The United Nations Sustainable Development Goals: Efficient and effective regulatory systems are the tide that raises all boats

By: Mary Lou Valdez, M.S.M., and Kristin Wedding

Lou Valdez

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

Do you think it’s possible to ensure healthy lives and promote well-being for all people of all ages by 2030? That’s just one of the United Nations 17 Sustainable Development Goals (SDGs), which the world’s leaders agreed to in September 2015. And, FDA has an important role in supporting these goals.

On June 23-24, 2016, we had the opportunity to participate in the National Academies of Science, Engineering, and Medicine’s Forum on Public-Private Partnerships for Global Health and Safety (PPP Forum). The two-day workshop focused on engaging the private sector and developing partnerships to advance health and the SDGs.

Good health and well-being are linked to many of the SDGs, including zero hunger, ending poverty, economic growth, industry, innovation and infrastructure, and reduced inequalities. But what, you might ask, are FDA’s potential contributions as a regulatory agency in achieving the SDGs?

Regulatory Systems and the SDGs: the Challenges

Kristin Wedding

Kristin Wedding is International Policy Analyst in FDA’s Office of International Programs

Strong functioning regulatory systems for food and medical products are at the nexus of public health, economic development, trade, and investment. Within our public health mission, effective regulatory systems often are a necessary precursor for economic development and growth, including private sector investment. Conversely, the absence of effective regulatory systems is an underlying threat to achieving many of the SDGs. For example:

  • unsafe food contributes to malnutrition and jeopardizes food security (Goal 2);
  • lack of access to safe and effective medical treatments exacerbates chronic diseases (Goal 3), and impedes people from getting and keeping a job (Goal 8).
  • illness hampers children’s learning and school attendance (Goal 4), and often disproportionately impacts girls (Goal 5); and,
  • insufficient access to clean water and sanitation (Goal 6) results in the death of more than 1,000 children each day from preventable diarrheal diseases.

Regulatory Systems and the SDGs: the Opportunities

At the workshop, FDA chaired an expert panel on the critical role of regulatory systems and PPPs in promoting global public health, economic development, and sustainable investments to achieve the SDGs. We were joined by Dr. Juergen Voegele of the World Bank, Dr. Rajeev Venkayya of Takeda Pharmaceuticals, and Dr. Dan Hartman of the Bill & Melinda Gates Foundation.

Despite our diversity, we sent a unified message that regulatory systems are essential drivers for the success and sustainability of global health investments to meet the SDGs. It is the responsibility of all of us – as stakeholders, donors, and partners – to make our investments matter.

UN Panel Discussion

Panel discussion at National Academies of Science, Engineering, and Medicine’s Forum on Public-Private Partnerships (PPPs) for Global Health and Safety: A Workshop on Engaging the Private Sector and Developing Partnerships to Advance Health and the Sustainable Development Goals (SDGs).
Mary Lou Valdez, M.S.M, Associate Commissioner for International Programs, FDA, and Juergen Voegele, Ph.D., Senior Director, Agriculture Global Practice, The World Bank.

FDA participates in a number of global partnerships aimed at strengthening regulatory systems, including the World Bank-led Global Food Safety Partnership (GFSP) the PPP Forum, as well as our work with multilateral institutions such as the World Health Organization.

We look forward to continuing the discussion about future pathways for collaboration and action in demonstrating the critical roles regulatory systems play in the attainment of the SDGs. The public health of U.S. citizens – and others around the globe – can benefit from our efforts now and in the future.

As Dr. Hartman so aptly noted during the panel session, in this time of globalization “efficient and effective regulatory systems are the tide that raises all boats.”

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

Kristin Wedding is International Policy Analyst in FDA’s Office of International Programs

FDA Advisory Committee Members and ‘Appearance Issues’

By: Michael Ortwerth, Ph.D.

FDA relies on its advisory committees as a source of independent scientific and technical expertise and advice on challenging public health issues. Most advisory committee members are appointed as “special government employees” (SGEs). Like regular government employees, these committee members are subject to Federal conflict of interest laws and regulations.

Michael OrtwerthA lack of understanding about our selection and evaluation process has, at times, resulted in confusion and misunderstandings by the public.  We’ve been working to bring greater transparency to how the financial interests of committee members are evaluated.

In 2008, we published “Guidance for the Public, FDA Advisory Committee Members, and FDA Staff on Procedures for Determining Conflict of Interest and Eligibility for Participation in FDA Advisory Committees.” That guidance describes how we apply financial conflict of interest requirements.

