America’s Got Talent – Regulatory Science Style

By: Stephen Ostroff, M.D.

Veni Vidi Vici. It translates into English as “I came, I saw, I conquered.” It also happens to be the name chosen by one of the winners of the recently held America’s Got Regulatory Science Talent Competition.

America's Got Regulatory Science Event

Dr. Ostroff and FDA staff discuss projects with students from the University of Maryland CERSI.

FDA recognizes that young scientists are our future. Now in its fifth year, America’s Got Regulatory Science Talent is one of a number of initiatives FDA supports to encourage young scientists to pursue careers in the rapidly maturing field of regulatory science.

Each year, teams from the University of Maryland’s Center of Excellence in Regulatory Science and Innovation (CERSI), and the University of Rochester’s Clinical and Translational Science Institute (CTSI), compete by presenting their proposed solutions to a current challenge in regulatory science. The students identify the needs by consulting eight priority areas identified in FDA’s Strategic Plan for Regulatory Science.

Winners are decided by a panel of judges after evaluating each presentation for its quality and novelty, and the proposed solution’s potential significance and feasibility. The winning teams come to FDA to formally present their ideas and have discussions with Agency scientists who are working in their project area. The event, held on April 12th, was sponsored by the Office of Regulatory Science and Innovation (ORSI) which is located in the Office of Chief Scientist. The winning teams certainly came, saw, and conquered.

This year’s winners are:

University of Maryland CERSI

Dr. Ostroff with the University of Maryland teams

Dr. Ostroff with the teams from the University of Maryland CERSI

1st Place Team – Veni Vidi Vici

A high-visibility universal labelling system to communicate risks of hazardous drugs. Wonder if your prescription medication has some dangerous side effects that may be noted in “fine print” – or even nowhere – on the label? A universal symbol in red and yellow in a prominent place on the label is the “Veni Vidi Vici” Team’s solution.

2nd Place Team – Biomarker Boys

Platform to improve transparency for biomarker integration in Accelerated Approval pathway. Tackling a challenge experienced in this growing area of biomedical innovation, the “Biomarker Boys” created a form that facilitates transparent and structured integration of biomarkers into rare disease state drug development.

University of Rochester CTSI

Dr. Ostroff with the University of Rochester teams

Dr. Ostroff with the teams from the University of Rochester CTSI

1st Place Team – Simple English Explanation Directive (SEED)

Making clinical trial results more accessible and functional. Team “SEED” takes the incredibly complicated language that is often found when describing a clinical trial, and puts it in easy-to-understand form.

2nd Place Team – 3-Defining Patient Matched Implants

A streamlined process to test 3-D printed personalized implants. The “3-Defining Patient Matched Implants” Team decided that a quality systems approach is needed to streamline the process of validating the integrity of individual patient-matched 3-D printed implant systems. Their proposal introduces an alternative approach to the current method used in 3-D printing to ensure implants are safe for implantation.

This competition reminds us that good science makes for good regulation. And it was great to see the outside-the-box thinking and innovative approaches these contestants took in addressing some of the challenges that FDA faces with the products we regulate. It’s also a good reminder that the future of regulatory science depends on training and education – and we cannot underestimate the importance of educational activities like these.

The innovative approaches from this year’s teams also show the power of collaboration, mirroring the collaborative approach FDA takes in leveraging the brainpower of our teams of scientists, engineers, statisticians, social and behavioral scientists, medical officers, communicators, and others. The teams from the University of Maryland and the University of Rochester demonstrate just how teamwork produces great results.

Congratulations to the schools for organizing the competitions and to the FDA mentors who encouraged the competitors. Each year the quality of the work improves and I’m certain it will benefit patients and consumers over the coming years. Please check out this year’s talent –including a presentation from a freshman at Maryland. Who knows? Maybe one of these students will be FDA Commissioner some day!

To see the finalists present their innovative solutions to regulatory science challenges, visit FDA’s America’s Got Regulatory Science Talent web page.

