FDA Takes Action against Zika Virus

By: Robert M. Califf, M.D., and Luciana Borio, M.D.

Zika virus was first identified in 1947 in Uganda and for decades only sporadic cases and a few outbreaks were recognized in a number of locations, including parts of Africa, Asia, and the Pacific. Since 2015, the situation has changed dramatically, with 48 countries and territories reporting a first outbreak of Zika virus as of July 2016. In the United States, cases of Zika virus disease acquired by the bite of an infected mosquito have only been reported in U.S. territories; to date, cases of Zika virus infection reported in the continental United States have involved travelers and in some instances their sexual contacts. However, given the number of Zika cases among travelers visiting or returning to the United States and the increased mosquito activity in the summer months, we expect that imported cases could result in local spread of the virus in some areas of the United States.

Robert Califf

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

The FDA is taking important steps to rapidly respond to the Zika virus outbreak. We are engaged with our partners across the U.S. Government, the private sector, and the international community—including the World Health Organization and ANVISA (the Brazilian Health Regulatory Agency)—to help minimize the impact of this outbreak.

Protecting Tissues and the Blood Supply

One of the FDA’s first actions was to take important steps to help protect the safety of the blood supply. The FDA issued guidance in February 2016 recommending the deferral of individuals from donating blood if they have been to areas with active Zika virus transmission, were potentially exposed to the virus, or have had a confirmed infection. The guidance also recommends that areas with active Zika virus transmission, like Puerto Rico, obtain whole blood and blood components from areas of the United States without active virus transmission unless a blood donor screening test for Zika virus is used. Because there were no blood donor screening tests available for Zika virus at the time, HHS arranged for and funded shipments of blood products from the continental U.S. to Puerto Rico to ensure an adequate supply of safe blood for residents until a blood donor screening test became available. The FDA worked closely with developers in a highly accelerated time frame to make available an investigational test for blood screening in March 2016. The availability of this investigational test, which has been in use in Puerto Rico since early April, has allowed blood establishments to safely collect blood in areas with active Zika virus transmission. A second investigational blood screening test was made available in June 2016. Together, these tests have also enabled blood donor screening to be put in place in areas of the United States where local virus transmission is anticipated, but not yet detected, helping to maintain the safety of the blood supply.

Dr. Lu Borio

Luciana Borio, M.D., is FDA’s Acting Chief Scientist

Zika virus also poses a risk for transmission by human cells, tissues, and cellular and tissue-based products (HCT/Ps) such as corneas, bone, skin, heart valves, and semen used for medical, surgical, or reproductive procedures. Because of this risk, the FDA issued guidance recommending that donors of HCT/Ps be considered ineligible if they were diagnosed with Zika virus infection, were in an area with active Zika virus transmission, or had sex with a male with either of those risk factors, within the past six months.

Supporting Diagnostic Development

The ability to accurately detect and diagnose Zika virus infection is critical for a robust response to this public health threat. The FDA is actively working with manufacturers to support their diagnostic development programs, helping to ensure that their tests are properly validated before they are used to inform patient care. This collaboration has been very successful, and since the beginning of the year, we have authorized the use of five diagnostic tests for Zika virus under FDA’s Emergency Use Authorization authority—four tests to diagnose active infection and one test to assess whether individuals who may have recently been exposed to Zika were actually infected. This test is especially important for women given the link between Zika virus infection and microcephaly and other poor pregnancy outcomes in babies of mothers who were infected with Zika virus during their pregnancy.

Strategies to Suppress Mosquito Population

FDA—as well as our colleagues at EPA— are reviewing the use of innovative strategies to help suppress the population of virus-carrying mosquitoes to help mitigate the threat of vector-borne epidemics, such as Zika virus, which is thought to spread to people primarily through the bite of an infected Aedes aegypti mosquito.