What has not been previously addressed in guidance is something called “appearance issues.” Sometimes FDA advisory committee members who do not have interests and relationships that are financial conflicts of interest nevertheless have interests and relationships that may create the appearance that they lack impartiality. Appearance issues are addressed in a government-wide regulation regarding standards of ethical conduct for government employees at 5 CFR 2635.502 (informally known as “Section 502”).

Some examples include:

  • When a member of the household works or is seeking to work for the sponsor with a product before the committee;
  • When a member has had past financial interests with the sponsor with a product before the committee; and,
  • When a member has a current consulting contract with a sponsor but the contract is not related to the product or issue before the committee.

We have recently published new draft guidance describing FDA’s procedures for evaluating appearance issues and how we determine whether to grant an authorization for a member with an appearance issue to participate in an FDA advisory committee.

Section 502 implements the ethical principle that a government employee should be impartial in performing their official duties, meaning that they must not give preferential treatment to any private organization or individual or use public office for private gain. To the extent that an advisory committee member’s performance of official duties might appear to benefit themselves or certain other individuals who are close to them, they must take appropriate steps to avoid an appearance of violating these ethical principles.

We also explain in the draft guidance the circumstances that FDA considers when determining whether an appearance issue may exist. We evaluate the circumstances and assess whether the interests, relationships, or circumstances would cause a reasonable person with knowledge of the relevant facts to question the advisory committee member’s impartiality in the matter before the committee. For example, if an advisory committee member serves on the board of directors of a nonprofit organization and that organization receives donations from the sponsor that is presenting before the committee, we review the details of the donation to determine whether the member should be cleared for service on the advisory committee.

FDA has flexibility and discretion in deciding whether an advisory committee member with an appearance issue should be authorized to participate in the advisory committee meeting. We evaluate whether the government’s interest in the advisory committee member’s participation outweighs the concern that a reasonable person may question the integrity of the agency’s programs and operations. If so, FDA may authorize the member to participate in the meeting.

Although FDA advisory committees provide advice and input to the Agency, FDA makes the final decisions.

The draft guidance is being issued for public comment before we issue a final guidance. Under Federal law, FDA is not permitted to disclose confidential information provided by advisory committee members related to appearance issues. But we are specifically requesting comments on whether the agency should request that advisory committee members voluntarily disclose if they have been granted an appearance authorization.

FDA is committed to ensuring that appropriate expertise and experience is brought to bear on the critical public health issues facing the agency. Often, we convene advisory committee meetings to obtain independent expert advice and perspective. At the same time, it is important that the process we use to screen advisory committee members for participation in meetings be as transparent as possible, and that we protect the credibility and integrity of advisory committee advice. We welcome your comments on how the agency can continue to meet these important goals.

Michael Ortwerth, Ph.D,. is FDA’s Director of the Advisory Committee Oversight and Management Staff

Leveraging the Power of Collaboration – FDA’s New Oncology Center of Excellence

By: Richard Pazdur, M.D.

I am honored to be selected by Commissioner Califf today as the acting director of FDA’s new Oncology Center of Excellence (OCE) in support of the Vice President’s National Cancer Moonshot Initiative.

Dr. Richard PazdurThis new center will be a place where the combined skills of regulatory scientists and reviewers with oncology clinical expertise in drugs, biologics, and devices will come together to support an integrated approach to the advancement of cancer treatment.

The OCE emulates both academia and cancer care centers, which are increasingly organized in multidisciplinary models to enhance collaboration, which is so essential when confronting a complex disease like cancer.

Such a collaborative approach – the sharing of ideas, information and best practices – closely fits my own vision for oncology at the FDA.

When I first joined FDA from the MD Anderson Cancer Center in Houston Texas in 1999, oncology products were reviewed in different divisions within the Center for Drug Evaluation and Research (CDER), in addition to those reviewed by other centers. My current Office of Hematology and Oncology Products (OHOP) was created in 2005 in an attempt to consolidate the review of oncology products within CDER. Additional reorganization into disease-specific teams followed in 2011. This reorganization greatly enhanced both our retention and recruitment of professional staff from leading academic centers. Disease-specific expertise expedited review processes and fostered multiple outreach activities to patient and professional groups. Between 2010 to the present, OHOP approved 61 new molecular entities to treat a variety of cancers – and most approvals were well before their deadlines.

The OCE will build on FDA’s integrative approach to medical product development and the collaborative work that has been a hallmark of the broader FDA oncology community for nearly a decade such as our cross-center monthly meetings to discuss key oncology issues, collaborative workshops and programs and the work we’ve done together on research and scientific publications.

