New FDA/EMA rare diseases and patient engagement clusters underway

By: Jonathan Goldsmith, M.D., FACP, and Sandy Kweder, M.D., RADM (Ret.) US Public Health Service

Drug development and approval happens across the globe and we at FDA strive to collaborate with other countries and international regulatory agencies to ensure public health. One of our most valuable collaborators is the European Medicines Agency (EMA) — our counterpart agency for drug regulation in Europe that coordinates a network of 4,500 scientists and evaluates and supervises medicines for more than 500 million people in 31 countries.

Dr. Jonathan Goldsmith

Jonathan C. Goldsmith, M.D., FACP, FDA’s Associate Director Rare Diseases Program, Center for Drug Evaluation and Research, Office of New Drugs

For more than a decade, FDA and EMA scientists have collaborated to help solve some of our biggest challenges. We work with them in groups called “clusters.” The first cluster was initiated in 2004. Since then clusters have been formed to focus on treatments for children; establish effective measures for the development and use of biosimilar medications as cost effective alternatives to brand name biologic drugs; evaluate new treatments for patients with cancer; set standards to help develop medicines personalized to a patient’s genetic makeup, and much more. Both agencies have benefited from this joint work. The EMA summarizes these and our other clusters on its website.

We are excited about the initiation of our most recent cluster activity with our EMA colleagues. Just last month we established a cluster that will work to advance treatments for patients with rare diseases. This cluster’s primary goal is for FDA and EMA scientists to share valuable information about their work and to collaborate on certain review aspects of rare disease drug development programs. FDA’s core members of the cluster include experts from FDA’s Center for Drug Evaluation and Research’s Rare Diseases Program, the Office of Pediatric Therapeutics, the Center for Biologics Evaluation and Research’s director’s office, and the Office of Orphan Products Development, but other experts will be engaged on specific topic areas as the cluster evolves. Among many other important activities, our agencies will collaborate on:

  • Identification and validation of trial end points;
  • Potential trial designs when only small populations of patients are available for testing the safety and effectiveness of prospective new therapies;
  • Ways to apply flexibility in evaluation of drug development programs;
  • Expediting the review and approval of drugs to treat rare diseases to bring new drugs to patients in need as soon as possible.
Sandra Kweder

Sandra Kweder, M.D., Rear Admiral (Ret.) US Public Health Service, FDA’s Deputy Director, Europe Office, and Liaison to European Medicines Agency

Our work also builds on another exciting and recent development — a patient engagement cluster formed in June 2016 to incorporate the patient’s involvement and viewpoint in the drug development process. FDA and EMA are interested in understanding patient’s experiences and gaining input on their tolerance for risk and uncertainty, on current therapy and its benefits or shortcomings and on the benefits that patients seek. This cluster, among other valuable efforts, will:

  • Help each agency learn how the other involves patients in their work, and to develop common goals of expanding future engagement activities with patients;
  • Discuss ways for finding patients that can serve as spokespersons for their community;
  • Explore ideas to help train selected patients and advocates to effectively participate in agency activities, and;
  • Develop strategies for reporting the significant impact of patient involvement.

Given the focus of both of these new clusters, we expect they will address new areas of interest and also draw on expertise from all of the other clusters, such as oncology, pediatrics, and orphan diseases, contributing to more advanced and robust collaborations across both of our organizations.

Focusing on patients with rare diseases and working to advance patient input enhances the value of our cluster activities. With our colleagues at the EMA we look forward to accomplishing more than what we can individually.

Jonathan C. Goldsmith, M.D., FACP, FDA’s Associate Director, Rare Diseases Program, Center for Drug Evaluation and Research, Office of New Drugs

Sandra Kweder, M.D., Rear Admiral (Ret.) US Public Health Service, FDA’s Deputy Director, Europe Office, and Liaison to European Medicines Agency

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

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

By: Robert M. Califf, M.D.

