The Unique Voices of Our Patient Representatives

By: Robert M. Califf, M.D., and Heidi C. Marchand, Pharm.D.

We recently met with 21 inspirational patients and patient caregivers who have made the extraordinary commitment to become FDA patient representatives. These volunteers were in Washington to participate in our two-day Patient Representative Workshop so they can receive training that will allow them to help FDA meet its critical responsibility of guiding the development and evaluation of safe and effective medical products.

Robert Califf

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

The patient representative program has existed since 1999 and is integral to fulfilling FDA’s strong commitment to ensure that the needs and choices of patients – as well as their families, caregivers, and advocates – are incorporated in ever greater ways in the work we do.

Patients add context and content to the cutting-edge science and other empirical evidence that is so important in our regulatory decision-making.  Including their perspectives and voices in our work along the entire medical product continuum, from development to review and evaluation to post-market surveillance, offers opportunities to enhance our knowledge of the benefits and risks of medical products. It’s not only smart science; it just makes good sense. We know, for instance, that patients who live with a chronic disease are experts in the tangible effects of that disease and its treatments.

The training that patient representatives receive helps prepare them to serve on FDA advisory committees, meetings and workshops, where they are knowledgeable about what it is like to cope with their disease – including such topics as side effects from treatments and important lifestyle issues. They also provide valuable contributions as consultants to our review staff.

Heidi Marchand

Heidi C. Marchand, Pharm.D., Assistant Commissioner in FDA’s Office of Health and Constituent Affairs

To give you an idea of the unique set of skills and experiences patient representatives bring to their work, consider the stories and experiences we heard at the workshop.

One was an elite world class athlete, who initially thought her pain was muscular in nature before it was diagnosed as a serious blood clot. She has been on a series of different products since then and is now intimately familiar with what it is like to be on anticoagulants – reflecting on both the benefits and risks of taking these medications.

Two of our patient representatives are caregivers who have a personal experience with a rare disease, Batten’s Disease, a fatal, inherited disorder of the nervous system. Sadly, each lost a young son to the disease. But in the face of this tragedy, these two mothers have advocated tirelessly to find a cure for this disease and worked to educate other parents.

Another mother related the story of her daughter who, at age 16, survived two craniotomies to remove a lemon-sized brain tumor. The daughter went on to receive of 48 weeks of chemotherapy and 8 weeks of brain and spine radiation. The daughter is now 33 years old and doing well. And the mother told us how critical it was for her daughter to take an opioid to relieve her pain. This kind of input, from those who have experienced it first hand, is critical to our future decisions.

2016 FDA Patient Representative Group photo

FDA Patient Representatives at the 12th Annual FDA Patient Representative Workshop, hosted by FDA’s Office of Health and Constituent Affairs

The stories that these patient representatives tell are moving. But even more moving – and indeed inspirational – is their commitment to the future. That’s why they were selected – because of their individual involvement with their respective patient communities, their analytical skills, and their ability to maintain an open mind and consider options.

While we will help train them about the nuts and bolts of FDA – such as the various pathways that products take to get to market – it is their personal experience and their ability to understand and to articulate the perspectives, concerns, and experiences of patients – that makes them truly special.

As we continue to evaluate potential treatments and cures for different diseases, we must make sure that patients are more than simply statistics in this equation. They are real people, with names, faces, and, thanks to these patient representatives, important voices who represent an essential piece of the puzzle to be solved.

FDA is committed to looking for new and better ways to integrate the patient voice. Our patient representatives are an important piece of this commitment. They have an extraordinary impact. We thank them for their service and commitment, and look forward to working with them.

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

Heidi C. Marchand, Pharm.D., is Assistant Commissioner in FDA’s Office of Health and Constituent Affairs

Practical Applications of FDA Regulations for the Indian Food Industry

By: Dean Rugnetta

Dean RugnettaGlobalization of the food supply chain and advances in food processing technologies have led American consumers to develop a taste for a variety of foods and cuisines from different countries. Increasingly, U.S. grocery stores sell foods from Asia, Latin America, and many other parts of the world. Indian exporters have recognized this marketing opportunity, and FDA information shows an increase in U.S. imports from India over the past 10 years. A wealth of ready-to-eat Indian specialties can be found in cans and bottles on U.S. store shelves including Indian curries (a.k.a. gravies), canned sweets, pickled cucumbers, and Indian pickles (chopped fruits and vegetables marinated in brine).

