Protecting and Promoting Public Health: Advancing the FDA’s Medical Countermeasures Mission

By Anna Abram

The U.S. Food and Drug Administration’s wide-ranging public health responsibilities include the vital role we play on the frontlines of national security by facilitating the development and availability of safe and effective medical countermeasures. These are the vaccines, diagnostics and therapeutics that are needed to protect our nation from chemical, biological, and radiological and nuclear threats, whether naturally occurring, accidental, or deliberate. As in so many areas of public health, our work here is critical, and we are ever-cognizant of its urgency.

One of the many areas in which the agency is continuing to take steps to facilitate the development of medical countermeasures to protect Americans is with respect to the threat of smallpox. The World Health Assembly declared naturally occurring smallpox eradicated worldwide in 1980, following an unprecedented global immunization campaign. However, small amounts of the variola virus – the virus that causes smallpox – still exist for research purposes in two labs; one of these labs is in the U.S. and the other in Russia. Despite the eradication of naturally occurring smallpox disease, there are longstanding concerns that the variola virus could be used as a weapon. Since routine vaccination was discontinued in the 1970s, many people would be at high risk of getting very ill or dying if exposed to this highly contagious virus.

Medical Countermeasures Against Smallpox

The development of medical countermeasures for smallpox presents complex and unique challenges. It is not possible to conduct clinical trials involving patients with naturally occurring smallpox and exposing humans to the variola virus would be ethically unthinkable. To address this challenge – which also applies to many of the high-priority threat agents for which medical countermeasure are being developed – the FDA in 2002 established the Animal Rule, which allows efficacy data to be obtained solely from studies in animals when studies in humans are not ethical or feasible, provided the results can be reasonably extrapolated to expected human use and plans can be made for follow-up study when appropriate. (The FDA finalized guidance on product development under the Animal Rule in 2015).

Anna Abram

Anna Abram is FDA’s Deputy Commissioner for Policy, Planning, Legislation, and Analysis

However, the variola virus poses additional issues for drug developers. Unlike other products studied under the Animal Rule, studies of smallpox countermeasures require not just a surrogate host but also a surrogate pathogen. Most pathogens are capable of infecting multiple host species and therefore can be studied in other, nonhuman, species. But the variola virus only infects humans, which means that variola virus animal models are unlikely to convincingly resemble the human disease. To help delineate a path forward, the FDA issued a draft guidance “Smallpox (Variola) Infection: Developing Drugs for Treatment and Prevention” in 2007 and brought these important issues to an FDA public workshop in 2009 and an FDA advisory committee meeting in 2011. The revised draft guidance issued last week incorporates this input, providing developers with additional clarity on the regulatory path for products intended to treat smallpox. It recommends that efficacy be demonstrated based on studies in two animal models infected with related viruses – such as a monkey model using monkeypox and a rabbit model using rabbitpox. This guidance underscores how the FDA is continually working to identify and apply efficient solutions based on the most up-to date science in its regulation of safe and effective medical products.

The ultimate testament to the success of these efforts is the approval on July 13 of TPOXX (teconvirimat), the first drug with an indication for the treatment of smallpox and the 14th medical countermeasure approved under the Animal Rule. In conjunction with this product approval, the sponsor was awarded the first Material Threat Medical Countermeasure Priority Review Voucher, established by the 21st Century Cures Act, to incentivize the development of certain medical countermeasures against some of the most serious threat agents.

The FDA’s Other Recent Work on Medical Countermeasures

Smallpox isn’t the only area of medical countermeasure work ongoing at the FDA. On July 10, we approved an autoinjector which provides a one-time dose of the antidote atropine to block the effects of a nerve agent or certain insecticide poisonings (organophosphorus and/or carbamate).

We also recently issued an Emergency Use Authorization (EUA) to the Department of Defense (DoD), permitting the emergency use of a specific freeze-dried plasma product manufactured to treat U.S. military personnel with severe or life-threatening hemorrhage or coagulopathy (a condition that affects the blood’s ability to clot) due to traumatic injuries sustained in the conduct of military operations in situations when plasma is not available or when its use is not practical. The use of plasma in combat settings is severely limited by logistical and operational challenges, such as the need for refrigeration and, in the case of frozen plasma, a long thawing period. In January 2018, the FDA and DoD announced a joint program to prioritize the efficient development of safe and effective medical products intended to save the lives of American military personnel.  We are working closely with our DoD colleagues in these important priority areas, including the goal of having a licensed freeze-dried plasma product as soon as possible.

These are just some of the ways in which the FDA has been hard at work to advance our medical countermeasure mission. But there is more work to do and the agency is committed to doing it. We are constantly reminded that chemical, biological, radiological, and nuclear threats – whether deliberate, naturally occurring or accidental – can, and often do, emerge with little to no warning. Emerging threats are often not deterred by geographical boundaries in our modern times. The recent Ebola outbreak in the Democratic Republic of Congo is a reminder of the need to remain ever vigilant in our work to advance medical countermeasures as part of protecting and promoting public health.

We are committed to doing all that we can to continue to facilitate the development and availability of medical countermeasures. The FDA’s Medical Countermeasures Initiative (MCMi), established in 2010, is focused on providing clear regulatory pathways for medical countermeasures, advancing regulatory science to support regulatory decision-making, and articulating important regulatory policies and mechanisms to facilitate the timely development and availability of medical countermeasures. These actions are translating into tangible results. Since 2012, the FDA has approved, licensed or cleared more than 120 medical countermeasures (including supplemental changes to already approved applications and modifications to diagnostic devices) for a diverse array of threats including anthrax, smallpox, botulinum toxin, plague, and pandemic influenza.

Under the MCMi, the FDA is taking key actions to address many of the challenges associated with countermeasure development. For example, we still do not have adequate animal models to support the development of medical countermeasures against many potential biothreats nor do we have sufficient biomarkers to assist in supporting the extrapolation of data generated in animal models to humans. Without such tools, it can be difficult to generate the data necessary to support regulatory decision-making.

Given the urgency inherent in our medical countermeasure work, addressing these regulatory science gaps remains a high priority for the agency. To help address these challenges, the FDA has established a broad and robust portfolio of cutting-edge research under the MCMi Regulatory Science Program and is working with our private sector and government partners, including DoD, to help facilitate the translation of discoveries in science and technology into safe and effective medical countermeasures. Congress has also provided vital support and our recent actions in this space underscore how we are fully leveraging the authorities Congress has given us, including measures enacted as part of the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 and the 21st Century Cures Act.

