The Race to bring Penicillin to the Troops in WWII

By: John P. Swann, Ph.D.

John SwannThis Veterans Day we remember that nearly 75 years ago dozens of American academic, commercial, nonprofit, and governmental institutions – including FDA – joined together in a race to provide a promising but complex and unstable medicine to troops fighting in World War II — penicillin. Knowing that infection is the major killer in wars, not battle injuries, their goal was to help turn a British discovery into a crucial wartime medical contribution and what would become an indispensable therapeutic agent long after that conflict ended.

Many people are familiar with the story of Alexander Fleming’s 1928 discovery of a Penicillium mold that had contaminated — and surprisingly destroyed — his cultures of pathogenic organisms.

The strain of Penicillium notatum that Fleming discovered at St. Mary’s Hospital in London

The strain of Penicillium notatum that Fleming discovered at St. Mary’s Hospital in London.

Though Fleming and several others in the next decade studied the mold filtrate, known as penicillin, it was Howard Florey and his colleagues at Oxford who uncovered the drug’s chemotherapeutic potential. Their work began with studies in mice in May 1940 and transitioned to a handful of clinical cases nine months later. However, the drug was difficult to purify. Also, it presented an immense challenge to produce in sufficient quantities for study, and with Britain under siege firms there were too involved in other aspects of the war effort to offer much assistance. So Florey and a colleague came to the U. S. in the summer of 1941 for help.

Northern Regional Research Lab

A meeting of NRRL staff in the 1940s (courtesy of the American Institute of the History of Pharmacy).

Among the first sites they visited was the Department of Agriculture’s Northern Regional Research Laboratory (NRRL) in Illinois, which had extensive experience in fermentation work, and from there they contacted several drug and chemical companies to drum up support.  Americans quickly combined forces to tackle the challenge. The federal Office of Scientific Research and Development (OSRD), the federal entity that organized and facilitated investigations to support the war effort, arranged to act as a clearing-house for the latest research on chemical and other studies of penicillin, exchanging data with dozens of organizations in the U.S. and Britain. NRRL developed several production modifications that increased the yield of penicillin by 100 fold.

Penicillin Moisture Testing

An FDA analyst in the 1950s carries out part of the procedure in testing penicillin for moisture content.

FDA’s first experience with the potential wonder drug was around September 1942, when the NRRL Director approached FDA about testing the antibacterial effectiveness of a small quantity of penicillin. A year later, enough of the drug had been produced to confirm in 200 patients what the early results at Oxford had suggested, and penicillin was ready to enter the war. First, however, OSRD asked that FDA certify every lot produced by the half-dozen or so manufacturers, a task the agency also performed for insulin under statutory authority that began in 1941. Six FDA technicians certified samples for potency, absence of fever-producing contaminants, toxicity, sterility, and optimum moisture, which can affect the drug’s stability. So scarce was penicillin that companies always reconditioned the occasional rejected lot rather than destroying it.

By the end of the war, some of the participating firms had increased purity of the drug from the Oxford group’s one percent to about 85 percent. Penicillin was not only more potent, it was also more abundant, its production having increased by a factor of 500 from 1943 to 1945. In fact, by 1945 the output of penicillin, formerly under severe restriction outside of military and scientific use, was now available for most civilian needs as well. In a few years the cost of producing penicillin had decreased so much that the glass used to store ampules of the drug cost more than the drug itself. FDA’s wartime work was codified in the Penicillin Amendment of 1945, which mandated FDA’s certification of penicillin and, through subsequent laws, most other antibiotics — a responsibility that continued for nearly four decades, when the need for government testing no longer existed based on industry’s record of production.

But it all started with an international effort to provide a lifesaving drug to the armed forces, bringing together all sorts of scientific and medical institutions, including FDA. Like so many others participating in this collaboration on a scale unseen up to that point, FDA played a small but critical role to support our troops at this time of global crisis.

John P. Swann, Ph.D., is an FDA Historian

Consumer expenditure on FDA regulated products: 20 cents of every dollar

By: Sheri Walker, Ph.D., and Clark Nardinelli

Sheri Walker

Sheri Walker, Ph.D., is an FDA Senior Economist

One of the much-cited statistics about FDA is this: that FDA-regulated products account for about 20 cents of every dollar of annual spending by U.S. consumers. Add up 20 cents of every dollar and it amounts to more than $2.4 trillion in annual consumption that includes medical products, food and tobacco.