Stephen Ostroff, M.D., is currently Acting Commissioner of the U.S. Food and Drug Administratio

FDA flickr photos from FDA’s America’s Got Regulatory Science Talent 

‘Organs-on-Chips’ Technology: FDA Testing Groundbreaking Science

By: Suzanne Fitzpatrick, Ph.D.

There are many things you might envision putting on a chip. It’s unlikely that a human organ is one of them.

Suzanne FitzpatrickBut creating human organ systems in miniature on micro-engineered chips about the size of a AA battery is a revolutionary testing technology that has captured the attention of food scientists at FDA. And FDA has a leading role in evaluating this science, designed to provide a more precise model for studying the effects of potentially harmful chemical and biological hazards in food, cosmetics or dietary supplements than is now available.

On April 11, 2017, FDA announced a multi-year research and development agreement with a company called Emulate Inc. to evaluate the company’s “Organs-on-Chips” technology in laboratories at the agency’s Center for Food Safety and Applied Nutrition, one of a number of FDA efforts to help evaluate this chip technology. The flexible polymer organ-chips contain tiny channels lined with living human cells and are capable of reproducing blood and air flow just as in the human body. The chips are translucent, giving researchers a window into the inner workings of the organ being studied.

Research will begin with a liver-chip but the agreement may expand in the future to cover additional organ-chips, including kidney, lung and intestine models. The ultimate goal is to predict how specific organs will respond to exposure to potential chemical hazards found in foods, cosmetics and/or dietary supplements with greater precision than other methods currently being used, such as cell-culture or animal-based tests.

Emulate Chip

Chip image courtesy of Emulate Inc.

Organs-on-chips have been the focus of a public-private collaboration between FDA, the federal Defense Advanced Research Projects Agency (DARPA) and the National Institutes of Health (NIH) since 2012. Millions of dollars in grants have been awarded to universities nationwide to advance this research, including Harvard University and the Massachusetts Institute of Technology. Emulate was founded by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University.

The chips were first developed to evaluate the effectiveness of drugs but have come to be seen as a potentially useful technology in our efforts to ensure the safety of the foods and cosmetics we regulate. For example, they can be put to work to see how the body processes an ingredient in a dietary supplement or a chemical in a cosmetic and how a toxin or combination of toxins affects cells, information that ultimately can be used to help assess risks to human health.

In some ways, science is like a recipe in that both can go through a number of incarnations before they work. There’s a lot of experimenting and tweaking, collaborating and comparing. And that’s what we’ll be doing at FDA with the organs-on-chips research. Science is the foundation of FDA’s decisions but many people don’t realize how much scientific research is conducted by the agency. We’re excited to be at the forefront of this ground-breaking research, which may one day be routinely used to safeguard public health.

Wondering how this Organs-on-Chips technology works? Click here.

Suzanne Fitzpatrick, Ph.D., is the Senior Advisor for Toxicology in FDA’s Center for Food Safety and Applied Nutrition

PRISM Identifies Vaccine Safety Issues

By: Azadeh Shoaibi, Ph.D., M.H.S.

The word “prism” might make you think of a triangular piece of glass that separates white light into a rainbow of colors.

Azadeh ShoaibiBut at FDA, it means a powerful, computer-based system that separates critical bits of information from vast streams of healthcare data in order to investigate adverse events and determine if there is a connection to a specific vaccine. And while the FDA prism–called Post-licensure Rapid Immunization Safety Monitoring System (PRISM)—might not have such a colorful name, it’s a bright light in the agency’s continual efforts to identify adverse effects in a timely manner.

PRISM is a cooperative effort between FDA’s Center for Biologics Evaluation and Research and its partners in the health care and medical insurance communities. It analyzes health insurance claims data from four national healthcare plans: Aetna, HealthCore (Wellpoint), Humana, and OptumInsight (United Healthcare).

Prism image

PRISM is a computer-based vaccine safety monitoring system that separates out critical information from vast streams of healthcare data. A part of the Sentinel Initiative of FDA, PRISM broadens the agency’s ability to monitor critical healthcare products in support of its mission to protect and advance public health.

