and appropriate use of ER/LA opioids takes the help and commitment of all of us, including our partners in the healthcare community. We are committed to working together to help ensure that healthcare providers can prescribe ER/LA opioids properly and better monitor and educate their patients.

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

CFSAN: Pinpointing Priorities, Protecting the Public Health

By: Michael Landa 

When I started my first tour with FDA in 1978, I could not have foreseen the challenges we would face today in our mission to protect and promote the public health. 

Who could have predicted the expanding globalization of the food supply? Or the extent to which technology would transform the foods and cosmetics industries and the ways we regulate them? Who knew that today many consumers would be committed to eating fresh, minimally processed, locally sourced foods? 

As director of the Center for Food Safety and Applied Nutrition (CFSAN) at FDA, I have seen these and other developments in the shifting landscape of food and cosmetic safety. And I am responsible for helping to establish the priorities that will guide our work. 

To this end, I am pleased to share with you the CFSAN Plan for Program Priorities, 2013-2014. The two-year plan - which is well underway at this time – identifies six key program goals and details how we will achieve them. The goals are: 

  1. Reduce foodborne illness rates and cosmetic injury rates each year.
  2. Establish regulations, policies, guidances, and inspection and compliance strategies based on the best science and strategies for prevention and minimizing public health risk.
  3. Increase compliance with new controls focused on preventing foodborne illness and other health hazards. This includes promoting best agricultural practices to farmers, educating consumers on safe food handling practices, and ensuring that safety standards are consistent for both foreign and domestic foods and cosmetics.
  4. Implement science-based strategies that facilitate healthy diets.
  5. Develop and swiftly deploy the fastest, most effective methods for identifying, containing, and eliminating food and cosmetic hazards.
  6. Achieve optimal use of staff and resources. This includes strengthening leadership and management capabilities, enhancing relationships with other regulatory entities at home and abroad, and reviewing and clarifying administrative roles and responsibilities. 

This is not by any means an exhaustive list of all CFSAN initiatives. The Center is continuing other important work that includes reviewing manufacturer premarket notifications for infant formulas; carrying out pre- and post-market regulation of food ingredients and packaging; monitoring for the presence of chemical contaminants in regulated products; authorizing health and nutrient content claims on food products; seeing to it that violative product labeling for cosmetics is corrected; and reviewing premarket notifications for new dietary ingredients in dietary supplements.  

We remain focused on dedicating our resources – human and otherwise – to meeting all of these goals and responding to the challenges ahead.

I encourage you to look at the strategies we will use and the regulatory blueprints we will follow to ensure that the foods you eat and the cosmetics you and your family use are safe. 

Michael M. Landa is Director of FDA’s Center for Food Safety and Applied Nutrition

On Farms and in Labs, FDA and Partners Are Working to Get Answers on Arsenic in Rice

By: Margaret A. Hamburg, M.D.

This week, my colleagues and I traveled to California to learn more, first-hand, about the presence of arsenic in rice.

FDA Commissioner Margaret Hamburg and Deputy FDA Commissioner for Foods and Veterinary Medicine Michael Taylor, center, don hip waders to go out into the rice fields at Lundberg Family Farms in Richvale, Calif. At left is Bryce Lundberg, the farms' vice president of agriculture, and at right is Mike Denny, vice president of farming operations.

This grain, like other foods, contains traces of arsenic, a chemical element found in water, air and soil. However, rice plants absorb more arsenic than most other crop plants. FDA has been monitoring arsenic levels in foods, including rice, for decades.

On Wednesday, Sept. 4, we toured a research facility in which scientists are working to find ways to improve the quality and safety of rice. And we visited the historic farming community of Richvale — a short drive north of Sacramento — known as the birthplace of California rice.

In each of these places I saw a true commitment to public health and a shared goal of ensuring that any risk is minimized so that people around the world can continue to eat rice and rice products as part of a varied diet.

Today, FDA released the results of tests performed on a total of more than 1,300 samples of rice and rice products. What we found was that the levels of inorganic arsenic are well below the levels that would result in any immediate or short-term health risks. This information will now be considered by FDA in looking at the potential long-term health effects associated with the consumption of arsenic in rice and rice products.