Recently, the FDA released for public comment a draft environmental assessment (EA) submitted by Oxitec, Ltd. (Oxitec). The EA assesses the potential environmental impacts of a proposed field trial of the company’s genetically engineered (GE) Ae. aegypti mosquitoes. The FDA also released for public comment a preliminary Finding of No Significant Impact (FONSI) agreeing with the conclusion in Oxitec’s draft EA that the proposed field trial of the company’s GE mosquitoes would not result in significant impacts on the environment.

The goal of the proposed field trial is to determine whether released Oxitec GE mosquitoes will mate with local wild-type Ae. aegypti and suppress their population at the release site. The FDA is reviewing the thousands of comments received during the public comment period before determining whether to finalize the EA and FONSI or prepare an environmental impact statement (EIS). Oxitec will not proceed with the field trial of the GE mosquitoes until FDA issues its final EA and FONSI or EIS. Oxitec’s GE mosquitoes are one possible approach that could be incorporated into an integrated vector control program to help mitigate the threat of vector-borne epidemics; however, it is too early to say with any certainty whether such an approach would be successful.

Facilitating Medical Product Development

There are currently no vaccines or treatments for Zika virus that have been shown to be safe and effective. Facilitating the development and availability of vaccines is one of the highest priorities for the FDA and the international community. The FDA continues to actively engage with commercial and government developers, including the NIAID and BARDA, to advance the development of investigational vaccines for Zika virus as soon as possible. We are also working with ANVISA to assist in their efforts to expedite the development of vaccines for Zika virus. As was recently reported, a commercial company announced plans to begin evaluating the first investigational Zika virus vaccine in a Phase I clinical study.

Unfortunately, during outbreak situations, fraudulent products claiming to prevent, treat or cure a disease almost always appear. FDA is monitoring for fraudulent products and false product claims related to Zika virus and will take appropriate action to protect consumers when necessary.

More than 120 FDA staff from across the Agency are  responding to the Zika virus outbreak, working together to address the complex range of issues that this evolving epidemic continues to present in order to protect and promote the public health, both domestically and abroad. This type of teamwork exemplifies the capacity of people at FDA to rally together to solve problems, often with little explicit credit other than the satisfaction of meeting the mission of promoting and protecting the public health. There are many fundamental scientific questions that need to be addressed with respect to Zika virus, and our scientists are working to help answer some of these questions in our own laboratories. We stand ready to use our expertise and authorities to the fullest extent to help facilitate the development and availability of products that may help mitigate the Zika virus outbreak.

Visit our Zika response web page for more information, including the latest Zika virus response updates from FDA.

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

Luciana Borio, M.D., is FDA’s Acting Chief Scientist

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

Sleuthing, and a Little Help from Consumers, Helps FDA Track Down Bacteria in Flour

By: Stephen Ostroff, M.D., and Kathleen Gensheimer, M.D., M.P.H.

When many people buy flour, they empty it into a canister and throw out the bag. But three people at the center of a recent outbreak of foodborne illness didn’t do that. They kept their flour in the original packaging, and in so doing enabled the FDA to track down what was making people sick.

Stephen Ostroff, M.D.

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

The story of the recent recall of 10 million pounds of baking and cooking flour is one in which federal agencies, consumers and the food company – in this case, General Mills – all had a role in doggedly tracking down the source of an outbreak that has made dozens of people across the country sick and getting the suspect product off the market.

It all began with a signal, or more accurately, with multiple signals that were monitored by FDA’s Coordinated Outbreak Response and Evaluation (CORE) network. This team looks for “signals” that may point to a pending outbreak, including reports of human illness from the Centers for Disease Control and Prevention (CDC), FDA-collected data on food samples and inspections, and related information on illnesses and inspections from state and local public health and regulatory agencies.

The signals this time came from CDC, which in February identified a string of illnesses that began in December as an outbreak of infections caused by Shiga toxin-producing E. coli O121. This pathogen is a much less common cause of foodborne illness than its better-known cousin E. coli O157. Investigators began to interview patients about the foods they had eaten in the week before they became ill. But identifying flour as the source of the outbreak was not easy. Initially, it seemed that produce or other foods might be the culprit.

