Using Symbols to Convey Information in Medical Device Labeling

By: Antoinette (Tosia) Hazlett, MSN, RN, and Scott Colburn CAPT, USPHS

Symbols convey important messages for navigating everyday life; whether it’s a traffic sign or a graphic image indicating that no smoking is allowed in a building. Symbols in medical device labeling can also convey important information. However, to be an effective means of communicating information, it’s critical that symbols on medical devices are understood by the individuals who use them.

Tosia Hazlett

Antoinette (Tosia) Hazlett, MSN, RN, Senior Policy Analyst at FDA’s Center for Devices and Radiological Health

In June, FDA issued the Use of Symbols in Labeling final rule, which describes the circumstances in which manufacturers can use a stand-alone symbol in device labeling without any adjacent explanatory text. For example, if certain requirements are met under the final rule, manufacturers of sterile syringes could opt to use the symbol for “do not reuse” on a syringe package without adding the actual words “do not reuse” to the package.

Using Symbols

The “Use of Symbols in Labeling” final rule which went into effect on September 13, 2016, does not mandate the use of stand-alone symbols in device labeling. Under the final rule, device manufacturers have three options. They can choose not to use symbols, use symbols with adjacent explanatory text, or use stand-alone symbols that have been established in a standard if certain requirements are met, including providing an explanation of the symbols in a symbols glossary that is included in the labeling for the device.

Adding the option of stand-alone symbols is expected to reduce design costs for manufacturers because it is more consistent with how devices are currently labeled in Europe and other foreign markets. Replacing small and difficult-to-read text with a symbol will also help make some labeling more user-friendly and understandable. That is critical in medical device labeling, where space may be limited. The use of stand-alone symbols on a global scale may help promote better understanding through consistent labeling across products distributed in the U.S. and foreign markets.

Scott Colburn

Scott Colburn CAPT, USPHS, FDA’s Director, Center for Devices and Radiological Health Standards Program

Before this rule, FDA recognized five consensus standards that address the use of stand-alone symbols. On the same day this rule was issued, FDA updated its currently recognized consensus standards list and added three new standards containing more symbols in a published standards-recognition notice.

Symbols Glossary

The required symbols glossary is intended to help users become familiar with the meaning of the stand-alone symbols and serve as a reference for users to look up any definitions they may not recall.

The symbols glossary may be in a paper or electronic format as long as it is included in the labeling for the device. Additionally, the labeling on or within the package that contains the device must bear a prominent and conspicuous written statement identifying the location of the symbols glossary.

Symbol Statement “Rx Only” or only”

The rule also allows for the use of the commonly used symbol statement “Rx only” or “℞ only” in the labeling for prescription devices.

Learn More

On Monday, July 25, 2016, FDA conducted a webinar to help industry and patient groups learn more about this final rule and the new standards recognition notice. The slides, recording and transcript from the webinar entitled, “Final Rule: Use of Symbols in Labeling” is available on the CDRH Learn  and Webinar webpages.

Antoinette (Tosia) Hazlett, MSN, RN, is a Senior Policy Analyst at FDA’s Center for Devices and Radiological Health

Scott Colburn CAPT, USPHS, is FDA’s Director, Center for Devices and Radiological Health Standards Program

FDA’s Clinical Investigator Training Helps Support the Drug Development Process

By: Leonard Sacks, M.D., and Mili Duggal, Ph.D., M.P.H.

Though many people do not know it, FDA does much more to facilitate drug approval than evaluate new drug applications. We are also actively involved in drug development well before the application stage. One important way we do this is by training scientists who conduct the clinical trials for drugs in development. This helps ensure that the drug studies conducted by investigators meet the applicable regulatory requirements and that the applications submitted meet regulatory standards.

