Additional Protections for Children Who Participate in Clinical Research

By: Robert “Skip” Nelson, M.D., Ph.D.

Parents and guardians of seriously ill children often face difficult decisions about their child’s medical care. As a physician practicing for about 20 years in a pediatric intensive care unit, I knew that many of the interventions I used, while potentially life-saving, had no guarantee of success and carried a risk of significant harm or even death.

Robert "Skip" Nelson, MD PhD When faced with a life-threatening disease for which there are few good options, parents sometimes want to try a promising drug that is still under development. I have lived through this situation with parents many times, both in the intensive care unit and as a medical ethicist. Some parents see the drug as a lifeline where none had existed before. It is a natural instinct for parents to want to leave no stone unturned.

Many of the drugs that we use in children have not been approved by FDA for that use, and may not have been studied at all in children. They are available on the market because they have been studied and approved for use in adults, but not necessarily for the same disease for which they might be used in children. There are data available in adults describing the risks, benefits and side effects of drugs already in the marketplace. This information may reassure us a bit about the potential effects of a drug in children. But when that same drug is studied in children, we often discover that we should have been using a different dose, that the drug does not work, or that children may experience a concerning side effect.

The lack of information about the likely effects of a drug in children is more of a problem when the drug hasn’t yet been approved for any use. Most drugs in the early phases of drug development fail, either because they are ineffective in humans, or because of unacceptable side effects. So while it may be tempting to want to try any experimental drug in children with a life-threatening disease, we must be cautious.

Recently, my colleague Richard Pazdur shared his insight into the FDA “expanded access” regulations that allow patients with serious and life-threatening diseases or conditions access to investigational drugs outside of clinical trials. There are two important values at stake when considering expanded access in children. We want to do everything we can to restore a child to health, but we also want to protect that child, and other current and future children from ineffective, and potentially dangerous, interventions.

Physicians can apply for expanded access use for a patient by submitting certain medical information about the patient and important scientific and clinical information about the drug and its intended use to FDA. FDA then reviews this information and determines whether certain important criteria are met. These safeguards are in place to avoid exposing patients to unnecessary risks. Even if FDA determines that an expanded access request may go forward, the company manufacturing the drug has to be willing to supply it.

In implementing its expanded access regulations, FDA tries to strike a balance between two social goods: treating an individual child and demonstrating that a medical product is safe and effective. Children with a serious or immediately life-threatening disease for which there is no comparable or satisfactory alternative therapy are able to have access to investigational agents outside of a clinical trial. However, there must be some evidence that the potential benefit to the child justifies the risks of the treatment and that those risks are not unreasonable in the context of the disease to be treated. Providing the investigational drug must not interfere with the ability to initiate, conduct or complete a clinical trial of that drug that could be used to support its marketing approval for the disease. Otherwise, we would never collect the essential data needed to establish that the drug is truly safe and effective for that use, or whether one child’s seemingly miraculous response was the result of the drug or of something else.

FDA strongly supports the inclusion of children in FDA-regulated clinical trials, provided the trials are conducted in an ethical and scientifically sound manner. For the past 15 years, FDA has been actively involved in initiatives aimed at improving medical product research in children (including under the legislative mandates provided by the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act). Children must be protected from exploitation and exposure to unnecessary risks related to their inclusion in clinical research, and from the unwarranted use of investigational drugs outside of a clinical trial.

I am often asked about FDA’s role in protecting children who are receiving experimental treatments and who are participating in clinical trials. FDA’s regulations provide for specific additional protections to help ensure that children who participate in research are involved in ways that protect the children’s rights, safety, and welfare.  Protections include, for example, review of research by an Institutional Review Board (IRB) supplemented by pediatric expertise as appropriate. The risks posed by research interventions must be low if the interventions are done for the sake of knowledge rather than for the child’s medical benefit. For higher risk interventions, the intervention must offer the child a sufficient prospect of direct medical benefit to justify the potential risks. Investigators must also obtain permission from the child’s parent(s) or guardian(s), and in most clinical trials must obtain each child’s assent when the child is developmentally capable of providing it.