Kathleen Gensheimer

Kathleen Gensheimer, M.D., M.P.H., director of FDA’s Coordinated Outbreak Response and Evaluation (CORE) network

Then there was a break. By April, investigators had found that all of the people interviewed in depth had been baking at home, and many of them said they used Gold Medal flour. Multiple interviewees also mentioned eating raw cookie dough that had been made at home with the flour.

CORE was now faced with the daunting task of proving that specific batches of flour caused the majority of the illnesses. The reports from some patients could not initially be confirmed because key information about the brand and lot numbers was not available – it had gone out in the garbage with the flour bags.

But in the weeks that followed, investigators made two important discoveries:

Three people who had become ill still had the original flour package. Two of the labels showed that the Gold Medal Brand flour had been packaged at a General Mills facility in Kansas City, Missouri, and that they were packaged on consecutive days. The third was made at that plant within a week of the other two.

And the FDA team became aware of illnesses linked to restaurants that would supply balls of raw dough for children to play with. These illnesses were among children who had eaten different meals at restaurants in separate states. The CORE team learned that the flour used by the restaurants during the estimated time of the children’s exposure was supplied by the same General Mills production facility.

The FDA decided not to wait for laboratory confirmation that there was E. coli in the flour before contacting the company. On May 27, FDA and CDC investigators briefed General Mills leadership about the information they had received from patients and on May 31 the firm voluntarily recalled a massive amount of flour — 10 million pounds produced in the Kansas City plant over a three-week period in November and December of 2015.

The FDA continued its analysis of a sample of flour collected from the home of a patient who had provided one of the labels. Laboratory microbiologists at the agency confirmed the presence of E. coli O121 in that flour sample. On June 10, FDA’s whole genome sequencing analysis of that sample also confirmed that the E. coli O121 was closely related genetically to bacteria found in people who had become ill. The final piece of the puzzle was put into place, although the investigation continues to ensure that all contaminated product is off the market.

This was just one of the hundreds of voluntary recalls that the FDA facilitates every year. Going forward, the agency’s compliance and enforcement strategies, including recalls, will get even stronger with the recent establishment of a decision-making body of key senior leaders to identify timely and efficient measures to mitigate public health risks.

Laying the groundwork for a recall can be a complex and lengthy process, with only bits and pieces of information coming in at any one time. But tenacity, collaboration and a willingness to be proactive in protecting consumers, enabled the FDA, its federal, state, and local partners, and General Mills to quickly and efficiently work to recall a potentially dangerous product and keep even more people from becoming ill.

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

Kathleen Gensheimer, M.D., M.P.H., is the director of FDA’s Coordinated Outbreak Response and Evaluation (CORE) network

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

Important steps toward streamlining access to investigational drugs for patients in need

By: Richard A. Moscicki, M.D.

FDA is only too aware that there are many patients who have a serious or life-threatening medical condition for which there is no available FDA-approved therapy. For such patients, one option may be to obtain access to an investigational drug that has not yet been approved by FDA. To do this, a physician submits an application to the FDA requesting authorization to use the investigational drug in the treatment of their patient. This is called expanded access to investigational drugs.

Dr. Richard MoscickiWhile FDA has been helping physicians navigate the system for many years, we are aware there have been physician and patient concerns about this process, which can be time consuming and difficult to understand. Consequently, FDA has recently made significant changes to streamline and simplify the process for single patient expanded access requests.

To make the expanded access process more efficient, we’ve just introduced a much simpler application form called the Form FDA 3926, which will be the form doctors now will typically fill out when they want to provide an investigational drug for a patient through expanded access. While the Form 1571 had 26 information fields and seven attachments, the new Form 3926 has fewer fields (11) and only one attachment. With this streamlined format, we estimate that physicians will be able to complete the form in just 45 minutes, as compared to the more difficult and time consuming effort required previously.