Leonard Sacks

Leonard Sacks, M.D., is Associate Director for Clinical Methodologies, Office of Medical Policy, at FDA’s Center for Drug Evaluation and Research

We are excited to announce our seventh annual Clinical Investigator Training Course, which will be held in collaboration with the University of Maryland’s Center of Excellence in Regulatory Science and Innovation (M-CERSI) from November 7-9, 2016, at the Civic Center, Silver Spring, Maryland. The course is designed for physicians, nurses, pharmacists, and other healthcare professionals who are involved in the design, conduct, and evaluation of clinical trials. Participants receive training by senior FDA experts and guest speakers from industry and academia, which enables them to learn the scientific, regulatory, and ethical aspects of clinical trials.

FDA has successfully conducted the Clinical Investigator Training Course since 2009, training more than 1,000 attendees from the U.S. and other parts of the world, including Germany, Spain, Zimbabwe, and China. Over the years, participants have included healthcare professionals from government organizations, regulatory bodies, academia, industry, and the healthcare sector.

Mili Duggal

Mili Duggal, Ph.D., M.P.H., is an ORISE Fellow, Office of Medical Policy, at FDA’s Center for Drug Evaluation and Research

FDA developed this course so that investigators could learn directly from our staff and interact with them. Clinical trial investigators play a critical role in the development of medical products. They are responsible for protecting the safety and welfare of study subjects and for acquiring adequate and reliable data to support regulatory decisions. FDA recognizes that investigators should be comprehensively trained to conduct trials efficiently. The course’s goal is to develop competence and expertise among clinical investigators, improve the quality of clinical trials, and support patient safety.

As we continue to build our program, FDA will work to integrate the latest scientific information and good clinical practices into our course. We anticipate a new round of exciting discussions with our attendees this year and we invite all who are interested and wish to attend to take a look at the course website for more details. We look forward to helping many more talented researchers hone their clinical investigator skills to advance new drug development for the American public.

Leonard Sacks, M.D., is Associate Director for Clinical Methodologies, Office of Medical Policy, at FDA’s Center for Drug Evaluation and Research

Mili Duggal, Ph.D., M.P.H., is an ORISE Fellow, Office of Medical Policy, at FDA’s Center for Drug Evaluation and Research

Making Sure ‘Healthy’ Means What It Says on Food Packages

By: Douglas Balentine, Ph.D.

With final rules on the Nutrition Facts label published, consumers soon will see an updated label on food packages that makes the calories and serving sizes of products easier to see and that gives them additional nutrition information, such as added sugars, vitamin D, and potassium.

Doug BalentineThe marketplace is teeming with rows and rows of foods – some new and some not; some healthier than others. Even for the well informed, choosing what to buy is challenging, especially if you want to choose a healthy diet for you and your families.

We know that many consumers use the Nutrition Facts label, especially when they are buying a food for the first time. Often, there are also a lot of other terms on food packages such as “healthy,” “low in fat,”or “good source.” We also know that many just don’t have the time to consider the details of nutrition information on every package they purchase. In fact, most purchase decisions are made quickly, within three to five seconds.

That’s why we’re looking at how we define the claim “healthy.” Companies can use this and other claims on the front of packages of foods that meet certain criteria to help consumers quickly identify nutritious choices.

As our understanding about nutrition has evolved, we need to make sure the definition for the “healthy” labeling claim stays up to date. For instance, the most recent public health recommendations now focus on type of fat, rather than amount of fat. They focus on added sugars, which consumers will see on the new Nutrition Facts label. And they focus on nutrients that consumers aren’t getting enough of, like vitamin D and potassium. By updating the definition, we hope more companies will use the “healthy” claim as the basis for new product innovation and reformulation, providing consumers with a greater variety of “healthy” choices in the marketplace.

We have started to consider the criteria or terms for an updated definition of “healthy” but don’t have all the answers. As a first step, we are asking for public input on a range of questions about what “healthy” should mean from a nutrition perspective and how consumers understand and use “healthy” food label claims.

For example, what current dietary recommendations should be reflected in the definition of “healthy”? What are the public health benefits of defining the term “healthy”? What do consumers expect of foods that carry a “healthy” claim? What factors and criteria should be used for the new definition of “healthy”? We are also planning to hold public forums to get additional input and inform us of what a broad range of stakeholders and consumers think. This may take some time, but we want to get it right.