Since it was first inaugurated in 2010, PRISM has made valuable contributions to public safety.

For example, FDA was able to use the system to reassure the public that there was no link between an influenza vaccine and increased risk of febrile seizure in children (convulsion or seizure brought on by a fever). Another PRISM study comprising more than 1.4 million doses of Gardasil doses found no evidence of venous thromboembolism after vaccination among females 9 to 26 years old. FDA also used PRISM to identify a link between a rotavirus vaccine (RotaTeq) and an increased risk of intussusception in infants.

These case studies, along with other information, were discussed at a public meeting in December called to discuss what the system has accomplished and how it’s used in the regulatory process. The purpose of the workshop was to describe the Sentinel Initiative (a national electronic system for medical product safety surveillance) and the PRISM program, illustrate how FDA uses PRISM for regulatory responsibilities, and discuss the future direction of PRISM, including its further integration into the regulatory review process.

Stakeholders, including manufacturers, academics, the public, and other federal agencies, who participated in the workshop had an opportunity to weigh in with their opinions about the system, discuss its limitations, and offer ideas for improving it.

PRISM is one component of FDA’s Sentinel Initiative, which monitors the safety of a variety of FDA-regulated medical products by examining information in electronic healthcare databases.

Sentinel performs what is called “active” surveillance, as opposed to “passive” surveillance. Passive FDA surveillance systems depend on industry, consumers, patients, and healthcare professionals to recognize and report suspected adverse events to an FDA web site, such as the Vaccine Adverse Event Reporting System (VAERS). This means that FDA might not become aware of potential problems related to a licensed product for months.

Unlike passive surveillance, Sentinel’s active surveillance lets FDA initiate its own studies using existing electronic healthcare data in a timely manner. Sentinel also lets FDA evaluate safety issues in targeted groups, such as children, or to evaluate specific conditions (e.g., heart attacks) that are not usually reported as possible adverse events of medical products through passive reporting systems.

So by adding an active surveillance capability to FDA’s toolbox, Sentinel broadens FDA’s ability to monitor the safety of a spectrum of licensed medical products in support of the agency’s mission to protect and advance public health.

Azadeh Shoaibi, Ph.D., M.H.S., is the Sentinel Lead at FDA’s Center for Biologics Evaluation and Research

A Shocking “Exercize”

By: Suzanne Junod, Ph.D., and John Swann, Ph.D.

Suzanne Junod and John Swann

Suzanne Junod, Ph.D., and John Swann, Ph.D., holding FDA artifacts.

In this second installment of FDA’s new history video series, the FDA’s historians venture into the “vault” to explore the Relaxacizor, originally sold in beauty salons as a device that stimulated and relaxed muscles, but subsequently marketed as a passive exercise machine.

Ads for the device assured users that they would lose weight while building muscle mass, a promise that was, of course, too good to be true. FDA took legal action against the company and by the early 1960s succeeded in having the devices removed from the market.

Keep an eye out for the reference to the TV show, “Mad Men,” which included a faux advertising campaign for Relaxacizor in the show’s first season.

Enjoy your visit to the FDA History Vault.

If you missed it, watch the first video – an introduction to the series here.

Suzanne Junod, Ph.D., and John Swann, Ph.D., are FDA Historians.

FDA: Helping Small Businesses Get Big Results

By: Brenda Stodart, Pharm.D., and Renu Lal, Pharm. D.

It is well known that small business is vital to the success of the American economy. Less known, though, is how instrumental it has been to the growth and innovation in drug development.

Brenda Stodart

Brenda Stodart, Pharm.D. Captain, United States Public Health Service, Program Director at the FDA’s CDER Small Business and Industry Assistance Program, Division of Drug Information

We may think of the pharmaceutical industry in terms of giant corporations, but the fact is that there are hundreds of small firms – with very few employees – that are developing many of the important drugs that we use every day. FDA defines a small business as one with fewer than 500 employees (including employees of affiliates), but many are much smaller.