Also, as part of our commitment to streamlining the expanded access process, on May 16, 2016, the FDA and the Reagan-Udall Foundation held a meeting with interested stakeholders to explore additional options that might help patients and their physicians understand the process to request access to unapproved drugs. A common theme of the meeting was that navigating the expanded access process really does take a village. The physician, the drug company, FDA, and the institutional review board (IRB) all have important roles and must work together for the expanded access process to succeed.

The FDA and Reagan-Udall Foundation convened this forum to listen to the public express their needs about expanded access and to discuss ideas with stakeholders on ways that the complex process can be made more efficient and effective. Much work on the details remains, but in general there was agreement on the need for a central repository or clearinghouse where useful and relevant information could be stored in one place — a sort of “one-stop-shop” for physicians and patients to seek information about the expanded access process. As our thinking about this resource develops, we’ll keep the public informed.

For physicians seeking more information about expanded access to an investigational drug, we have developed an educational webinar to help them become familiar with the new application form. This live webinar will occur on July 12 at 1:00 PM EDT and will offer one hour of Continuing Education (CE) credit. The webinar will be recorded for viewing without CE credit. We also have released a guidance regarding Form FDA 3926, a guidance with Questions and Answers on expanded access, as well as a guidance directed at industry addressing questions regarding charging for investigational drugs.

Expanded access is designed for seriously ill patients who have exhausted other options.  The last thing a patient suffering from a serious or life-threatening condition needs is red tape. For many years, FDA has dedicated staff to assist physicians and patients in navigating our system. We expect these important steps will help us continue our efforts to serve patients in need and to advance public health.

Richard A. Moscicki, M.D., is FDA’s Deputy Center Director for Science Operations, Center for Drug Evaluation and Research

CBER Laboratories in the Life Sciences-Biodefense Complex

By: Carolyn A. Wilson, Ph.D.

Wise management of research programs means more than selecting projects that will yield the most scientific information but also making sure that we are making wise use of the dollars we allot for research.

Carolyn A. WilsonThat’s why FDA’s Center for Biologics Evaluation and Research (CBER) thinks strategically when it plans research programs by the more than 70 principal investigators who work in our two-year-old laboratories in the Life Sciences-Biodefense Complex at FDA’s White Oak campus.

We ask ourselves how we can most efficiently – and cost-effectively – obtain the answers to our scientific questions that our regulators will need to achieve their mission of ensuring the safety, purity, and potency of biological products.  Products regulated by CBER include vaccines, allergenics (allergy diagnostics and treatments), cellular, tissue, and gene therapy products, and blood and blood products.

To sharpen our research planning we recently undertook a major evaluation of our center’s scientific and administrative strategies and programs with the assistance of an outside consulting firm.

The findings have enabled us to refine  our strategies for wringing the most new knowledge from every dollar we spend on regulatory science – the science of developing new tools, standards and approaches to assess the safety, efficacy, quality and performance of FDA-regulated products. These refinements to CBER’s research strategy include:

  • A Resource Committee that manages CBER’s annual budget, as well as a Regulatory Science Council that develops center-wide goals, guides office-level objectives, and oversees all research activities. These two councils will increase overall transparency of decision-making, make sure that research is prioritized, and aim to make budget planning more timely and responsive to our mission.
  • More direct control of funds by individual CBER offices and earlier allocation of that funding, and annual peer review of 25 percent of existing and new projects to ensure accountability for how they are run.
  • Systems to increase the transparency of CBER research and research funding, enhance management decisions, and facilitate tracking of funding allocated to activities and projects.
  • Elevating the culture of science through monthly presentations highlighting the public health impact and mission relevance of CBER research; biannual CBER-wide Science Symposium, providing opportunities for communication and potentially improved collaboration across all CBER research projects; and, enhanced prominence of CBER research fellows in the research enterprise.
jars of vegetables

Faulty home food preservation is one potential source of botulism. FDA scientists are developing methods that will help manufacturers to make a vaccine that will prevent this bacterial illness.