Our staff of 34 economists comes up with this estimate of FDA’s impact every year. We think it helps the public put in perspective the sheer scope of FDA’s responsibilities, especially when you recognize that FDA is only one of dozens of governmental agencies.

We largely rely on personal consumption expenditure data collected by the Bureau of Economic Analysis (BEA) every year to calculate total consumer spending in each of the major FDA product categories. These product categories include food (except alcohol and meat products regulated by USDA), drugs, medical devices, cosmetics, dietary supplements, and (since 2009) tobacco products.

Clark Nardinelli

Clark Nardinelli is FDA’s Chief Economist

Some BEA expenditure categories include more than one FDA product area. For example, biologics and dietary supplements are included in the expenditure for pharmaceutical and medical products (although, legally, dietary supplements are food). Cosmetic products are captured under the BEA expenditure category for personal care products. Pet food and animal drugs are estimated as a percentage of the pet-related products category. The estimate for medical device products is derived using data from the therapeutic equipment products category from the BEA and data from the Annual Survey of Manufacturers collected by the U.S. Census Bureau.

Food products represent the largest share of spending on FDA products, accounting for approximately 11 cents of every dollar of consumer spending. Without the addition of tobacco products, spending on FDA-regulated products would be slightly less than 20 cents per dollar.

20 cents pie chartWe know that some people say FDA oversees 25 cents of every consumer dollar. Maybe it’s an urban legend – or maybe it harkens back to decades ago. The 20 cents (or 20 percent of spending on consumer goods and services) has held steady over the past 5 years. Americans used to spend a much higher proportion of their income on food – with over 25 cents of every dollar going to food during World War II. But since then the share of food and tobacco in total consumer spending has been falling steadily while the share of consumer spending devoted to medical products has been steadily climbing. Whether those trends will continue, and whether FDA’s 20 cents will hold steady for the next 5 or 50 years, is impossible to predict.

Sheri Walker, Ph.D., is an FDA Senior Economist, and Clark Nardinelli is FDA’s Chief Economist

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

Where We Are/What We Have Done – Two Years After Releasing Our FDASIA 907 Action Plan

By: Janice Soreth, M.D.

Since it’s been more than two years since FDA unveiled its Action Plan to advance the inclusion of diverse populations in clinical trials, we’d like to update you on how much we have accomplished, and acknowledge that continued commitment is critical in order to build on this foundation.

Janice SorethThe Congressional mandate under Section 907 of the FDA Safety and Innovation Act of 2012 required FDA to develop a report examining the extent to which various demographic groups were included in clinical trials and their outcomes reported in labeling for medical products for which applications were submitted to FDA. The legislation also required FDA to develop an Action Plan based on the report findings and input from stakeholders, issued in August 2014. The Action Plan identified 27 discrete actions for FDA to take within the three priority areas: improving data quality, encouraging greater clinical trial participation, and ensuring more data transparency.

As we discussed at our public meeting on February 29th, we have made progress on nearly every one of our action items and we continue to make strides.

In June 2016, FDA issued the draft guidance, “Evaluation and Reporting of Race and Ethnicity Data in Medical Device Clinical Studies.” We are also updating the 2005 “Guidance for Industry Collection of Race and Ethnicity Data in Clinical Trials.”

Our popular Drug Trials Snapshots, providing information about who participated in clinical trials supporting FDA-approved drugs and biologics, have now been posted on some 75 products. This innovative program developed by our Center for Drugs Evaluation and Research also highlights whether there were any differences in the benefits and side effects among sex, race, and age groups

We have significantly advanced efforts to raise clinical trials awareness. FDA’s Office of Women’s Health instituted a new initiative on “Diverse Women in Clinical Trials” that is disseminating consumer resources in English and Spanish and tools for clinical researchers in partnership with NIH’s Office of Research on Women’s Health. Our Office of Minority Health developed a tool kit and posted several public service announcements on FDA’s YouTube channel aimed at engaging patient participation. And we are currently reviewing the public comments from a range of organizations that we received to the public docket that was opened at the time of the public meeting.

Finally, I want to announce that I recently took over the chairmanship of the steering committee charged with implementing this plan. I am currently the Acting Associate Commissioner for Special Medical Programs, which has oversight of our advisory committee programs, combination products, and pediatric and orphan products programs among other responsibilities. Since joining FDA as a primary medical reviewer 25 years ago, I have served as CDER’s director of the division of Anti-Infectives and Ophthalmology and most recently spent five years in London as Deputy Director of the FDA Europe Office and Liaison to European Medicines Agency.

