A Year Later, FDA Is Better and Stronger in Protecting Consumers from Unsafe Foods

By: William Correll and Douglas Stearn

We have made dramatic changes in our response to complex, potentially high-risk food safety situations that may be difficult to address quickly.

Bill Correll

William Correll is the director of the Office of Compliance in FDA’s Center for Food Safety and Applied Nutrition

Almost a year ago, we heard concerns that FDA was not doing enough to ensure that companies promptly and effectively initiate recalls of potentially dangerous food products in those rare instances in which a firm is not responding appropriately. FDA has always been committed to protecting the U.S. food supply, which is among the safest in the world, but we recognized the need to strengthen certain compliance and enforcement strategies in cases made more complex by factors that include the nature of the product, the scope of available evidence, and the company’s response.

And so, we took to heart issues raised by the Office of the Inspector General at the Department of Health and Human Services and have used them as a catalyst for change.

Doug Stearn

Douglas Stearn is the director of the Office of Enforcement and Import Operations in FDA’s Office of Regulatory Affairs

Not just change, but a culture change. At the heart of this change was the creation of SCORE, which stands for Strategic Coordinated Oversight of Recall Execution. We are the co-chairs of this group of senior leaders that gets involved in the most challenging food safety situations, working with field staff and district offices to evaluate the range of available options and deciding quickly what action to take. For example, SCORE can drive agency action if the company is not acting aggressively enough to recall their products, and can push for use of administrative or judicial remedies.

We now have FDA compliance, enforcement, and field leaders at the table, reviewing cases every week or more often, as needed. Science and medical officers are engaged in the conversation, as are field investigators, and lawyers.

What is the right action? What should FDA be doing? What should the company be doing? These are real time, high-level decisions, with the result being that field investigators are now empowered to immediately engage senior leaders in overcoming obstacles to the rapid removal from the marketplace of foods that are, or could be, contaminated. The process of raising a food safety issue up within the agency has thus been streamlined to put FDA leaders and field staff on the same page right away.

Among the thousands of product recalls that FDA oversees each year, SCORE has played a critical role in addressing the most significant risks to the public. SCORE’s involvement has ensured that multiple recalls involving high-risk products have been initiated, has improved tactical planning, and sped the use of enforcement tools when necessary.

In the past year, SCORE has been involved in cases that included lead contamination of dietary supplements, Salmonella contamination of powdered milk, E.coli O157:H7 in soy nut butter, and Listeria monocytogenes in hummus, soft cheese and smoked fish. In addition to facilitating recalls and import alerts for the detention of products entering the United States, SCORE initiated or expedited the process for suspending the registration of two food facilities, actions that block the facilities’ ability to distribute food.

The creation of SCORE is not the only change we’ve made. There is a new recall audit plan to assess the adequacy of a company’s recall efforts and more than two dozen procedural and policy changes that have either happened or are in the works. These include an expansion of public notification of recalls that may affect the most vulnerable consumers, including the very young and elderly.

Most companies readily initiate a voluntary recall when faced with evidence that their product is unsafe. But when there is an obstacle, we are determined to overcome it, using all of the tools we have available. We’ve always taken our job seriously and we’ve shown over the past year that we will use every opportunity to do it better.

William Correll is the director of the Office of Compliance in FDA’s Center for Food Safety and Applied Nutrition

Douglas Stearn is the director of the Office of Enforcement and Import Operations in FDA’s Office of Regulatory Affairs

FSMA Collaborative Training Forum: ‘Educate Before and While We Regulate’

By: Donald Kautter Jr. and Stephen Hughes

“We will educate before and while we regulate.”

That’s been a mantra for FDA as the rules that implement the FDA Food Safety Modernization Act (FSMA) have taken shape. Making sure that food producers understand the new requirements and have the knowledge they need to meet them is key to the success of this effort to prevent illnesses caused by domestic and imported foods.

However, FDA recognized early on that one size won’t fit all when it comes to training and that a variety of training options and delivery formats would be necessary to meet needs shaped by product, region, size, and other factors.

Enter the FSMA Collaborative Training Forum, convened in partnership by FDA and the U.S. Department of Agriculture. The forum is made up of the agencies, centers, associations, universities and others funded by FDA and USDA through cooperative agreements and grants to develop and deliver FSMA training. Communication between them is important to minimize overlap and improve coordination and efficiency.

The forum held its first meetings in April. Participants laid the groundwork for a vibrant collaboration that will support diverse food producers who are preparing to meet the FSMA standards.

photo of various produceThe diversity of the food producers is matched by the diverse community of training providers. The forum includes representatives of the public-private alliances funded primarily by FDA as a resource for industry: the Produce Safety, Food Safety Preventive Controls and Sprout Safety Alliances. It also includes the National Coordination Center (NCC) and four Regional Centers that were created in a partnership between FDA and USDA’s National Institute of Food and Agriculture to provide training opportunities for farmers, small food processors, and small produce merchant wholesalers.

In addition, the National Farmers Union Foundation and the University of Arkansas-Fayetteville, which entered into cooperative agreements with FDA to develop training curricula and delivery for local and tribal food producers, respectively, are among the training providers. The National Association of State Departments of Agriculture, which is engaged in a cooperative agreement with FDA to plan implementation of the produce safety rule, is also a member of the forum.

