Report Spotlights Achievements of FDA-Mexico Produce Safety Partnership

En Español

By: Stephen M. Ostroff, M.D.

The United States and Mexico are major trading partners in fresh produce. Each year, billions of dollars of fruits and vegetables move across the border. These include Mexican tomatoes, avocados, chilies, berries, cucumbers, lemons, and limes that reach U.S. consumers, as well as American apples, pears, grapes, onions, strawberries, potatoes, peaches and other produce that are sent to Mexico.

Stephen Ostroff, M.D.Both our countries benefit when we can help to ensure that these valuable commodities are safe for consumers on both sides of our borders. For that reason, the FDA-Mexico Produce Safety Partnership (PSP) was formed in July 2014, forging a stronger relationship between the FDA and Mexico’s National Agro-Alimentary Health, Safety, and Quality Service (SENASICA) and its Federal Commission for the Protection from Sanitary Risk (COFEPRIS).

We are pleased to share that our partnership is making real progress toward our goal of reducing the risk of foodborne illness associated with our produce trade. A new report, titled U.S. FDA-Mexico Produce Safety Partnership: A Dynamic Partnership in Action, provides some specific examples of this progress.

For example, the partnership recently worked to address the contamination of papayas grown in Mexico. In the fall of 2017, the FDA, SENASICA and COFEPRIS worked together to respond to four outbreaks of salmonellosis tied to Mexican-grown papayas. The Mexican agencies conducted inspections and sampled various farms and packing houses in several Mexican states, and shared their findings with the FDA. We were able to leverage their work and resources, along with the findings of our own outbreak investigation, to place four farms on import alert, thus providing information to the FDA inspectors who detained those products without having to physically examine them. SENASICA likewise implemented a regulatory response. In October 2017, Mexico strengthened its food safety oversight of papayas, which are subject to the Produce Safety Rule under the FDA Food Safety Modernization Act if they will be imported or offered for import in the U.S.

Chart - Mexico Exports of Fresh Produce to USAIn another example, in 2015, Listeria monocytogenes was detected in kiwi and apples grown in the U.S. and exported to Mexico. The exchange of information under the PSP, including the sharing of bacterial isolates and testing by both FDA and SENASICA laboratories, helped prevent more contaminated produce from entering Mexico. It also established a protocol for the future exchange of bacterial strains to improve detection and understanding of contamination.

These are just two of several instances in which the partnership has led to coordinated preventive activities in addition to enforcement activities that help to reduce the risk of foodborne illnesses and enable both countries to respond more rapidly to a potential or actual outbreak, better protecting both American and Mexican consumers.

Chart - U.S. Exports of Fresh Produce to MexicoBut the partnership has also provided benefits beyond individual outbreaks. Both countries have also been working collaboratively through working groups on institutionalizing approaches that reinforce preventive practices and rapid response to outbreaks. The groups have focused on information sharing, education and outreach, training, laboratory methods and processes, and how to respond effectively to outbreaks.

Looking to the future, the report outlines our five-year plan to increase engagement and the exchange of knowledge with key public and private partners. Through the partnership, we plan to also work on identifying common approaches for auditors and inspectors to better execute compliance and enforcement activities, and will create a strategy to conduct joint inspections and sampling. This will help both countries maximize their resources for the benefit of consumers on both sides of the border.

This is a long-term partnership. While there are differences in our systems, technologies, and environments, the U.S. and Mexico both want consumers to be confident in the safety of their food. By working together, we can achieve that goal.

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

Spring Unified Agenda: FDA’s Anticipated Upcoming Regulatory Work

By: Scott Gottlieb, M.D.

Today, the federal government published the Spring 2018 “Unified Agenda of Federal Regulatory and Deregulatory Actions” (Unified Agenda), which provides federal agencies with the opportunity to update the American public on our government’s regulatory priorities.

Dr. Scott GottliebFor its part, the U.S. Food and Drug Administration (FDA) continues to make swift progress on our regulatory agenda, which reflects the key strategic priorities of the FDA and the Administration. Our regulatory agenda reflects our adherence to science based decision making and our commitment to our mission to protect and promote public health.

I provided a detailed overview of many of our proposed regulations for 2018 around the release of the Unified Agenda last fall – most of which we continue to take forward. I’d like to take this opportunity to highlight for you some of FDA’s new contributions to the Spring Unified Agenda.

Addressing the Nicotine Addiction Crisis

Smoking remains the leading cause of preventable death and disease. And too many young people are still being initiated on tobacco products, and becoming addicted to nicotine.

We’ve taken steps to address the morbidity and mortality associated with tobacco through the comprehensive plan that we announced last summer. We’re considering regulating the nicotine levels in combustible cigarettes, to render cigarettes minimally or non-addictive.

At the same time, we’re continuing to advance our framework for how we’ll regulate both novel nicotine delivery products, such as e-cigarettes, and traditional tobacco products. One goal of our efforts is to encourage innovation of less harmful products. We will ensure that all tobacco products, whatever their nicotine content or delivery mechanism, are put through an appropriate series of regulatory gates to maximize any public health benefits and minimize harms.

To that end, we will be proposing a new regulation to establish product standards for electronic nicotine delivery systems or ENDS. The proposed standard will, among other things, address the levels of toxicants and impurities found in nicotine, propylene glycol, and vegetable glycerin e-liquid, as these toxicants and impurities can cause death or other adverse health effects.

As part of our comprehensive plan, we’re also working hard to prevent access to products we believe are adulterated or misbranded. We recently joined with the Federal Trade Commission to issue 13 joint warning letters to companies that misleadingly labeled or advertised nicotine-containing e-liquids as kid-friendly food products (juice boxes, candies, and cookies).

As part of our comprehensive approach, we’ll also be proposing new regulations to establish requirements for the administrative detention of tobacco products encountered during an inspection that an officer or employee believes to be adulterated or misbranded. These steps will allow us to more effectively block the distribution and use of products that are ultimately found to be violative, including products that are misbranded because their labeling or advertising causes them to resemble kid-friendly foods.