The FDA remains deeply committed to working closely with its partners to achieve our mission of protecting and promoting the public health, both at home and abroad, by doing our part to facilitate the timely development of safe and effective medical countermeasures to protect our nation.

Anna Abram is the FDA’s Deputy Commissioner for Policy, Planning, Legislation and Analysis.

The American Chamber of Horrors

By: Vanessa Burrows, Ph.D., Suzanne Junod, Ph.D., and John Swann, Ph.D.

In the early 20th century, Americans were inundated with ineffective and dangerous drugs, as well as adulterated and deceptively packaged foods.

A cosmetic eyelash and eyebrow dye called Lash Lure, for example, which promised women that it would help them “radiate personality,” in fact contained a poison that caused ulceration of the corneas and degeneration of the eyeballs. An elixir called Banbar claimed to cure diabetes as an alternative to insulin, but actually provided no real treatment and caused harm to those patients who substituted this for effective insulin therapy. Food producers short-changed consumers by substituting cheaper ingredients. Some products labeled as peanut butter, for instance, were filled with lard and contained just a trace of peanuts, and some products marketed as “jellies” had no fruit in them at all.  Unscrupulous vendors even sold products to farmers, falsely promising they could treat sick animals – in at least one case, a product called Lee’s Gizzard Capsules killed an entire flock of turkeys instead of curing them.

Although the FDA sought to remove these unsafe and misleading products from commerce, it was severely limited in its efforts by the 1906 Pure Food and Drugs Act.  That law laid the cornerstone for the modern FDA and marked a monumental shift in the use of government powers to enhance consumer protection by requiring that foods and drugs bear truthful labeling statements and meet certain standards for purity and strength.

Over time, however, the shortcomings of the Pure Food and Drugs Act became apparent, as it failed to take into account the extraordinary changes in industries, products, markets, and advertising tactics. Dangerous drugs were a particular problem. As long as a drug met the law’s labeling requirements, the agency did not have the authority to remove even clearly dangerous products such as radium water and drugs with poisonous ingredients from the market because legal action against a drug product required a finding of fraud. If a drug’s maker could convince a court that he truly believed his own therapeutic claims, he won his case. In addition, the law provided no authority over cosmetics or medical devices, and did not specifically authorize standards for foods, which limited the agency’s ability to take action on behalf of consumers.

A popular book of the day, “100,000,000 Guinea Pigs: Dangers in Everyday Food, Drugs, and Cosmetics,” claimed that consumers were being used as guinea pigs in a giant experiment by food companies and makers of patent medicines, with the authors blaming the FDA for failing to act. But the critics failed to acknowledge the limits of the agency’s authority under the law at the time.

In an effort to inform the public about the 1906 law’s shortcomings, the FDA’s Chief Education Officer, Ruth deForest Lamb, and its Chief Inspector, George Larrick, led the creation of an influential traveling exhibit in 1933 to highlight about 100 dangerous, deceptive, or worthless products that the FDA lacked authority to remove from the market.

The exhibition was put on display at events like the 1933 World’s Fair in Chicago, at state fairs, and on Capitol Hill. It was so shocking that it was dubbed the “American Chamber of Horrors” by a reporter who accompanied First Lady Eleanor Roosevelt to view the exhibit. Lamb also adapted the exhibit into a 1936 book in which she explained, “All of these tragedies…have happened, not because Government officials are incompetent or callous, but because they have no real power to prevent them.”

The exhibit, which was viewed by millions, was an enormous success, helping promote greater awareness and understanding about the FDA’s role in protecting the public and the need for greater consumer protection and the limitations on its power to do so. To this end, it played an important role in moving Congress to enact a stronger food and drug law – the 1938 Food, Drug, and Cosmetic Act.

The 1938 law, which has been amended many times and remains the law of the land today, brought cosmetics and medical devices under the FDA’s authority, and required that drugs be labeled with adequate directions for safe use. It also mandated pre-market approval of all new drugs, such that a manufacturer would have to prove to the FDA that a drug was safe before it could be sold. And it prohibited false therapeutic claims for drugs. The Act also corrected abuses in food packaging and quality, and it mandated legally enforceable food standards. It formally authorized factory inspections, and added injunctions to the agency’s enforcement tools. In short, it gave the FDA many of the means it has today to protect the American public.

Many of the products from the original Chamber of Horrors exhibit are in the FDA’s permanent collection, and, to commemorate the 80th anniversary of the 1938 law, they are part of a special display currently on exhibit at the FDA. The objects provide a compelling visual record of how far science has brought us from the worthless and dangerous elixirs, foods, and other consumer products of the early 20th century, as well as underscoring the essential role the FDA today plays in protecting and promoting American health.

Vanessa Burrows, Ph.D., Suzanne Junod, Ph.D., and John Swann, Ph.D., are FDA Historians

FDA Proposes Process Modernization to Support New Drug Development

By: Janet Woodcock, M.D.

The staff of the FDA’s Center for Drug Evaluation and Research (CDER) always tries to utilize cutting-edge science and up-to-date process management, befitting our stature as the global “gold standard” in drug regulation. Maintaining that standard requires us to keep up with evolving technology and the latest scientific, medical and regulatory advances. Current factors impacting drug development include the genomic revolution, the rise of targeted therapy, the availability of digital health data, the focus on patient involvement, complex drug-device combinations, globalization of drug development and harmonization of international standards. To be successful drug regulators, we reach well beyond the borders of the FDA. We collaborate with a wide variety of medical and scientific organizations such as those in biomedical research, the pharmaceutical industry, academia, global organizations and other regulatory agencies. Importantly, these collaborations also extend to patients and their caregivers and advocacy groups. All these interactions are critical to successful drug regulation.

Janet Woodcock

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

I have recently proposed changes to CDER’s new drug regulatory program. These changes are intended to free up resources so that our scientists and physicians have more time to focus on drug development, particularly for unmet medical needs, and on the multiple collaborations needed to make sure candidate drugs are developed and assessed properly, with appropriate input from external scientists, expert physicians and patient communities. The proposals include regulatory and review process changes, as well as organizational restructuring. We also intend to strengthen the support structures, including personnel and Information Technology (IT), that underpin the regulatory process.

As always, our goals are to expand access to safe and effective new drug therapies, conduct efficient and comprehensive safety surveillance, and ensure that accurate information about those drugs is available.