Last, but not least, there’s the Joint Institute for Food Safety and Applied Nutrition (JIFSAN), a partnership between the FDA and the University of Maryland that is focused on increasing global knowledge of effective food safety practices.

These first meetings focused on the new produce safety standards, which set science and risk-based requirements for the production of fruits and vegetables. All of these training programs are up and running, although they’re at different stages of development. But no matter where they are in this journey, they’re working together. The NCC, for example, has been coordinating with regional centers monthly and, through forum discussions, is now including those working with local and tribal food producers.

Everyone wants to measure success and to determine that they’re reaching the right audiences. Examining metrics and coordinating data will be a priority going forward so that all training providers have the same sense of what’s working and what isn’t.

Group members shared their experiences and knowledge in these first meetings. For example, a common experience has been that growers don’t use online training as much as other food producers. Lack of access to the internet or insufficient bandwidth to run the programs are the issues for some. We’ll reshape how the training is offered based on feedback as more data are collected.

This is just the beginning. There are plans to work with forum participants to post resource materials in a way that’s accessible to food producers around the world.

This is a great example of good governance – working in partnership and communicating across organizational boundaries to support those who will do the important work of strengthening our food safety system. The forum will meet every few months to help ensure that training programs meet the needs of those who must understand the new FSMA standards, no matter their size, nature, or location.

Donald Kautter Jr. is a Consumer Safety Officer in FDA’s Division of Plant Products and Beverages.

Stephen Hughes is a Team Leader in FDA’s Produce Safety Network.

They are the FDA co-leads of the FSMA Collaborative Training Forum, and partner closely with USDA to facilitate the forum.

FDA Takes Action Against Fraudulent Cancer Products

By: Donald D. Ashley, J.D., and Douglas Stearn, J.D.

A cancer diagnosis often provokes a sense of desperation. Unfortunately, rogue operations exploiting those fears peddle untested and potentially dangerous products, particularly on the internet. FDA responds in two ways: with compliance and enforcement actions against unscrupulous companies and with consumer education to decrease demand.

Donald Ashley

Donald D. Ashley is director of the Office of Compliance in FDA’s Center for Drug Evaluation and Research

Every one of FDA’s product centers and the FDA’s Office of Regulatory Affairs (ORA) has staff devoted to rooting out health fraud scams. These teams regularly investigate consumer complaints and monitor the stores and online marketplaces where such products are advertised. Recently the Center for Food Safety and Applied Nutrition and the Center for Drug Evaluation and Research teamed up with ORA to search the Internet and social media for bogus products that falsely claim to diagnose, treat or cure cancer, a violation of federal law.

It was a challenging assignment.

Those marketing fraudulent products – primarily or exclusively on the internet – attempt to subvert compliance and enforcement efforts by changing the names of their products, their companies, and/or their websites.

Nevertheless, today we are announcing that 14 companies peddling bogus cancer cures have received warning letters from FDA. Warning letters are a primary compliance tool that FDA uses to address violations of the Federal Food, Drug and Cosmetic Act.

Douglas Stearn

Douglas Stearn is director of the Office of Enforcement and Import Operations within FDA’s Office of Regulatory Affairs

These companies used slick ads, videos, and other sophisticated marketing techniques, including testimonials about miraculous outcomes. Often a single product was promoted as a treatment or cure for multiple diseases in humans and animals. Hoping to skirt the law on a technicality, some sellers made false claims and then in small print provided a disclaimer that their products are not intended to diagnose, treat, cure or prevent any disease.

Making such obvious claims and then saying later that you are not doing so might seem clever, but the technique does not comply with federal laws intended to protect public health.

Each of these companies has 15 working days to respond with a plan to come into compliance with the law.

If necessary, FDA also has authority to take further action, including criminal prosecutions, product seizures, and injunctions. Companies that fail to come into compliance after receiving a warning letter can for example, face criminal prosecution and court-ordered decrees that require them to recall products and get written permission from FDA before resuming operations. The violations identified in the warning letters, if not corrected, are punishable by up to one year in federal prison, five years’ probation and a fine of either $100,000 or twice the gain from the offense.

FDA works diligently to monitor and take action against companies marketing unsafe products online and has issued more than 90 warning letters over the past decade to companies marketing fraudulent cancer products.

image of fake cancer curesConsumer education is critical in combating the dangers posed by these types of products. Thus, our recent cancer fraud initiative includes a push to raise consumer awareness and thereby decrease demand. Efforts include contacting media outlets that reach millions of consumers, posting a Consumer Update article at FDA.gov, and encouraging consumer groups, trade associations, and others to help us spread this important “buyer beware” information.

The message to consumers is this: These products are untested. Some contain ingredients that may be a direct risk to your health. The ingredients may interact in a dangerous way with professionally-prescribed treatments. They are not a substitute for appropriate treatments. Using these products can waste your money, and, more importantly, endanger your health.

Donald D. Ashley is director of the Office of Compliance in FDA’s Center for Drug Evaluation and Research

Douglas Stearn is director of the Office of Enforcement and Import Operations within FDA’s Office of Regulatory Affairs

Redefining the Term “Healthy” on Food Packages – Public Process Plays a Crucial Role

By: Susan Mayne, Ph.D., and Douglas Balentine, Ph.D.