Our visit to California, at the invitation of the rice industry – including the USA Rice Federation – was FDA’s third fact-finding visit to rice-producing states, the earlier trips being to Arkansas and Missouri. My traveling companions included Michael Taylor, FDA’s Deputy Commissioner for Foods and Veterinary Medicine, and Andy Hammond, regional director of the U.S. Department of Agriculture’s Agricultural Research Service (ARS).

Our first stop on Wednesday was at the Rice Experiment Station in Biggs operated by the California Cooperative Rice Research Foundation. Research at the station is funded in large part by assessments on rice growers and involves close collaboration with experts at the University of California/Davis and ARS.

Touring the station’s research fields gave us a sense of the determination by all involved in this work, including industry, to better understand how arsenic gets into rice and what growing and processing strategies might be employed to reduce arsenic levels.

That afternoon we visited two multi-generation family farms in Richvale. Lyle Job and his family have been farming their land for more than 30 years. At the Lundberg Family Farms, in business since 1937, we learned about the different approaches of organic rice farmers.

These farmers take enormous pride in their work. They told us about the soil and climate conditions that make their land ideal to grow rice. At the Job farm, we climbed up into a huge harvester to see how it operates. At the Lundberg farm, we put on hip boots and waded out into flooded fields.

Standing beside these farmers, I was struck by their commitment to making the best product possible and the intensity of their desire to help us understand the challenges they face. Rice is not just a commodity to them; it’s their way of life.

Our last stop, on Thursday, Sept. 5, was to FDA’s laboratory in Alameda, where hundreds of rice samples were tested using a process called “speciation.” FDA scientists developed the speciation method used to measuring total arsenic levels, but most importantly to measure both the organic and the more toxic inorganic forms of arsenic.

So what does this all mean right now? As a mother I can imagine that many of you are asking yourself, “Should I be feeding it to my children?” Our best advice – consistent with that given by the American Academy of Pediatrics – is to eat a well-balanced diet that includes a variety of grains.

We don’t have all the answers yet, but we’re working on it. In collaboration with farmers, industry, academia and other public health agencies, we are doing everything possible to determine if the levels of arsenic in rice pose a long-term health risk and, if so, what can be done to reduce that risk.

The presence of arsenic in rice is a global health issue. The answers we seek will ultimately help protect consumers all over the world.

For more photos of our tour, visit Flickr.

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

FDA Builds on Experience and Cooperation to Respond to Foodborne Illness Outbreaks

By: Kathleen Gensheimer, MD, MPH

Two years ago, FDA put the Coordinated Outbreak Response and Evaluation (CORE) Network in place to improve the response to outbreaks of foodborne illness. In fact, the very day FDA announced the group’s formation, CORE was already responding to one of the deadliest foodborne illness outbreaks in decades. Sadly, that outbreak of Listeria monocytogenes linked to cantaloupe caused 33 deaths. However, through the coordinated efforts of the FDA, the Centers for Disease Control and Prevention (CDC), and state and local governments, the outbreak was stopped and lives were saved. 

Recently the New England Journal of Medicine published an article on that outbreak, so I thought I should revisit FDA’s role in the response and its actions to help prevent future outbreaks like this.

Just before the Labor Day weekend in 2011, Colorado state health officials announced that the number of listeriosis cases in that state was three times more than normal for August. FDA worked with the CDC and state partners on the issue and it was suspected that illnesses, spread over several states, might be linked to Colorado-grown cantaloupe. 

FDA quickly mobilized its field investigators and subject matter experts. Cantaloupe samples FDA collected from stores were found to be contaminated with Listeria monocytogenes. FDA reviewed records to determine the potential growers of these cantaloupes. Investigators from FDA and the state of Colorado inspected one of these growers, Jensen Farms, and collected cantaloupe samples and swabs of surfaces at the Jensen Farms packing house. Those samples were found to contain Listeria monocytogenes with the same DNA fingerprint that had been isolated from people who became ill. Shortly afterwards, Jensen Farms began a product recall. 

While FDA monitored recall activities, it also coordinated an environmental assessment at Jensen Farms. With Jensen Farms’ cooperation, experts in food safety, health, and agriculture from FDA, CDC, the Colorado Department of Public Health and Environment, the Colorado Department of Agriculture, and the Prowers County Department of Health worked to identify conditions or procedures potentially contributing to the outbreak. 