Modernizing and Harmonizing Standards

As part of our efforts to continue to ensure efficiency of existing regulations, we will be taking another step to modernize medical device regulation, by proposing a new regulation to replace certain aspects of existing Quality System regulations with specifications of an international consensus standard for medical device manufactures (ISO). This rule, if finalized, will harmonize domestic and international requirements and modernize the regulation to make it more efficient for manufacturers of medical devices seeking to sell their products globally, while also continuing to ensure they adhere to high, internationally-accepted quality systems.

Enhancing Clinical Trial Processes

The Spring Unified Agenda also will propose rules to support the clinical trial process, for instance regarding the requirements for cooperative research. We’re proposing a new rule that would, in most cases, allow any institution located in the U.S. that is participating in a multisite cooperative research to be able to rely on approval from a single institutional review board.

We also will be issuing a proposed rule to update the agency’s investigational new drug application regulations to define and clarify the roles and responsibilities of the various persons engaged in clinical investigations to enhance protection of the rights, safety, and welfare of subjects and better ensure the integrity of clinical trials.

In addition to the new proposed regulations I’m highlighting here, FDA will continue to pursue a multitude of other important rules across the Agency, such as taking forward our compounding policy priorities and advancing food and drug safety initiatives. Moreover, we continue to remove outdated rules or reconsider proposed rules in light of our evolving policy priorities. I want to note, however, that some previously identified regulations that weren’t included in this Unified Agenda may still remain FDA priorities. Just because you don’t see them here, doesn’t mean that we don’t intend to continue advancing some prior policy proposals.

While we continue to have a robust regulatory agenda for the coming year, regulation is only one way in which we can foster our mission and improve public health. We’ll continue to tackle many additional priority areas through guidance documents and other policy efforts. These areas will include efforts to reduce the cost of drugs by encouraging competition – including in biosimilars; spurring innovation across medical products; battling obesity through our various nutrition initiatives; and, continuing to attack the opioid addiction crisis facing our country.

I look forward to keeping you updated as we progress toward these goals.

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

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

FDA is Using Innovative Methods to Prevent Illegal Products with Hidden Drug Ingredients from Entering the United States

By: Scott Gottlieb, M.D., Melinda K. Plaisier, M.S.W., and Michael Kopcha, Ph.D., R.Ph.

One of the Food and Drug Administration’s important public health functions is to closely monitor the FDA-regulated products arriving at the nation’s international mail facilities (IMFs) every day to prevent unsafe, counterfeit, and unapproved products from entering the country. This sometimes includes interdiction of illicit products, in support of the U.S. Customs and Border Protection (CBP).

Dr. Scott Gottlieb

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

Given the volume of mail, the increasing sophistication of bad actors, and the amount of time it takes to inspect just one package, this is an increasingly challenging task. FDA is taking new steps to increase the scope and effectiveness of this mission. One tool that FDA has deployed is advanced screening technologies that can allow FDA inspectors to screen packages containing suspected drug products more efficiently and reliably.

According to a January 2018 report by the U.S. Senate Permanent Subcommittee on Investigations, in just three years from 2013 to 2015, the number of packages processed by the nation’s nine IMFs nearly doubled. Today, these combined facilities receive more than 275 million packages a year. Most of the mail arrives without advanced or specific identifying information. As a consequence, we have no way of knowing exactly how many packages contain FDA-regulated products.

What we do know is that every year thousands of packages are found to contain FDA-regulated products and a surprising percentage of those products are illegal. These products come in all different shapes and forms – some with sophisticated packaging and others in nondescript plastic bags.

They include unapproved products; counterfeit or substandard drugs; and purported dietary supplements being sold for weight loss, sexual enhancement, bodybuilding or pain relief. Many products promoted as dietary supplements contain potentially dangerous undeclared drug ingredients. Any package initially suspected of containing controlled substances is immediately referred to the U.S. Drug Enforcement Administration. Still, FDA is seeing an increase in the number of packages containing opioids including tramadol, codeine and morphine, making FDA’s investigators the last line of defense for drugs that may not be easily identified as narcotics.

Melinda Plaisier

Melinda K. Plaisier, M.S.W., FDA’s Associate Commissioner for Regulatory Affairs

Last year, FDA increased the number of investigators it has in the IMFs from 8 to 22 full time employees; taking the number of packages FDA is able to open and screen from 10,000 a year to 40,000. These are packages that our partners at CBP have flagged for additional screening in order to intercept and detail what are believed to be nefarious products prior to refusal of admission and possible destruction.

To do so, based on current laws, FDA must first establish that the products are drugs based on their intended use, then determine if the drug is subject to refusal of admission. This requires documenting the contents, which can be a labor-intensive process. Some of the packages may contain loose pills without any packaging or contain hundreds of small internal packages. Screening a single package can take about 20 minutes, while packages that contain multiple products or large quantities can take much longer. This limits the number of packages that FDA is able to inspect. CBP will only pull for inspection the number of packages that FDA is able to complete in a given day. CBP and FDA target the highest risk packages for physical inspection. This is where good intelligence work is key. But packages that can’t undergo a physical inspection will typically be sent on to their recipient. The more that FDA can improve the efficiency of its process, its authorities, and the tools that it uses to evaluate products; the more higher-risk packages that the agency is able to subject to vetting.

Although the agency’s professional staff works hard to examine and document suspicious contents, FDA investigators are only able to inspect a fraction of the incoming international mail packages. It’s estimated that FDA is able to physically inspect less than 0.06 percent of the packages that are presumed to contain drug products that are shipped through the IMFs. Recognizing these hurdles, we’re doing all we can by increasing our existing resources, working more efficiently and identifying innovative ways to extend our efforts.