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

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

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

Being Part of a Vibrant Collaborative Scientific Environment

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

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

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

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

Tackling the Most Challenging Scientific Issues

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

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

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

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

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

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

FDA Invests in Innovative Ways to Communicate to Hispanics

By: Gloria Sánchez-Contreras, M.A.

En Español

National Hispanic Heritage Month–celebrated annually from September 15 to October 15—gives Americans a great opportunity to celebrate the histories, cultures, and contributions of Hispanic Americans whose roots are in Spain, Mexico, the Caribbean, and Central and South America.

Gloria Sanchez-ContrerasAt FDA, we join in this celebration as we continue to use innovative ways to reach Hispanics as part of our mission to protect the public health. To achieve this goal, FDA uses media strategies that are culturally and linguistically tailored to Hispanics, who, according to research, are avid users of online and social media.

There are 54 million people of Hispanic origin in the United States, making them the nation’s largest ethnic or racial minority group, with 17 percent of the nation’s total population, according to the U.S. Census Bureau. The United States has the second-largest population of Spanish-speaking residents in the world, ahead of Colombia and Spain, and second to Mexico, a recent study by the Instituto Cervantes shows.

These statistics cannot go unnoticed. FDA recognizes the importance of connecting with this growing and diverse segment of our population. Consequently, we have increased our online consumer information in Spanish and developed a variety of bilingual communications strategies to reach and engage all Hispanics.

One of the most important strategies we use is to make sure that messages created for Hispanics speak to them effectively. We consider Hispanics’ informational needs, lifestyles, and cultural health beliefs both when creating new messaging and when translating messaging from English to Spanish.

For example, we know Hispanics respond better when communications are in their primary language – which can be English or Spanish – and when communications use images that relate to them. We do this by employing a bilingual and bicultural team that reviews messaging for cultural competence and adapts translations to ensure they are culturally sensitive and in plain language.

In addition to our English-language communications, we have developed strategies to reach out to Spanish-speaking Hispanics online. Our Consumer Updates and drug safety communications are regularly translated into Spanish. We share Spanish-language information through our social media channels, including Twitter, Facebook, Pinterest, and YouTube.

In addition, we also have a complete Web section in Spanish for consumers (www.FDA.gov/ArticulosConsumidor), a press room (“Comunicados de Prensa”), and a central page (www.FDA.gov/Espanol) that links to a variety of Spanish-language content developed across the Agency’s product centers and offices.

These are exciting times, and it is a privilege to lead some of these efforts for our agency. The Office of External Affairs works diligently across FDA to share important and timely public health news with Latino consumers, stakeholders, media, and community organizations. And during Hispanic Heritage Month—and all the months of the year–we want Hispanics to know that FDA is a trusted source of consumer information.

Gloria Sanchez-Contreras, M.A., is a Bilingual Public Affairs Specialist and the Spanish-Language Communications Lead in FDA’s Office of Media Affairs.

Frances Oldham Kelsey, Ph.D., M.D.: A Pioneer in Public Health and Protection of Patients

By: Stephen M. Ostroff, M.D.

Acting FDA Commissioner, Stephen Ostroff, M.D.

Stephen M. Ostroff, M.D., is Acting Commissioner of the Food and Drug Administration

Last week our nation lost a true pioneer in public health and consumer protection.

Frances Oldham Kelsey, Ph.D., M.D., who joined FDA in 1960 as a medical officer, was known worldwide as a leader in drug safety and the protection of patients. She established that reputation in one of first FDA assignments: reviewing the marketing application for a drug called thalidomide, which was already available in dozens of countries around the world.

Despite constant pressure from the company, Dr. Kelsey refused to approve thalidomide because of inadequate evidence about its safety. As a result of Dr. Kelsey’s expertise, diligence, and integrity, the drug was never approved in the United States and Americans were largely spared the tragic birth defects and deaths experienced by patients in those countries where thalidomide was available.