This team found, among other things, that the packing house floor allowed water to pool, the design of equipment made it difficult to clean and sanitize, and the temperature of the cantaloupe when they were refrigerated allowed moisture to form on them and may have allowed bacteria to grow. To inform the food industry and help them avoid similar problems, FDA made these findings public. As a result, the industry took a number of steps to enhance cantaloupe safety, one of which was to issue updated national food safety guidelines for cantaloupes

In addition, this year FDA initiated inspections and sampling at cantaloupe packinghouses in the United States to assess the current practices and conditions that may affect the safety of cantaloupe distributed to consumers.

Since that first test of FDA’s improved foodborne outbreak response, FDA has responded to more than 80 outbreaks of varied scope, severity and complexity.   

For example, in an outbreak linked to scrape tuna in sushi, a product recall protected consumers from more than 58,000 pounds of tuna that was potentially contaminated with Salmonella. In another outbreak related to Salmonella in peanut butter, we used a new authority granted by the FDA Food Safety Modernization Act (FSMA) to suspend the registration of a food processor, which effectively prohibits the distribution of potentially unsafe food domestically or abroad. 

Over the past two years, we have learned what works best and improved procedures to continue to protect consumers from contaminated food. That progress would not have been possible without the close collaboration with our many partners at the local and state public health and agriculture level, as well as with our federal partners within CDC, U.S. Department of Agriculture and FDA. 

We look forward to continued partnership and progress in the years to come. 

Kathleen Gensheimer, MD, MPH, is Chief Medical Officer and FDA’s Director of Outbreak Investigation and Response

The path toward a risk-based regulatory framework for health IT

By: Jodi Daniel, Bakul Patel and Matthew Quinn 

Yesterday, the Health IT Policy Committee (HITPC) accepted and approved recommendations from the Food and Drug Administration Safety and Innovation Act (FDASIA) working group for a risk-based regulatory framework for health information technology. The working group’s recommendations suggest a scope for an IT framework, risk and innovation criteria, and approaches for avoiding regulatory duplication. 

Only six short months ago, the Food and Drug Administration (FDA), the Office of the National Coordinator for Health IT (ONC), and Federal Communications Commission (FCC) kicked off the FDASIA workgroup of the HITPC to provide stakeholder input into a report on a risk-based regulatory framework that promotes safety and innovation and reduces regulatory duplication, consistent with section 618 of FDASIA. This provision permitted the Secretary of Health and Human Services (HHS) to form a workgroup in order to obtain broad stakeholder input from across the health care, IT, patients and innovation spectrum. The FDA, ONC, and FCC actively participated in these discussions with stakeholders from across the health care, IT, patients and innovation spectrum. The working group met more than 28 times, and yesterday FDASIA workgroup chair, David Bates, presented the final recommendations to the HITPC. 

In recognition of this important milestone, and on behalf of the three agencies, we want to express our deep appreciation to the members of the workgroup (and a special thanks to David Bates) for committing themselves to this aggressive timeline and delivering a suite of thoughtful recommendations.

Next Steps

As the FDASIA workgroup’s efforts conclude, the agencies’ efforts now intensify. Over the next few months the FDA, ONC, and FCC will review the HIT Policy Committee’s recommendations and the public comments submitted through the docket we opened on regulations.gov. Using these thoughtful inputs, ONC, FDA, and FCC will work closely together to develop a report (by the January 2014 statutory deadline) that proposes an overarching health IT regulatory strategy and provides recommendations on ways to appropriately promote innovation, protect patient safety, and avoid regulatory duplication. 

We recognize the complex nature of health IT and its importance to our nation’s health.  Therefore, we intend to provide an opportunity for public comment and additional stakeholder input on the draft report following its publication in January 2014. We look forward to continued collaboration with all stakeholders as we advance our thinking on this important topic. 

Jodi Daniel is Director, Office of Policy and Planning, Office of the National Coordinator for Health IT

Bakul Patel is Senior Policy Advisor, FDA’s Center for Devices and Radiological Health

Matthew Quinn is Director of Healthcare Initiatives, Federal Communications Commission (FCC)

FDA Systems Recognition: Ensuring Imported Foods Are Safe

By: Julie Callahan

FDA works on many fronts when it comes to making sure our food supply is safe—not just the foods we grow and process here in the United States, but also those that are shipped here from overseas.