When you see the word “healthy” used on a food package, what does that mean to you?

Susan Mayne

Susan Mayne, Ph.D., is Director of FDA’s Center for Food Safety and Applied Nutrition

It’s FDA’s job to make sure that terms like “healthy,” which many people rely on to make food choices for themselves and their families, are something that they can truly count on. And we’ve seen that the ability to include the claim “healthy” actually encourages food companies to produce healthier foods. Back in the 1990s, the agency used the best nutritional science available at that time to define what “healthy” meant. And so, over the past two decades, food packages could be labeled as healthy if they met certain criteria for the content of fat, saturated fat, sodium and cholesterol and contained certain minimum amounts of nutrients like vitamins and minerals.

But nutrition science has evolved. Whereas in the past we placed greater emphasis on total fat, we now know that not all fats are alike, and some are better for health than others.  And while the focus on ensuring that people are getting the right amounts of different nutrients still matters, other things matter as well, such as food groups or the combinations of different foods and beverages in the diet.

Doug Balentine

Douglas Balentine, Ph.D., is director of the Office of Nutrition and Food Labeling at FDA’s Center for Food Safety and Applied Nutrition

So the question is: Can FDA update the definition of “healthy” in a way that makes sense and reflects our most current understanding of nutrition science today? FDA’s answer is: We want to do that, and we want the public’s help to make sure we get it right.  We want to hear from food companies that make and market food, from experts who study nutrition, and from consumers who, after all, are the ones to whom “healthy” claims are directed.

That goal prompted us to hold a public meeting in March 2017 on the term “healthy” on food labels, and we were delighted that hundreds of participants joined in person or via webcast. But if we were looking for an easy answer and widespread agreement on the definition of healthy, we didn’t find it there! The range of opinions we heard underscores just how complex the process of revising the definition will be.

Let’s take, for example, the different views of four participants in a panel discussion on stakeholder perspectives.

  • Kind Snacks, which has petitioned FDA to change its “healthy” definition, proposed, in part, that foods be defined as healthy if they contain a “meaningful amount” of foods that comprise a healthy diet and that don’t contain low- or no-calorie sweeteners or synthetic colors.
  • ConAgra Foods presented a framework for defining “healthy” by ranking foods based on their nutritional makeup, an approach that permits greater flexibility. If higher amounts of “food groups to encourage” are present, then there is some room for a food to be listed as healthy even if there are some “nutrients to limit” as well.
  • The Center for Science in the Public Interest said that a “healthy label” shouldn’t be a marketing tool that helps marginally better processed foods compete with fruits, vegetables and other truly healthy foods.
  • And the Academy of Nutrition and Dietetics, after talking to its members, said it could not come up with a good definition for “healthy” that FDA should adopt.

There were different opinions on whether we should continue to define “healthy” based solely on specific nutrients that are considered to play a role in lowering the risk of chronic disease. In that regard, some favored having the new definition continue to include certain beneficial nutrients, such as vitamins, minerals and fat. Others suggested it be based instead on beneficial food groups to – such as whole grains, fruits and vegetables – while still others opted for a combination of the two.

Participants also urged us to consider the goal of redefining “healthy” before deciding the criteria. Is the term primarily an educational tool? If so, then we must be transparent about what the term means because people view the word healthy differently depending on their perspectives and values. Alternatively, is the definition intended to be a guideline for industry in making claims about their products, or, is it a way to spur product reformulation towards healthier foods?

We welcome the diversity of comments we received – they will be added to the nearly 900 we’ve received from the public since September 28, 2016 when we published a Request for Information on the word “healthy.” To give the public time additional time to comment after last month’s meeting, we are extending the comment period until April 26.

We will study the comments carefully as we consider how to move forward, knowing it will be a challenging task, given the diversity of opinions, as the public meeting demonstrated. But the meeting also showed that an updated, and appropriate, definition of healthy is important to the American people, industry, health care professionals, food scientists, and other experts. Towards that end, FDA is committed to continuing this important dialogue.

Susan Mayne, Ph.D., is director of FDA’s Center for Food Safety and Applied Nutrition

Douglas Balentine, Ph.D., is director of the Office of Nutrition and Food Labeling FDA’s Center for Food Safety and Applied Nutrition

Improving the Safety of Imported Foods Through Partnerships

By: Susan Mayne, Ph.D., Camille Brewer, M.S., R.D., and Donald Prater, D.V.M.

Susan Mayne

Susan Mayne, Ph.D., Director of FDA’s Center for Food Safety and Applied Nutrition

At FDA, we recognize that the partnerships we build with other nations are key to our success in giving American consumers confidence in the safety of the foods they choose to serve their families.

In passing the FDA Food Safety Modernization Act (FSMA), Congress provided FDA with new authorities to help ensure that domestic food is as safe as possible and that imported food meets U.S. food safety standards. These new authorities to enhance the safety of imported foods take into account a variety of food safety partnerships, including several that FDA has had in place for years.