A serious potential health risk in canned and bottled foods

FDA’s regulations for processing shelf-stable or commercially sterile food — such as certain canned and bottled foods — were promulgated in the 1970’s in response to deaths related to botulism poisoning. Botulism is a muscle-paralyzing disease caused by a toxin made by the bacterium called Clostridium botulinum.  FDA’s regulations require that processors heat and/or formulate low acid canned foods and acidified foods in a manner that eliminates favorable growth conditions for such toxins.

The regulations also require that supervisors in plants that manufacture such products be trained in appropriate processing methods. In the United States, FDA collaborates with industry groups, academia and other stakeholders to offer “Better Process Control Schools,” which typically provide two to five days of training.

Better Process Control School in India

Better Process Control School Class Group Photo

Students attending Better Process Control School in India

India now has a Better Process Control School where supervisors at any of the 300 FDA-registered facilities can attend training on how to safely process low acid canned foods and acidified foods. The school was established in 2010 when FDA’s India Office partnered with FDA’s Center for Food Safety and Applied Nutrition (CFSAN), and a local university in New Delhi, India. The school has convened three separate times since then, most recently this spring. The training helps local processors learn FDA’s regulatory requirements and fulfill a regulatory mandate. Processors that successfully complete the course receive a certificate.

The long-term goal of the training partnership in India is to establish a locally sponsored, self-sustaining class and demonstrates how FDA’s international outreach efforts are improving the safety of imported food products.

Dean Rugnetta is the Deputy Director of FDA’s India Office in New Delhi, India 

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Addressing Global Challenges through Transatlantic Cooperation

By: Howard Sklamberg, J.D., Lou Valdez, and Donald Prater

Howard Sklamberg

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

On a recent trip to Brussels, our FDA delegation met with many of our European Union (EU) regulatory counterparts and stakeholders to discuss ways to strengthen our shared commitment to product safety and public health.  

Reflecting the broad scope of our transatlantic dialogue, we engaged on an array of issues, including supply chain safety, quality metrics, risk-based surveillance, data integrity, mutual reliance, and food safety systems.

Building on previous exchanges between FDA and the European Parliament (EP), we first met with Members of the Environment, Public Health and Food Safety Committee, known as ENVI.  ENVI Committee members visited FDA in 2013 and 2015 to share their perspective on how certain health-related topics are being addressed in the European Union. In addition, our FDA delegation exchanged views on recent trilateral cooperation with India and China on Good Clinical Practices and food safety and other approaches to cooperation on the international stage.

Lou Valdez

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

We then met with the head of the European Commission’s Directorate General for Health and Food Safety (DG SANTE), Director General Xavier Prats-Monné, and his colleagues.

We shared our observations on several topics, including:

  • How drug development has changed, including globalization of suppliers and distributors;
  • The challenges among regulatory bodies in keeping pace with risk-based allocation of inspection resources;
  • The complexity of the global supply chain and the need to collaborate on enforcement;
  • The significant progress being made on the Mutual Reliance Initiative (MRI);
  • Pharmaceutical GMP inspections; and
  • The interaction among FDA’s Europe, China, and India offices and regulatory counterparts in the EU and Governments of China and India.
Donald Prater

Donald Prater, D.V.M., Director of the Europe Office in FDA’s Office of International Programs.

We then turned to food safety. Currently, the U.S. and the European Commission are working on a Food Safety Systems Recognition arrangement, a program that FDA has developed to increase regulatory cooperation and build toward reliance on the work of regulatory counterparts.

Such cooperation is facilitated through the reciprocal assessment of one another’s food safety systems to ensure the safety of foods produced under one another’s oversight. The United States already has an arrangement in place with New Zealand and recently signed one with Canada.