This new center will also continue to facilitate the incorporation of the patient view in our regulatory decision-making, which has become a personal mission for me since my wife Mary, an oncology nurse, died of ovarian cancer last November.

And by bridging the various medical product centers, the OCE will be ideally suited to support innovation and to address the recognition that multiple treatment and diagnostic options are in the best interest of patients.

Certainly the key to OCE’s future success will be leveraging the talents of the staff at FDA. The very first thing I plan to do as acting director is to meet  with those involved in oncology medical product development and review across centers to hear their ideas for the OCE and how we can work together to enhance our efforts across the agency.

Developing the structure of the OCE is an ongoing process. Working closely with the center directors we will develop a staged approach for establishing the new center while ensuring the work across centers continues without disruption.

I look forward to guiding the agency through this initial phase, building our cross-disciplinary review staff, providing external outreach to diverse stakeholders and streamlining administrative processes to ensure rapid review of important cancer products to the American public.

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

FDA: A Great Place for Science…and for Scientists on the New Frontier of Regulatory Science

By: Robert M. Califf, M.D.

Robert CaliffAs FDA Commissioner, I’m proud of our agency’s extraordinary commitment to using the best available science to support our mission to protect and promote the health of the American public. This is especially critical today, as rapid scientific and technological advances are helping to expand our understanding of human biology and underlying disease mechanisms and to identify the molecular profile of a food contaminant.

These breakthroughs offer unprecedented opportunities for us to develop new treatments and cures and to protect our food supply with a robust system that meets the challenges of globalization.

But there’s another benefit that derives from our application of cutting-edge science to the challenges we face, which has become increasingly evident to me through my conversations with some of FDA’s more than 10,000 scientists. And that’s the deep personal and professional satisfaction gained from working in FDA’s state-of-the-art laboratories on front-line issues that make a real difference in the lives of all Americans. As one FDA scientist commented, “At FDA, your work is really at the crossroads of cutting-edge technology, patient care, tough scientific questions, and regulatory science.”

Being Part of a Vibrant Collaborative Scientific Environment

Whether you’re a biologist, chemist, epidemiologist, pharmacist, statistician, veterinarian, nurse, physician, or an engineer and whether you’re a recent graduate or a seasoned scientist, FDA offers an unmatched opportunity to be a part of a vibrant, collaborative culture of regulatory science.

FDA scientists gain a bird’s eye view of the pharmaceutical and food industries, and develop a thorough familiarity and understanding of the regulatory structure that guides these industries. As one young FDA scientist recently commented, “We see a tremendous breadth of different products here, which helps us learn quickly and makes our jobs interesting and challenging.” Another newly trained FDA scientist shared, “We have the chance to work with highly trained colleagues, within and across disciplines, to build and keep our scientific training cutting-edge.”

While the work of FDA scientists helps to advance scientific understanding, it goes much further than that. That’s because our work is directly tied to regulatory decisions. As such it has a powerful and immediate effect on the health of millions of Americans. As another FDA scientist explained, “We get to see how these basic science and clinical advances get applied to producing medical treatments and devices and how these can make differences in people’s lives.”

FDA offers a number of fellowship, internship, graduate, and faculty programs through which newly-minted scientists can join FDA and continue to apply and develop their skills. Many of these individuals remain on as full-time FDA scientists. One former FDA Fellow said they appreciate how “FDA makes room for and respects voices of young, qualified scientists.”

Tackling the Most Challenging Scientific Issues

So, although I may frequently boast about FDA’s responsibility and ability to do rigorous scientific research and its importance for the American public, I’m speaking as much about our scientists as our science. And I hope that when other young talented scientists consider these testimonies from our multifaceted scientific workforce they will be encouraged to join us.

I want to see more professionals take advantage of the opportunities FDA offers to collaborate on some of the most transformative scientific issues of our times – both for their benefit and for the nation’s. We need the best scientific minds to tackle the challenges of food safety, medical product development, and to evaluate how emerging technologies are affecting FDA-regulated products so that our reviewers can make science-based decisions about a product’s benefits and risks.

That’s why we’ve successfully added thousands of qualified new employees over the last several years and worked hard to fill mission-critical positions. It’s also why we continue to seek more hiring flexibilities and other ways that enable us to be more competitive with private-sector salaries for these positions.

The career opportunities at FDA are enormous, and I look forward to welcoming the next generation of scientists of every stripe to help us fulfill our mission. It’s not only good for science and essential to FDA’s ability to protect and promote public health; it’s a unique opportunity for these talented scientists and their careers.