While we are working on the “healthy” claim, we also will begin evaluating other label claims to determine how they might be modernized. We want to give consumers the best tools and information about the foods they choose, with the goal of improving public health. And, we will also engage with industry to explore other ways to encourage companies to change their products to have better nutrition profiles. The end result will be more healthy dietary choices for consumers, and that is a worthy goal.

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

First Major FSMA Compliance Dates: Landmarks and Learning Experiences

By: Stephen Ostroff, M.D., and Howard Sklamberg, J.D.

The phrase “where the rubber meets the road” is one that comes up in conversations about different subjects, from athletics to academics, when carefully laid plans are put to a crucial test. That’s where we are today with the arrival of the first major compliance dates under the regulations developed by FDA to implement the FDA Food Safety Modernization Act (FSMA).

Stephen Ostroff, M.D.

Stephen Ostroff, M.D., is FDA’s Deputy Commissioner for Foods and Veterinary Medicine

This is the day when larger businesses must comply with certain new standards under the preventive controls rules for human and animal food, two of the main rules developed to drive down the incidence of foodborne illnesses in our country. Larger human food facilities must meet preventive controls and modernized Current Good Manufacturing Practice requirements (CGMPs); larger animal food facilities must meet CGMPs. (The human and animal food rules have staggered compliance dates; animal food businesses have additional time to meet the preventive controls standards, as do smaller producers of human foods.)

The preventive controls rules were the first two of seven foundational FSMA rules to become final starting in September 2015. Human food facilities are required to have a food safety system in place that includes an analysis of hazards and risk-based preventive controls to minimize or prevent those hazards. The standards that animal food facilities must meet mark the first time that CGMPs have been broadly required for the safe production of animal food.

FSMA was signed into law in 2011 in the wake of mounting concerns by consumers and lawmakers about outbreaks of foodborne illness that kill thousands of people and animals every year. What followed was an unprecedented effort by FDA to involve the diverse landscape of food safety stakeholders, including growers, manufacturers, importers, distributors, consumer groups, and academic institutions, in the formulation of rules that are practical, flexible and effective for the food industry at home and abroad while protecting the public from contaminated food.

Howard Sklamberg

Howard Sklamberg, J.D., is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

Since FSMA was enacted in 2011, we have literally traveled the world to get input on the rules we proposed in 2013 and early 2014 to implement the law. FDA teams have been involved in approximately 600 engagements, including public meetings, webinars, listening sessions, farm tours, visits to manufacturing plants and extensive presentations and meetings with various stakeholder groups.

As a result of these conversations, we made significant changes in September 2014 to four of the FSMA proposed rules, including the preventive controls rules, to make them more feasible and, ultimately, more effective.

So what happens now? This is a new chapter for all of us. FDA is focusing on providing the support that companies need to comply with the new requirements with education, training and technical assistance. We will be looking at how facilities are working to comply with the new food-safety standards and protect consumers from unsafe food. Of course, our mandate is to protect public health and, when necessary, the agency will act swiftly to do so.

The conversations we had with stakeholders in creating the rules will continue as we move further into the implementation phase with the preventive controls and other rules. We will be sharing our thinking on how requirements should be met in guidance documents and asking for the public to continue to provide feedback. If necessary, changes will be made; aspects of the rules will be fine-tuned. This first wave of compliance dates is important to the entire spectrum of FSMA implementation; the lessons learned will be invaluable in the years ahead when smaller food facilities are held to the new standards.

So today, the rubber meets the road. But these compliance dates aren’t the beginning of the end of our work to make FSMA a reality. They’re the end of the beginning. The partnership that FDA has forged with food producers of all kinds, and with its state, local, tribal and international regulatory partners, will ultimately protect consumers for generations to come.

Stephen Ostroff, M.D., is FDA’s Deputy Commissioner for Foods and Veterinary Medicine; Howard Sklamberg, J.D., is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

Evaluating FDA’s Approach to Cancer Clinical Trials

By: Richard Pazdur, M.D.