My heart goes out to those parents of children with a life-threatening disease for whom there are no satisfactory treatments. My personal belief is that responsible clinicians and investigators caring for critically ill children, parents, and FDA can work together to find the right path forward for our present and future children. 

Robert “Skip” Nelson, M.D., Ph.D., is Senior Pediatric Ethicist in FDA’s Office of Pediatric Therapeutics

Better Process Control Schools Around the World

By: Irene Chan

When you open a can of creamed corn soup, your expectation is that you can consume it without fear of getting sick. We rely on commercially sterile foods, such as canned foods and other shelf-stable vacuum packaged foods, for everyday meals, as well as for emergency situations, such as natural disasters. In all of these situations, the safety of food is vital. The airtight, low-acid environment of many commercially-sterile foods is a prime target for the growth of bacteria that can produce a lethal toxin that causes botulism.

Irene ChanFortunately, since FDA established low-acid canned food (LACF) and acidified food (AF) regulations in the 1970’s, the commercial processing of commercially sterile foods in the United States has become much safer. One of FDA’s requirements is that, with few exceptions, manufacturing supervisors at canneries must have taken an appropriate training course to understand how to make a safe commercially-sterile product. FDA must approve these so-called Better Process Control Schools (BPCS), which numerous large universities throughout the United States offer. These courses provide essential information about how to effectively control the risks associated with the manufacturing of commercially-sterile foods, and how to comply with U.S. law.

With the increasing globalization of the food supply, FDA has recognized that the need for BPCS training has gone beyond our shores. And until recently, it was a challenge for foreign manufacturers to send persons to attend BPCS in the United States because of travel and language barriers. But through FDA’s foreign offices, we have supported local universities throughout the world with the capability to host approved BPCS training courses right where they are needed.

China, where there are several hundred establishments registered with FDA to export canned foods to the United States, is a prime example of a robust food export market. In September 2011, through collaboration between FDA’s China Office and experts in FDA’s Center for Food Safety and Applied Nutrition (CFSAN), the first-ever, locally sponsored BPCS course in China was conducted at China Ocean University in Qingdao, Shandong Province. Attendees were able to obtain the content of the course in Mandarin Chinese from local food technology professors, while an FDA technical advisor was available for questions. This June, the university held its second course, with eager attendees coming from mainland China as well as Taiwan.

Closer to home, the Latin American region has established itself as the pantry for the United States, supplying a myriad of food products throughout the year. There are hundreds of food manufacturers in the region that would greatly benefit from the opportunity to send supervisors to a local, approved BPCS. The Latin America Office has identified three universities as having the knowledge base and infrastructure to conduct BPCS courses: Costa Rica’s Center for Food Technology Research (CITA), Guatemala’s Del Valle University, and Peru’s National Agrarian University- La Molina.  In addition, FDA’s Latin America Office worked with the Inter-American Developmental Bank to obtain funding to provide the approved course materials for the universities in Guatemala and Peru to conduct their own BPCS. These universities will soon provide these courses at a low cost, with capable instructors who speak the local language and understand the local realities of the industry. In Peru, the university recently completed their first BPCS on August 17th, 2012. Representatives from FDA’s Latin America office, FDA’s Office of Regulatory Affairs, and CFSAN were present to answer questions and assist with the delivery of the class. In Costa Rica, CITA has scheduled their first BPCS for August 27-31, 2012, and expects attendees from the Caribbean and Central America region.  These are pilot programs, and we have already heard from other countries and institutions that want to participate in similar efforts.

Indian manufacturers produce hundreds of different varieties of vacuum packed ready-to-eat dinner entrees that are imported into the United States. Before 2011, no in-country BPCS was available for these manufacturers. In March 2011, local faculty at Bhaskaracharya College of Applied Sciences in New Delhi taught a BPCS course for the first time. The course cost each student only about $200—this sum paid for instruction, catering for meals and course materials. Students came from throughout India to attend the course.  A FDA technical advisor’s participation in the course allowed students to ask questions about process filings and engage in technical discussions with FDA. This year, the college held a second class in Sri Lanka for LACF and AF producers located in that country.  A third class is planned for later this year.