This “near miss” spurred Congress and the White House to revive pending proposals to revitalize the oversight and regulation of pharmaceutical products. In the wake of the thalidomide episode, the Kefauver-Harris Drug Amendments became law in 1962. That law mandates “substantial evidence” of a drug’s effectiveness (in addition to evidence of safety that was previously required) and today continues to provide this road map for how unapproved pharmaceutical products are tested in humans.

Dr. Kelsey

Frances Oldham Kelsey, Ph.D., M.D.

It is fair to state that these amendments, as implemented by FDA, ushered in the modern era of science-based proof that the medicines we use are both safe and effective, a level of evidence that created a standard still in effect today.

Dr. Kelsey’s original work on the thalidomide application stands today as a legendary example of how FDA carries out its public health mission: judicious exercise of authority and oversight to protect consumers and patients.

Dr. Kelsey joined FDA during a different era and was a trailblazer in many ways, including the role of women in science. And yet, although this is a new era, our mission endures: to promote innovation while protecting the health and welfare of Americans. And FDA continues to be defined by the same rigor, dedication, and integrity that informed Dr. Kelsey’s work.

Our nation owes a great debt of gratitude to Dr. Frances Oldham Kelsey for her decades of service to public health.

Stephen M. Ostroff, M.D., is Acting Commissioner of the Food and Drug Administration

More information about Dr. Kelsey’s life and career is available in her “Autobiographical Reflections,” which FDA released on the occasion of her 100th birthday in 2014.

FDA Science Forum 2015: Views of FDA

FDA’s 2015 Science Forum attracted more than 800 people from the scientific community. Here’s what some attendees said about the innovative research going on at the agency and why FDA can be a valuable collaborator in research aimed at transforming food safety and medical product development. If you couldn’t attend the FDA science forum, you can still see all the presentations on our web site.

Helping patients and health care professionals better understand the risks and benefits of medications for pregnant and breastfeeding women

By: RADM (Ret.) Sandra L. Kweder, M.D., F.A.C.P.

Good news for moms and expecting moms across the country. We have a new way of helping health care professionals and patients better understand the effects of medicines used during breastfeeding and pregnancy.

Sandra KwederToday, after years of careful consideration — and listening to public feedback — FDA has published a final rule that sets standards for providing a consistent way for drug manufacturers to provide information about the risks and benefits of prescription drug and biological products used during pregnancy and lactation (the medical term for producing milk). It also includes requirements for ways of communicating relevant information for women and men of reproductive potential.

The new rule eliminates an old and possibly confusing way of communicating risk during pregnancy and breastfeeding, which used letter categories of A, B, C, D, and X, to classify various types of risks. It may look simple, but this system was anything but. As a result, the letter categories that have been a familiar presence in drug labeling since the 1970s were often misinterpreted as a sort of grading system of risks, which gave an overly simplified view of product risks.

Our new method provides for explanations, based on available information, about the potential benefits and risks for the mother, the fetus, the breastfeeding child, and women and men of reproductive age.

Here’s a quick overview: Prescribing information for health care professionals provided by manufacturers will now contain required subheadings within the Pregnancy and Lactation subsections: risk summary, clinical considerations, and data. These subsections will provide more detailed information regarding, for example, human and animal data on the use of the drug, specific adverse reactions and information about dose adjustments needed during the pregnancy and post-partum (after giving birth) periods. It will apply not just to new drugs approved from now on, but also to older drugs approved since 2001 that have been marketed for years without their labeling being updated to incorporate important new information related to pregnancy and lactation.

Also today, FDA is issuing what we call a “draft guidance” for industry, to assist drug manufacturers in including information about pregnancy and lactation in their prescribing information according to the requirements of the new rule. We’ll finalize that draft guidance after receiving and incorporating input from the public. To provide comments on this draft guidance, visit this link.