These research and administration refinements are helping us better identify and prepare for tomorrow’s needs.  And when you consider the approximately 70-80 research programs we have underway, we’re doing a lot. A few examples include:

  • Studying botulism toxoids (inactivated illness-causing chemicals released by bacteria) to support development of the first vaccine to prevent this potentially fatal infection. CBER scientists are designing new tests to predict what vaccine approaches may be protective. These tests may also help screen vaccines that protect against other toxins such as those from anthrax, as well as the plant-derived toxin ricin.
  • Determining the critical immune events that provide protective immunity to intracellular microbes (bacteria and parasites that live inside human cells). Based on this, FDA scientists will develop new measurements to predict protection that may help evaluate new vaccines for these microbes.

    Girl sneezing in a field of flowers.

    Allergies can turn nature walks into annoying sneezing fits. FDA scientists are developing new tools to help manufacturers produce more potent allergy shots and enhance their safety.

  • Developing new tools and data to help manufacturers produce more potent allergy shots and enhance their safety.
  • Helping to develop a test for cow intestine to ensure heparin harvested from this tissue is not contaminated with the agent causing the bovine transmissible spongiform encephalopathy (TSE, also known as “mad cow disease”), a known risk to humans. This would help to ensure a safe, reliable, domestic source of heparin, which is now obtained mostly from China.
  • Developing new methods and technologies for rapid-testing detection and characterization of emerging infectious pathogens that threaten the safety of tissue and tissue-based products. In the course of developing these technologies, the lab has found previously unidentified microbial contaminants in archived tissues used for these studies. These findings provide preliminary evidence to support the potential for application of rapid test technologies in evaluation of emerging infectious disease transmission risks associated with the implantation, transplantation, infusion, or transfer of human tissue.

As CBER continues to advance regulatory science in its Life Sciences-BioDefense Complex, our projects will adapt to new challenges that the science of biologics will inevitably pose to FDA. And CBER will address those challenges, keeping in mind both the public health and our fiduciary responsibility to make every research dollar count.

Carolyn A. Wilson, Ph.D., is Associate Director for Research at FDA’s Center for Biologics Evaluation and Research

A Tale of 3 Countries: Applying FSMA Standards Globally

By: Stephen Ostroff, M.D., and Camille Brewer, M.S., R.D.

Over the past two months, we have been part of FDA delegations visiting three very diverse countries—Canada, China and Mexico—to discuss food safety. As we are doing in the United States with the FDA Food Safety Modernization Act (FSMA), each country we visited is addressing their national food safety objectives in unique and creative ways.  And each has committed to taking a strong role in supporting compliance with the new food safety regulations mandated by FSMA.

Stephen Ostroff, M.D.

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

Looking at how these nations are different – and how they are the same – opens a window on the challenges and opportunities presented by FSMA implementation on a global scale. The seven foundational FSMA rules are now final and they will have a profound effect on foreign food producers that want to export their products to the United States.

We visited Canada on May 10 and 11 for public meetings on FSMA in Toronto and Ottawa. Canada is modernizing its own food safety system under the Safe Foods for Canadians Act, which, like FSMA, places a strong emphasis on preventive controls. Our nations have a strong interest in achieving as much convergence as possible on food safety standards.

We had the opportunity to explain that the recently signed systems recognition arrangement with Canada does not create a “green lane” for foods shipped to the United States. Instead, it is a reciprocal regulatory cooperation tool that will foster greater risk-based targeting of resources and will foster cooperation in many areas, such as risk assessment and research. The systems recognition arrangement with Canada, signed on May 4, affirms that while our countries’ domestic food safety systems are not identical in all aspects, they currently do achieve a comparable degree of food safety protection.

In addition, considerable interest was expressed in the Voluntary Qualified Importer Program (VQIP), which does provide facilitated entry for food shipments to the United States.