The FDA overseas offices are proud to have helped stand up these important training events in various parts of the world, and to support local universities as they develop the capacity to put on these courses. And the next time we open that pouch of vacuum-packed curry lentils, we will know that the effort to keep our food safe is truly global.

Irene Chan is the Deputy Country Director of FDA’s China Office. Edmundo Garcia, Jr., Assistant Regional Director for FDA’s Latin America Office, Daniel Geffin, Food Technologist in FDA’s Office of Food Safety, Food Process Evaluation Team, CFSAN, and Bruce Ross, Country Director of FDA’s India Office, contributed to this post.

Is it Something My Pet Ate?

By: Bernadette Dunham, D.V.M., Ph.D.

As a practicing veterinarian I saw first-hand that pets tend to eat odd things, from foreign objects such as stones, fish hooks or sewing needles with thread…to car antifreeze, sometimes with unfortunate outcomes. However, when it comes to the main staple of our pet’s nutritional diet we usually turn to commercially produced pet food that we reach for on the store shelves. 

Millions of pets consume pet food without any problems, but once in a while, as is the Bernadette Dunham, D.V.M., with human food, bacteria or chemicals may contaminate pet food or pet treats and our pets may get ill. If you think your pet may have become ill from eating pet food or pet treats then I have some important steps for you to follow:

First, call your veterinarian! It is important that your pet receive prompt medical attention. Your veterinarian will most likely ask if your pet vomited, had diarrhea, or was acting lethargic and how soon any of these signs appeared after eating.

Second, while your veterinarian will tend to your pet’s condition, you or your veterinarian can help FDA’s Center for Veterinary Medicine (CVM) investigate your pet’s illness. You or your veterinarian can electronically report cases of animal illness associated with pet foods through the Safety Reporting Portal, or by calling the FDA Consumer Complaint Coordinators in your state.

But before you log-on or pick up the phone, here’s what we need to know:

  • What kind of pet do you have?  Is it a dog, cat, rabbit, fish, bird, or other species?
  • What is the age, weight, and breed of your pet? Is she pregnant or spayed? Is he neutered?
  • How much of the suspected pet food does your pet normally eat at each feeding — and how much has already been eaten from that package?
  • How long has your pet been eating the suspected pet food? Did the signs of illness appear following feeding a new or partially used container of the food?
  • How much of the product do you still have?
  • Also, did any other pets in your household eat the same product? Did they become ill too, or were they unaffected?
  • What other foods or treats does your pet eat?
  • Did your ill pet spend time outside unsupervised (back to they eat odd things) and why do you suspect the pet food caused the illness?
  • Does your pet have any current or previous health problems, and do you give your pet any other food, treats, dietary supplements, or drugs?

The condition of your pet is paramount to determining what happened and why, but also necessary is the information provided on the pet food package. If you transfer dry pet food into other containers for easier handling, please save the original packaging until the pet food has been consumed. FDA will want to know the exact name and the description of the product as it is stated on the label. The type of container such as box, bag, can, or pouch can be useful information as well.

FDA’s investigators will be looking for the lot number, which identifies in which plant your pet’s food was manufactured, and when. Is there a best by, best before, or an expiration date on the package? This, along with the UPC code, or bar code, and the net weight are facts useful to FDA’s investigators. It may also help for you to let us know when and where you purchased the pet food, and how the food was stored, prepared, and handled.

Pet owners should also call the pet food manufacturer to report a suspected pet food illness in their pet. The contact information will be printed on the package.

Like any scientific investigation, there are numerous questions to consider and your ability to provide the information to your veterinarian and to FDA’s CVM is most essential in helping to determine what happened. It is very much like putting on Sherlock Holmes’ thinking cap to solve a mystery.