Here are some highlights of our proposal:

  • Recruiting the best and brightest individuals from many disciplines – Scientific leadership is vital for our ongoing success. After hiring talented scientists, we need to develop long-term career paths for them so they can become our next generation of seasoned leaders. Our recruitment efforts, strengthened by hiring incentives and other provisions in a new law called the 21st Century Cures Act, will help provide the staffing necessary for continued success in supporting the development and approval of innovative new therapies that meet previously unmet medical needs.
  • Enhancing our focus on multidisciplinary teams – Setting standards for approval and assessing innovative new drugs requires large and well-coordinated teams of highly trained professionals with many different types of expertise. CDER’s Office of New Drugs (OND) has a staff of more than 1,000 individuals who work together in many ways. New drug development and approval also requires coordination across many offices within CDER, including the Office of Translational Sciences (OTS), the Office of Surveillance and Epidemiology (OSE) and the Office of Pharmaceutical Quality (OPQ). A central component of our proposed changes involves stronger integration of our talented staff so they can better work together – within and across offices, a concept we refer to as “integrated assessment.” Previously, CDER reviewers would seek consults from specialists in other scientific disciplines (as issues were identified in the course of review). For greater collaboration, a cross-disciplinary team will be assigned to work on a new drug application at the outset.
  • Prioritizing operational excellence – Staff throughout CDER face a staggering pace of work, much of which involves attention to detailed administrative procedures. Our proposal would centralize project management functions within OND. CDER currently has 19 separate review divisions that regulate drugs. Over time, many divisions have developed procedures specific to their areas of review. We are proposing a single and consistent process: One organization with one process. Our aim is to enable our scientific and clinical experts to focus on what they know best – science and medicine – and our regulatory experts to manage the many processes we conduct.
  • Improving knowledge management – The information we process in our work is vast and diverse. Knowledge management is essential to control the data we receive from outside sources as well as what we generate from within the FDA. We plan to enhance our IT capabilities and access to information to better enable the storage and management of the collected experience of our scientific review staff. Accurate historic information from many past drug reviews is essential to informing current and future reviews – and to assure consistent regulatory decision-making. We want to make it easy for staff to find and use scientific and regulatory data, information and precedents. We’re also proposing changes that will increase the number of offices that oversee our review divisions from five to nine – and we’re envisioning 30 review divisions within those offices – up from our current 19. In addition to enabling greater efficiency, these envisioned changes will help us to better understand the diseases intended to be treated by the drugs we evaluate for approval – another way we aim to enhance our knowledge management.
  • Emphasizing the importance of safety across a drug’s lifecycle – Safety remains a key component of our new plans. We will work to establish a unified post-market safety surveillance framework to monitor the benefits and risks of drugs across their lifecycles, both before and after approval.
  •  Incorporating the patient voice – Patients are the FDA’s most important stakeholder and our vision includes incorporating the patient voice in modern patient-focused drug development. In fact, all the elements in our proposal have a common thread: they ultimately serve to improve health for patients.

Last year, CDER approved 46 novel drugs, 100% of which were reviewed on time – fulfilling our commitments under the Prescription Drug User Fee Act (PDUFA). Our system is effective, but we can always improve. Our new plan is designed to help us generate efficiencies so we can build stronger external collaboration capabilities and enhanced support for the scientific, clinical and technological innovation necessary for new drug therapies.

This proposal to modernize our new drug review processes will help us maintain and advance our global leadership, and better support our deeply committed staff. Both science and technology are changing at a blistering pace, and we need to keep up. Patients depend on the FDA to do what is necessary to provide access to safe and effective drug therapies. They take FDA-approved drugs because they trust us. While we have many steps to go before we can realize these changes, we feel confident that they will reinforce that trust and align us for ongoing success.

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

Statement from FDA Commissioner Scott Gottlieb, M.D., on proposed modernization of FDA’s drug review office

 

 

Emerging issues of misuse and abuse of OTC loperamide challenge FDA to address a new turn in the opioid addiction crisis, while maintaining access for patients

By: Scott Gottlieb, M.D.

The opioid epidemic has reached tragic proportions. Yet it continues to take many new, and troubling turns. If there’s one lesson we’ve learned from this crisis, it has been the ability of the mounting abuse and misuse to evade our interventions. This history challenges us to deal more quickly and aggressively when new aspects of the addiction crisis emerge. For example, we’re seeing a crisis that began largely with the misuse of prescription opioids evolve into an epidemic that’s increasingly being driven by an influx of street drugs like illicit fentanyl and heroin. We must be alert to these new patterns of abuse and misuse of different drugs.

Dr. Scott GottliebOne such concern relates to the inappropriate use of loperamide – an FDA-approved drug to help control symptoms of diarrhea, including travelers’ diarrhea. Loperamide is sold under its over-the-counter (OTC) brand name Imodium A-D, as store brands and as a prescription drug. Loperamide is an opioid agonist, and it’s safe and effective at its approved doses. The drug acts locally, inside the gut, to treat the symptoms of diarrhea.

But when loperamide is abused and taken at extremely high doses, some of it can cross the gut lining, giving users an opioid like “high.” We’re aware that those suffering from opioid addiction see loperamide as a potential alternative to manage opioid withdrawal symptoms or to achieve euphoric effects. But at these very high doses, it’s also dangerous. We’ve received reports of serious heart problems and deaths, particularly among people who intentionally misuse or abuse high doses. Sometimes people are using as much as 100 times the recommended dose.

As with other new patterns of abuse and misuse related to the opioid crisis, the FDA acted with urgency to address the issues related to loperamide. We’ve issued a Drug Safety Communication and worked with sponsors to revise both prescription and OTC drug labeling to warn about serious heart problems associated with high doses of loperamide. We’re also encouraging changes to packaging of the OTC products to help deter abuse, such as the use of blister packs. And we’ve reached out to online sellers of these products to inform them of the public health risks and ask for their attention to the issue and their commitment to stop selling large quantities of the product.

At the same time, we’re very mindful of balancing benefit and risk and the needs of patients in our mission to promote and protect public health. We recognize that there are important and legitimate uses of loperamide, including for patients suffering from chronic diarrhea in adults associated with inflammatory bowel disease (IBD), including Crohn’s disease. We need to take the additional steps I outlined to address the abuse and misuse of loperamide. But preserving appropriate access to this treatment for patients who need it is something we take seriously. So we’re seeking input from the patient community on how best to strike this careful balance. In order to ensure that we don’t create access issues for such patients, we’re proceeding in a step-wise, deliberative fashion to ensure that the actions we take in relation to OTC loperamide use are reasonable and scientifically sound, and that these actions are necessary to achieve safe use of the drug and to address the issues of abuse and misuse.