Since the announcement of the FDA Oncology Center of Excellence (OCE) two months ago (June 29, 2016) as part of the White House’s Cancer Moonshot, we’ve been working to further FDA’s efforts to get new oncology products into the hands of patients. We are committed to meet the needs of patients and health care communities by driving progress in the prevention, diagnosis, and treatment of cancer.

Dr. Richard PazdurAt the core of the OCE’s work – and of the Cancer Moonshot – is taking a new look at what we have been doing in the past so we can operate more efficiently in the future. The OCE will leverage the combined skills of oncologists and scientists with expertise in drugs, biologics, and devices to employ the best and most innovative approaches to bring forth safe new oncology products.

The vision set forth by the Vice President underscores our commitment to optimally designed clinical trials that efficiently provide answers to important questions. Given the recent advances in our understanding of cancer and our improved technological capabilities, we are now placing an emphasis on evaluating how we design clinical trials to make the system more efficient to more rapidly deliver safe and effective products for patients.

We are working with stakeholders across government and industry to revisit the criteria used for determining whether a patient is eligible to participate in a trial. Modifying the eligibility criteria could expand the number of people who qualify and therefore open new opportunities for participation and enhance the generalizability of what we learn. Of course, regardless of adjustments, patient safety will remain paramount.

We recently published our perspective on shifting away from the conventional phase one, phase two, and phase three drug development paradigm to a more seamless approach that could expedite the regulatory pathway, providing earlier access to highly effective therapeutic drugs. Adopting this approach could complement FDA’s expedited regulatory programs such as breakthrough designation and accelerated approval to get products to patients in the most efficient manner possible.

Another initiative is the use of common control trials. These trials, sharing a common control arm, involve multiple different drugs for the same indication and may involve different companies. When a common control arm is used, it decreases the overall number of patients that need to be recruited and enrolled, optimizing clinical trial resources and potentially decreasing the time it takes to get a new study off the ground.

Encouraging the use of large simple trials is another way to make more efficient use of clinical trial resources. These trials generally use easily-measured endpoints that are well understood, optimizing the collection of data for safety or secondary efficacy endpoints and thus reducing the amount of data needed compared to conventional randomized trials.

As befits the Center of Excellence, one of our top goals is striving for excellence both in drug and device regulation and in emerging oncology science. To achieve that goal we must also collaborate with academia, industry, patient groups, professional societies, and other international regulators. We have already begun this work by scheduling several public meetings that will provide a forum to interact with patients and other stakeholders.

These initiatives will allow us to expedite drug development and approval of truly novel agents that will have a major impact on our patients, while allowing us to make thoughtful decisions regarding the risk-benefit of oncology drugs.

Richard Pazdur, M.D., is FDA’s Acting Director, Oncology Center of Excellence

On Dauphin Island, FDA Scientists Work to Keep Seafood Safe

By: Capt. William Burkhardt III, Ph.D.

On a barrier island in the Gulf of Mexico, two dozen scientists and staff in the FDA’s only marine research laboratory have one common goal: to keep consumers safe from contaminated or unsafe seafood.

I am the director of the FDA’s Gulf Coast Seafood Laboratory (GCSL) on Dauphin Island, Alabama, where we detect chemical and biological hazards and work to reduce the likelihood of illness associated with seafood. In early August, the agency invited U.S. Rep. Robert Aderholt to tour the facility and see our work first-hand. Rep. Aderholt represents Alabama’s Fourth Congressional District and chairs the House Appropriation Committee’s Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies.

Gulf Seafood Lab

Robert Hayes Aderholt feeds crabs at the Gulf Coast Seafood Laboratory as his father, U.S. Rep. Robert Aderholt, and biologist Kathy El Said look on.

At the GCSL, we use the latest technology to detect and identify things that can potentially contaminate seafood. There are drug and chemical residues that may be present from the use of antibiotics and other chemicals in aquaculture production. There are also petrochemicals from off-shore drilling.