FDA recently held a two-day public hearing in which we received input from domestic and international food safety experts on how we can build on these strategic partnerships. The safety of imported foods is of great interest to all of us and of utmost concern to the American public. About 15 percent of the U.S. food supply is imported, including nearly 50 percent of fresh fruit, 20 percent of fresh vegetables, and 80 percent of seafood. Those imports to the United States come from more than 200 countries and about 125,000 firms.

Camille Brewer

Camille Brewer, M.S., R.D., Director of International Affairs at FDA’s Office of Foods and Veterinary Medicine.

What we took away from this hearing, a call to action that will guide us going forward, was a clear message from experts: There are a range of partnership tools that can enhance the safety of imported foods – from capacity building, to credible third party audits and certifications, to sophisticated forms of regulatory cooperation – and each should be used in a way that ensures it is appropriate for its intended purpose.

Countries that export food to the U.S. represent a continuum of food safety capacities and capabilities, and for that reason, one size doesn’t fit all when it comes to partnerships. Experts shared their experiences on how we can work with trading partners that need help in building their food safety systems, which, in turn, can help improve the safety of food imported into this country. Attendees discussed how capacity-building programs can be implemented, and how we can make these programs accessible and useful to various regions in the world.

At the other end of the spectrum: How does FDA leverage the knowledge and best practices of countries that have robust food safety systems, and that we have officially recognized as providing a comparable level of public health protection? So far, FDA has completed official recognition with three such countries – New Zealand, Canada and, just this week, Australia.

Don Prater

Donald Prater, D.V.M., Acting Assistant Commissioner for Food Safety Integration in FDA’s Office of Foods and Veterinary Medicine

Imported foods must be produced in a way that provides the same level of public health protection as that required of domestic food producers. Some of the questions we considered included: How will it be decided that a measure or procedure used in lieu of an FDA requirement provides the same health protection? How are countries ensuring parity in audits, inspections, verification, and overall oversight?

We also discussed whether, and how, federal agencies might leverage activities and resources with the private sector. How can we consider the role of private entities, such as companies that audit against various private food safety standards, in our oversight of imports?  And we considered the value of export control programs that are specific to certain commodities in terms of risk-based surveillance and planning.

The bottom line? We can use a variety of approaches to enhance the safety of imported food.

Overall, the hearing provided us with a rich tapestry of ideas, opportunities, and challenges that FDA will consider as we enhance our partnership activities. The key is understanding that one size doesn’t fit all.

Click here for the hearing webcast, transcript and additional background. 

Click here for ‘A Conversation with Donald Prater’ on advancing the safety of imported food.

Susan Mayne, Ph.D., is Director of FDA’s Center for Food Safety and Applied Nutrition

Camille Brewer, M.S., R.D., is Director of International Affairs at FDA’s Office of Foods and Veterinary Medicine

Donald Prater, D.V.M., is Acting Assistant Commissioner for Food Safety Integration in FDA’s Office of Foods and Veterinary Medicine

‘Organs-on-Chips’ Technology: FDA Testing Groundbreaking Science

By: Suzanne Fitzpatrick, Ph.D.

There are many things you might envision putting on a chip. It’s unlikely that a human organ is one of them.

Suzanne FitzpatrickBut creating human organ systems in miniature on micro-engineered chips about the size of a AA battery is a revolutionary testing technology that has captured the attention of food scientists at FDA. And FDA has a leading role in evaluating this science, designed to provide a more precise model for studying the effects of potentially harmful chemical and biological hazards in food, cosmetics or dietary supplements than is now available.

On April 11, 2017, FDA announced a multi-year research and development agreement with a company called Emulate Inc. to evaluate the company’s “Organs-on-Chips” technology in laboratories at the agency’s Center for Food Safety and Applied Nutrition, one of a number of FDA efforts to help evaluate this chip technology. The flexible polymer organ-chips contain tiny channels lined with living human cells and are capable of reproducing blood and air flow just as in the human body. The chips are translucent, giving researchers a window into the inner workings of the organ being studied.

Research will begin with a liver-chip but the agreement may expand in the future to cover additional organ-chips, including kidney, lung and intestine models. The ultimate goal is to predict how specific organs will respond to exposure to potential chemical hazards found in foods, cosmetics and/or dietary supplements with greater precision than other methods currently being used, such as cell-culture or animal-based tests.

Emulate Chip

Chip image courtesy of Emulate Inc.

Organs-on-chips have been the focus of a public-private collaboration between FDA, the federal Defense Advanced Research Projects Agency (DARPA) and the National Institutes of Health (NIH) since 2012. Millions of dollars in grants have been awarded to universities nationwide to advance this research, including Harvard University and the Massachusetts Institute of Technology. Emulate was founded by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University.

The chips were first developed to evaluate the effectiveness of drugs but have come to be seen as a potentially useful technology in our efforts to ensure the safety of the foods and cosmetics we regulate. For example, they can be put to work to see how the body processes an ingredient in a dietary supplement or a chemical in a cosmetic and how a toxin or combination of toxins affects cells, information that ultimately can be used to help assess risks to human health.

In some ways, science is like a recipe in that both can go through a number of incarnations before they work. There’s a lot of experimenting and tweaking, collaborating and comparing. And that’s what we’ll be doing at FDA with the organs-on-chips research. Science is the foundation of FDA’s decisions but many people don’t realize how much scientific research is conducted by the agency. We’re excited to be at the forefront of this ground-breaking research, which may one day be routinely used to safeguard public health.