It’s also the case that loperamide is available by prescription for patients who require maintenance therapy for chronic disease and are under the care of a health care provider.  We’ve also heard concerns that the changes to packaging could drive up the price. Affordability of medicines is one of my key concerns. We’re carefully evaluating the impact that our actions could have on the cost of this medicine. Based on our analysis to date, we don’t expect that the steps we’re taking will have much, if any, impact on cost, given that loperamide is available as a generic drug and manufactured by a range of competitors.

OTC loperamide is currently approved in packages of 8 to 200 tablets, which are often sold in multipacks of more than 1,000 tablets at a time. This is more than a three-year supply if the drug is taken according to the product label. Evidence suggests that reasonable packaging limitations and unit-of-dose packaging may reduce medication overdose and death.

Therefore, as we announced in January, the FDA has sent letters to the OTC brand manufacturers requesting that they implement packaging changes. We’re currently evaluating the maximal package size appropriate for OTC use, and plan to take into account data manufacturers provide on consumer use and needs; current OTC labeling and indications; the dose-response relationship of loperamide to cardiac events and known adverse event data; and importantly, the feedback of patients who rely on this medicine.

The agency is discussing implementation timeframes to ensure that manufacturers can continue to meet consumer need while package reconfiguration is taking place.

I also recently wrote to online distributors asking them to take two voluntary steps to help reduce the risks of loperamide abuse and misuse. First, I asked them not to sell bundled amounts of loperamide that contain more than one package of the drug. And second, I asked them to ensure that consumers can easily access and read the product labeling and warnings for drugs sold on shelves or on websites before purchase.

We appreciate the responsiveness from both the manufacturing and retail industry. Several companies are already committing to implement these packaging changes or purchasing safeguards. For example, Walmart has already taken a number of concrete steps to address the FDA’s request. These include ensuring that all loperamide products sold by Walmart/Sam’s Club have the product labeling clearly visible on the website; limiting purchase of 200 count tablet products in stores or online to a single bottle; and, moving the sale of bundled products at Sam’s Club behind the pharmacy counter and limiting sale to a single package. Walmart is also working to remove all loperamide “marketplace products” (i.e. products sold on their website by a third-party vendor) from their website. These vendors appear to be the primary source of bundled products and products that do not display product labeling on the Walmart site.

Amazon also has already taken some steps to address our recommendations and eBay has stated publicly that they also intend to follow our recommendations. We continue to work with other retailers to encourage them to take steps to help prevent abuse and misuse of loperamide.

All of us must do our part to address the public health challenges posed by the opioid addiction crisis.

The FDA will continue to assess the loperamide safety issue, and monitor adverse events, scientific literature, and data submitted by the public. We want to ensure that the steps we’re taking improve the safety of loperamide without limiting OTC access for consumers using the product according to labeling. The FDA’s actions to address drug misuse and abuse must be informed by an understanding of the complex social environment in which changing patterns of drug consumption occur. The agency is committed to addressing emerging issues of abuse and misuse while taking steps to safeguard the needs of patients who depend on these medicines.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

Ironed Out

By: Vanessa Burrows, Ph.D.

During the early part of the 20th century, the growing scientific knowledge that certain diseases were caused by vitamin and mineral deficiencies sparked public interest in products that touted these substances. But the public had little understanding of this emerging health care field and, as a result, was often easy prey for unscrupulous marketers who used phony claims that their products had therapeutic value.

Vanessa BurrowsOne such charlatan was a man named E. Virgil Neal, whose past schemes included palm-reading and hypnotism performed under the name Xenophon LaMotte Sage; a mail-order health and self-improvement program, which earned him a conviction for mail fraud; and a French cosmetics company that marketed false hair regenerators and bust enhancers.

Operating at the dawn of the modern advertising age, Neal employed a sophisticated and misleading marketing campaign to sell Nuxated Iron pills, which included iron and nux vomica, a derivative of the strychnine tree, which is highly toxic to humans and other animals. Beginning in 1917, Neal’s advertisements used celebrity endorsements that touted the product’s invigorating and strength-building qualities, promising to alleviate “that tired feeling.” However, the pills contained so little iron that their health impact was questionable, and so much strychnine that, in at least one case, they caused the fatal poisoning of a young boy.

Neal’s fraudulence was exposed by the American Medical Association and journalists in the early 1920s, but FDA was unable to prosecute him because the misbranding provisions of the 1906 Pure Food and Drugs Act did not outlaw misleading promotional material of the type that Neal distributed. Neal’s product actually contained some iron, albeit negligible amounts, and only made therapeutic claims in promotional materials. It wasn’t until 1944, after the passage of the 1938 Federal Food, Drug, and Cosmetic Act, when FDA was able to take action against the product on new types of misbranding grounds, which forbid, among other things, misrepresenting the quantity of ingredients contained in the product.

Today, FDA continues to play a critical role in protecting consumers from fraudulent, adulterated, and misbranded products like Nuxated Iron.

We hope you enjoy your visit to the History Vault.

Vanessa Burrows, Ph.D., is an FDA Historian

We’re Committed to Guarding Against the Intentional Adulteration of Food and Implementing the New Rule Efficiently

By: Scott Gottlieb, M.D.

The U.S. food supply is among the safest in the world. But to keep it safe we must recognize that our foods are vulnerable – not just from unintended contamination, but from those who would seek to deliberately do us harm.

Dr. Scott GottliebEnsuring that we’re prepared to minimize the risk of an intentional attack on our food supply is a goal that we share with the food industry and consumers.

The FDA Food Safety Modernization Act (FSMA) charges FDA with addressing the burden of foodborne illness by requiring that producers, importers and distributors of food take systematic steps to prevent contamination. Congress passed FSMA with a view of the unique risks posed by a global food supply. Six of FDA’s seven “foundational rules” for FSMA focus on the safe production, storage, and transport of human and animal food by addressing conventional food safety hazards

But a different reality shapes the seventh rule on Intentional Adulteration. This provision seeks to prevent acts of terrorism meant to harm and kill many people.

Food facilities covered by this rule (both domestic and foreign facilities that export to the United States) are required to implement — for the first time — a food defense plan that identifies vulnerabilities and ways to reduce the risk of intentional adulteration.

Congress directed FDA to focus its efforts to prevent intentional adulteration on the highest risks to the food supply. That’s why the Intentional Adulteration Rule primarily covers large food companies whose products reach many people.

Extensive analysis shows that some of the most significant risks are posed by an attack perpetrated by someone who has legitimate access to a facility, perhaps under the guise of an employee. This is why the new rule asks facilities to focus their efforts on processing activities that — if deliberately attacked by a rogue insider — could potentially result in widespread contamination of products.