There are marine biotoxins that occur naturally, such as harmful algal toxins that go up the marine food chain and eventually get into fish. There are bacteria that occur naturally in marine waters, such as vibrios, that can cause serious, even deadly, illnesses. And there are viruses, such as the norovirus, in marine water that are ingested by shellfish.

We routinely test a wide array of samples from public and private sources, and work closely with FDA’s compliance and enforcement teams in and out of the country so that action can be taken when appropriate.

Our scientists are often brought in when a natural or man-made disaster threatens to contaminate fish or an outbreak is tied to seafood. We’re involved right now in the response to an outbreak of hepatitis A in Hawaii tied to imported scallops, providing microbiological support to identify the virus that has sickened more than 200 people.

Group photo at Gulf Seafood Lab

U.S. Rep. Robert Aderholt (front row, center) poses with FDA’s team at the marine research laboratory. Also in the front row are lab director Capt. William Burkhardt III (left) and William Jones, deputy director of FDA’s Office of Food Safety (right).

When the Deepwater Horizon oil rig exploded in 2010, spilling an estimated 4.9 million barrels of oil into the Gulf of Mexico, we staffed sampling locations. A year after that spill, we allayed the concerns of fishermen participating in the Alabama Deep Sea Fishing Rodeo tournament, billed as the largest fishing tournament in the world. FDA’s Office of Regulatory Affairs set up a mobile laboratory in our parking lot and together we tested samples that fishermen brought in, working round-the-clock for two weeks. We were able to assure the fishermen that there was no oil or dispersants in their fish.

In 2005, we were heavily involved in the response to Hurricane Katrina, in which there were concerns that chemicals would be swept into the Gulf and then into the fish. We deployed staff to sample crabs, shrimp and other seafood and send them by courier back to our labs. Ultimately, we found some elevated levels of bacterial contamination, but that dissipated relatively quickly during the time in which the area was closed to fishing.

We are also invited by other countries to assist in emergency response. For example, six years ago we traveled to Chile after an earthquake there and used our technology to detect norovirus in the drinking water.

When Haiti was hit with a cholera outbreak in 2010, we responded in collaboration with the Centers for Disease Control and Prevention. Our tests found cholera in seafood collected from Port au Prince. These findings were used to tighten recommendations on the movement of ballast water in and out of ships to minimize transmission of the outbreak.

We work with the seafood industry to find practical solutions to common problems. For example, we’re working with oyster fisherman to identify strategies to control bacterial (vibrio) growth. And we’ve advised barracuda fishermen to avoid certain parts of the Caribbean where the fish are vulnerable to biotoxins.

As I showed Rep. Aderholt around our labs, it was a good opportunity to reflect on the important work we do here and the impact we have. Whether it’s in the United States or overseas, we want to be known as a group of scientists that helps people everywhere enjoy seafood safely.

Capt. William Burkhardt III, Ph.D., is the Director of FDA’s Division of Seafood Science and Technology

FDA and Access to Medications

By: Janet Woodcock, M.D.

A severe allergic reaction called anaphylaxis is a medical emergency that affects the whole body and, in some cases, leads to death. If you have had an anaphylaxis episode, you always face the risk of another one. To mitigate the risk you or your caregiver should carry an emergency treatment called epinephrine at all times, because every second counts.

Janet WoodcockAt the FDA, we understand how important it is for this treatment to be safe, effective, and work correctly every time. And in the case of a very severe reaction such as anaphylaxis, when there may be no second chance, the device that delivers the medication is just as critical. EpiPen, a popular form of emergency epinephrine that auto-injects the dose, is one of these treatments.

But sometimes, when medications become prohibitively expensive, some people lose access to a potentially life-saving treatment. When that happens, people often look to the FDA. Recent news about the price spike of EpiPen has caused concern. In addition, the EpiPen product has patents listed through 2025 that could delay generic competition. And so we are asked, what role does the FDA play?