There are more than 6 million pregnancies in the United States every year, and pregnant women take an average of three to five prescription drugs during pregnancy, so we’re excited about this rule, which will provide an extra layer of safety and informed decision making for patients and health care professionals.

Protecting pregnant women and children of breastfeeding mothers from adverse reactions from medications and informing patients and health care providers about their benefits is an ongoing effort we must constantly update and advance. This new rule is one of many steps along the way — and we believe it will help make a strong and positive difference in safeguarding the American public.

Sandra L. Kweder, M.D., is the Deputy Director of the Office of New Drugs at FDA’s Center for Drug Evaluation and Research

FDA Working to Keep Patients Well Informed

By: Steve L. Morin R.N., B.S.N.

Steve Morin_2823My job in the Food and Drug Administration’s Office of Health and Constituent Affairs (OHCA) is to serve our nation’s patients in two ways: by listening to their concerns regarding FDA’s policy and decision-making and advocating for them in our agency;  and by informing many patients and patient organizations about FDA’s mission and its work to advance the development, evaluation and approval of new therapeutic products.

This dialogue was formalized and greatly expanded in 2012 when, after a series of listening sessions with many patient advocacy organizations, OHCA created the Patient Network.

Specifically designed for patients, caregivers, patient advocates and disease-specific patient advocacy organizations and the communities that advocate on their behalf, this program serves two goals. It facilitates patient engagement with FDA policy and decision makers, and it educates its audience about the process that brings new medications – both prescription and over-the-counter ­– and medical devices from a concept to the marketplace.

Our Patient Network covers a range of FDA-specific topics and conducts numerous activities that are of interest to patients and patient advocates. One of these activities were webinars with information about upcoming public meetings hosted by FDA.

For example on March 31, 2014, OHCA was pleased to host the first-of-its-kind “LiveChat” with the diabetes community. This online discussion gave patients an opportunity to interact with FDA experts and to better understand a recently released draft guidance dealing with the studies and criteria that FDA recommends be used when submitting premarket notifications (510(k)s) for blood glucose meters.

On September 10, 2014, our Third Annual Patient Network Meeting titled “Under the Microscope: Pediatric Product Development” brought together more than 100 patients, patient advocates, representatives of academia and industry, and FDA leaders. The participants discussed pediatric product development and the ways patient advocates can participate in it.

And on September 17, 2014, our Patient Network webpages were upgraded. The “For Patients” section on FDA’s website is presented in a clear manner with easy-to-use formats. Also, a “For Patients” button is located on our homepage.

We have continued to pursue our goals of informing the public and engaging with patients by building upon the patient-centered webpages and enhancing activities that express our desire to be helpful and transparent. This is our philosophy that has helped the Patient Network evolve to what you see today.

As the Patient Network program continues to grow, I hope to expand it to have more interactive webinars like the “LiveChat” that address specific concerns  of the patient communities. Also, we will continue to make it possible for patients to learn from FDA experts who approve medical products.

The FDA realizes that listening to the “patient voice” and conducting our dialogue is important, and it continues to develop its model for patient involvement through the Patient-Focused Drug Development Meetings and other OHCA sponsored meetings and webinars. We hope patients and those who care for them will join us in that effort, and make it still more helpful in protecting and promoting the public health.

Steve L. Morin, R.N., B.S.N., is a Commander of the United States Public Health Service and the Manager of the Patient Network in FDA’s Office of Health and Constituent Affairs

FDA’s Program Alignment Addresses New Regulatory Challenges

By: Margaret A. Hamburg, M.D.

Over the last year, a group of senior FDA leaders, under my direction, were tasked to develop plans to modify FDA’s functions and processes in order to address new regulatory challenges. Among these challenges are: the increasing breadth and complexity of FDA’s mandate; the impact of globalization on the food and medical product supply chains; and the ongoing trend of rapid scientific innovation and increased biomedical discovery.