In addition to tripling the size of our staff, we’ve invested in, and would like to enhance, our screening equipment at the IMF locations and laboratory equipment for the forensic confirmations needed – all of which serves to increase efficiency and strengthen our ability to more quickly identify and assess suspect products entering through IMFs. FDA’s current analytical process requires sending samples to an FDA laboratory for analysis. It can take days or weeks to get results and during that time products would have to be held within the IMF’s limited space, restricting the number of products that can be tested by FDA.

Michael Kopcha

Michael Kopcha, Ph.D., R.Ph., Director, Office of Pharmaceutical Quality at FDA’s Center for Drug Evaluation and Research

One of the most promising technical developments is the successful use of various portable screening devices that will allow us to rapidly test for unsafe ingredients at the IMFs with similar reliability and accuracy as the current laboratory methods. FDA recently concluded a successful six-month pilot at two IMFs, testing whether we might be able to increase the number of packages we screen by making use of a portable screening device called an ion mobility spectrometer. This is the same technology used by airport security to swipe your luggage for explosives and by prisons to screen visitors for illegal narcotics. The device works by comparing the chemical signature of the unknown substance against the chemical signatures of known compounds in a process that takes less than 30 seconds.

For the pilot, the device was loaded with a custom-built library of pharmaceutical compounds to test whether products marketed for weight loss and sexual enhancement contained undeclared drug compounds such as sibutramine, phenolphthalein and sildenafil. These compounds have significant safety concerns and are often counterfeited; and are commonly found within packages coming into the IMFs. When criminals secretly spike products with these compounds, consumers do not know that they are at higher risk of harm from the products.

An astonishing 65 percent of the samples we screened tested positive for the presence of undeclared pharmaceutical ingredients, results that were confirmed in a FDA laboratory. Based on these results, we’re able to demonstrate that the device was reliable, efficient, and produced valid results. As a result of this pilot, we’ve decided to expand the use of this new technology and add devices at two additional IMFs. Our aim is to refine our use of this device, and eventually install it in all nine of our IMF facilities so that our staff can more quickly determine whether products contain undeclared drug ingredients.

This is a significant milestone.

The scanner’s methods are flexible enough to be used to detect the presence of an active ingredient in a drug product or to identify active ingredients in counterfeit drug products, simply by adding new pharmaceutical libraries developed by FDA laboratories. This will allow the agency to more quickly identify and respond to emerging issues. Already we’re actively working on developing an opioid screening method for the device. We hope to initiate a pilot study using this method very soon.

As we advance the science behind rapid, deployable, screening methods, we aim to shift the paradigm of how FDA screens products; increasing the effectiveness of our oversight. It’s an example of the creative measures we’re taking to keep harmful products out of the U.S. marketplace.

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

Melinda K. Plaisier, M.S.W., is FDA’s Associate Commissioner for Regulatory Affairs

Michael Kopcha, Ph.D., R.Ph., is Director, Office of Pharmaceutical Quality, at FDA’s Center for Drug Evaluation and Research

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

Read more: U.S. Food and Drug Administration and the International Mail Facilities

Visit FDA’s Flickr photo album: FDA and the International Mail Facilities

Looking ahead: Some of FDA’s major policy goals for 2018

By: Scott Gottlieb, M.D.

Twice a year the federal government publishes the “Unified Agenda of Federal Regulatory and Deregulatory Actions” (Unified Agenda), which provides the American public with insight into regulations under development or review throughout the federal government. For the U.S. Food and Drug Administration (FDA), it gives us an opportunity to outline some of our efforts to modernize our approach to our work and improve our efficiency, while fulfilling our mandate to protect and promote the public health and uphold FDA’s gold standard for regulatory decision-making. While many of FDA’s policies are advanced through guidance documents and other proposals, this annual list of proposed regulations provides one element of our policy agenda.

Dr. Scott GottliebPatients and consumers across our country depend on us to regulate products in a predictable, efficient, science-based manner. We also serve the public health by efficiently advancing innovations and therapies that improve patient care, enhance choice and provide competition; by aggressively taking action against serious threats to public health, such as opioid addiction and addiction to the nicotine in cigarettes; by empowering patients, consumers and healthcare providers with accurate and up-to-date information; and by recognizing when scientific innovations warrant new, more flexible regulatory approaches in order to make sure advances in care can reach patients. In addition to these goals, we must continually adapt our regulations to enhance efficiency, improve our effectiveness, and update old and out-of-date requirements.

FDA’s contributions to the Fall 2017 Unified Agenda address a number of these areas of policymaking under way at the agency, and are directly aligned with our key priorities:

Addressing the Nicotine Addiction Crisis

To reduce the morbidity and mortality associated with combusting tobacco, we are proposing meaningful actions to advance our new, comprehensive approach to nicotine and the regulation of combustible cigarettes. These efforts include an Advance Notice of Proposed Rulemaking asking critical questions related to our pursuit of regulation that would result in a targeted reduction of the nicotine levels in combustible cigarettes to eliminate or dramatically reduce their addictive value. At the same time, FDA is taking new steps to facilitate innovation in products that can deliver satisfying levels of nicotine to adults who want or need such access without the same health risks associated with combustible tobacco.

As part of this plan, FDA will also be issuing an Advanced Notice of Proposed Rulemaking to look at how to best regulate flavors in tobacco products to limit their appeal to youth, while considering the potential role that some flavors may play in helping users transition away from combustible products. Further, FDA will be issuing an Advance Notice of Proposed Rulemaking to solicit information that may inform regulatory actions FDA might take with respect to premium cigars, asking certain questions related to how we might define and regulate “premium cigars,” taking into consideration the health effects of these products and their patterns of use.

Advancing Drug Safety

FDA will issue several regulations on drug compounding to help ensure the quality of medicines that patients need. We want to make sure that outsourcing facilities clearly understand which drugs they may compound and allow these firms to adopt more efficient, streamlined manufacturing standards, while ensuring they observe necessary safety and quality measures.

Focusing on the safety of prescription drugs, FDA is also pursuing a proposed rule to establish national standards for the licensing of prescription drug wholesale distributors and third-party logistics providers, as part of track-and-trace requirements. By establishing national standards for all State and Federal licenses issued to key parts of the supply chain, these regulations will allow for the effective and efficient distribution of prescription drugs throughout the U.S.