The FDA doesn’t regulate drug prices – prices are set by the drug makers or distributors. It’s our job to ensure medications, including emergency medications, are safe and effective. We also recognize when we approve new drugs, including generic versions of a drug, it may improve competition in the marketplace. The good news is that the FDA has already approved four epinephrine auto-injectors to treat anaphylaxis in an emergency, and two are currently marketed. The EpiPen does not have any FDA-rated therapeutic equivalents. But like EpiPen, these alternative products are approved by the FDA as safe and effective for treating anaphylaxis. As always, patients should check with their doctor on whether a particular treatment is appropriate and available.

We stand ready to quickly review additional applications that come to us from manufacturers, especially applications for generic versions. To speed along the process, our Office of Generic Drugs prioritizes and expedites our review of applications for first generics, making sure that the first applicants to make a generic are moved to the head of the queue and given priority review.

We at the FDA are also doing all we can to encourage manufacturers to develop innovative new auto-injectors that ensure a life-saving drug can be administered easily and safely by anyone. To help development, we built a roadmap that will get these products on the market faster. In June 2013, the agency provided technical information for industry about designing and testing auto-injectors. In February, the FDA provided industry with draft guidance on how to determine if patients can effectively use the new devices. We do not want substandard quality products to come to market, because a patient suffering a life-or-death event has to be able to pick up and use a device without a moment’s hesitation.

The FDA is committed to ensuring that consumers can trust the products that are available. Anaphylaxis is a condition some people can’t avoid, but cost should not be the reason someone cannot access care.

Janet Woodcock, M.D., is the FDA’s Director of the Center for Drug Evaluation and Research

FDA Cooperative Agreements with States to Advance Food Safety

By: Stephen Ostroff, M.D.

Today, the FDA is honoring an important commitment by awarding millions of dollars to the states that will help implement the new produce safety rule mandated by the FDA Food Safety Modernization Act (FSMA) to protect consumers from foodborne illness.

Stephen Ostroff, M.D.In FSMA, Congress envisioned a strong partnership between the FDA and the state agencies that have a greater understanding of the growing and harvesting practices in their areas. Many have longstanding relationships with farmers and produce associations.

To support this partnership, the FDA is awarding $21.8 million in cooperative agreements to 42 states in support of their work to help implement the new produce rule. These funds will provide states with the resources they need to develop a produce safety system, considering the specific and unique needs of their growers for education, outreach, and technical assistance.

The funding for each state is based on the estimated number of farms in the state that grow produce covered by the FSMA rule.  The goal is to provide resources that will enable the states to develop a multi-faceted, multi-year plan that includes an assessment of their produce safety landscape, including an evaluation of existing state authorities to implement a produce safety program and ways to develop a strong outreach and education program with growers.

The produce safety rule, which became final in November 2015, establishes science-based standards for the safe growing, harvesting, packing, and holding of fruits and vegetables. State leaders were key partners as the produce provisions were being developed, providing valuable input on how to make the requirements as practical and flexible as possible for growers while still protecting public health.

The cooperative agreements build on a foundation laid long before the produce rule became final. Enacted in 2011, FSMA included several important provisions aimed at strengthening the National Integrated Food Safety System so that the more than 3,000 state, local, and tribal government agencies involved in food safety are fully integrated in FDA’s work to fulfill FSMA’s mandate.

We have been steadily building this system, and in our FY2017 budget request we have asked Congress for an additional $11.3 million in new budget authority to further support the development of state produce safety programs.

In 2014, the FDA entered into a five-year cooperative agreement with the National Association of State Departments of Agriculture (NASDA) that brought together state partners to collaboratively plan implementation of the produce safety rule. The framework developed by NASDA will guide and inform states as they work on their own regulatory programs.

The cooperative agreements are part of a long-term strategy to strengthen this working partnership with the states. We’re in this together and the FDA will continue to support its state partners as we work to make the vision of a preventive and risk-based food safety system a reality.

Stephen Ostroff, M.D., is FDA’s Deputy Commissioner for Foods and Veterinary Medicine