Margaret Hamburg, M.D.The Directorates, Centers and the Office of Regulatory Affairs (ORA) have collaborated closely to define the changes needed to align ourselves more strategically and operationally and meet the greater demands placed on the agency. As a result, each regulatory program has established detailed action plans. Specifically, each plan describes the steps in transitioning to commodity-based and vertically-integrated regulatory programs in the following areas: human and veterinary drugs; biological products; medical devices and radiological health; bioresearch monitoring (BIMO); food and feed; and tobacco.

These action plans focus on what will be accomplished in FY 2015 and outline the need to develop detailed future plans for the next five years in some cases. The plans represent what each Center and ORA have agreed are the critical actions to jointly fulfill FDA’s mission in the key areas of specialization, training, work planning, compliance policy and enforcement strategy, imports, laboratory optimization, and information technology.

Because each Center has a unique regulatory program to manage, there are understandably variations among the plans. However, there are also common features across most of the plans: the need to define specialization across our inspection and compliance functions; to identify competencies in these areas of specialization and develop appropriate training curricula; to develop risk-based work planning that is aligned with program priorities and improves accountability; and to develop clear and current compliance policies and enforcement strategies.

Below are some highlights from the plans that illustrate these features:

  • Establish Senior Executive Program Directors in ORA. In the past, for example, the Center for Drug Evaluation and Research (CDER) would work with several ORA units responsible for the pharmaceutical program. Now, the Centers will have a single Senior Executive in ORA responsible for each commodity program, allowing ORA and the Centers to resolve matters more efficiently.
  • Jointly develop new inspection approaches. The Center for Devices and Radiological Health (CDRH) and ORA plan, for example, will begin to focus some inspections on characteristics and features of medical devices most critical to patient safety and device effectiveness. ORA investigators will perform these inspections utilizing jointly developed training.
  • Invest in expanded training across ORA and the Centers. The Center for Biologics Evaluation and Research (CBER) and ORA will jointly develop a biologics training curriculum, redesign investigator certification, and cross-train Center and ORA investigators, compliance officers and managers.
  • Expand compliance tools. Field investigators will be teamed with subject matter experts from the Center for Food Safety and Applied Nutrition and the Center for Veterinary Medicine to make decisions in real time, working with firms to achieve prompt correction of food safety deficiencies and to help implement the preventive approaches outlined by the FDA Food Safety Modernization Act (FSMA). If industry does not quickly and adequately correct critical areas of noncompliance that could ultimately result in food borne outbreaks, we will use our enforcement tools, including those provided under FSMA, as appropriate.
  • Optimize FDA laboratories. ORA and the various Centers will establish a multi-year strategic plan for ORA scientific laboratory work, including hiring and training analysts, purchasing and using equipment, and allocating resources and facilities. At the same time, ORA is committed to conducting an ongoing review of its labs to ensure that they are properly managed and operating as efficiently as possible.
  • Create specialized investigators, compliance officers, and first-line managers. A bioresearch monitoring (BIMO) working group is developing a plan for a dedicated corps of ORA investigators to conduct BIMO inspections, and a dedicated cadre of tobacco investigators is being established.

Working together to implement these action plans will take time, commitment, and continued investment and we’ll need to monitor and evaluate our efforts. These plans will help us implement the new FSMA rules announced in September, as well as the Agency’s new medical product quality initiatives under the FDA Safety and Innovation Act and Drug Quality and Security Act.

FDA’s Program Alignment is a well-thought out approach that responds to the needs of a changing world. I look forward to the ways in which these action plans will ultimately enhance the FDA’s public health and regulatory mission.

Margaret A. Hamburg, M.D., is Commissioner of the U.S. Food and Drug Administration

A Blueprint for Helping Children with Rare Diseases

Editor’s Note: This blog has been updated to provide additional information about our use of expedited programs to speed rare disease medical product development.

By Jill Hartzler Warner, J.D.