And there are many. In fact, imports of food to the U.S. have more than doubled in the past decade.      

FDA has systems in place to help ensure that foods imported are as safe as those produced in the U.S., and under the FDA Food Safety Modernization Act (FSMA), consumers can have even more confidence in the safety of imported food.  Under FSMA, FDA is setting standards for domestically produced and imported foods that would prevent contamination and is requiring that importers verify that their overseas suppliers are producing food consistent with these requirements. 

But FDA has even more tools in its toolbox to make imported food safer. For example, FDA is working with countries to build their capacity so that their food safety systems improve. FDA also wants to recognize countries that are so reliable that we can consider them “comparable.” 

New Zealand is the first country with which FDA completed a systems recognition assessment, and we signed a systems recognition arrangement with its food safety authority, the Ministry for Primary Industries, in December 2012. Today, we published “Information for Foreign Governments: Frequently Asked Questions on Systems Recognition,” to provide more information on this topic.

Recognition under this new program, which we continue to pilot test, is a high bar to reach. These are countries that have preventive, risk-based programs in place and can respond and follow up on any food safety incidents that may occur. In recognizing countries under this program, we want assurance that the country’s authorities will be able to swiftly track down the source of a foodborne illness and take corrective actions as necessary to stop it in its tracks—and to help prevent such an incident from happening again. 

If a country does not have a systems recognition arrangement in place it can still export products to the U.S. However, participating in a reciprocal systems recognition arrangement with the FDA offers countries that have very robust food safety control systems an opportunity to participate in a closer regulatory partnership. For example, with New Zealand, we can use some of the data they generate to help us make decisions about their imports. We can also use systems recognition determinations as one factor in prioritizing resources dedicated to foreign facility inspections, import field exams, and import sampling. 

As we tackled ways to identify the top-performing food safety systems in an objective, transparent, and importantly, reproducible way, we first looked at the way that we evaluate our own food safety programs in every state. In doing so, we developed the International Comparability Assessment Tool (ICAT). The ICAT is based on the approach that we use here in the U.S.; that is, evaluating all aspects of the system, from the regulatory foundation, to training, inspection, compliance programs, and how outbreaks and trace-backs to identify the contaminant are conducted.

Under systems recognition we assess a country’s entire food safety control system, from soup to nuts and every other food that FDA regulates. Of course, how things look on paper doesn’t always reflect how they work in practice. So we include on-site reviews as part of the systems recognition assessment process, to see first-hand how a country implements the programs they’ve described in the ICAT. It’s the difference between actually using a Smartphone and just reading the user manual.

Why New Zealand? In the past, New Zealand and the U.S.had certain commodity-specific arrangements in place, such as ones for seafood and certain dairy products. Our next scheduled review of these arrangements coincided with the time FDA was starting to develop its systems recognition program. As we were already working closely with New Zealand to update these arrangements, it made sense to expand our review.

Here’s where things get interesting.

Recently, you may have seen New Zealand’s food safety system in the news, associated with a potentially contaminated whey protein product commonly used in infant formula and sports drinks. Although the product had not been exported to the U.S., the New Zealand authorities discovered that a package of 21 candy bars containing whey protein from the potentially dangerous batch had been sent to a company here for market testing. As soon as they identified the product, they contacted FDA to let us know that they had traced it to a particular company and had contacted the company. They made sure that the product had not been sold to any consumers in the U.S. and accounted for all of the candy that had been shipped here.

In the end, the whey protein that was recalled had not been contaminated after all—it proved to be a false alarm. 

New Zealand authorities had acted swiftly and effectively, exhibiting a level of detail, commitment to communication, and sophistication that confirmed FDA’s assessment of their food safety system. The New Zealand authorities brought the same care to notifying other countries that had received the recalled product, as well as any other product that contained the whey protein as an ingredient.

Currently, we are in the process of piloting another systems recognition assessment with Canada, and we hope to expand our effort to more countries in the near future. As we move from the pilot phase towards implementing a new program and identifying additional countries with food safety systems that are comparable to our own, we will continue to strengthen our regulatory partnerships and focus our resources where most needed, to ensure that consumers in the U.S. can feel safe, whether their food was grown here in the U.S. or far away across the globe.