FDA Scientists Discuss Their Cutting-Edge Research in FDA Grand Rounds Webcasts

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

FDA Celebrates the 40th Anniversary of the Medical Device Amendments

By: Jeffrey Shuren, M.D., J.D.

In 1976, Steve Jobs and Steve Wozniak founded Apple and a gallon of gas was $.59. And in another action that has had long term impact, President Ford signed the Medical Device Amendments that closed the dangerous gap between what he called FDA’s “horse and buggy authority” and “laser age problems.”

Jeffrey Shuren, M.D., J.D.

Jeffrey Shuren, M.D., J.D., FDA’s Director of the Center for Devices and Radiological Health, speaking at FDA’s Celebration of the 40th Anniversary of the Medical Device Amendments

Unlike the pharmaceutical industry, which was born from large chemical companies that discovered medical uses for the products they made, the device industry sprung to life as a scrappy sibling—mostly mom-and-pop businesses addressing the needs of individual patients and physicians through invention.

Although Congress had first given FDA explicit authority over medical devices in the 1938 Food, Drug, and Cosmetic Act, the focus was on fraudulent products. Efforts to extend FDA’s oversight on medical devices failed in 1962 and again in 1970.

Then in 1975, reports emerged that thousands of women had been harmed, some even died, from pelvic inflammatory disease, as the result of using the Dalkon Shield, an intrauterine device for contraception. Congress responded the following year by enacting the Medical Device Amendments, which authorized FDA to classify all medical devices based on risk into one of three classifications, to require premarket approval for Class III devices, and for devices to comply with reporting and GMP requirements.

The law ushered in a new era for medical technology innovation, patient access, and patient safety, but also created a tension, contributing to a political environment where the pendulum continues to swing between these objectives, defining and driving the medical device ecosystem ever since.

In signing the legislation, President Ford noted that, when “well designed and well-made and properly used” medical devices “support and lengthen life.” But when medical devices are “poorly designed, poorly made, and improperly used” they can “threaten and impair” life.” His words still ring true today.

The initial Medical Device Program started with about 180 people. Today, FDA’s Center for Devices and Radiological Health (CDRH) is 1,700 strong; a vibrant family of individuals with a wide range of scientific, clinical, engineering, legal, and other expertise, who hail from a variety of backgrounds, and who are ready to tackle the latest scientific advancement.

And the mom and pop industry has transformed into a world of sophisticated software algorithms, miniaturization, combination products, wearable sensors, non-invasive procedures and diagnostics, robotics, and artificial intelligence.

Along the way, CDRH has adapted its expertise and regulatory approaches to meet the needs of such rapidly evolving innovation. While we will continue to adapt, more importantly, we are focusing on proactively anticipating where we need to be so that regulatory innovation is out in front of medical device innovation. We’re doing this now in the digital health space, by designing regulatory frameworks around the type of technology and its unique evidence generation and innovation cycle rather than applying a one-size-fits-all approach.

We are implementing new models for evidence generation. They include the establishment of a National Evaluation System for health Technology, or NEST, that could transform the historical tension between device innovation, patient access and patient safety into an alignment of interests to drive the development and more timely access to life-saving, life-enhancing, and life-advancing devices. This is consistent with our vision: That patients in the U.S. have access to high-quality, safe and effective medical devices of public health importance first in the world.

And we are also going to new places with patients by establishing a foundation for engaging with them as our partners and routinely incorporating their perspectives in our decisions. And that’s fitting because improving the health and the quality of life of patients by assuring they have timely access to medical technologies that will benefit them is at the heart of who we are and what we do.

As we look ahead to the future, it is our work, our care and our dedication that will allow us to reach our vision.

Jeffrey Shuren, M.D., J.D., is FDA’s Director of the Center for Devices and Radiological Health

For more information read: Remarks at FDA’s Celebration of the 40th Anniversary of the Medical Device Amendments, by Jeffrey Shuren, M.D., J.D.

Be A Champion for Clinical Trial Diversity

By: Jonca Bull, M.D.

The FDA is launching a campaign to encourage minorities to participate in clinical trials for all medical conditions.

Jonca Bull, M.D., is Director of FDA’s Office of Minority HealthThe first part of the campaign will be launched on June 19, 2016, World Sickle Cell Day, observed annually to help increase public knowledge and raise awareness of Sickle Cell Disease, which primarily affects people of African and Hispanic descent. We want to encourage diverse communities to learn more about how they can become a part of the research process to bring new therapies to the market.