FDA is committed to making the implementation of the Intentional Adulteration rule as practical and flexible as possible for the food industry. Even though the initial compliance date for the largest businesses is July 2019, more than a year away, I’m taking steps right now to fully understand stakeholder concerns and challenges, and address them.

As part of this fact-finding process, I recently visited the Nestlé Dreyer’s Grand Ice Cream facility in Laurel, Maryland. My FDA colleagues and I were taken on a tour of the facility, from the receiving dock to the production line to the packaging equipment. It was very helpful for me to see, first hand, the processes and practices that Nestlé has in place that could be used to guard against deliberate contamination.

Addressing Misconceptions

Having this kind of direct interaction with stakeholders is important. This is new regulatory territory for both FDA and industry. We need to make sure we implement these new requirements in a way that achieves its public health goal, without creating unnecessary burdens or costs on industry. From my interactions, I’ve come to believe that there may be misconceptions about how we’re expecting the food industry to implement this rule.

I want to use this opportunity to provide more transparency on our work.

Food facilities covered by the rule will be able to choose from a wide range of options to identify and reduce their vulnerabilities. They have the flexibility to tailor individual options that are cost-effective and make sense for each particular facility.

We recognize that many companies have already made significant efforts to reduce their vulnerability in response to terrorism concerns since the attacks of 9/11. These are important steps. And we believe these existing efforts can help food facilities meet many of the intentional adulteration rule requirements.

Existing measures may be in place for reasons related to business, food safety, and food defense. Many current steps companies take can become important parts of a food defense plan to meet the Intentional Adulteration requirements. However, we also know that there are some areas where additional measures will be needed.

We want to make sure these new measures can be implemented in a way that’s the least burdensome while achieving its intended, food protection purpose.

We agree with food companies that the “inherent characteristics” of food production equipment and processes should be considered when conducting a vulnerability assessment. At Nestlé, for example, vats of chocolate with hatches at the ground level can’t be opened without creating a flood of chocolate, which certainly wouldn’t escape notice. Our rules are meant to be practical. In this case, the inherent characteristics of chocolate vats make the ground-level hatches a low area of vulnerability. This means that mitigation steps may not be needed at this point of access.

During discussions with stakeholders, we’ve also heard that some people believe that plants might be required to construct vast enclosures for their equipment, invest in advanced computer systems, or reengineer whole processing lines.

That’s not the case. We want expectations to be clear to industry stakeholders.

We’ve also heard that some companies believe they’ll have to hire more workers for the sole purpose of observing other workers. We don’t believe that’s going to be the case.

Moreover, we’ve also heard concerns that implementing some food defense measures required under the rule may create conditions that negatively impact worker safety, food safety and food quality. During our extensive work with industry to develop the proposed rule, we’ve identified a variety of strategies that are very practical to implement and don’t impact food production or safety of any kind.

I want to be very clear about this point. Facilities will be given enough flexibility in selecting options for mitigation strategies that there should be no conflicts between food defense and food safety. We’ll work with any company that has those concerns.

And make no mistake, food safety is — and will remain — our first priority. In implementing the requirements of the intentional adulteration rule; we don’t want facilities to take any steps taken that could jeopardize food or worker safety.

I’ve also heard concerns expressed about the potential paperwork requirements associated with the rule and costs associated with monitoring the food defense protective measures required in the rule. We’ll provide examples of how to minimize paperwork and templates for recordkeeping so that costs are kept to a minimum.

We also expect that many of the options for monitoring can be incorporated into an employee’s existing responsibilities. And the frequency of monitoring for some strategies can also be kept to a minimum while still assuring the measures are working, thereby reducing costs.

Upcoming Guidance

Part of the feedback that we received during the Nestlé tour was the need for FDA to provide a guidance document to provide clarity on how firms can more easily meet the new requirements. That’s something we’re working on right now. We plan to publish this new guidance document well in advance of the initial compliance date in 2019.

We’ll soon be publishing the first chapters of this three-part draft guidance to focus on important questions that I’ve heard. Our hope is that this guidance will help manufacturers focus on those measures that have a meaningful impact on protecting food from intentional adulteration. We plan to publish the remaining two parts of the guidance this summer. The entire draft guidance will be available for public comment.

The first two installments of the guidance focus on the greatest concerns expressed by the food industry and the requirements that drive costs.

The first installment includes a simple, cost-effective way to identify the most vulnerable parts of the production process. It details numerous ways to guard against deliberate contamination, including some existing and cost-effective measures, as well as additional ways to monitor the operation to make sure that protections are working.

The second installment includes guidance on an additional, detailed, and flexible method to identify a facility’s most vulnerable points.

Finally, the third installment focuses on corrective actions, verifying that the system is working, how to reanalyze the plan and its parts, and record keeping.

Protecting Against an Inside Attacker

Importantly, the guidance will also address measures facilities can take to address the risk of an inside attacker. The rule identifies that the greatest risk comes from an inside attacker rather than from an outsider. The new measures require that the assessment of vulnerabilities must consider the potential threat from within a facility.

While the possibility of an inside attacker is hopefully not likely at a particular facility, we’re not talking about a theoretical danger. The threat landscape for intentional adulteration continues to grow regarding an inside attack even since the rule was finalized in 2016.

To take one vivid example: There was a recent report of a foiled terror plot in the United Kingdom that involved an employee at a food manufacturing plant who had been investigating ways to poison supermarket-ready foods.

FDA has worked on food defense assessments for more than a decade in collaboration with food manufacturers, universities, and government partners — including the intelligence and law enforcement communities. Our interactions with intelligence and law enforcement communities have repeatedly indicated that an inside attacker presents the greatest potential danger.

Some existing, protective measures in food facilities, such as perimeter fencing and general visitor protocols, are focused on thwarting an outside threat. These measures are also important. But they don’t address the full scope of risks, including an inside attacker, that must be considered when identifying a facility’s most vulnerable points.

The guidance document will provide examples of how to protect against an inside attacker using a range of measures that can be adapted to best meet individual facility needs. In many cases, food facilities will be able to leverage their existing protections.

Next Steps

Industry has also asked about the availability of training on these new requirements, both for food facilities and regulators. We’re working on both fronts to create training and technical assistance for food facilities that’s consistent with other FSMA-related training. And we’ll be training both federal and state regulators as well.

I was grateful to meet and learn from the professionals at Nestlé. I’m impressed by their commitment to food safety and food defense. I know that their efforts, and their commitment, reflect the ethic that’s in place at a lot of leading food companies.