We also reviewed the Food Safety Modernization Act (FSMA) and discussed ways FDA and the European Commission can assist suppliers in the EU to better understand the FSMA requirements. Acknowledging that food safety standards are quite high in the United States and the EU, we discussed ways we can leverage the systems on both sides of the Atlantic to further protect consumers and more efficiently use our oversight resources globally.

FDA and EU Delegations in Brussels

A U.S. Food and Drug Administration (FDA) delegation met with many of their European Union (EU) regulatory counterparts in Brussels to discuss ways to strengthen the shared commitment to product safety and public health. Pictured from left to right are: Karin Kadenbach, Member European Parliament (MEP); Sandy Kweder, Deputy Director, FDA’s European Office; Lou Valdez, FDA’s Associate Commissioner for International Programs; Matthias Groote, MEP; Howard Sklamberg, FDA’s Deputy Commissioner for Global Regulatory Operations and Policy; and, Susanne Melior, MEP.

Next up were meetings on medical devices and cosmetics with the Directorate General for Internal Market, Industry, Entrepreneurship, and SMEs, also known as DG GROWTH.

We were welcomed by Carlo Pettinelli, Head of the Directorate for Consumer, Environmental and Health Technologies, and we discussed the key objectives of the Medical Device Single Audit Program (MDSAP) of the International Medical Device Regulators Forum (IMDRF). Mr. Pettinelli acknowledged the importance of MDSAP, and indicated that the European Commission would continue to provide coordination and communication to support the engagement of EU Member States in the program.

We also set aside time for discussion with key industry stakeholders representing medical products – primarily drugs and devices, including, the American Chamber of Commerce Healthcare Committee to the EU and the European Federation of Pharmaceutical Industry Association (EFPIA). There we reviewed FDA’s Pharmaceutical Quality and MRI initiatives.

Our trip concluded with a media roundtable and a briefing to the Deputy Chief of Mission and staff at the U.S. Mission to the European Union. Our FDA Europe Office is based at the USEU and provides critical support to U.S. Ambassador Anthony Gardner.

Throughout all our meetings, one theme was crystal clear: Transatlantic cooperation is vitally important to address the challenges and opportunities of a globalized marketplace.  By carefully evaluating and understanding each other’s regulatory systems, there is tremendous potential to better allocate our resources based on risk, and improve the safety of food, medical products, cosmetics, and other products around the world.

Howard Sklamberg, J.D., is the Deputy Commissioner for Global Regulatory Operations and Policy

Mary Lou Valdez is the Associate Commissioner for International Programs

Donald Prater is Director of FDA’s Europe Office

The Rise in Orphan Drug Designations: Meeting the Growing Demand

By: Gayatri Rao, M.D., J.D.

Developing drugs for rare diseases, once considered a rare phenomenon itself, has fast become a mainstay for many companies’ drug development pipelines. This is exciting news for the 30 million Americans with rare diseases and their families.

Dr. Gayatri RaoCongress played no small role in making this a reality when it passed the Orphan Drug Act in 1983.  One of the key features of this Act was the creation of the Orphan Drug Designation Program, which provides important financial incentives to encourage companies to develop drugs and biologics for rare diseases. This legislation includes major tax credits to defray the cost of conducting clinical trials, as well as eligibility for seven years of market exclusivity. As a result of later amendments to the Act, no user fee is required for orphan drug product submissions, except when an application includes an indication for a non-rare disease or condition.

The number of requests for orphan drug designation received by FDA’s Office of Orphan Products Development (OOPD) has grown dramatically in recent years and is prompting FDA to adjust its timeframes for reviewing orphan drug designations in order to meet the demand. In 2014, we saw a 30% increase over the prior year’s record number. Yet, that record was broken the very next year when we received close to 470 requests. And the pace does not seem to be slowing. In fact, comparing the number of new requests received so far in 2016 with the corresponding date in 2015, there appears to be yet another 30% increase.

We strive to review these requests in an efficient and timely manner because we understand how critical designation can be for companies to move forward with their drug development plans. At the same time, we endeavor to safeguard the intent of the Orphan Drug Act by conducting a thorough review to ensure that the drugs we designate fully satisfy the criteria for designation and the financial incentives associated with designation.