Clinical trials are a critical step in making new medical products available. Medical products—from vaccines to drugs for blood pressure or diabetes management — are tested in clinical trials.

Although FDA generally does not conduct clinical trials, we do the critical work in reviewing the data to assess the safety and efficacy of medical products before they can be used in medical practice. None of this is possible without clinical trials and the patients who go the extra mile by being research participants.

In order to help ensure that medical products are safe for everyone, we need a diverse pool of research participants—racial and ethnic minorities, women, even the elderly.

We know that certain diseases impact some populations differently. For example, diabetes occurs  more frequently in blacks and Hispanics, high blood pressure and heart failure occurs more frequently and severely in blacks; and, Asian American communities experience more hepatitis B.

Clinical trials participants need to more closely mirror the patients who will ultimately use the medicine. This is especially important when considering health disparities — diseases that occur more frequently or appear differently in non-white populations. But most clinical trials participants are white and male. That means we may miss vital data that could be used to be make better evidence-based, regulatory decisions. If we do not develop a more diverse pool of research participants, health disparities may persist because we will not know if a medical product is safe and effective in the actual population that will ultimately use it.

And that’s why we’re launching our campaign, which includes a series of educational aids such as videos, a blog, and an infographic. In these videos Shirley Miller, who lives with sickle cell disease, talks about her experience participating in clinical trials and encourages her peers to learn more about research studies.

In another video Dr. Luciana Borio, FDA’s Acting Chief Scientist, discusses why clinical trial diversity matters from FDA’s perspective.

This campaign is taking us one step closer to a world where health equity is a reality for all. It supports FDA’s initiative: “The Year of Clinical Trial Diversity.”

It is a part of our larger effort to improve clinical trials diversity — we also work with stakeholder groups, support research, develop multi-lingual resources, and use social media to promote a community of “Clinical Trials Champions.”

You can be a “Champion” by watching and sharing the videos and related resources.

Everyone has a stake in the game —health care providers, researchers, and patients. Share these videos and other materials. Start a conversation today.

Videos:

More information about this campaign and FDA’s OMH can be found here: www.fda.gov/minorityhealth

Follow us on Twitter @FDAOMH

Dr. Jonca Bull is FDA’s Assistant Commissioner for Minority Health, Office of Minority Health

Globalization and FDA’s New Partnerships to Ensure Product Safety

By: Howard Sklamberg

Globalization is posing challenges for public health. For FDA, part of that challenge is the ever-increasing volume and complexity of FDA-regulated products coming to America’s shores.

Howard SklambergIn fiscal year 2015, there were more than 34 million shipments of FDA-regulated products into the United States, up from just 15 million shipments a decade ago. These products are handled by 130,000 importers, and are manufactured, processed, or packaged at more than 300,000 foreign facilities.

We know this global trade expansion has ramifications for our nation’s public health. We also know we cannot be the inspectors for the world. Hence, we need to effectively direct our resources in a risk-based manner as we grapple with this tremendous volume of imported goods.

How? One way is to identify foreign regulators whom we can rely upon to partner with in verifying that safety standards are being met and then construct an approach that will meet the requirements of multiple regulatory jurisdictions. We are currently engaged in three innovative programs that meet this challenge.

The Medical Device Single Audit Program

The Medical Device Single Audit Program, or MDSAP, is an international approach to the auditing and monitoring of the manufacture of medical devices to ensure their safety and efficacy. This audit program will allow a single regulatory audit of a medical device manufacturer’s quality management system that satisfies the requirements of multiple regulatory jurisdictions.

Currently, five nations – Australia, Brazil, Canada, Japan, and the U. S. – are participating in the MDSAP Pilot. It began 18 months ago and will run through the end of 2016. The program’s goals include:

  • Enabling regulatory oversight of medical device manufacturers’ quality management systems;  and,
  •  Promoting more efficient use of regulatory resources through work-sharing and mutual acceptance among regulators.

Mutual Recognition Agreements

In 2014, FDA launched the Mutual Reliance Initiative (MRI), a strategic collaboration between the FDA and the EU Member States. The goal of the program is to determine if the FDA and EU can agree to recognize each other’s drug Good Manufacturing Practice (GMP) inspections, a potentially time-saving approach.

If successful, we could rely upon EU experts to inspect facilities within their own borders, a more practical way of overseeing the large number of drug manufacturing sites outside of the United States. And it would be similarly more practical if the EU relied on FDA experts to inspect facilities within the United States.