We’ll continue to work through the issues raised by food manufacturers covered by the Intentional Adulteration rule. We need to make sure we implement these requirements in a way that’s cost-effective and efficient. Safeguards that are too costly to put into place, or are too hard for firms to adhere to, don’t work. They don’t meet their purpose.

I look forward to continuing to engage personally in this dialogue. Keeping food safe from contamination during production, storage and transport remains a primary focus of the FSMA rules. And food defense is an important component of achieving that goal.

While intentional adulteration is unlikely, a successful attack could have devastating public health consequences. FDA and the food industry are committed to the overarching goal of protecting consumers from these and other risks. I look forward to partnering with industry to ensure that appropriate measures are in place to give us all confidence that the food supply is as safe as possible from hazards of all kinds.

Scott Gottlieb, M.D., is the Commissioner of the U.S. Food and Drug Administration

Predicting Stem Cell Activity to Ensure Safe and Effective Therapies

By: Steven R. Bauer, Ph.D.

We can admire an individualist for being independent and self-directed. But these traits can be disruptive and troublesome when they’re shared by cells called mesenchymal stem cells (MSCs). When these cells (also called human multipotent stromal cells, or MSCs) are being prepared for use as therapies to treat human diseases or medical conditions, what’s important is predictability.

Steve Bauer

Steve Bauer, Ph.D., chief of the Cellular and Tissues Therapy Branch, Division of Cellular and Gene Therapies, in the Office of Tissues and Advanced Therapies, at CBER.

MSCs are called ‘multipotent’ because they can produce more than one type of specialized cell of the body, but not all types. For example, they will respond to various types of substances called growth factors by differentiating − or specializing − into cartilage, bone, or fat. MSCs may also help the body control inflammation by suppressing immune cell functions. These processes, immunosuppression and differentiation, justify MSC use in regenerative medicine clinical trials investigating their use to protect, restore, or repair tissues in the body.

But there’s a catch. As of January 2018, no MSC-based clinical trials have resulted in FDA-approved treatments. One significant challenge is ensuring that the MSCs will work together to perform the same desired function when they are administered to patients. So FDA scientists have been developing ways to predict whether specific populations of MSCs intended for use as a therapy are made up of individualists or sufficient numbers of team players. It turns out that MSCs are very responsive to their environment. In a lab-based manufacturing process, MSCs are exposed to an environment very different from the body — one that could change the way they respond to growth factors and one that could result in MSC preparations with lots of unexpected – and undesirable – individualism. Additionally, this might change the way the cells behave after they are put into a patient. For example, they might not suppress inflammation very well, might form tissue where it isn’t wanted, might form the wrong tissue, and even form tumors.

Recognizing these potential issues, FDA’s MSC Consortium is trying to develop methods that would predict with more certainty how manufactured or isolated MSCs will behave in patients.

My own laboratory has been developing ways to predict the behavior of MSCs that have been stimulated by growth factors. Our study has involved identifying changes in the size and shape (or morphology) of stimulated MSCs that may predict their future behavior. We call this approach functionally-relevant morphological profiling. It’s made possible by powerful imaging technologies that make it practical for us to routinely monitor and analyze the changes in the size and shape of many thousands of cells in a matter of hours.

Stem Cell lab photo

Human multipotent stromal cells undergo morphological changes after being stimulated by growth factors. FDA scientists have demonstrated that these changes can predict the ability of the cells to develop specialized properties that might support their use in regenerative medicine clinical trials.

Why are sizes and shapes so important to predicting MSC activity?

Think of it this way: you can tell the difference between basketball players and baseball players by looking at their uniforms. And you know what kind of behavior you can anticipate when they’re playing their respective games. Likewise, morphological profiling can help scientists predict whether stimulated MSCs are going to differentiate into specific cells that do specific tasks.

We’ve used this approach to follow MSCs that were stimulated to undergo a process called mineralization, the laying down of minerals that support bone growth. Previously, we had to wait for over a month to see if stimulated MSCs would mineralize. But, by using our profiling method, we can predict with over 90 percent certainty on day three whether the stimulated cells would mineralize by day 35.

In another study, we measured more than 90 morphological features — including their sizes and shapes, and the shapes of internal structures — of stimulated MSCs. Based on our knowledge of the changes in the size and shapes of MSCs that go on to develop immunosuppressive activity, we could predict which MSCs would suppress a certain type of immune cell (T cell). Immunosuppression makes these stimulated MSCs potentially effective treatments for inflammatory diseases, such as Crohn’s disease (chronic inflammation of the intestine), and multiple sclerosis (loss of nerve cell signaling).

In short, this type of profiling allows us to measure the extent to which there are similarities or differences in these cell preparations and to compare our findings with the profile of specific cell types associated with the biological functions we are seeking. That may help us predict whether the cells will perform the function we want if they are administered to patients.

MSC-based therapies are not available yet. But the ability to predict specific functions of different preparations of MSCs in the lab may be a big step toward getting safe and effective FDA-approved treatments to patients. We think our work is widely applicable to a variety of potential stem-cell based products, and it will help us determine if new techniques for stimulating MSCs to differentiate will produce safe and effective therapies.

Steven R. Bauer, Ph.D., is the chief of the Cellular and Tissues Therapy Branch, Division of Cellular and Gene Therapies, in the Office of Tissues and Advanced Therapies at FDA’s Center for Biologics Evaluation and Research.

The FDA Grand Rounds on March 8 features Steven Bauer discussing his research.

Taking New Steps to Meet the Challenges of Rare Diseases — FDA Marks the 11th Rare Disease Day

By: Scott Gottlieb, M.D.

Today 30 million people in the United States – or one out of every 10 Americans – lives with at least one of more than 7,000 rare diseases. These conditions include rare cancers to inherited metabolic disease. And tragically, half of those affected by rare diseases are children.

Dr. Scott GottliebThis week, the U.S. observes the last day of February as Rare Disease Day to raise awareness about rare diseases and their impact on patient’s lives. Unfortunately, finding treatments for these conditions does not become easier or less costly with the rarity of a disease.

In many cases, developing a treatment for a rare disease can be especially hard and present unique challenges. Each success is the end of a long uphill climb. It requires the concerted efforts of many stakeholders, including scientists, product developers, regulators, policy makers, and of course, the energy and organization from patient advocacy groups.

For FDA, Rare Disease Day offers an opportunity to take measure of the progress we’ve made to help people affected by rare disease; and evaluate what more we can do to meet our commitment to advance the needs of patients with rare diseases and their families.

Thirty-five years ago there were few drugs and biologics for rare diseases and even fewer devices. Enacting the Orphan Drug Act in 1983 with its financial incentives and other inducements was an important start to enabling more investment and development of treatments targeted to rare diseases. Also important was legislation passed in 1990, creating a rare disease path for medical devices; known as the Humanitarian Device Exemption (HDE).