Industry sources indicate that, over the past decade or so, more than half of the novel drugs (i.e., those not previously marketed in the United States) developed in this country and approved by FDA, have been developed by small companies. Small companies also impact the generic drug industry creating market choice, competition, and increased access. According to FDA data, of the 2,176 new and generic drug applications submitted to the agency in 2014-2015, at least 639, or about 29 percent, were submitted by firms with fewer than 500 employees.

Small companies have certain advantages. They can be nimble with decision-making and can quickly progress with new ideas. A smaller drug development pipeline allows them to focus on a single or few products. But they also have unique challenges. A small workforce tends to require employees to wear multiple hats, as opposed to their larger counterparts who typically employ teams of specialists. And because many small companies are focused on developing one drug at a time, they often operate on a “high reward-high risk” model. There is a smaller margin for error for a small company that has invested all its resources in developing one drug than for a large company that is able to spread its risk across several products it is developing simultaneously.

Renu Lal

Renu Lal, Pharm.D., pharmacist at FDA’s Division of Drug Information, CDER Small Business and Industry Assistance Program

For many years, to help level the playing field, FDA has been assisting small pharmaceutical companies to maximize their opportunities for success. The Generic Drug Forum on April 4-5, 2017, is one example of the work we do to support small businesses. Organized by FDA’s Center for Drug Evaluation and Research Small Business and Industry Assistance (SBIA) staff, representatives from a wide range of pharmaceutical companies will gather to learn about the development, testing, review, and approval of generic drugs. CDER SBIA holds at least four meetings a year as part of a series called the Regulatory Education for Industry (REdI) conferences.

REdI conferences typically attract significant international attendance (in-person or via webcast). This global reach is important, as about 80 percent of active pharmaceutical ingredients used in U.S-manufactured drugs come from more than 150 different countries. The map below shows the geographic distribution of our most recent REdI conference registrants. Thirty percent of registrants were from outside the U.S., representing 55 countries worldwide.

CDER SBIA Conference Map

International participation at CDER SBIA REdI Conference [September 2016]

Many of these companies have never submitted an application for approval to FDA. Whether new or experienced, many are very early in the drug development process. In CDER’s SBIA program, 43 percent of the companies we work with have fewer than 100 employees, and 17 percent have fewer than 10 employees.

Although the mission of CDER SBIA is to help small business, our educational products are available to the entire pharmaceutical industry. In addition to REdI conferences, SBIA also offers webinars with live question and answer sessions by FDA subject matter experts on timely topics of interest to small companies.

SBIA recently held a half-day live webinar, which featured CDER experts from the Office of Pharmaceutical Quality (OPQ) discussing specific microbiology issues. CDER SBIA also provides a variety of helpful resources including a bimonthly electronic newsletter, CDER SBIA Chronicles, an audio podcast, CDERLearn, and online tutorials developed by CDER subject matter experts. We also interact with our constituents through our presentations and exhibits at conferences, and we are always available to help out via phone and e-mail. All slides, webcasts, and documents that we develop to help small companies are posted on the CDER SBIA Learn webpage after the event. REdI conferences and all other SBIA services are available at no cost to all who wish to attend and participate, which is particularly helpful to smaller companies with limited resources.

At a time when quality manufacturing and the safety and effectiveness of drugs in development is as important as ever, CDER understands that providing support to small businesses through education and resources is vital to advancing innovation and protecting public health.

Brenda Stodart, Pharm.D., Captain, United States Public Health Service, is a Program Director at FDA’s CDER Small Business and Industry Assistance Program, Division of Drug Information

Renu Lal, Pharm.D., is a pharmacist at FDA’s Division of Drug Information, CDER Small Business and Industry Assistance Program

FDA in India – Championing a Culture of Quality

By: Mary Lou Valdez

One of FDA’s most strategic outposts is in India, the seventh largest supplier of food and second largest supplier of pharmaceuticals and biologics to the United States. The agency’s office, located in the capital, New Delhi, works to ensure the safety and security of food and the safety and efficacy of medical products exported from India to the U.S.