Both the EU and the FDA are in the process of evaluating each other’s processes. The EU has visited several of FDA’s district offices in the United States and one drug laboratory and evaluated the work they do. The FDA has a different challenge since each country in the EU has at least one inspectorate, and in Germany, each state has their own inspectorate. To date, FDA has observed eight audits – in Sweden, Greece, Croatia, Germany, Hungary, Italy, the Czech Republic, and the United Kingdom – and will continue to observe audits of other Member States this year and in 2017.

Food Safety Systems Recognition

Preventing problems at relevant points along the global food supply chain can be a daunting job. FDA is soliciting help by leveraging foreign food safety systems that are similar to our own.

The agency’s Systems Recognition program determines whether another country has comparable regulatory programs and public health outcomes to what we have in place in the U.S.

A major advantage of Systems Recognition is that it allows FDA to be more risk-based in its oversight of imported food and we can more wisely plan our overall inspection activities, including foreign facility inspections, import field exams, and import sampling.

Thus far, we’ve completed: New Zealand and the U.S. signed a Systems Recognition Agreement (in 2012) and recently another agreement was signed with the Canadian Food Inspection Agency.

What’s Next? 

The three initiatives I’ve briefly outlined represent the best of FDA innovation and expertise in grappling with the increasing amount of imported FDA-regulated products. Our work will focus on a continued careful reliance on trusted foreign partners; a move away from duplicative work; more risk-based inspections; better data; and the minimization of public health risks globally.

Howard Sklamberg is FDA’s Deputy Commissioner for Global Regulatory
Operations and Policy

Celebrating a Year of the Expedited Access Pathway Program for Medical Devices

By: Erin Cutts, B.S., Owen Faris, Ph.D., and Jeffrey Shuren, M.D., J.D

The U.S. Food and Drug Administration (FDA) is committed to supporting patient access to high-quality, safe, and effective medical devices of public health importance — as quickly as possible.

Erin Cutts

Erin Cutts, B.S., Policy Lead, Q-Submission Program (acting), Office of Device Evaluation in FDA’s Center for Devices and Radiological Health

For patients suffering from life-threatening conditions and who have few, if any, options, this access becomes critical. About a year ago, FDA’s Center for Devices and Radiological Health created the voluntary Expedited Access Pathway (EAP) program to facilitate the development of and access to new technology for these patients who desperately need them.

The EAP program represents a collaborative approach to help manufacturers with product development and evaluation. Products in the EAP program ultimately undergo either Premarket Approval (PMA) or de novo review.

Other device programs may focus specifically on premarket review once a submission has been made. But EAP allows FDA and sponsors to focus on the early stages of product development, which can be helpful for new products that address the unmet — and critical — life-threatening patient needs. In fact, we think the EAP program will have most impact when sponsors request EAP designation prior to beginning an IDE pivotal study. That way we can work with the sponsor to make sure the data being collected in the pivotal study are appropriate to include in the device’s manufacturing submission.

Owen Faris

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

For the devices in the EAP program, FDA, including senior leadership, maintains a high level of interaction with sponsors and provides advice on efficient device development. What does this mean? While working with the device sponsor, FDA carefully considers the risks and benefits of the new device, as well as the risks of delaying a new therapy to patients who have few or no other options. It may be appropriate to accept more initial uncertainty for devices in the EAP program so that an important technology can reach patients sooner. This uncertainty can be further addressed by collecting additional data once the device is on the market.

Jeffrey Shuren

Jeffrey Shuren, M.D., J.D., Director of FDA’s Center for Devices and Radiological Health

Over the past year, FDA has made 29 decisions on requests for EAP designation: 17 have been accepted into the program, and 12 have been denied. These decisions were typically made in 30 days.

EAP designation requests have included devices for the heart, brain, and kidneys that are manufactured by small start-up companies and large corporations. We expect that our resources and focus on these promising technologies under the EAP program will allow them to be evaluated and enter the market more quickly, therefore providing options to the patients who need them most.

Projects should meet certain criteria to qualify for the EAP program:

  • The device should treat or diagnose a life threatening or irreversibly debilitating disease or condition;
  • The device should address an unmet need, which is usually shown by comparing the device to other available options; and,
  • The company should have a Data Development Plan outlining what will be included in future submissions to FDA. This plan helps FDA and the company agree on the high level items up front to prevent confusion and delays later in the FDA review process.