While there is no statutory or regulatory review deadline, it has been our internal goal to review 75% of designation requests within 90 days of receipt. By streamlining our programs, modifying work priorities, and restructuring workloads, we have generally been able to meet or exceed that internal goal. However, the sustained increase in designation requests over the last three years, coupled with the increasing number of incentive programs and competing workload priorities, have forced us to reconsider our internal review target. Reviewing these applications in an efficient and timely manner continues to be a top priority, but to ensure we continue to conduct these reviews with the appropriate level of care and consideration, our current goal is to review on average 75% of designation requests within 120 days of receipt.

We will continue to evaluate workload in relation to resources, and may need to further adjust review timelines in the future.

Companies can play a critical role in ensuring that the new review timeframe does not translate into a delay in obtaining orphan drug designation by doing their part to reduce the number of review cycles needed (i.e., when OOPD needs additional information from the sponsor prior to determining the outcome of an orphan drug designation request).

On average, a request for designation today goes through two such review cycles. Sponsors can shorten this process by ensuring that designation requests are complete and fully address all requirements. We recommend sponsors review the information at www.fda.gov/orphan for helpful hints and FAQs when developing their requests.

The rise in the number of requests for orphan drug designation holds promise for the future of rare disease drug development. We remain committed to the timely and effective administration of the Orphan Drug Designation Program with the shared hope of bringing safe and effective products quickly to the patients who need them most.

Gayatri Rao, M.D., J.D., is FDA’s Director for The Office of Orphan Products Development

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

Charting a Path Forward on Food Safety, Nutrition and Animal Health

By: Stephen Ostroff, M.D., Susan Mayne, Ph.D., and Tracey Forfa, J.D.

Stephen Ostroff, M.D.

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

At FDA, we need to be prepared for the opportunities and challenges of today as well as those of tomorrow, and the FDA Foods and Veterinary Medicine Program’s new Strategic Plan for fiscal years 2016-2025 helps us to do just that.

Our new Strategic Plan makes it clear that we must have an overarching and risk-based approach that encompasses our broad portfolio of responsibilities. The plan organizes this work under four key goals: food safety, nutrition, animal health and organizational excellence.  Whether it’s chemical safety, dietary supplements, cosmetics, genetic engineering, nutrition labeling, antimicrobial resistance, review of animal drugs, or ensuring that we have the right technologies to identify hazards in the commodities we regulate—all of these issues impact the public health.  FDA is a public health agency first and foremost—and that is where our focus will be, using the core principle of science and tools such as regulation and guidance, research, and outreach and education to get us there. This fall, we’ll be issuing a broad implementation plan which will highlight specific actions under these four goals.

Susan Mayne

Susan Mayne, Ph.D., is Director of the FDA’s Center for Food Safety and Applied Nutrition

Over the past several years we’ve made a lot of progress in a number of key areas. We have been very focused on developing the implementation framework for the Food Safety Modernization Act (FSMA), an enormous undertaking to modernize our preventive approach to food safety, and that work will continue. At the same time, we’ve made great headway on nutrition, modernizing the Nutrition Facts label, publishing draft, voluntary targets for reducing sodium in various foods, and making a final determination that partially hydrogenated oils are no longer “generally recognized as safe.”  We’ve addressed the impact of animal agriculture on antimicrobial resistance by phasing out the use of medically important antimicrobials for production use and bringing remaining uses under the direction of veterinarians. And whole genome sequencing has helped us to identify the sources of foodborne illness outbreaks with speed and precision.

Tracey Forfa

Tracey Forfa, J.D., is Acting Director of the FDA’s Center for Veterinary Medicine

One important lesson we learned from our work on FSMA that we can apply moving forward is the importance of transparency and active stakeholder engagement. We transformed the way we do business, and it helped to make our work on FSMA successful. Sometimes, our perspectives may differ from those of our stakeholders, but the important thing is that we seek common areas of alignment to solve problems. We plan to use this approach more broadly.