Julie Callahan, Ph.D., is an International Policy Manager in FDA’s Center for Food Safety and Applied Nutrition.

Considering Women’s Needs in Developing Medical Devices: Here’s ‘HoW’

By: Michelle McMurry-Heath, MD, Ph.D. 

Women differ from men in anatomy, physiology, risk factors and disease symptoms. They are also likely to use more medical devices over the course of their lives than men do.

That is why FDA is actively trying to learn more about how medical devices uniquely affect women, and how women can be better served by them.

This month we published a snapshot of how FDA is doing with such efforts. A congressionally-required report (Section 907 of the Food and Drug Administration Safety and Innovation Act) looked at the inclusion and analysis of women and other demographic subgroups in clinical studies supporting the approval of medical devices and other FDA-regulated medical products. After reviewing 2011 product applications, including 37 premarket approval applications, or PMAs, for devices, we found that in the majority of cases, sponsors provide information about women, conduct subset analyses and share information with the public in a variety of ways.

One specific activity highlighted in the report was a workshop sponsored earlier this summer by the Center for Devices and Radiological Health (CDRH) to formally launch a new program designed to more closely look at medical device use and the health of women (HoW). The three main goals of HoW are to:

  • Improve the availability, consistency and communication of information to patients and providers that is specific to women’s needs for the safe and effective use of medical devices.
  • Address identified gaps and unmet needs through targeted resources.
  • Foster the development of innovative strategies, technology and clinical study models.

Nearly 200 representatives from industry, academia, health care, federal agencies, patient and advocacy groups, gathered to discuss the issues related to medical devices and health in women and to brainstorm about effective strategies to address clinical research needs in this population.

This work builds on a December 2011 draft guidance, also highlighted in this month’s 907 report. That guidance outlined CDRH’s proposed expectations regarding sex-specific enrollment in clinical studies, data analysis, and reporting of study information. Ideally, the final guidance will provide a clear decision-making framework for when and how to analyze and communicate data involving women in device clinical studies.

The CDRH HoW program also plans to complement this by developing, in partnership with other stakeholders, strategies for communicating information about differences to the people who most need to know: health care professionals, clinical investigators, the medical device industry, and most importantly, patients.

With these activities, we are laying the groundwork for making sure the unique health needs of women are considered in research agendas and device innovation. The goal is to strengthen the focus of FDA, industry and the clinical community in developing medical devices designed to meet the unique clinical needs of women, and to communicate new information as we learn more about how differences affect treatment options and outcomes.

Now, with the issuance of the 907 report, and an accompanying docket to receive comments from the public, we hope to gain an even more in-depth understanding about demographic subgroups. The input we receive will become the starting point for developing an Action Plan, to be released next year.

These are all important steps towards ensuring that medical devices developed will take into account the unique needs of women.

Michelle McMurry-Heath, M.D., Ph.D., is the Associate Director for Science at the FDA’s Center for Devices and Radiological Health

FDA Scientists Showcase Cutting-Edge Research

By: David G. White, Ph.D.

It’s an impressive sight – 161 posters representing the work of FDA scientists involved in researching food safety and animal health.

This third annual food and veterinary science conference taking place at FDA yesterday and today demonstrates the depth and scope of research conducted by FDA scientists using the most sophisticated, state-of-the-art technology available in the world.

Our research portfolio is rich and diverse for a good reason. We need answers to help us meet our regulatory responsibilities, whether it’s making sure the food you eat, the food your pet eats or the cosmetics you may use are safe. This means knowing how to prevent contamination in produce and other foods, which is the reason behind the FDA Food Safety Modernization Act.  It also means having the right technology to detect contamination to keep harmful products out of the marketplace. 

Several posters, for example, detail how we are at the forefront in our use of a technology called DNA biochips, or microarrays – small, solid supports (glass slides, silicon chips or nylon membranes) onto which thousands of different microscopic gene sequences are immobilized, or attached, at fixed locations. Such microarrays are used to quickly compare the DNA in a sample to previously-identified DNA.