Camille Brewer

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

In late April, our public and private meetings in Mexico strengthened what has become a true partnership between our two countries. In 2014, we started the Produce Safety Partnership with the National Service for Agro Alimentary Health, Safety and Quality (SENASICA), and the Federal Commission for the Protection from Sanitary Risks (COFEPRIS)—our regulatory partners in Mexico—to help prepare growers and packers there to comply with the FSMA requirements. This flagship program forms the basis for extensive collaboration on produce issues.

Mexico continues to modernize and strengthen its own regulatory regime for food safety. Our strong and growing relationship with the Mexican government is a model for partnerships we’d like to forge with other nations. One of our central FSMA themes is working closely with foreign governments that share our food safety goals, and whose own food safety efforts can contribute to the safety of imported food. Our FDA office in Mexico helps to build and sustain our mutual food safety goals.

This is a priority for both Mexico and the United States because of the large volume of produce we trade and the importance of produce safety from a public health and confidence standpoint. Much of the produce we eat in the U.S. is grown in Mexico, including produce that would otherwise be hard to find in the winter months. A lot is at stake for both sides, and our meetings in Mexico reinforced our shared commitment to food safety.

A week before the Mexico trip, we traveled to Beijing for a FSMA public meeting and meetings with our regulatory counterparts in China—the General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ), the China Food and Drug Administration (CFDA), and the China National Center for Food Safety Risk Assessment (CFSA). China also has new food safety laws. The interest in meeting FSMA requirements is so intense that the public meeting was shared across China by webinar, with more than 5,200 participants in government agencies, academic institutions, and industry.

There were meetings with Chinese officials about issues of mutual interest and strategic importance, in addition to subjects unique to China, such as the regulation of ceramic tableware and traditional Chinese medicine.

Like FDA, government regulators in China have been working to refine the food-safety infrastructure based on new laws. The sheer vastness of the country and the rapid pace of economic development and change  are key factors that government officials are taking into account as they refine their laws to control and monitor food production.

Progress is being steadily made and the FDA Office in China continues to work effectively with Chinese authorities to identify points of synergy. The visit culminated in a meeting of representatives of China, the European Union and FDA to discuss core food safety principles and other subjects.

So you can see our partnerships take on different forms. What we learned in our travels to Mexico, China and Canada is that each nation has a strong resolve to make their food supply safer for their own citizens and for export to other nations.

We will continue traveling to countries willing to partner with us in this mission. No matter where you live, no matter where you govern, everyone wants safe food.

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

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

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

Our Goal in Enforcing Food Safety: A Rapid, Science-Based Response

By: Stephen Ostroff and Howard Sklamberg

Recalls of potentially unsafe foods are an important food safety tool. The FDA most often works with companies to bring about voluntary recalls, with the goal of getting the product out of the marketplace as quickly and efficiently as possible.

Stephen Ostroff, M.D.

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

The FDA Food Safety Modernization Act (FSMA) empowers the FDA to act when a company does not voluntarily cease distribution and recall a potentially dangerous food product. The enforcement tools provided by FSMA include mandatory recall.

Because the vast majority of companies choose a voluntary recall when presented with science-based evidence that their products are unsafe, or reasonably likely to be unsafe, the FDA has only rarely needed to use its mandatory recall authority. In most instances, companies choose to initiate a recall when faced with the prospect of an enforcement action.

The HHS Office of the Inspector General (OIG) has raised concerns about the sufficiency of processes and procedures the FDA has in place to ensure that firms take prompt and effective action in initiating voluntary recalls. To consumers hearing about the OIG alert, we want to be clear that the FDA is totally committed to its public health mission of ensuring the safety of the food supply. The United States has one of the world’s safest food supplies. The work we do—performing facility and site inspections, conducting surveillance sampling both domestically and at the border, and using laboratory and other analyses to help determine prevalence of food-borne risks—contributes to its safety each and every day.