Wondering how this Organs-on-Chips technology works? Click here.

Suzanne Fitzpatrick, Ph.D., is the Senior Advisor for Toxicology in FDA’s Center for Food Safety and Applied Nutrition

FDA in India – Championing a Culture of Quality

By: Mary Lou Valdez

One of FDA’s most strategic outposts is in India, the seventh largest supplier of food and second largest supplier of pharmaceuticals and biologics to the United States. The agency’s office, located in the capital, New Delhi, works to ensure the safety and security of food and the safety and efficacy of medical products exported from India to the U.S.

Mary Lou Valdez with India Office Staff

from left: Dean Rugnetta, FDA Deputy Director, India Office; Mary Lou Valdez, FDA Associate Commissioner for International Programs; Mathew Thomas, FDA Director, India Office

To achieve that goal, the India Office, directed by Mathew Thomas, conducts inspections of Indian medical products and foods facilities that export to the U.S. The office also assists and trains regulators, industry, and other stakeholders in developing and maintaining the quality, safety, and effectiveness of the FDA-regulated products they export.

It’s important for the office to consult regulatory authorities in India to build confidence in each other and to develop quality standards that both countries can trust.

I had the privilege of joining Director Thomas last month for meetings with our regulatory counterparts – the Indian Export Inspection Council (EIC), the Food Safety Standards Agency of India (FSSAI), the Drugs Controller General of India (DCGI), and the Joint Secretary of the Ministry of Health and Family Welfare.

Despite the diversity of these agencies’ mandates and priorities, a common theme coming out of these meetings was the recognition of the mutual benefits we realize by working together to enhance the effectiveness of our regulatory systems and to advance risk-based and science-based approaches to food and medical product regulation.

Along with other FDA experts, I also participated in a Global Food Safety Partnership (GFSP) Governing Council meeting and the Indian Pharmaceutical Alliance (IPA) Second Forum, titled “Towards Excellence in Quality.” Hosted by the Word Bank, the GFSP is a public private partnership, established in 2012, which brings together governments, industry, multilateral organizations, and other stakeholders in support of stronger food safety systems. Since its founding, the GFSP has worked with China, Indonesia, and Vietnam. During my visit, we had initial GFSP meetings with Indian regulators, to explore potential synergies as they look to bolster their food safety systems and maximize their investments. FDA’s India Office is well-positioned to help the Partnership and India explore how best to meet these goals.

The IPA Forum brings together CEOs of pharmaceutical firms, manufacturers, regulators, and other national and global stakeholders who have a role in shaping India’s complex and diverse manufacturing environment to produce safe, effective, high-quality medical products.

Over the past decade, the Indian pharmaceutical market has grown by nearly 14 percent and continues to experience massive growth. However, in order to fully realize the nation’s potential as an important player in the global pharmaceutical industry, India’s regulatory infrastructure must keep pace to ensure that global quality and safety demands are met. Quality issues are an ongoing challenge for the Indian pharmaceutical industry. Of 42 warning letters issued by FDA’s Office of Manufacturing Quality last year, nine went to Indian facilities. The IPA is working to communicate to its diverse members why quality matters and how to achieve it. Thus, the general theme of its Second Forum “Towards Excellence in Quality,” was an incredibly relevant topic if the global market for FDA-regulated products is to be strong and secure.

No one wants resources wasted on ineffectual development and weak processing or manufacturing systems that could actually impede product success. We all want greater competition, increased options for consumers and patients, and more affordable alternatives to comparable products.

Participants agreed that achieving quality requires regulators and industry alike to champion and advance a quality culture throughout the product life-cycle, by effectively employing the use of data and science and requiring greater transparency.

While I was in India, it was really gratifying to witness the high-esteem and trust Indian regulators and industry have for FDA, and our India Office. In turn, whether it is through their response to inspectional observations, their participation in trainings and seminars or their readiness to share strategic information, we see India committing to quality and compliance. Indian regulators and industry both recognize that a quality culture is imperative if India is to increase productivity, reduce compliance risk, lessen rework, and minimize supply interruptions that result in lost revenue and increased risks to public health.

This greater emphasis on quality will also allow India to participate more fully in existing global venues such as the International Council for Harmonisation (ICH) and the Pharmaceutical Inspection Cooperation Scheme (PIC/S) – which will enable stronger collaboration and synergies among regulators.

Quality is good for economic development, the market, and most importantly, patients and consumers everywhere. FDA’s Office in New Delhi looks forward to continued collaboration with our Indian regulatory colleagues to champion a culture of quality.

Mary Lou Valdez is FDA’s Associate Commissioner for International Programs

Mixing Kentucky Spirits with Food Safety to Protect Spent Grains Used to Feed Animals

By: Jenny Murphy, M.S.

“Spent grains” is the general term for the remnants of corn, rye, barley and other grains used to make alcoholic beverages. While they are a byproduct of human-food production, spent grains have a long history of being used as a valuable source of nutrients to feed many animal species. They also have been the subject of ongoing concerns among beverage distillers and brewers over the past few years as the FDA drafted rules that will implement the FDA Food Safety Modernization Act (FSMA).