It’s important that our plan stays current. It will be updated to reflect emerging science, technology, innovation, and trends in globalization. It will keep pace with emerging hazards and risks in the products we regulate. That is why we are establishing an open docket. Comments can be submitted at any time, so that we can consider them and update the plan at least every two years.

We encourage you to take a look at the plan and let us know what you think. We will have plenty of opportunity for discussion in the months and years to come as we work to improve the public health together.

Read the Foods and Veterinary Medicine (FVM) Program’s Strategic Plan Fiscal Years 2016–2025

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

Susan Mayne, Ph.D., is Director of the FDA’s Center for Food Safety and Applied Nutrition

Tracey Forfa, J.D., is Acting Director of the FDA’s Center for Veterinary Medicine

Registration of Food Facilities: A Key Link in the Safety Chain

By: Erwin C. Miller, M.S.

The FDA’s mission to protect consumers from unsafe food follows different paths. The seven rules that have been finalized since last fall to implement the 2011 FDA Food Safety Modernization Act (FSMA) will require food producers, importers, and transporters to take science- and risk-based actions to help prevent the contamination that leads to foodborne illness.

Erwin MillerToday, the agency finalizes another rule to implement FSMA, one that updates the requirements for the registration of domestic and foreign food facilities that manufacture, process, pack, or hold food for consumption in the United States, whether for people or for animals. Under the final rule, additional information will be required that will ultimately support the FDA’s ability to respond quickly to food-related emergencies and that will also help the agency more efficiently use the resources it has for inspections.

The registration rule also will affect establishments located on farms and “farm-operated businesses” by expanding the definition of a “retail food establishment,” which is not required to register as a food facility. The expansion of this definition would allow the inclusion of sales directly to consumers at roadside stands, farmers markets, Community Supported Agriculture (CSA) programs and other such direct-to-consumer platforms in determining an establishment’s primary function and thus whether it meets the definition of a retail food establishment. Congress, through FSMA, directed FDA to amend this definition. (Under the final rule, a farm-operated business is a business managed by one or more farms and that conducts manufacturing/processing not on the farm.)

The registration of food facilities has long been considered a key component of food safety. The September 2001 terrorist attacks highlighted the need to enhance the security of the infrastructure of the United States, including the food supply. Congress responded by enacting the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (called the Bioterrorism Act). This law directed the FDA to require food facilities that manufacture, process, pack, or hold food for consumption in the United States to register with the agency.

Nine years later, FSMA required that facilities renew their registrations biennially, among other new registration requirements. The biennial renewal requirement was effective upon enactment of FSMA, and the final rule codifies this and other registration requirements. The final registration rule also requires some new information, including the type of activity conducted for each category of food product and certain email address information to help expedite communication between the facilities and the agency. In addition, the final rule establishes mandatory electronic registration (with the availability of a waiver process) beginning January 4, 2020.

Facilities also will be required to provide a unique facility identifier (UFI) number as part of the registration process. This will allow the FDA to verify the facility-specific address associated with the UFI and help the agency ensure the accuracy of the registration database in a way that has not been possible under the current system. FDA plans to issue a guidance document to support compliance with the UFI requirement. Food facilities will be required to provide a UFI beginning October 1, 2020.

Together, the requirements in the final rule will be invaluable in providing the FDA with more accurate information about facility locations and information about the activities within facilities—thus aiding investigators in responding to foodborne illness outbreaks or earthquakes, floods, or other disasters. The final rule will also help the agency identify high-risk facilities and ensure that personnel with the proper training are dispatched to conduct an inspection.

While there is no fee for registration, some in the food industry submitted comments stating that certain aspects of the proposed rule would be too burdensome. In response to these comments, the agency has postponed the requirement for mandatory electronic registrations and the submission of a UFI to 2020 to ensure that facilities have ample time to comply.

The next biennial registration period will be October 1 through December 31, 2016. The FDA is committed to working with the food industry to facilitate implementation of this rule and address any questions that arise.

Erwin C. Miller, M.S., is the Chief for the Data Systems Integration Branch in FDA’s Center for Food Safety and Applied Nutrition

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