Promoting Food Safety

FDA continues to take steps to improve its oversight of food safety. To address critical issues related to the overall safety of the food we eat, FDA intends to propose a rule on lab accreditation, which would establish a program to accredit labs to do food safety testing and to require that these accredited labs be used in certain situations.

Additionally, in the Unified Agenda, FDA committed to pursuing a rulemaking that will clarify registration requirements for food facilities to better align how facilities and farms that perform similar activities are treated under the preventive controls rules and the produce safety rule.

Empowering Consumers

Many of our agenda submissions are part of a broader effort to empower consumers and patients to make more informed and effective health decisions and ensure they have appropriate autonomy over their choices, while continuing to ensure the products they consume and use are safe and effective. Consumers tell us that they want this information. We also know that consumers who have access to more diverse, safe and effective options – and who have improved information about those choices – make better, more cost-effective decisions. 

  • Providing Better Information on Drugs: We have included a rulemaking that proposes a new type of patient medication document that would help ensure that patients have access to clear, concise, and useful written information about their prescription drugs or biologics, delivered in a consistent and easily understood format, each time they receive a medication from the pharmacy. We want to give patients the ability to make high value decisions about the medicines they take, and help them use drugs safely and effectively.
  • Broadening Access to Nonprescription Drugs: We are considering innovative action in the nonprescription drug area to expand the scope of drug products that can be made available to consumers without a prescription. We will be proposing to allow certain innovative approaches for demonstrating that a drug product can be used safely and effectively in a nonprescription setting. This will allow some drugs that would otherwise require a prescription to be marketed without a prescription through the use of innovative technologies and other conditions that will ensure appropriate self-selection and/or appropriate actual use of the nonprescription drug product by consumers. Examples of such conditions could include use of self-selection questions on a mobile medical app prior to permitting access to the drug, or other innovative technologies to improve safety. Through use of these types of additional conditions, we hope to create a new paradigm of drug safety with greater flexibility that will benefit patients and public health. We are committed to advancing this new framework to enable a potentially broader selection of nonprescription products for consumers, empowering them to self-treat more common conditions and chronic conditions. This also could help lower costs by increasing the availability of products that would otherwise be available only by prescription.

Modernizing Standards

Importantly, we also are working to ensure efficiency of existing regulations – a key focus of the Unified Agenda – by making sure that our standards are clearly defined, that they advance our public health goals and help promote the protection of consumers, and achieve these goals in an efficient way that does not place unnecessary burdens on those we regulate. We also want to ensure that our standards and regulations are modern and reflect the latest science, and have not become outdated, obsolete or otherwise not applicable to the current environment.

  • Harmonizing Global Standards: We will be updating FDA’s requirements for accepting foreign clinical data used to bring new medical devices to market. While helping to ensure the quality and integrity of clinical trial data and the protection of study participants, this rule should also reduce the burden on industry because it will harmonize with the standards currently used in drug regulation.
  • Modernizing Mammography Standards: We will be proposing a rule to modernize mammography quality standards that will improve women’s health. Our aim is to recognize advances in technology and help to ensure women get the most relevant, up-to-date information about their breast density, which is now recognized as a risk factor for breast cancer. This information can help doctors and patients make more informed decisions about further imaging.
  • Embracing Electronic Submissions: We will propose a new framework that will allow FDA and product developers to take greater advantage of the efficiency of electronic, rather than paper, submissions for devices and veterinary drugs.
  • Removing Outdated Rules: We will propose to remove an outdated inspection provision for biologics and outdated drug sterilization requirements to remove barriers to the use of certain sterilization techniques.

Looking to the Future

FDA serves Americans by delivering on the critical mission of protecting and promoting the public health. The more than 70 actions we have identified, as part of the Fall 2017 Unified Agenda, will help us even better deliver on this mission. But regulation is only one way in which we can foster our mission and improve American health.

Over the next year, we will also tackle many additional priority areas through guidance documents and other policy efforts. These areas will include efforts to reduce the cost of drugs by encouraging competition, spur innovation across medical products, give consumers access to clear and consistent nutrition information, create greater regulatory efficiencies in bringing products to market, and put a dent in the opioid addiction crisis facing our country.

Further, just because a previously identified regulation does not appear on this Unified Agenda submission does not necessarily mean the agency does not consider it a priority or will not continue to consider it moving forward. Look for additional information about the many initiatives identified in the Fall 2017 Unified Agenda as we advance all of these goals.

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

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

Bringing Early Feasibility Studies for Medical Devices Back to the United States

By: Maureen L. Dreher, Ph.D., Andrew Farb, M.D., and Owen Faris, Ph.D.

Ten years ago, when medical device manufacturers wanted to gain early clinical experience with their new devices they often went overseas to conduct first-in-human or small clinical studies. Moving a device from bench to bedside for use in patients is a critical step along the development path. However, going overseas delayed access to potentially beneficial devices for American physicians and patients.

Medical Device image

The Early Feasibility Studies (EFS) Program is supporting medical device innovation and enhancing early patient access to new technologies.

Today, FDA’s Center for Devices and Radiological Health (CDRH) has an Early Feasibility Studies Program (EFS) that provides a route for innovators, sponsors, FDA review teams, and clinicians to work together to facilitate the early clinical evaluation of medical devices in the United States under the investigational device exemption (IDE) regulations.

An EFS is a limited clinical study on a device early in its development, typically before the device design has been finalized, for a specific indication. It may be used to evaluate the device design concept with respect to initial clinical safety and device functionality. The EFS Program includes enhanced opportunities for collaboration, increased regulatory flexibility, and consideration of benefit-risk principles, while maintaining appropriate patient protection measures.