Jenny Murphy holding spent grains

Jenny Murphy, a consumer safety officer in FDA’s Center for Veterinary Medicine (CVM), with handful of dried spent grain at the Wild Turkey distillery. In background, from left: Shannon Jordre, a consumer safety officer in CVM’s Division of Compliance, Jim Sanders, Distillery Manager at the Wild Turkey Distillery, Steve Barber, director of FDA’s Cincinnati District Office, and Jennifer Erickson, a regulatory policy analyst in CVM’s Office of Surveillance and Compliance.

Those concerns brought an FDA team to the rolling hills of central Kentucky this month to visit distilleries and a craft brewery and to meet members of the distilled spirits and brewers industry. The team was led by Stephen Ostroff, M.D., who was then FDA’s deputy commissioner for foods and veterinary medicine and who is now the acting FDA commissioner. I represented the agency’s Center for Veterinary Medicine (CVM) because of the connection between spent grains and animal health.

Congress included language in FSMA to exempt most alcoholic beverage manufacturing facilities from most of the FSMA requirements. But every day these manufacturers produce tons of spent grain, which are commonly used as animal food rather than being discarded in a landfill. Whether or how spent grains would be regulated under FSMA has been a point of some uncertainty for industry.

Based on the information available at this time, FDA considers the potential animal food safety hazards associated with spent grains from the alcoholic beverage industry to be minimal. The agency has assured these manufacturers that they will only be required to ensure that the byproducts are properly labeled and kept safe from contamination while they are held for distribution if these conditions are met: They continue to follow current good manufacturing practice (CGMP) requirements for human food in the production of their alcoholic beverages, and the resulting spent grains are not further processed. If the grains are further processed, such as by drying, they must follow CGMP requirements, with the flexibility to follow either the human food or animal food CGMPs.

But we have been encountering some confusion among brewers and distillers about these CGMP requirements for human and animal foods and how they would apply to spent-grain products. We wanted to reach a greater level of understanding on both sides, and what better place to do that? Kentucky is, after all, the birthplace of bourbon, according to the Kentucky Distillers Association. Recognized by Congress as a distinctively American product, bourbon is a $3 billion industry in Kentucky that generates 15,400 jobs. Kentucky also has a growing craft beer brewing industry.

containers of wet spent grain

Adam Watson (center), managing member and brewer at Against the Grain Brewery in Louisville, shows the visitors the containers of wet spent grain waiting for pickup outside the brewery.

We were a large group – about 20 participants from FDA’s headquarters and district office, the Kentucky Department of Agriculture, the state Division of Regulatory Services based at the University of Kentucky, and industry, including the Distilled Spirits Council and Brewers Association. Over the course of two days, we visited the Woodford Reserve, Wild Turkey, Jim Beam’s Booker Noe plant and Clermont distilleries, as well as the Against the Grain brewery.

This opportunity for education and outreach was extremely productive for all involved. FDA participants were able to allay many concerns and provide clarity about the framework for the CGMPs that the distillers and brewers are expected to meet for both human and animal food. And the distillers and brewers opened their doors, bringing us into their world in a way that was very informative and instructive. There is no substitute for actually seeing how these beverages are produced and how the spent grains are handled.

Although the basic processes are the same, each of the distillers and brewers we visited approaches its work somewhat differently. When it comes to spent grains, there are some operations that simply hold the grain and others with more elaborate processes to distribute the grain because of the large volume produced. We learned distinctions in terminology as the distillers showed us a variety of spent grain products, including wet and dry grains, syrups and cakes.

FDA engaged in this kind of outreach when the FSMA rules were taking shape. Now that the regulations are becoming a reality, we believe these conversations are just as important to help food producers understand what’s expected and avoid any misunderstandings. For FDA, these exchanges help us better understand what, if any, challenges industry may be facing as they strive to meet these new requirements.

Our next step is to take the knowledge we acquired and the lessons we learned and use them to help shape training for regulators and outreach to this industry in support of our shared commitment to keep both human and animal foods safe.

Click here to view FDA’s flickr album from this month’s visit to Kentucky.

Jenny Murphy, M.S., is a consumer safety officer in FDA’s Center for Veterinary Medicine

FDA’s Science-based Approach to Genome Edited Products

By Robert M. Califf M.D., and Ritu Nalubola, Ph.D.

Recent scientific advances now make it possible to more efficiently and precisely alter the genome of plants, animals, and microorganisms to produce desired traits. These genome editing technologies are relatively easy to use and can be applied broadly across the medical, food and environmental sectors, with potentially profound beneficial effects on human and animal health. However, there are also potential risks ranging from how the technology affects individual genomes to its potential environmental and ecosystem impacts. Additionally, genome editing has raised fundamental ethical questions about human and animal life.

Genome editing technologies can be used to introduce, remove, or substitute one or more specific nucleotides (letters in the DNA code) at a specific site in the organism’s genome, and is achieved with the use of protein-nucleotide complexes. Several classes of these complexes exist, the most recent discovery is known as CRISPR/Cas9.