Rare Disease Treatment GraphSince 1983, we’ve seen significant progress in treating rare diseases. FDA has approved more than 650 therapies for rare indications. This includes new molecular entities and biologics, as well as new rare disease indications for drugs approved for another indication. We’ve also seen progress in the development of devices for rare diseases. Since 1990, the FDA has approved 72 medical devices for an orphan indication under the agency’s HDE program.

In recent years, the increasing emphasis on personalized medicine, including genetically targeted drug development, has enabled even more opportunities to develop treatments aimed at rare diseases. As a result, during the past five years, the number of requests to have a drug designated as serving an orphan population has steadily increased. In 2017, there were over 700 requests for designation. This was more than double the number of requests received in 2012. Last year we also saw 80 treatments approved by FDA for rare indications, the highest number ever.

FDA’s orphan drug program focuses its efforts on the full range of rare diseases, including relatively more rare or ultra-orphan diseases. In 2010, Miles Braun and other FDA researchers used data from 1983-2008 to show that there’s substantial effort with regard to the rarest diseases. The categories with the most orphan drug designations and the most approvals had very low prevalence levels. New analysis of more recent data shows this trend has been maintained. This experience suggests that the orphan drug program may continue to grow in importance as medicine becomes increasingly personalized, and better able to target the underlying molecular and genetic basis of even very uncommon disorders.

Despite these successes, we recognize that thousands of rare diseases still have no approved treatments. Indeed, FDA’s recent needs assessment survey, done in collaboration with the NIH’s National Center for Advancing Translational Sciences, identified a major public health need for innovative medical devices to care for children and adults with rare diseases.

FDA is committed to doing its part to facilitate continued progress toward more treatments and even potential cures for rare diseases. New scientific opportunities enabled by advances in cell and gene therapy hold out more opportunities to develop these potential cures. With efficient regulation, proper incentives for product development, and the continued support of patients, providers, and innovators; we’re more able to pursue these opportunities than ever before.

In June, I announced FDA’s Orphan Drug Designation Modernization Plan. Our aim was to create a more efficient, scientifically advanced, predictable, and modern approach to the approval of safe and effective treatments for rare diseases. Since then, we’ve eliminated the backlog of orphan drug designation requests. In addition, we’re fully implementing a 90-day timetable for processing new designation requests. We also established an FDA Orphan Products Council to further address scientific and regulatory challenges pertaining to orphan products.

Through our long-standing Orphan Products Grants Program we recently provided $17 million in funding to directly support 15 new clinical trials on products for rare diseases and to fund natural history studies for the first time. These four natural history studies, and an additional two studies funded through an NCATs partnership, could provide key information about how rare diseases develop and progress. This information can be vital for product development.

Of note, I also recently communicated our desire to expand upon these efforts to help foster investment and innovation in, and medical product development for, rare diseases by developing clinical trial networks to create an understanding of the natural history (such as individual patient experiences and progression of symptoms) and clinical outcomes of rare diseases. FDA’s 2019 budget includes a request for resources to make additional investments in rare disease natural history models. It’s clear more work can be done to advance these efforts.

Today I’m pleased to announce several new actions FDA is taking as part of our ongoing commitment to support and expedite the development of rare disease products. They include:

  • A new pilot for more efficient orphan designation requests, including a new fillable form that will make the submission process easier for sponsors to complete designation requests; and make it more efficient for FDA to review. This also includes an on-line tutorial to guide sponsors through the submission process. We’ve also developed a new inter-center consult process to streamline and standardize our communications process.
  • We are entering into a new Memorandum of Understanding with the National Organization for Rare Disorders to conduct outreach with our new Patient Affairs Staff on ways to enhance the incorporation of patient experience into regulatory discussions. As part of this process, we’re planning a joint series of pilot listening sessions on rare diseases. We recognize that early and iterative engagement can improve clinical and regulatory understanding of diseases and conditions; provide a common understanding of the most urgent patient needs; and inform drug development programs.
  • We’re planning a public meeting that will help us prepare for the changing landscape of orphan drug development posed by the growth in targeted therapies and molecularly defined diseases. At an upcoming meeting, we’ll seek input on complex scientific and regulatory issues related to cancer drugs and biologics that target a tumor’s specific genetic features rather than its location in the body (i.e., tissue agnostic approvals). We’ll also consider the appropriate application of orphan incentives to this new paradigm of drug development, and how we apply designations to these indications.

To provide the public with a more complete discussion of the scope of FDA’s rare disease activities, we’ve also created a new, enhanced web page that features videos from our three center directors plus other materials. I invite you to take a look.

Over the course of 2018 we’ll continue our efforts to increase the consistency and efficiency of our reviews of rare disease products. We remain committed to supporting rare disease research on diagnostics, therapies, and potential cures. We’ll also continue to evaluate how to best support investment in rare diseases; and to encourage the development of drugs that target rare, unmet patient needs. A lot of devastating and rare conditions still lack approved therapy. During this Rare Disease Week, it’s gratifying to review the steps we’ve taken, and to commit to more progress in the future, and making sure that our framework supports the needs of patients.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

You Spoke, FDA Listened: New Patient Engagement Collaborative, Call for Nominations

By: Nina L. Hunter, Ph.D., and Rachel E. Sherman, M.D, M.P.H.

The FDA is committed to collaborating with patients, caregivers, and advocates, as well as incorporating the various perspectives from these groups into the FDA’s regulatory decision-making processes. And we know that patients and other stakeholders agree with the agency’s commitment to improving and increasing patient involvement in FDA matters. In fact, members of the patient and stakeholder communities commented in public feedback on Section 1137, Patient Participation in Medical Product Discussions, of the Food and Drug Administration Safety and Innovation Act (FDASIA). Stakeholders recommended that the FDA create an outside group to provide input on patient engagement across the agency. We are pleased to announce that in response to that feedback and to accelerate the FDA’s efforts in this area, today the FDA published a request for nominations to join the FDA’s Patient Engagement Collaborative (PEC).

Nina Hunter

Nina L. Hunter, Ph.D., FDA’s Deputy Director for Medical Programs, Office of Medical Products and Tobacco

The PEC will be coordinated by the FDA and the public-private partnership, the Clinical Trials Transformation Initiative. FDA is seeking a group of diverse representatives from the patient community to participate in the PEC including:

  • Patients who have personal disease experience
  • Caregivers who support patients, such as a parent, child, partner, other family member, or friend, and who have personal disease experience through this caregiver role
  • Representatives from patient groups who, through their role in the patient group, have direct or indirect disease experience

The PEC will provide an ongoing forum to discuss how to achieve more meaningful patient engagement in medical product development and other regulatory discussions. Topics to be discussed may include making patient engagement more systematic; how to improve transparency, education and communication; new strategies for enhancing patient engagement; and new models for patients to collaborate as partners in the medical product development and FDA review process.