As we look back at our accomplishments, we believe that transparency in reporting about clinical trial inclusion will make a difference in encouraging broader demographic diversity and want to thank the former chair, Barbara Buch, M.D., of CBER, for her accomplishments. Going forward, I encourage you and all of our key stakeholders – patient and disease advocates, health professionals, and industry to continue partnering with us to advance this important work in ensuring demographic diversity and representation.

Janice Soreth, M.D., is Chair of the FDA Safety and Innovation Act Section 907 Steering Committee and the Acting Associate Commissioner for Special Medical Programs

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

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

Have a Problem? Contact the New Ombudsman in the Office of Regulatory Affairs

By: Melinda K. Plaisier

Melinda PlaisierWhether we are inspecting your facilities, sampling your products, or conducting investigations, the primary goal of FDA’s Office of Regulatory Affairs (ORA) is to protect the public. But I understand the impact our actions can have on you, so I am committed to making ORA’s processes as transparent as possible and quickly addressing problems you may encounter.

That’s why I’m happy to announce a new resource: an ORA ombudsman who can help you with unresolved concerns. While you may continue to bring issues to my staff, Ombudsman Jessica Zeller is dedicated solely to helping you with assessing and resolving problems.

Jessica, who has worked in both industry and government, understands that FDA’s perspective is often different from that of industry and other stakeholders. Her experience makes her an ideal candidate to carry out two primary objectives:

  • To informally and in an unbiased manner, find solutions, when possible, to problems that arise with our external partners, including industry, other governmental agencies, and consumers.
  • To improve communications between ORA employees and stakeholders through outreach and education, helping both sides become more aware of each other’s needs.

“Understanding the pressures that each side faces are critical to working out solutions and allaying fears,” says Jessica. “I intend to hear what you are saying and feel what you are feeling. I will not always be able to get you what you want, but I promise you will have an opportunity to share your concerns, and I will attempt to achieve the best solution possible.”

Although Jessica reports directly to me, and ORA leaders will continue to make final decisions, Jessica is an unbiased third party who will consider and work on your concerns. You may contact her by phone or email, and she will keep conversations as confidential as possible within the limits of the law.

Jessica gained her expert knowledge from more than a decade of work in FDA regulation. During her eight-year tenure at FDA, from 2004 to 2013, she served in the Office of the Chief Counsel and as deputy director of the Office of Compliance and Enforcement in the Center for Tobacco Products. From 2013 until she returned to FDA late last year, Jessica was in-house counsel for Proctor & Gamble. She also previously worked as a congressional staffer, earned a law degree and a master’s degree in bioethics from the University of Virginia, and a bachelor’s degree in biology.

The International Ombudsman Institute defines an ombudsman as a person of prestige and influence who operates with objectivity, competence, efficiency, and fairness. We are proud that Jessica fits that lofty definition so well. I encourage you to reach out to her when issues remain unresolved.

Melinda K. Plaisier is FDA’s Associate Commissioner of Regulatory Affairs

Launching a New Natural History Grants Program: Building a Solid Foundation for Rare Disease Treatments

By: Katherine Needleman, Ph.D. and Gumei Liu, M.D., Ph.D.

Today, on Rare Disease Day 2016, FDA’s Office of Special Medical Programs/Office of Orphan Products Development (OOPD) is proud to announce the launch of a new grants program to fund natural history studies with the hope of bringing new and important diagnostics and therapeutics to patients with rare diseases.

Kathy Needleman

Katherine Needleman, Ph.D., is the Director of the Orphan Products Grants Program of FDA’s Office of Orphan Products Development

A rare disease, by definition, affects fewer than 200,000 individuals in the United States. Its impact, however, is far from rare. Altogether, about 7,000 known rare diseases affect about 30 million Americans. Yet the vast majority of rare diseases do not have adequate diagnostic tools or treatments.

Developing such diagnostics or treatments — whether it’s a drug, biologic, or medical device — has been compared by many to building a house. Both require a solid, sound foundation. For any rare disease treatment development program, that foundation consists of having a thorough understanding of the natural history of a disease.

How do you define the natural history of a disease? Think about it as the course a disease takes – from the time of its onset, progressing through its pre-symptomatic phase and clinical stages, to the end of the disease. Insight into a disease’s natural history can help lead to better, more well-designed trials that can accelerate the development of life-saving diagnostics and therapeutics.