Maureen Dreher

Maureen L. Dreher, Ph.D., Research Biomedical Engineer in the Office of Science & Engineering Laboratories and Early Feasibility Study Program Representative in FDA’s Center for Devices and Radiological Health

Since the release of our EFS guidance document in October 2013, and our  promotion of the EFS Program as part of the 2014-2015 Strategic Priorities, we’ve seen more early clinical studies on devices inside the United States. Specifically, the number IDEs submitted for EFS has more than doubled with 26 submitted in the first year after the EFS guidance document was finalized as compared to 57 submitted in fiscal year 2017.

More importantly, most of these studies have received timely FDA approval. During the last two years, 75% of the IDE submissions which are required to conduct any clinical study on an investigational device, have been either approved or approved with conditions by FDA within one 30-day review cycle.

There are many examples of how the EFS Program is supporting device innovation and enhancing early patient access to new technologies. One is Mitralign, Inc., which is developing a novel treatment for tricuspid regurgitation (TR). TR occurs when the heart’s tricuspid valve does not open and close properly. Many TR patients are not candidates for open heart surgery due to high risk comorbidities. But the Mitralign valve repair system may expand treatment options for these patients through the use of minimally-invasive transcatheter technology. Mitralign’s IDE approval in only 28 days enabled them to conduct a U.S.-based EFS that saved time, money, and the human resources to conduct the study:

Andrew Farb

Andrew Farb, M.D., Medical Officer in the Division of Cardiovascular Devices, Office of Device Evaluation in FDA’s Center for Devices and Radiological Health

“The EFS program has given Mitralign the opportunity to advance our Tricuspid program clinically, technologically and also from a regulatory pathway perspective. It is a clear example of the FDA striking the right balance between the need to advance healthcare technology for the US population and the need to protect the patients who may one day benefit from that advancement.” —Rick Geoffrion, President & CEO, Mitralign. 

Enabling medical device innovation with EFS has a direct and positive impact on all medical device developers, and may be particularly important for small manufacturers. About half of the EFS IDEs are submitted by medical device manufacturers, most of which are small companies for whom early clinical experience is crucial for obtaining financial resources. This was true for Enspire DBS, a startup medical device company, which used the EFS Program to begin a first-in-human study of their Deep Brain Stimulation technology in combination with physical rehabilitation to restore function in stroke patients:

The FDA was engaged and quite interested in working with us to find a mutually acceptable way to move forward with our early feasibility study. We were happy with the interactive review and having an approved IDE significantly helped the company in securing funding.” —Enspire DBS.

Owen Faris

Owen Faris, Ph.D., Director of the Clinical Trials Program, Office of Device Evaluation in FDA’s Center for Devices and Radiological Health

An important lesson learned from the EFS Program so far is that the enhanced opportunities for collaboration between the sponsor and FDA’s review team are crucial for success. Martha Murray, M.D., at Boston Children’s Hospital found this to be a significant advantage of the EFS Program when she approached FDA about translating her novel bridging scaffold, invented at an academic medical center, to treat anterior cruciate ligament injuries:

“Participating in the Early Feasibility Studies Program opened up the door for us to see how collaborative working with the team at CDRH could be. The program gave us access to a team of experts as we tested our device in the preclinical studies. Knowing we had that depth of expertise behind us made us more confident we had done as much as possible to ensure the safety of the subjects in our First-in-Human trial.” —Martha Murray, M.D., Orthopedic Surgeon, Boston Children’s Hospital.

The success of the EFS Program requires stakeholder collaboration beyond FDA. The Medical Device Innovation Consortium (MDIC) is a non-profit, public-private partnership whose mission of advancing medical device regulatory science for patient benefit is aligned with CDRH’s EFS program. MDIC EFS working groups are identifying opportunities to improve the EFS ecosystem by increasing administrative and clinical efficiencies and developing resources for device innovators, such as tools that increase efficiencies in contracting between developers and clinical sites.

We invite manufactures to visit our new webpage devoted to Early Feasibility Studies. With the availability of this webpage, we hope to expand awareness of this important pathway and provide the medical device community with a one-stop shop for EFS resources.

The program represents a critical component of CDRH’s larger efforts to streamline the clinical trial initiative, to increase access for patients in the U.S. to high-quality, safe and effective medical devices as quickly as possible.

Maureen L. Dreher, Ph.D., is a Research Biomedical Engineer in the Office of Science & Engineering Laboratories and Early Feasibility Study Program Representative in FDA’s Center for Devices and Radiological Health

Andrew Farb, M.D., is a Medical Officer in the Division of Cardiovascular Devices, Office of Device Evaluation in FDA’s Center for Devices and Radiological Health 

Owen Faris, Ph.D., is the Director of the Clinical Trials Program, Office of Device Evaluation in FDA’s Center for Devices and Radiological Health

PEPFAR: FDA Approves 200th HIV/AIDS Therapy

By: Scott Gottlieb, M.D.

Since 1981, when the first case of AIDS was reported in this country, U.S. and foreign governments, scientists, grassroots and global community health organizations, patients, and their families have worked hard to address the impact of this virus.

HIV/AIDS is responsible for one of the most destructive pandemics in human history.

Dr. Scott Gottlieb

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

World AIDS Day is a time for us to honor the 36 million people who have died from AIDS and HIV infections, to rededicate ourselves to helping the more than 35 million people living with HIV/AIDS today, and to pay tribute to the caregivers, families, and communities who support them.

As we contemplate the enormity of these numbers and the far-reaching impact of AIDS and HIV on our world, we can also take some heart at efforts to combat the disease, through the development of more effective treatments, and efforts to expand access to these therapies.

The men and women of FDA remain dedicated to these efforts as a core part of our mission.

Earlier this week, FDA approved – or tentatively approved – the 200th antiretroviral drug application, including 30 solid formulations specific for children, under the President’s Emergency Plan for AIDS Relief (PEPFAR). The plan was launched in 2003 to address the global HIV/AIDS epidemic by stimulating the development of new HIV therapies, many of which were new combinations of generic medicines and were purchased with American funds at low cost, to expand opportunities in countries that lacked good access to treatment.