Our scientists have custom-made chips that, for example, contain the DNA of every strain of five pathogens that cause foodborne illness, like E. coli and Salmonella. They’ve also identified and catalogued over 2,900 genes in harmful bacteria that are responsible for antibiotic resistance.

The data has numerous applications for consumers. For example, it can rapidly provide information about how to treat foodborne illnesses, because it can show whether a particular strain of a bacteria is genetically-resistant to an antibiotic that a physician might consider prescribing. If it is, the physician can immediately choose another antibiotic that will be more effective. 

Scientists from FDA’s Center for Veterinary Medicine (CVM) are using the technology to monitor the emergence of pathogens that could become resistant to antibiotics due to their use in food-producing animals.

This technology also allows us to define how virulent a particular organism is – that is, its ability to cause disease — and to identify the mechanisms that make the bacteria resistant to antibiotics.

FDA has also invested in a laboratory process that determines the complete DNA sequence – or order of nucleic acids in a DNA molecule – of a pathogen at a single time. This process, whole genome sequencing, combined with DNA chips will allow scientists tracing the outbreak of a foodborne illness to say definitely, “This person was made sick by this kind of produce, grown and packaged by this company.” The proof is in the genetics. For example, E. coli is made up of about 5,000 genes. Each strain will have some genetic differences. If the genes from E. coli found on a certain bag of sprouts matches the genes of E. coli collected from a sick person, the puzzle of what caused an illness can be solved more quickly.

These projects and many others summarized at the conference were all conducted primarily by scientists from three FDA units – CVM, the Center for Food Safety and Applied Nutrition and the Office of Regulatory Affairs. The conference being held in our headquarters in Silver Spring,Md., on Aug, 27 and 28, 2013, allows scientists from these three centers to share and discuss their work with colleagues across the agency as well as with federal partners at agencies such as the Centers for Disease Control and Prevention and the United States Department of Agriculture.

Our world-class scientists, doctors, and veterinarians include those with specialties in epidemiology, microbiology, chemistry, toxicology, and pharmacology, to name a few. We are also investing in scientists from a great variety of disciplines and specialties critical to carrying out our mandate to ensure food safety.

We’re in the midst of analyzing all current and anticipated research with the aim of prioritizing what we do so that it’s aligned with the most critical steps needed to protect the U.S.food supply. We are doing that in our labs, in the field, and in the offices where strategic plans are made.

As new hazards emerge and as we develop new technologies, our approaches will change in what is a continual challenge to keep pace with new developments.

The conference demonstrates the brilliance and commitment of our researchers. Their work demonstrates great promise for the future of the agency tasked with ensuring the safety of the food supply.

David G. White, Ph.D., is chief science officer and research director at FDA’s Office of Foods and Veterinary Medicine.

FDA takes step to encourage pediatric drug studies

By: Lynne Yao, M.D. 

We all know that children are not just small adults. Many changes occur in children as they grow and develop that can affect how a drug works. In fact, some drugs that work in adults may not work at all in children. There may be different safety concerns compared to when they are used by adults, or they may need to be given in a different dose. That’s why products that are used in children must be studied in children. 

Congress enacted two laws that will increase the study of drugs in children: The Best Pharmaceuticals for Children Act (BPCA) provides an incentive for drug companies to conduct FDA-requested pediatric studies by granting an additional six months of marketing exclusivity. The Pediatric Research Equity Act (PREA) requires drug companies to study their products in children under certain circumstances. When pediatric studies are required, they must be conducted with the same drug and for the same use for which they were approved in adults. 

Before BPCA and PREA became law, more than 80% of the drugs approved for adult use were being used in children, even though the safety and effectiveness had not been established in children. Today that number has been reduced to about 50%. 

Under PREA, FDA can waive studies in children if the studies are not necessary. For example, if the disease for which the drug is being used in adults does not exist in children, such as prostate cancer, FDA would waive studies for children. In some cases, FDA has allowed sponsors to defer pediatric studies, depending on the circumstances. However, deadlines for deferred studies have often been missed. 