Gumei Liu

Gumei Liu, M.D., Ph.D. is a reviewer and grant project officer in FDA’s Office of Orphan Products Development

A lack of understanding of the natural history is often a major obstacle to developing life-saving products for patients with rare diseases. Without it, it becomes very difficult to decide what to study, know what to look for within a study, and capture the data necessary for approval of a treatment or even a cure.

OOPD’s new Natural History Grant Program is intended to provide much needed support and complement ongoing efforts to help change the trajectory of rare disease product development. The funded studies should help characterize the natural history of a rare disease or condition, identify genotypic and phenotypic subpopulations, and develop and/or validate clinical outcome measures, biomarkers, and companion diagnostics.

There are several ways to conduct natural history studies. They can look back in time (retrospective), look ahead (prospective), or be a survey study (collection of data through questionnaires). Each has its pros and cons and the method will to a great extent depend on what we know about a specific rare disease and the currently available treatment options.

Patient advocacy groups can and do play a critical role in collecting natural history data as is highlighted in FDA’s video discussion (watch video below) on natural history studies featuring perspectives from patient advocates. Often what prevents organizations, like patient advocacy groups, from conducting natural history studies is funding. And that’s where the grants program can make a difference.

The Orphan Products Natural History Grants Program is open to funding all types of natural history studies that are appropriate for the rare disease being studied and can aid in development of diagnostics and treatments. There are two funding levels and durations that will be offered:

  • A maximum of $400,000 in total costs per year for up to five years for prospective natural history studies involving clinical examination of affected individuals; and
  • A maximum of $150,000 in total costs per year for up to two years for retrospective natural history studies or survey studies.

The Orphan Products Natural History Grants Program is built upon OOPD’s Orphan Products Grants program that was established by the Orphan Drug Act more than 30 years ago and which has typically funded clinical trials. OOPD has successfully utilized its budget to help bring over 50 products to market with that clinical trial grant program.

We hope that this new Orphan Products Natural History Grants Program will help build the important foundation necessary to accelerate the development of life-saving diagnostic and treatments for the many rare disease patients who need them.

Katherine Needleman, Ph.D., is the Director of the Orphan Products Grants Program of FDA’s Office of Orphan Products Development

Gumei Liu, M.D., Ph.D. is a reviewer and grant project officer in FDA’s Office of Orphan Products Development

FDA Offers Free, Continuing Education Course to Help Health Care Providers Understand ‘Biosimilars’

By: Leah Christl, Ph.D.

You may have heard about a new category of products called “biosimilars.” What are biosimilars and how do they relate to biological products already widely in use?

Leah ChristlBiological products derived from living organisms can treat patients with cancer, chronic kidney disease, rheumatoid arthritis, inflammatory bowel disease, and other serious conditions. Biological products that are “biosimilar” to, or “interchangeable” with, an already-approved FDA biological product (an FDA-licensed reference product) are one way to improve access and increase treatment options at potentially lower cost for our nation’s health care system.

These products are licensed through a new pathway created in the United States in 2009. FDA is well aware that health care professionals–including prescribers, the nurses who will administer them, and the pharmacists who will dispense them–need to understand how these drugs work and how they are intended to be used.

To that end, FDA has developed a free, Continuing Education Course for health care professionals – titled, FDA Overview of Biosimilar Products – to help them strengthen their knowledge and understanding of biosimilars and interchangeable products. Biosimilars and interchangeable products, for instance, are not generic products, and this education course will help health care professionals fully appreciate the distinction.

There’s a growing interest in biosimilars and interchangeable products in the pharmaceutical industry. The first biosimilar in the U.S. was approved in 2015. It boosts the production of white blood cells and helps to ward off infection in patients receiving strong chemotherapy for some tumors. FDA is reviewing several other marketing applications for proposed biosimilar products.

This course also will help health care professionals understand how a biosimilar can be prescribed and dispensed, and how and when an interchangeable product can be substituted for another biological product.

The program will inform healthcare professionals about the development process and approval pathway for biosimilars and interchangeable products. It also includes information about FDA’s general review process for these products that will help attendees gain a better understanding of the relationships between biosimilars and interchangeable products.

The course is available to health professionals on FDA’s CDERLearn Website, and can be completed on a tablet for those on the go and not at their desktop computer.

Leah Christl, Ph.D., is the Associate Director for Therapeutic Biologics in the Office of New Drugs, at the Center for Drug Evaluation and Research at FDA