Howard Sklamberg

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

As a public health agency, the FDA continually works to improve its processes and appreciates the input from the OIG. In fact, the agency is now expediting changes already underway to strengthen its compliance and enforcement strategies, including voluntary and mandatory recalls. This includes, in individual situations, specifying timeframes for voluntary action by the firm and, if necessary, enforcement action by the agency.

But before we get into those changes, it’s helpful to consider what generally occurs before a voluntary recall takes place. The FDA’s actions have to be based in science and we go where the evidence leads us. The scope of a contamination must be ascertained to determine how much of a product must be recalled. The time needed to collect evidence can vary, but to request a recall without evidence risks recalling the wrong product and leaving consumers vulnerable to contaminated food that is still on the market.

Because the FDA acts on science-based evidence, it has credibility with food producers (and their internal and external legal teams) and consumers. Companies know that when they are approached by the agency, the danger is real and must be acted upon promptly. So the FDA, time and again, is able to protect consumers by engineering timely voluntary recalls.

The OIG’s concerns about the FDA’s food recall process are based on their selection of a “judgmental sample” of 30 voluntary recalls between October 1, 2012 and May 4, 2015 chosen based on their risk factor. The alert focuses in particular on two recalls in which the companies did not initiate recalls of all affected products for months despite the fact that FDA notified them as soon as the agency had evidence of a contamination. This finding is unacceptable–no question about that. It bears noting, however, that in those three years, the FDA worked with companies to successfully bring about thousands of recalls to keep unsafe food out of the market and homes of consumers with an average recall initiation time of less than a week.

We fully agree with the OIG that we must move as expeditiously as possible. We also agree that timeframes should be set, but they must be done on an individual basis rather than by setting arbitrary deadlines. The complexities surrounding recall events make it difficult for the FDA to establish a single timeline applicable to all situations.

To speed the FDA’s response when regulated foods are tied to real and potential public health risks, including outbreaks of human illness, the agency has recently established a new process to help streamline and strengthen decisions about compliance and enforcement actions.

We have established the Strategic Coordinated Outbreak Response and Evaluation (SCORE) team, a decision-making body of key senior leaders that will be co-chaired by those responsible for directing compliance and enforcement activities in the foods program and field operations. Team members are from FDA’s Foods and Veterinary Medicine program, the Office of Regulatory Affairs, and the Office of the Chief Counsel. They are advised by senior scientific, medical, communications, and policy experts. This builds on FDA’s establishment of the Coordinated Outbreak Response and Evaluation (CORE) network in 2011 to coordinate and streamline outbreak response, working with state and local authorities and other federal agencies.

What this team brings to the table is an integrated approach to identifying timely and efficient measures to help mitigate public health risks, goals shared by the OIG. It will review investigations that have, or may have, a link to specific foods or a food facility when there is a serious human health risk. It will also be involved when the case involves complex policy questions, when additional expert support is needed, or when response timelines have not been met. The SCORE team’s involvement will speed the FDA’s response by evaluating the whole range of options for use of compliance and enforcement authorities as quickly as possible.

The SCORE team has only recently been established, and we will be reviewing how it works, refining its functions and performance as needed.

There are other ways in which our enforcement strategy is already being strengthened. Since 2014, we have been using whole genome sequencing in the laboratory as a regulatory tool to more rapidly identify foodborne contaminants and trace them to their source with unprecedented speed and precision. This technique has already proven to be a game-changer in outbreak response, and will be increasingly valuable in the future.

Looking ahead, protections will be further strengthened by the FSMA-mandated preventive controls rules for human and animal food, which require covered food facilities to identify potential hazards and take steps to minimize or eliminate risks. They are also required to have a recall plan. Compliance dates begin for certain firms in September 2016.

Our stated mission to protect public health is more than just words on paper. We are always working to be better at our job and will use the OIG’s input as it was intended–to further strengthen our protection of the food supply.

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