Mary Lou Valdez with India Office Staff

from left: Dean Rugnetta, FDA Deputy Director, India Office; Mary Lou Valdez, FDA Associate Commissioner for International Programs; Mathew Thomas, FDA Director, India Office

To achieve that goal, the India Office, directed by Mathew Thomas, conducts inspections of Indian medical products and foods facilities that export to the U.S. The office also assists and trains regulators, industry, and other stakeholders in developing and maintaining the quality, safety, and effectiveness of the FDA-regulated products they export.

It’s important for the office to consult regulatory authorities in India to build confidence in each other and to develop quality standards that both countries can trust.

I had the privilege of joining Director Thomas last month for meetings with our regulatory counterparts – the Indian Export Inspection Council (EIC), the Food Safety Standards Agency of India (FSSAI), the Drugs Controller General of India (DCGI), and the Joint Secretary of the Ministry of Health and Family Welfare.

Despite the diversity of these agencies’ mandates and priorities, a common theme coming out of these meetings was the recognition of the mutual benefits we realize by working together to enhance the effectiveness of our regulatory systems and to advance risk-based and science-based approaches to food and medical product regulation.

Along with other FDA experts, I also participated in a Global Food Safety Partnership (GFSP) Governing Council meeting and the Indian Pharmaceutical Alliance (IPA) Second Forum, titled “Towards Excellence in Quality.” Hosted by the Word Bank, the GFSP is a public private partnership, established in 2012, which brings together governments, industry, multilateral organizations, and other stakeholders in support of stronger food safety systems. Since its founding, the GFSP has worked with China, Indonesia, and Vietnam. During my visit, we had initial GFSP meetings with Indian regulators, to explore potential synergies as they look to bolster their food safety systems and maximize their investments. FDA’s India Office is well-positioned to help the Partnership and India explore how best to meet these goals.

The IPA Forum brings together CEOs of pharmaceutical firms, manufacturers, regulators, and other national and global stakeholders who have a role in shaping India’s complex and diverse manufacturing environment to produce safe, effective, high-quality medical products.

Over the past decade, the Indian pharmaceutical market has grown by nearly 14 percent and continues to experience massive growth. However, in order to fully realize the nation’s potential as an important player in the global pharmaceutical industry, India’s regulatory infrastructure must keep pace to ensure that global quality and safety demands are met. Quality issues are an ongoing challenge for the Indian pharmaceutical industry. Of 42 warning letters issued by FDA’s Office of Manufacturing Quality last year, nine went to Indian facilities. The IPA is working to communicate to its diverse members why quality matters and how to achieve it. Thus, the general theme of its Second Forum “Towards Excellence in Quality,” was an incredibly relevant topic if the global market for FDA-regulated products is to be strong and secure.

No one wants resources wasted on ineffectual development and weak processing or manufacturing systems that could actually impede product success. We all want greater competition, increased options for consumers and patients, and more affordable alternatives to comparable products.

Participants agreed that achieving quality requires regulators and industry alike to champion and advance a quality culture throughout the product life-cycle, by effectively employing the use of data and science and requiring greater transparency.

While I was in India, it was really gratifying to witness the high-esteem and trust Indian regulators and industry have for FDA, and our India Office. In turn, whether it is through their response to inspectional observations, their participation in trainings and seminars or their readiness to share strategic information, we see India committing to quality and compliance. Indian regulators and industry both recognize that a quality culture is imperative if India is to increase productivity, reduce compliance risk, lessen rework, and minimize supply interruptions that result in lost revenue and increased risks to public health.

This greater emphasis on quality will also allow India to participate more fully in existing global venues such as the International Council for Harmonisation (ICH) and the Pharmaceutical Inspection Cooperation Scheme (PIC/S) – which will enable stronger collaboration and synergies among regulators.

Quality is good for economic development, the market, and most importantly, patients and consumers everywhere. FDA’s Office in New Delhi looks forward to continued collaboration with our Indian regulatory colleagues to champion a culture of quality.

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

This is Not a Test: RMAT Designation Goes Live

By: Peter Marks, M.D., Ph.D.