As the program has grown in the past year, we’ve  learned that companies who benefit most from this program are those that have a preliminary proof of principle for how their device works, but haven’t undertaken formal studies to support future submissions to FDA. For these companies, discussing their Data Development Plan with the FDA and agreeing on a roadmap to their marketing application and beyond is an important part of a successful review.

So what’s next? As we look forward to the EAP program’s second year,we remain excited about the possibilities it presents – and to be working with industry to quickly bring new and innovative devices to patients.

Erin Cutts, B.S., is Policy Lead, Q-Submission Program (acting), Office of Device Evaluation in FDA’s Center for Devices and Radiological Health.

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

Jeffrey Shuren, M.D., J.D., is Director of FDA’s Center for Devices and Radiological Health.

From Competition to Collaboration: precisionFDA Challenges

By: Taha Kass-Hout, M.D., M.S., Zivana Tezak, Ph.D., and Elaine Johanson

Next week, we will announce the winners of the first precisionFDA challenge.

Taha Kass-Hout

Taha A. Kass-Hout, M.D., M.S., FDA’s Chief Health Informatics Officer (CHIO) and Director of FDA’s Office of Health Informatics

We set up precisionFDA as an online, cloud-based, virtual research space to allow scientists from academia, industry, health care organizations, and government to work together on creating tools to evaluate a method of “reading” DNA known as next generation sequencing (or NGS). The ultimate goal of precisionFDA is to foster innovation and develop regulatory science around NGS tests, which are essential to achieving the promise of President Obama’s Precision Medicine Initiative. So far, the response to precisionFDA has been gratifying, with participants calling precisionFDA “refreshing”, “innovative,” and “a new paradigm in regulatory science.” The community currently boasts more than 1,500 users from 600 organizations, with more than 10 terabytes of genetic data stored.

To engage users and encourage sharing of data and ideas, precisionFDA has offered two competitions to date. These competitions are motivating community members to demonstrate the effectiveness of their tools, test the capabilities of the precisionFDA platform, and engage the community in discussions and data analysis that will provide new insights and serve as a comprehensive source of information about reference data and software pipelines used to analyze sequencing results.

Zevana Tezak

Zivana Tezak, Ph.D., Associate Director for Science and Technology at FDA’s Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health

The first precisionFDA challenge, the Consistency Challenge, closed in April 2015, with 21 entries from 17 submitters. Participants were given two datasets of whole genome sequences from a known human sample, sequenced at two different sites and generously donated to precisionFDA by Garvan Institute of Medical Research and Human Longevity, Inc. Challenge participants were instructed to use the informatics pipeline (software) of their choice to identify genetic variants and check for consistency between results in the provided datasets. The top performers will be announced in person by FDA Commissioner Robert Califf on May 25, 2016. At the time of his announcement, we will post detailed information here on all the recognitions and how the top performers were selected. So stay tuned!

The second challenge, the Truth Challenge, closes on May 26, 2016, and was designed in collaboration with the Genome in a Bottle consortium and the Global Alliance for Genomics and Health. Participants are expected to identify genetic variants in one known and one unknown sample dataset. The goal is to see how close they come to the truth when analyzing data from a human sample with variant results unknown to them, which we will reveal at the end of the challenge. An exciting characteristic of this challenge is that the Genome in a Bottle consortium will release for the first time new high confidence variant calls for the unknown sample dataset (we refer to in this challenge as “truth dataset”) for the human sample at the end of the contest.

Elaine Johanson

Elaine Johanson, precisionFDA Project Manager and Deputy Director of FDA’s Office of Health Informatics.

The knowledge generation potential for precisionFDA is immense, and leverages the collaboration of the global community to help solve challenges that will ultimately provide insight to regulation to ensure the safety and efficacy of genetic tests. The platform offers users the ability to assemble and run apps, learn from other experts, share lessons learned, participate in competitions, and help to develop standards for assessing the effectiveness of genetic tests.

With new challenges and opportunities for ongoing discussions and collaborations between FDA and the global community, we look forward to the precisionFDA community facilitating and advancing development and assessment of new tools and tests in this fast growing field of genetic testing.

 

Taha A. Kass-Hout, M.D., M.S., is FDA’s Chief Health Informatics Officer (CHIO) and Director of FDA’s Office of Health Informatics

Zivana Tezak, Ph.D., is Associate Director for Science and Technology at FDA’s Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health

Elaine Johanson, is precisionFDA Project Manager and Deputy Director of FDA’s Office of Health Informatics

What We Mean When We Talk About EvGen Part II: Building Out a National System for Evidence Generation

By: Rachel E. Sherman, M.D., M.P.H., and Robert M. Califf, M.D.