Research is currently underway that would use these technologies to:

  • Treat HIV, cancer or rare diseases by genetically altering specific types of cells;
  • Control or alter organisms that carry infectious diseases (for example, mosquitoes that are vectors of viruses/parasites causing dengue fever, Zika or malaria; or mice that transmit bacteria causing Lyme disease);
  • Improve the health and welfare of food producing animals, (for example, hornless cattle, pigs resistant to African swine fever or porcine reproductive and respiratory virus); and
  • Alter specific traits of food plants or fungi (for example, non-browning mushrooms).

Accompanying the enthusiasm about these promising technologies are questions about whether FDA is prepared to ensure the safety of regulated products that use this technology. Providing appropriate and balanced regulatory oversight for applications involving an emerging technology is not a new or unique challenge for FDA, but the potential breadth of applications and the fundamental nature of altering the genome call for the participation of multiple constituencies in considering the most effective regulatory policies to address any potential risks.

Robert Califf

Robert M. Califf, M.D., FDA Commissioner

Maintaining product-specific, risk-based regulation

Genome editing applications are relevant to three main FDA-regulated product classes. The specific regulatory approaches for each of these classes vary, reflecting differences in underlying statutory authorities. FDA is maintaining a product-focused, science-based regulatory policy, in accordance with specific legal standards applicable to each type of product and consistent with overarching U.S. Government policy principles.

Human medical products that apply gene editing to exert their therapeutic effect are regulated under our existing framework for biological products, which include gene therapy products. “Gene editing” here refers to non-heritable situations somatic cell gene therapy only, and not to heritable conditions (germ line gene therapy). The FY16 appropriations bill restricted use of federal funds “in research in which a human embryo is intentionally created or modified to include a heritable genetic modification.” FDA’s Center for Biologics Evaluation and Research (CBER) has a well-established program and policies in place to evaluate gene therapy products. Although different types of gene editing have potential clinical applications, currently only one type of gene editing, zinc finger nuclease- (ZFN) mediated, has been announced by their sponsors as being applied in clinical trials underway in the United States. Proposals for NIH-funded human gene therapy clinical trials are discussed and reviewed for scientific, clinical, and ethical issues by the NIH’s Recombinant DNA Advisory Committee (RAC). The RAC recently discussed (and did not find any objections to) the first clinical protocol to use CRISPR/Cas9-mediated gene editing. The potential for “off-target” effects such as insertions or deletions at unintended genetic loci has been identified by experts in the field as a key concern.

Similarly, FDA’s Center for Food Safety and Applied Nutrition and Center for Veterinary Medicine have in place programs to adequately address foods derived from plants produced using genome editing and animals produced using genome editing. In these two product areas, we are issuing documents to clarify our current thinking and seek scientific information. With respect to foods derived from plants produced using genome editing, FDA has a longstanding program for foods derived from new plant varieties, including those developed by recombinant DNA (rDNA) techniques. We are requesting information on whether human and animal foods derived from genome edited plants pose additional risks compared to those from traditionally bred plants. FDA’s decades of experience providing oversight of foods from new plant varieties, coupled with scientific evidence and data received, will help inform our thinking on risk considerations going forward.

When animals are produced using genome editing, FDA has determined that, unless otherwise excluded, the portion of an animal’s genome that has been intentionally altered, whether mediated by rDNA or modern genome editing technologies, is a drug because it is intended to alter the structure or function of the animal and, thus, subject to regulation under our provisions for new animal drugs. We have updated our existing guidance for genetically engineered animals to include genome editing within its scope, and are issuing it in draft form for public comment. We are also seeking input on whether certain types of genome editing in animals pose low or no significant risk, and we may modify our regulatory approach based on this input.

Our efforts to gather necessary scientific data aside, industry remains responsible for ensuring that its products meet all applicable requirements, including safety standards. FDA has historically made itself available to meet with developers and we encourage them to engage with us to help ensure they meet their statutory and regulatory obligations. And we will continue to provide technical advice and guidance for industry, as necessary.

Collaborating with Federal agencies

The White House Office of Science and Technology Policy (OSTP), FDA, the U.S. Environmental Protection Agency (EPA), and the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS) initiated an effort in 2015 to ensure public confidence in the regulatory system for biotechnology products and improve the transparency, predictability, coordination, and, ultimately, efficiency of that system. After reviewing public comment to a docket and holding three public meetings, the agencies produced A National Strategy for Modernizing the Regulatory System for Biotechnology Products, to help ensure that the federal regulatory system is prepared to assess future biotechnology products, issued in September; and, earlier this month, a 2017 Update to the Coordinated Framework for the Regulation of Biotechnology (CF Update), to clarify each agency’s role.

Ritu Nalubola

Ritu Nalubola, Ph.D., Senior Policy Advisor, FDA’s Office of Policy

APHIS is proposing to revise its regulation regarding genetically engineered organisms that may pose plant pest or noxious weed risks. As FDA, APHIS, and EPA formulate policies, there may be differences in approaches, reflecting differences in the scope of their authorities and the types of risks addressed. Under the CF Update, interagency coordination and cooperation will continue, including on appropriate terminology, identification of hazards, and approaches to addressing risks, within the constraints imposed by regulatory paradigms for different product areas.