Fortunately, FDA now has tools to discourage companies from missing deadlines for deferred pediatric studies. When Congress reauthorized PREA last year as part of the Food and Drug Administration Safety and Innovation Act, or FDASIA, it gave FDA new authorities. FDA can grant extensions for deferred pediatric studies at a sponsor’s request if there is good cause for a delay in completing the studies. For example, if the sponsor has diligently attempted to recruit patients, but is having difficulty recruiting enough pediatric patients to complete the study, FDA can grant a deferral extension. However, if a sponsor has failed to seek or obtain a deferral extension, has failed to submit deferred pediatric studies by the final due date agreed to with FDA, or has failed to request approval for a required pediatric formulation, FDA can send a non-compliance letter to the sponsor and publish the letters on the web. 

This week, FDA is publishing the first of these non-compliance letters and the sponsors’ responses. They will be posted to a public FDA web page on an ongoing basis. We believe this important step demonstrates our ongoing commitment to getting these studies done for the benefit of all infants and children. 

Lynne Yao, M.D., is Associate Director, Pediatric and Maternal Health Staff, in FDA’s Center for Drug Evaluation and Research’s Office of New Drugs

Defining Boundaries for Caffeine in Today’s Marketplace

By: Michael R. Taylor

We all know that healthy adults have consumed caffeine in coffee, tea and chocolate for centuries. Caffeine has also been added to certain soft drinks for many years. These uses of caffeine are considered by most people to be safe, but the availability of caffeine in these products has been accompanied by a sense of boundaries and some health-related advice: Coffee has traditionally been thought of as a drink for adults; pregnant women have been advised to limit caffeine intake; and parents have monitored young children’s consumption of caffeinated soda.  

In addition, most of these traditional products have not typically been marketed for their stimulant properties, though it’s no secret that caffeine, whether naturally present or added, is a remarkably effective central nervous system stimulant.  And today’s marketers have caught on to this fact in a big way. Caffeinated “energy” drinks hit the shelves over a decade ago, and, more recently, we have seen caffeine added to non-traditional products like waffles and syrup to snack foods, candy, chewing gum, and a variety of beverages – all marketed to provide “energy” through the presence of widely varying levels of added caffeine.

By breaking far outside the traditional boundaries surrounding caffeine as a component of the food supply, these products pose challenging public health and regulatory questions. They stem from the fact that these products are being marketed explicitly for their stimulant properties, are prone to being consumed under a range of new and different conditions, and are providing caffeine in forms that are attractive and accessible to children and adolescents.

From a public health standpoint, does it matter that a cold energy drink might be chugged by young athletes before or after they engage in high stress activity? Does it matter that caffeine in chewing gum is absorbed directly through the oral cavity? How will the availability of caffeine from a much wider range of products affect total intake? Will new sources substitute for traditional ones or be additive? How will children and adolescents be affected?

The regulatory questions are equally challenging. The legal framework for substances like caffeine is complicated, but one thing is clear: Companies adding caffeine to foods and beverages have an obligation to ensure there is a sound scientific basis for concluding that their uses are safe. FDA’s job is to be sure they have met that obligation. To ensure safety, FDA has the authority to place limits on the amount of caffeine that is added to food, if the science warrants such a step. Working within our statutory and public health mandate, we will take whatever actions are needed in the interest of protecting the health of consumers.  

But an understanding of the relevant science surrounding caffeine comes first and that’s why FDA turned to the Institute of Medicine (IOM), the arm of the National Academy of Sciences charged with providing the federal government with science-based input on health issues.  At FDA’s request, the IOM convened a two-day workshop earlier this month on the potential health hazards of caffeine consumption. We received valuable scientific input and heard diverse perspectives from a wide range of researchers, clinicians, and stakeholders. Caffeine is a widely studied substance, but we learned there are few simple answers to some of the questions raised by its new uses, and there are gaps in the data on some of the questions we are asking. Our commitment is to incorporate what we learned at the workshop into our ongoing scientific assessment and to consider the regulatory needs and options on that basis.  

In the interest of everyone, and drawing on the perspectives of such groups as the American Academy of Pediatrics and the American Medical Association, we think there needs to be a scientifically grounded and common sense approach to the addition of caffeine to the food supply. We applaud the restraint many food companies are exercising as we figure this out, and we will rely on collaboration with the scientific community, consumers, and the food and beverage industry to shape that approach in the context of today’s new uses of caffeine.

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