In an earlier FDA Voice blog post, we discussed a pair of concepts – interoperability and connectivity – that are essential prerequisites for the creation of a successful national system for evidence generation (or “EvGen”). In this post, we take a look at how we would apply these constructs as we go about building such a system.

Building EvGen

Rachel Sherman

Rachel E. Sherman, M.D., MPH, is FDA’s Associate Deputy Commissioner for Medical Products and Tobacco

Creating knowledge requires the application of proven analytical methods and techniques to biomedical data in order to produce reliable conclusions. Until recently, such analysis was done by experts operating in centers that typically restricted access to data. This “walled garden” approach evolved for several reasons: the imperative to protect the privacy and confidentiality of sensitive medical data; concern about the negative consequences that could arise from inappropriate, biased, or incompetent analysis; and, the tendency to see data as a competitive asset. Regardless of the specific reason, the result has been the same: widespread and systemic barriers to data sharing.

If we are to reverse these tendencies and foster a new approach to creating evidence of the kind envisioned for EvGen, we must bear in mind several critical principles:

  1. There must be a common approach to how data is presented, reported and analyzed and strict methods for ensuring patient privacy and data security.
  2. Rules of engagement must be transparent and developed through a process that builds consensus across the relevant ecosystem and its stakeholders.
  3. To ensure support across a diverse ecosystem that often includes competing priorities and incentives, the system’s output must be intended for the public good and be readily accessible to all stakeholders.

What Would EvGen Look Like in Practice?

Robert Califf

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

What would a robust national platform for evidence generation look like? It may be helpful to envision EvGen as an umbrella for all activities that help inform all stakeholders about making treatment decisions.

The task of evaluating drugs, biologics, or devices encompasses different data needs and methods. However, all share a common attribute: the characterization of individuals and populations and their associated clinical outcomes after they have undergone diagnostic or prognostic testing or been exposed to a therapeutic intervention.

Moreover, when medical practice itself is part of the evaluation, characterization of the organization and function of delivery systems is critical. In other words, the kinds of evidence needed to evaluate medical products for safety and effectiveness and the kinds of evidence needed to guide medical practice overlap substantially.

Over the last decade, there has been enormous progress in the area of “secondary use,” in which data collected for one purpose (for instance, as part of routine clinical care) can be reused for another (such as research, safety monitoring, or quality improvement).

The Sentinel Initiative, launched in response to a Congressional mandate to develop an active postmarket risk identification and analysis system, is one example. Modeled after successful programs such as the Centers for Disease Control and Prevention’s Vaccine Safety Datalink, Sentinel allows FDA to conduct safety surveillance by actively querying diverse data sources, primarily administrative and insurance claims databases but also data from electronic health record (EHR) systems, to evaluate possible medical product safety issues quickly and securely.

Another example, the National Patient-Centered Clinical Research Network (PCORnet), is a national system that includes many of the attributes needed for EvGen. PCORnet includes participation from government, industry, academia, and patients and their advocates. Whereas FDA’s Sentinel system is built primarily on claims data repurposed for safety surveillance, PCORnet is designed to leverage EHR data in support of pragmatic clinical research.

The NIH’s Health Care Systems Research Collaboratory has demonstrated through its Distributed Research Network that the concept of secondary data use can be extended into the realm of prospective pragmatic interventional trials. The NIH Collaboratory program, which includes many of the same health care systems involved in Sentinel and PCORnet, has 10 active trials underway.

In addition, the Reagan-Udall Foundation Innovation in Medical Evidence Development and Surveillance (IMEDS) Evaluation Program is exploring governance mechanisms to ensure that private-sector entities, notably regulated industry, can collaborate with Sentinel data partners to sponsor safety queries about marketed medical products. Such measures have the potential to expand the involvement of private-sector partners beyond the arena of methodology, further helping to ensure that Sentinel continues its expansion into a national resource.

Similarly, efforts are underway to establish a National Device Evaluation System (NDES). As currently envisioned, the NDES would be established through strategic alliances and shared governance. The system would build upon and leverage information from electronic real-world data sources, such as data gathered through routine clinical practice in device registries, claims data, and EHRs, with linkages activated among specific data sources as appropriate to address specific questions.

As substantial work already is being done in all of these areas, valuable experience is being gained. The next step is to ensure that these pioneering efforts coalesce into a true national resource. More on that in future postings.

Rachel E. Sherman, M.D., M.P.H., is FDA’s Associate Deputy Commissioner for Medical Products and Tobacco

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