Jill WarnerThe U.S. Congress and the Food and Drug Administration have long focused on bringing new therapies to patients with rare diseases, including children.

Two years ago this week, Congress made another contribution to this effort by enacting the Food and Drug Administration Safety and Innovation Act (FDASIA). The law directs our agency to take two actions to further the development of new therapies for children affected by rare diseases: (1) to hold a meeting with stakeholders and discuss ways to encourage and accelerate the development of new therapies for pediatric rare diseases, and (2) issue a report that includes a strategic plan for achieving this goal.

There are unique challenges when developing drugs, biological products and medical devices for the pediatric population. Not only is there the potential for children to respond differently to products as they grow but there are also additional ethical concerns for this patient population.

But these challenges are further compounded when developing therapies for pediatric rare diseases. For example, rare disease product development, by definition, means there is only a small potential group of patients available to participate in clinical studies that can help determine whether a product is safe and effective.

In our FDASIA meeting in January, we heard a variety of suggestions on clinical trial design and data collection from hundreds of the participating stakeholders from academia; clinical and treating communities; patient and advocacy groups; industry and governmental agencies.

These discussions helped inform our Strategic Plan for Accelerating the Development of Therapies for Pediatric Rare Diseases, which we posted on our website today. It outlines how we plan to meet the following four objectives:

Enhance foundational and translational science. Our strategy is to fill essential information gaps through such measures as fostering the conduct of natural history studies for pediatric rare diseases and by identifying unmet pediatric needs in medical device development. We also plan to issue guidance for sponsors on common issues in rare disease drug development and to refine and expand the use of computational modeling for medical devices.

Strengthen communication, collaboration, and partnering. Robust cooperation within FDA, among agencies, governments and private entities is necessary to enable the exchange of information on the issues of developing treatments for pediatric rare diseases. Single entities by themselves usually don’t have sufficient resources or expertise to overcome the product development challenges posed by pediatric rare diseases.

Advance the use of regulatory science to aid clinical trial design and performance.  Regulatory science helps develop new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all FDA-regulated products. Of note, we plan to facilitate better understanding of biomarkers and clinical outcome assessments that are useful for the development of treatments for pediatric rare diseases. We also plan to further develop the expedited approval pathway for medical devices intended to treat unmet medical needs; and use FDA’s web-based resources to update and expand awareness of issues involving the development of medical products for pediatric rare diseases.

Enhance FDA’s review process. Our strategies include fostering efforts to learn patients’ and caregivers’ perspectives and incorporating this information into medical product development. We also plan to further develop and implement a structured approach to benefit-risk assessment in the drug review process and establish a patient engagement panel as part of the medical device advisory committee process.

The report notes our use of expedited programs to speed rare disease medical product development. For example, the accelerated approval program allows for approval of products to treat serious and life-threatening diseases based on an effect on a surrogate marker, such as blood test, urine marker, or an intermediate clinical endpoint, that is believed to be reasonably likely to predict clinical benefit to the patient. Under accelerated approval, further studies are required after approval to confirm that the drug provides a clinical benefit to the patient.

More than 80 new products have been approved under the accelerated approval program, and many of these have been for rare diseases. But it’s important to note that in some cases FDA exercises regulatory flexibility to approve drugs under the traditional approval pathway, rather than under the accelerated approval program. In fact, most of the recent new drug approvals for rare diseases have been approved under the traditional approval pathway because FDA has determined that the drug provides a clinical benefit to the patient. Such approvals make new drugs available to patients, and also mean that companies are not required to do confirmatory trials after approval.

FDA is committed to continuing its use of expedited programs and regulatory flexibility to speed development and approval of safe and effective drugs for all patients with rare diseases, and the strategies outlined in this plan will help us achieve a major goal of FDASIA and for our agency, which is to speed the development of therapies for children with rare diseases.

 

Jill Hartzler Warner, J.D., is FDA’s Associate Commissioner for Special Medical Programs