FDA brings a multitude of resources to pet food investigations. As we evaluate the circumstances that led to your pet’s illness, a variety of FDA experts join forces to solve the puzzle. Investigators with expertise in proper manufacturing practices, plus food and feed safety, examine the manufacturing plants, warehouses and the trucks used for shipping the pet food. They are supported by scientists and other experts at FDA headquarters who can help them determine what might have caused a pet food or pet treat problem.

When a pet food is suspected of causing illness in animals, samples of the food might be sent to FDA laboratories and perhaps FDA’s Forensic Chemistry Center where scientists perform original research to identify any possible contaminants or other hazardous materials in the product.

In addition, CVM has established a veterinary response laboratory network (Vet-LRN), which assists in the investigation by examining samples from pets that have become ill. Vet-LRN works with your veterinarian and the collaborating network laboratories whenever clinical or tissue samples are needed to help diagnose the problem with the pet food.

FDA is committed to the health and well-being of your pet and by working together, you, your veterinarian, and FDA can not only respond to, but more importantly prevent any pet food-borne illness from happening again.  Thank you!

Dr. Bernadette Dunham is the Director of FDA’s Center for Veterinary Medicine

National Conference on Tobacco or Health: Convening for a Healthier Future

By: Lawrence R. Deyton, M.S.P.H., M.D.

As director of FDA’s Center for Tobacco Products (CTP), I am delighted that representatives from many areas within CTP will be participating in the National Conference on Tobacco or Health (NCTOH). NCTOH is one of the oldest and largest meetings on tobacco education and action, bringing together more than 2,500 national, state, territorial and local tobacco control scientists, program managers, communicators and other professionals in the field every three years. The mission of the conference is to improve the reach and effectiveness of tobacco control programs and activities throughout the United States.

This is the first time that CTP has participated in this meeting. The Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) which gave the FDA the authority to regulate tobacco products, was actually passed by Congress during the last NCTOH meeting in 2009. When the vote was announced, it drew large cheers from the participants.

Some of the staff from the FDA’s Center for Tobacco Products attending NCTOH stand in the FDA exhibit. (from left to right): Tarsha McCrae, David Ashley, Les Weinstein, Laura Shay, Sarah Landry, Andrea Frydl, Greta Tessman, and Gail Cherry-Peppers.

FDA’s participation in this year’s conference comes at a critically important point in our history. Since CTP was established we have achieved success in moving science-based regulation forward with historic advances in public health.

Key accomplishments include:

  • enforcing the ban on candy-like characterizing flavors in cigarettes;
  • restricting youth access to cigarettes and smokeless tobacco;
  • enforcing requirements for larger smokeless tobacco health warnings;
  • enforcing prohibition of misleading advertising claims;
  • restricting cigarette and smokeless tobacco marketing to youth;
  • awarding nearly $43 million in contracts to 37 states and the District of Columbia for conducting inspections of retail establishments. So far they have conducted more than 86,000 inspections to determine whether the establishments are complying with regulatory requirements which, among other things, forbid selling cigarettes and smokeless tobacco products to minors;
  • issuing more than 3,500 warning letters and 290 fines to retailers for violating the law.

Sharing what we’ve learned and accomplished will be an important part of CTP’s participation in the NCTOH conference. I will be giving remarks during the opening and closing plenaries as well as presenting during a panel session. Many other CTP staff members will be moderating or presenting during the conference on critical tobacco-related issues including:

  • key elements of FDA’s regulatory authorities;
  • consumer perceptions of dissolvable tobacco products;
  • the development of data systems to support tobacco regulation;
  • national tobacco education campaigns; and
  • strategic partnerships for retail tobacco enforcement.

If you are participating in the meeting, we encourage you to engage with us by attending our sessions and visiting our booth. CTP experts will be looking forward to taking your questions, sharing information and hearing about the activities in your community that are helping to reduce tobacco use and keeping young people from starting to smoke. 