To implement the goals of PEPFAR, FDA used its expedited review process to provide review of life-saving antiretroviral drugs produced by manufacturers all over the world. Through guidance and an active outreach program to the pharmaceutical industry, FDA encouraged sponsors worldwide to submit U.S. marketing applications for single entity, fixed dose combination (FDC), and co-packaged versions of previously approved antiretroviral therapies. These new drugs were typically combinations of medicines that were being combined or packaged together to make their administration easier. FDA worked closely with manufacturers who had not interacted with FDA previously to help them develop an FDA application and to prepare for the requisite FDA inspections of their manufacturing facilities.

By combining medicines into once a day pills, or co-packaging drugs, it helped facilitate treatment in areas of the world, particularly in parts of Africa that lacked advanced health care infrastructure, and where a one-pill-once-a-day regimen helped expand access to treatment.

Under the program, these fixed dose combination drugs could be fashioned even in circumstances where there was still patent or exclusivity market protection for one or more of the components in the U.S. The sponsors agreed not to assert their patent rights, so long as the drugs were sold in markets that lacked the resources to otherwise make these drugs available. In recent years, subsequent legislation applied updated classifications for speed of review.

The process enabled developing markets that were hard hit by the virus to get more widespread access to effective treatments tailored to their health care needs, while making sure that these products underwent FDA evaluation and met the agency’s gold standard for safety, efficacy, and quality. These products could then be purchased with U.S. funds under the President’s PEPFAR Fund. Due to the significant public health impact of these products, FDA prioritized the review of these marketing submissions.

Over the years, FDA’s scientific and regulatory contributions have helped the U.S. respond with compassion and effectiveness to the needs of those who are living with AIDS throughout the world, including many children who face unique challenges getting appropriate treatments.

Since October 2016, the most recent date for which numbers are available, the PEPFAR program has provided life-saving antiretroviral (ARVs) treatment for nearly 11.5 million people in its global efforts to battle the HIV/AIDS epidemic.The FDCs helped enable more widespread treatment.

PEPFAR also has supported collaboration by FDA and HHS with the Department of State Office of the Global AIDS Coordinator; the United States Agency for International Development; the World Health Organization; the Global Fund to Fight AIDS Tuberculosis, and Malaria; and other organizations that help countries build and strengthen their health care systems and regulatory capacities.

This country’s response to the global HIV/AIDS crisis, through programs like PEPFAR, and through the dedicated work of both global and country partners, has created an opportunity to change the course of the HIV/AIDS pandemic, with a potential end to it as a public health threat firmly in sight. We are working to seize this opportunity.

The PEPFAR Strategy for Accelerating HIV/AIDS Epidemic Control (2017-2020) (“Epidemic Control Strategy”), released in September, sets a bold course for achieving control of the HIV/AIDS epidemic by the end of 2020 in 13 countries which represent the most vulnerable communities to HIV/AIDs.

This will be accomplished in partnership with and through attainment of Joint United Nations Programme on HIV/AIDS 90-90-90 framework – in which 90% of people living with HIV will know their status, 90% of people who know their status are accessing treatment, and 90% of people on treatment have suppressed viral loads – and an expansion of HIV prevention.

FDA remains fully committed to these efforts. By working closely with other governments and public and private agencies and organizations, we can build on the impact and success of the life-saving PEPFAR program, expanding transparency, accountability, and partnership, so that the world can finally overcome one of the most devastating public health challenges in history.

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

Follow Commissioner Gottlieb on Twitter @SGottliebFDA




FDA, International Regulators Look at Common Challenges, ‘Innovation’

By: Lou Valdez, M.S., Dara Corrigan, J.D., and Peter Stein, M.D. 

Lou Valdez

Lou Valdez, FDA’s Associate Commissioner for International Programs

Regulatory experts from around the world, including FDA, gathered recently to discuss issues such as regenerative medical products, international collaboration to fight antimicrobial resistance (AMR), and developing strategies to combat substandard or falsified medical products.

With “Innovation” as the theme, the Heads of Medicines Summit and the International Medicines Regulatory Authorities (ICMRA) annual meeting in Kyoto, Japan, Oct. 23-27, 2017, provided unique opportunities for us to share and learn about regulatory issues of mutual concern.

The gatherings bring together leadership from selected national medicines regulatory authorities (MRAs), who represent regulatory agencies of varying maturity. This year, regulators from 28 countries attended, along with representatives from FDA, the European Commission, the European Medicines Agency (EMA), and the World Health Organization (WHO).

Peter Stein

Peter Stein, M.D., is the Deputy Director, Office of New Drugs, in FDA’s Center for Drug Evaluation and Research

In the AMR arena, the EMA, the Japanese Pharmaceuticals and Medical Device Agency and FDA have taken further steps to align their approaches to the evaluation of antibiotics. In combatting falsified/substandard medical products, MRAs will work with the WHO for its November 29, 2017 release and dissemination of a Global Report on the public health and socio-economic impacts of falsified/substandard medicines.

Peter Stein, M.D., Deputy Director of FDA’s Center for Drug Evaluation and Research, delivered a presentation on the use of real world evidence (RWE) in pre- and post-market activities for new products. Health care communities currently are using RWE to support coverage decisions and to develop better tools for use in clinical practice. And medical product developers are using RWE to support clinical trial designs. Now, MRAs, including FDA, are considering increasing the use of RWE to support decisions on medical products.

Dara Corrigan

Dara Corrigan, J.D., FDA’s Acting Deputy Commissioner for Global Regulatory Operations and Policy

The final day of the five-day event included a symposium that brought together more than 500 regulatory, academic and industry experts from Japan. Dara Corrigan, FDA’s Acting Deputy Commissioner for Global Regulatory Operations and Policy, discussed the need for international cooperation among pharmaceutical regulatory authorities as part of a panel that included members from the EMA, Japan, Canada, and Ireland. The panelists highlighted increased sharing of inspectional results, collaborating on pharmacovigilance needs, and advancing regulatory science.