The PEC builds on the agency’s existing patient engagement efforts, such as the Patient Focused Drug Development meetings (for drugs and biologic products) and the Patient Preference Initiative (for medical devices).

Rachel Sherman

Rachel E. Sherman, M.D., M.P.H., FDA’s Principal Deputy Commissioner

The new collaborative will be modeled after the European Medicines Agency’s Patients’ and Consumers’ Working Party (PCWP) which “has enabled the Agency to build upon its existing interactions with patients and consumers.” Examples of PCWP accomplishments include having patients review information on medicines ahead of publication to ensure that the information is “clear and relevant,” deciding on the eligibility criteria for patient and consumer groups who will be working with EMA, and involving patients as experts in EMA regulatory activities.

The PEC will be spearheaded by the FDA’s new Patient Affairs Staff (PAS) in the Office of Medical Products and Tobacco (OMPT), which is responsible for the coordination of agency-wide and cross-center projects related to patient engagement. The PAS will work closely with the medical product centers, the Office of External Affairs (OEA), and other offices across the agency to complement and support ongoing patient engagement efforts. Specifically, the PAS will focus on the following key areas:

  • Creating and assisting with public and private collaborations and partnerships with external groups of patients to discuss topics around medical product development and regulatory policies
  • Coordinating cross-cutting programs and activities to leverage best practices and enhance patient engagement
  • Facilitating consistent cross-center policy-making and common standards to enhance integration of patient perspectives into the regulatory and scientific process
  • Building a framework for hosting and maintaining a shared database of patient engagement information
  • Providing navigation services to triage inquiries from patients and patient organizations
  • Establishing a centralized point of entry into the FDA for patients and their advocates (existing FDA interactions will not be affected)
  • Enhancing our external communication platform to create awareness of the FDA’s patient engagement activities and regulatory processes

The PAS will be led by longtime FDA staffer and patient advocate Andrea Furia-Helms, who is currently the Acting Director of the PAS. Ms. Furia-Helms spent the past ten years in the FDA’s Office of Health and Constituent Affairs where she directed the FDA Patient Representative Program. Ms. Furia-Helms has been joined by Samir Shaikh, who is currently the Acting PAS Deputy Director. Mr. Shaikh has been a part of OMPT, supporting efforts in organizational development and process improvement that have had impacts across the agency. Ms. Furia-Helms and Mr. Shaikh will work closely with the centers to complement and support the FDA’s ongoing patient engagement efforts.

This new Collaborative is also facilitated by provisions in both the 21st Century Cures Act of 2016 and the Food and Drug Administration Reauthorization Act of 2017. Both sought to foster patient participation and incorporate patient experiences in the regulatory process. The goal of the nomination process announced today is to identify individuals interested in serving as members of the PEC. For more information about joining the PEC, read today’s announcement.

For more information about Patient Affairs and the new Patient Engagement Collaborative, visit the For Patients webpage. 

Nina L. Hunter, Ph.D., is FDA’s Deputy Director for Medical Programs, Office of Medical Products and Tobacco 

Rachel E. Sherman, M.D., M.P.H., is FDA’s Principal Deputy Commissioner

FDA Launches Predictive Toxicology Roadmap to Enable Advances in Toxicity Testing

By: RADM Denise M. Hinton and Suzanne Fitzpatrick, Ph.D.

Toxicology testing plays a pivotal role in ensuring the safety of FDA-regulated products. During the development and evaluation of almost all FDA-regulated products, testing is performed on people or animals to identify any potential risk from chemical, physical, or biological agents.

RADM Denise Hinton

RADM Denise M. Hinton, is FDA’s Acting Chief Scientist

Today, novel methods such as organs on a chip or mathematical modeling are being developed for toxicity testing that are generating unique opportunities to improve our ability to quickly and more accurately predict potential toxicities and reduce associated risks.

We expect these advances will help us move products to market faster while preventing products with increased toxicological risk from ever reaching the market. Moreover, in many cases, these technologies are reducing the need for animal testing – advancing FDA’s long sought goal of refining, reducing, and replacing testing on animals.

For a new testing method to be accepted for use in determining the safety of an FDA-regulated product, there must be sufficient convincing data to ensure that the method can be relied upon for both product development and regulatory decision-making. FDA evaluates the test or series of tests for their applicability, limitations, relevance, reliability, reproducibility, and sensitivity. Undergoing this process requires continuous dialogue and feedback among all our relevant stakeholders, beginning with developers and ending with qualification and acceptance by regulatory authorities.

A High-Priority for FDA

In 2016, FDA’s Commissioner tasked the agency’s Toxicology Working Group with developing a more efficient process for identifying and qualifying emerging predictive toxicology technologies. Established in 2015 and comprising senior FDA toxicologists across the agency, the Working Group has deep expertise in the various FDA product areas and knowledge of the differing legal authorities for evaluating safety and toxicity in those product areas.

This week the Working Group laid out FDA’s Predictive Toxicology Roadmap, a six-part framework for integrating predictive toxicology methods into safety and risk assessments. Among other recommendations, it calls for FDA research to identify data gaps and to support intramural and extramural research to ensure that the most promising technologies are developed, validated, and integrated into the product pipeline. The roadmap also identifies toxicology issues that need addressing for FDA-regulated products and toxicology areas that could benefit from improved predictivity.

Suzanne Fitzpatrick

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

FDA will be holding a public workshop as part of our efforts to foster opportunities for sharing ideas, discussing new technologies, and highlighting collaborations that are developing and testing new methods.

And, we want to encourage stakeholders to work with FDA as we leverage the collaborative expertise of our toxicologists across the agency to develop performance standards for emerging toxicity testing methods.

Because this is a high priority for the agency, FDA’s Toxicology Working Group will be reporting yearly to FDA’s Chief Scientist on progress made in this important effort. We’re confident that the successful implementation of FDA’s predictive toxicology roadmap and the continuing engagement of our diverse stakeholders will enable FDA to fulfill its regulatory mission today while preparing for the challenges of tomorrow.

RADM Denise M. Hinton, is FDA’s Acting Chief Scientist

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

For more information please read:

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

FDA Collaborates on Human on a Chip