Lawrence R. Deyton, M.S.P.H., M.D., is the Director of FDA’s Center for Tobacco Products

Information Technology, Tools, Tobacco Products and Public Health

By:  Cindy Miner, Ph.D.

Providing stakeholders with easy to find information that they need to know on FDA’s web site is paramount.

Cindy Miner, Ph.D.Today, I am pleased to announce a new tobacco product section on FDA’s website that organizes important information on tobacco product regulation. This new section brings together information on the three pathways available to legally market new tobacco products under the Federal Food, Drug, and Cosmetic Act, as amended by the Family Smoking Prevention and Tobacco Control Act (TCA).

We created this section, called Tobacco Product Review and Evaluation, to centralize information on the pathways for review and evaluation of new tobacco products, before they are marketed. This information does not replace the TCA or any other legal document – it simply guides the user through the key elements of each of the three pathways to market.

Using a creative new interactive tool, users can determine which of the three pathways is most appropriate when seeking to market a new tobacco product. To legally market a new tobacco product in the United States, manufacturers must seek and receive permission from FDA by either:

Although FDA may issue a marketing order for a tobacco product to be marketed, that order does not indicate the tobacco product is either safe or “approved.” The marketing order means the manufacturer has complied with the requirements under the law to bring its product to market. With the passage of the TCA, manufacturers of tobacco products are now required to submit scientific information and seek permission from FDA prior to marketing a new tobacco product, including when making changes to existing products. Learn more about how FDA is protecting public health through tobacco regulation.

This section will also serve as a building block for more information as we develop it. We have already added additional content on modified risk tobacco products and guidance on how to request a meeting with FDA’s Center for Tobacco Products Office Science.

Three years after the Tobacco Control Act was signed into law, we have taken great strides in implementing its provisions. Making sure stakeholders can get the information they need quickly and in a user-friendly manner is a critical aspect of our overall mission.

Cindy Miner is the Associate Director for Scientific Communication, Office of Science, at FDA’s Center for Tobacco Products

Meet the Men and Women of CORE—FDA’s Outbreak Teams

By Kathleen Gensheimer, M.D., M.P.H.

Too many people die or become very sick after innocently eating a food that is contaminated with bacteria, such as Salmonella, Listeria or E. coli. FDA is taking innovative steps to prevent this from happening.

A year ago, FDA changed direction in its approach to outbreaks of foodborne illnesses. Last August, FDA launched the Coordinated Outbreak Response and Evaluation (CORE) Network, a full-time staff working with counterparts in local, state and federal agencies to investigate, control and prevent these outbreaks. Previously, FDA staff from across the agency would be pulled in on temporary assignments to combat an outbreak.

Kathleen Gensheimer, M.D., M.P.H.During CORE’s first week on the job, it came face-to-face with one of the deadliest outbreaks in this country in decades—Listeria monocytogenes in cantaloupes. Each of the CORE teams—a mix of outbreak veterans and new additions from across FDA—swung into action to identify the source and get the product off the market.

It was trial by fire—and only the first one. By the end of their first year, the CORE teams would deal with major outbreaks involving frozen tuna used in sushi, sprouts, frozen oysters and Turkish pine nuts. They would also face human illnesses linked to the handling of contaminated pet food.

Starting today, FDA will be issuing a series of Consumer Updates, beginning with an overview, that explains how CORE works, what it has accomplished, and what challenges it faces. Look for upcoming articles that feature each of the three CORE teams:

  • Signs and Surveillance: Finding the outbreak.
  • Response: Stopping the outbreak.
  • Post-Response: Preventing the next outbreak.

These articles will introduce you to the men and women of CORE. They come from different backgrounds, and include epidemiologists, veterinarians, public and environmental health specialists, and consumer safety officers. FDA is far more than a name, a group of buildings, or its inventory of equipment.  FDA is its people. People with families like yours. People just like the ones you’ll meet in these stories. This is not just a job to them. It is their mission, and that mission is to keep you and your family safe.

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