Summits like this one in October are critical for those involved in the regulation of medical products. The challenges for medicines regulatory authorities are complex, wide-ranging, and global in nature. Regardless of the size of a regulatory authority, many are grappling with issues of shared concerns.

In 2018, these two summits will merge and will be known as the ICMRA Summit. FDA will host the inaugural 2018 ICMRA Summit.

Established in 2012, ICMRA is a high-level, strategic coordinating, advocacy and leadership group of MRAs that provides direction for actions common to many MRAs’ missions and goals. Over time, ICMRA will enable a global framework to support enhanced communication, information-sharing, coordinated crisis responses, and increase awareness of and appreciation for the importance of strong regulatory systems and functions.

Lou Valdez, M.S., is FDA’s Associate Commissioner for International Programs

Dara Corrigan, J.D., is FDA’s Acting Deputy Commissioner for Global Regulatory Operations and Policy

Peter Stein, M.D., is the Deputy Director, Office of New Drugs, in FDA’s Center for Drug Evaluation and Research

Making the Case for Using Whole Genome Sequencing to Fight Foodborne Illness Globally

By: Steven Musser and Eric L. Stevens

FDA is laying the foundation for the use of whole genome sequencing (WGS) to protect consumers from foodborne illness in countries all over the world.

CODEX speaker

FDA’s Steven Musser speaks at the Codex Alimentarius Commission conference in Geneva.

We recently traveled to Geneva to join a meeting of the Codex Alimentarius Commission, an international organization that works to protect consumer health and promote fair practices in food trade. There, we participated in a panel discussion on how best to share WGS globally to fight foodborne illnesses and elicit support from the world’s governments in this effort.

There’s no time to waste. The World Health Organization (WHO) estimates that as many as 600 million people in the world fall ill every year after eating contaminated food and 420,000 of these people die.

FDA has been a leader in the use of WGS to identify the nature and source of bacteria that contaminate food and cause outbreaks of foodborne disease. By sequencing the chemical building blocks that make up the DNA of these pathogens, WGS reveals their genetic fingerprint, offering clues about their geographic source, antimicrobial resistance, and other key markers that help scientists respond more effectively to food contamination, preventing illnesses.

CODEX meeting Head table

FDA’s Steven Musser (left) and Eric Stevens (second from right) participate in an international panel on the efforts to share whole genome sequencing globally.

In the last few years, WGS has fundamentally changed the way that we detect, identify and monitor microbiological food safety hazards within the United States. This technology is rapid, precise, cost-effective, easy-to-use, and can be applied universally to all foodborne pathogens.

In 2012, FDA started the GenomeTrakr, a now-international network of laboratories sequencing microbial foodborne pathogens and uploading the data to a common public database in real time. The goal of GenomeTrakr is simple: to assemble a large, freely accessible database of genetic sequence information and accompanying metadata (e.g. geographic location and date) from food, environmental and human clinical isolates of bacterial pathogens. This information can be used by scientists on the trail of disease-causing bacteria, unmasking each contaminant’s identity and offering clues to where and how it got into the food supply.

Recently, public health institutions, including FDA, WHO and FAO (the Food and Agriculture Organization of the United Nations), have been working to raise awareness about the importance of WGS and the benefits of sharing both sequence information and metadata.

In Geneva we talked about how this technology is being utilized in some countries to support their foodborne disease surveillance system or outbreak investigation activities. We all understand that food is a global commodity, with complex shipping and distribution networks that can easily result in contaminated food being sold in more than one country. Thus, the most effective use of WGS in foodborne disease surveillance requires coordination and collaboration, and the panel emphasized the global health benefit of every country sharing their data. One approach would be sharing the data through FDA’s GenomeTrakr.

We are certain that the public health benefit of WGS will only become more evident with every foodborne pathogen’s genomic sequence that is shared. Already, GenomeTrakr has collected more than 142,000 sequenced strains, has made them freely available to anyone in the world, and continues to demonstrate how a large database of this kind is being used effectively for food safety within the United States, and throughout the world.

As the food supply becomes increasingly global, the use of WGS in a way that crosses national borders will ultimately help keep us all safe from foodborne illness.

Steven Musser, Ph.D., is the Deputy Director for Scientific Operations in FDA’s Center for Food Safety and Applied Nutrition (CFSAN).

Eric L. Stevens, Ph.D., is a Staff Fellow in FDA’s Division of Microbiology at CFSAN.

FDA’s plan to engage the public in the agency’s new effort to strengthen and modernize FDA’s regulatory framework

By: Anna Abram

Anna AbramWe’re at a moment of extraordinary opportunity to improve the public health. New innovations are giving us fundamentally better ways to address disease. Some of the same technology is providing consumers with a broader selection of foods that can improve peoples’ diets, and products that can expand their choices. At the same time, we also face a lot of new challenges. The steps FDA takes to advance these opportunities, and address uncertainties, will directly impact the lives of families. As part of our commitment to protect and promote the public health, we’re undertaking a comprehensive review of our regulations. Our aim is to ensure that our policies and regulations keep pace with the challenges we face in protecting consumers, and the opportunities we have to improve their lives. As in all our actions, science will remain FDA’s North Star when it comes to our role in devising regulatory policy.

Over the past few months, FDA has announced a number of broad policy efforts to address public health opportunities in areas such as regenerative medicine, tobacco products, and access to affordable medicines. As with everything that we do, this work is rooted in our mission to protect and promote the public health, foster safe and effective innovation that can benefit patients, adopt regulatory approaches that enable the efficient development of new innovations, and provide for a safe, healthy and nutritious food supply. For example, we’re looking at places where FDA’s rules concerning new drugs are being used in ways that may create obstacles to the timely entry of generic competition. We want to make sure our policies aren’t being misused in ways that thwart the competition that Congress intended when it created the modern generic drug framework. We know that vigorous generic competition can help benefit patients by lowering drug costs, which improves access to medicines. It’s one example of where a closer analysis of our existing policies can help make sure our regulations are having their intended purpose.