FDA also has a longstanding collaborative relationship with the NIH office that oversees the RAC. FDA serves as a non-voting liaison on the committee, hears the discussions first-hand, and receives the written recommendations.  These recommendations may be considered during our overall review of investigational new drug applications (INDs) submitted to FDA.

Scientific engagement and horizon-scanning

Being ready to evaluate innovative emerging technologies is a top FDA regulatory science priority. FDA is co-sponsoring two studies, conducted by the National Academies of Sciences, Engineering, and Medicine (NASEM). Both are expected to be completed this year. FDA is also conducting its own horizon-scanning through its Emerging Sciences Working Group, an FDA-wide science-based forum, and opened a public docket to receive input on emerging technologies.

Working with international partners

Scientific advances do not adhere to national boundaries and therefore it is critical that we understand the evolving views of our international counterparts. Given the leadership role of the United States in biomedical and biological sciences, we cannot afford to fall behind in this exciting scientific frontier. As expected, international regulatory agencies, too, are currently working in this area. FDA’s CBER is an active member of the International Pharmaceutical Regulators’ Forum (and its Gene Therapy working group), which provides a forum for members to identify and exchange information on issues of mutual concern and undertake targeted regulatory cooperation activities.

Going forward

FDA is committed to fulfilling its mission to safeguard public health, while encouraging innovation and competitiveness. The actions we have taken to date, including release of the CF Update, National Strategy, and FDA’s documents – are steps in a series of ongoing activities. We will continue to collaborate with our federal and international partners, and actively communicate with stakeholders to help ensure confidence in FDA’s regulatory system. However, oversight provided by FDA is one aspect of broader governance necessary for safe and responsible research and development of genome editing applications. Moreover, the expansive scope of intentional genomic alterations using modern genome editing technologies has triggered debate on fundamental ethical and social issues, which will continue to influence public opinion and acceptance of genome editing applications. Even as FDA implements necessary steps for effective regulation to ensure the safety of products, the role of broader, inclusive public discussion involving multiple constituencies (e.g., scientists, developers, bioethicists, and public interest and community groups) to address the larger societal considerations should not be overlooked.

Robert M. Califf, M.D., is Commissioner of the Food and Drug Administration

Ritu Nalubola, Ph.D., is a Senior Policy Advisor in FDA’s Office of Policy

 

Why FDA Is Making Data Extracted from Reports of Adverse Events for Foods and Cosmetics Available to the Public

By: Susan Mayne, Ph.D., and Katherine Vierk, M.P.H.

Transparency in the actions we take as an agency, and our reasons for taking them, is an important value for FDA in its mission to protect public health.

Susan Mayne

Susan Mayne, Ph.D., is Director of the FDA’s Center for Food Safety and Applied Nutrition

That is why we are, for the first time, making public the data that FDA’s Center for Food Safety and Applied Nutrition (CFSAN) receives about adverse events related to foods, including conventional foods and dietary supplements, and cosmetics regulated by FDA. This is information that was once only available through Freedom of Information Act (FOIA) requests, but will now be easily available to researchers, consumers, and health professionals.

This first posting of data from CFSAN’s Adverse Event Reporting System (CAERS) includes data from reports submitted by consumers, medical professionals and industry from 2004 through September 2016. The term “adverse event” is an umbrella term for a number of poor outcomes, including bad reactions, illnesses or deaths. We plan to update this information quarterly to ensure that the public has the most current information available.

Katherine Vierk

Katherine Vierk, M.P.H., is the Director of the Division of Public Health Informatics and Analytics at FDA’s Center for Food Safety and Applied Nutrition

The goal of CAERS is to provide indications, or “signals” of potential hazards. FDA uses these adverse event reports to monitor the safety of foods, including conventional foods and dietary supplements, and cosmetics. This information can, and has, led to investigations of specific products, targeted inspections and product testing, import alerts, warning letters, and enforcement actions.

Examples of how adverse event data has been used to support multiple actions by FDA include recalls of HydroxyCut and OxyElite Pro dietary supplements, and investigations of cosmetic products, such as EOS lip balm and Brazilian BlowOut hair smoothing treatment.

A few caveats about CAERS: The data from the reports is what was reported to the agency. FDA has not necessarily determined that the events reported were actually caused by the product in question. And there often are gaps in the information provided, which should ideally include the product name, symptoms, outcome, consumer’s sex and age, and the date the adverse event was experienced.

Going forward, FDA intends to modernize the system to make reporting adverse events as user-friendly as possible. You can expect to hear more about that in about a year. But in the meantime we didn’t want to delay giving the public access to data we have. The CAERS data will be posted on fda.gov and is also available through OpenFDA, launched in 2014 to make it easier to access the agency’s publicly available information.

We’re hoping that this increased transparency will result in more detailed and complete reports that will help us to more rapidly identify red flags about a possible safety issue with products we regulate. Anyone can report a safety or quality issue with an FDA-regulated food (conventional foods and dietary supplements) and cosmetics. To do so, visit fda.gov.

Susan Mayne, Ph.D., is the Director of FDA’s Center for Food Safety and Applied Nutrition

Katherine Vierk, M.P.H., is the Director of the Division of Public Health Informatics and Analytics at FDA’s Center for Food Safety and Applied Nutrition