As part of my commitment to help oversee the development and implementation of key policy issues, and to help advance these broader policy efforts, I’ve been working closely with FDA Commissioner Scott Gottlieb, M.D., and other senior agency colleagues, to explore ways to modernize our regulations in a manner that will benefit all Americans. To achieve this, we’re not only looking at what new regulations or policies we need in order to be most effective in fulfilling our public health responsibilities. We’re also taking a closer look to see if we need to revise, update, and in some cases eliminate existing regulations to help us better keep pace with scientific advancement and the people that we serve. We need policies that are as modern as the products that we’re being asked to evaluate, and a regulatory framework that uses efficient tools to achieve our vital consumer protection role.

This comprehensive review is a large undertaking given the breadth of our public health mission and the fact that FDA-regulated products account for about 20 cents of every dollar consumers spend each year. It involves the support of FDA’s senior leaders and many of our staff. FDA has long played a vital role in protecting and promoting public health, and since its founding in 1906, the scope and charge of the agency’s work has grown to include many products that Americans rely on every day. Over time, the agency has also assumed an increasingly global footprint. Along the way, we’ve taken many steps to modernize our policies and practices and evaluate our portfolio of regulations to make sure they’re keeping pace with our challenges. But our 100-plus-year history lends itself to a closer examination of the regulations that have guided our work. Some have been in place for decades, and may not reflect the most up-to-date approach to achieving our public health mission. We have a lot of ground to cover. Today, FDA’s regulations comprise more than 4,000 pages in the Code of Federal Regulations. Some regulations may not adequately reflect advances in science, technology or changes in industry practice. Others may be geared toward products and practices that have largely ceased to exist. In a world of increasing challenges and opportunities, we need to be risk-based in everything we do in order to make sure we’re using our resources efficiently. Our goal is to have regulations that reflect modern risks and opportunities, and use the full scope of our authorities to achieve our consumer protection mission.

As part of this process we’re asking ourselves and others to think about how current regulations could be reshaped to achieve our public health objectives through more efficient approaches. We are opening a number of public dockets to solicit feedback from patients, consumers, health providers, caregivers, industry, health groups, academia, as well as state, local and tribal governments, and public health partners. We’re also exploring other opportunities to solicit input from stakeholders on this effort. We believe that engaging both internal and external stakeholders are critical to focusing our attention on where our policies might need updating; to ensure FDA’s work maximizes our public health purpose.

Our approach also aligns our efforts with the Administration-wide goal for federal regulatory reform to improve how government serves the American people. At FDA we take seriously our responsibility to protect and promote the public health. This will be our guiding principle. We’ll use this opportunity to make sure our regulations reflect the new benefits that science and technology offer to advance opportunities for patients to improve their lives, and to strengthen our mandate to protect consumers. We look forward to your input and will continue to communicate our plans as we move forward on this endeavor.

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

For more information on how to provide input on FDA’s regulations, please visit:

Building a Customized Plan to Help Ensure Food Safety

By: Jenny Scott

Every day we evaluate potential hazards in our lives, and take steps to avoid them. We wear our seatbelts. We baby-proof our homes when we have young children. We use passwords to protect secure information online. You might say that when we know hazards exist we put preventive controls in place to protect ourselves.

Preventive controls – steps taken to reduce or eliminate risk – also are at the heart of the rules mandated by the FDA Food Safety Modernization Act (FSMA). They ask the food industry to approach potential hazards in much the same way that we do in our personal life: identify them and take action to prevent them from harming us.

In September 2015, FDA finalized the Preventive Controls for Human Food rule, which requires owners and operators of food facilities to develop a food safety plan that identifies hazards and puts preventive controls in place to minimize or prevent those hazards. But where should owners and operators start? If they haven’t had issues in their facilities before, what should they be looking for? How do they compile their information about hazards and controls in a systematic way?

To help food manufacturers and others comply with these new requirements, FDA is providing a new tool called the Food Safety Plan Builder. This software program can help owners and operators develop customized food safety plans for their facilities. The program can be downloaded for free.

This new tool takes the user through a series of questions that will help identify potential hazards and the preventive controls to have in place to address those hazards. For example, a hazard could be an allergen, like peanuts, and the preventive control could be ensuring that the allergen is properly labeled on the finished product. Another preventive control could be to ensure that the equipment used to process a peanut-containing product is properly cleaned after use to prevent the allergen from contaminating any products that are subsequently processed on the equipment. The food safety plan also must include information about how a facility will ensure that its preventive controls are working, as well as what corrective actions to follow if they are not.

Information provided by the user in response to the questions will automatically populate the Food Safety Plan. Users can store the electronic file on their computers or print hard copies if they prefer. The Food Safety Plan Builder is a desktop Windows application that resides only on the user’s computer. FDA will not track or monitor use of the Food Safety Plan Builder, nor will it have access to any content or documents developed using this tool. We also have published a User Guide and a series of videos to walk users through how to use the tool.

While use of the FDA’s tool is optional, Food Safety Plans are not. Right now, the Centers for Disease Control and Prevention estimates that roughly 48 million people get sick, 128,000 are hospitalized, and about 3,000 people die from foodborne illness each year in the United States. In many cases, these illnesses can be avoided by preventing contaminants from reaching food, and by stopping contaminated food from reaching consumers – exactly what these food safety plans aim to do.

Prevention requires us to take a look into the future at what could happen, which isn’t always easy. That said, both FDA and the food industry have experience in this area. We have seen where things have gone wrong, we have investigated those circumstances, and we have learned from those experiences.

One of our goals at FDA is to educate as we implement FSMA. The Food Safety Plan Builder is part of that commitment to support the partnership we have with the food industry to meet our shared goal of keeping the food supply safe.

Jenny Scott, M.S., is a senior advisor in the Office of Food Safety within the FDA’s Center for Food Safety and Applied Nutrition.