The field of regenerative medicine encompasses a wide scope of innovative products including cell therapies, therapeutic tissue engineering products, human cell and tissue products, and certain combination products using such therapies. Examples include genetically-modified cellular therapies, such as chimeric antigen receptor T-cells (CAR-T cells) and human tissues grown on scaffolds for subsequent use. These products hold great promise in addressing serious unmet medical needs. For example, data from a number of different published studies indicate the potential for CAR-T cells to treat certain relapsed or refractory blood cancers.

Peter MarksRecognizing the importance of this field, Congress included several provisions related to regenerative medicine in the 21st Century Cures Act, signed into law on Dec. 13, 2016. Building on the FDA’s existing expedited programs available to regenerative medicine products, one of these provisions established a new program to help foster the development and approval of these products: Regenerative Medicine Advanced Therapy (RMAT) Designation.

Sponsors of certain cell therapies, therapeutic tissue engineering products, human cell and tissue products, and certain combination products may obtain the RMAT designation for their drug product if the drug is intended to treat serious or life-threatening diseases or conditions and if there is preliminary clinical evidence indicating that the drug has the potential to address unmet medical needs for that disease or condition. Sponsors may make such a request with or after submission of an investigational new drug application and the agency then will take action on the requests within 60 calendar days of receipt.

Sponsors of RMAT-designated products are eligible for increased and earlier interactions with the FDA, similar to those interactions available to sponsors of breakthrough-designated therapies. In addition, they may be eligible for priority review and accelerated approval. The meetings with sponsors of RMAT-designated products may include discussions of whether accelerated approval would be appropriate based on surrogate or intermediate endpoints reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of sites.

Once approved, when appropriate, the FDA can permit fulfillment of post-approval requirements under accelerated approval through the submission of clinical evidence, clinical studies, patient registries, or other sources of real world evidence such as electronic health records; through the collection of larger confirmatory datasets; or through post-approval monitoring of all patients treated with the therapy prior to approval.

The FDA’s Center for Biologics Evaluation and Research is committed to helping make regenerative medicine advanced therapies that are shown to be safe and effective available as soon as possible, particularly for patients with serious or life-threatening diseases or conditions lacking other treatment options.

We have started receiving RMAT designation requests and expect that, as with Breakthrough Therapy Designation, early and frequent communication facilitated by the RMAT designation will help reduce overall product development times. We very much look forward to continuing to work with sponsors of these products and other stakeholders to help make these exciting new therapies available to those in need.

Peter Marks, M.D., Ph.D., is the director of the Center for Biologics Evaluation and Research at the U.S. Food and Drug Administration.

Opening the FDA’s History Vault

By: Suzanne Junod, Ph.D., and John Swann, Ph.D.

Welcome to the FDA’s History Vault, which contains more than 10,000 artifacts that provide a journey through American history and document the critical role played by one of the nation’s oldest public health agencies in support of its mission to promote and protect American health.

Suzanne Junod and John Swann

Suzanne Junod, Ph.D., and John Swann, Ph.D., holding FDA artifacts.

The items featured in this new series of short videos reflect the constant changes in science and society. It is the responsibility of the FDA’s history office to document and share these changes through the collection, management, and display of these rare, and in many cases, irreplaceable items.

Besides collecting and maintaining these articles, our office embraces the broader role of history: to inform, explain, and educate, so that future decisions are made with the best available knowledge and science.

The collection includes deceptive and dangerous foods, medicines, and so-called medical products that the FDA helped remove from commerce and that led to important changes in laws and regulations.

For example, it includes:

  • a sample of Elixir Sulfanilamide, a 1937 wonder drug that was formulated with a poisonous solvent that killed more than 100 people, including many children. The 1937 disaster spurred passage of the Federal Food, Drug, and Cosmetic Act of 1938, the basic law under which the FDA still operates.
  • a can of Bon Vivant vichyssoise soup (contents removed) that sparked an outbreak of botulism in the early 1970s and significant new food protections for consumers
  • the Dalkon Shield intrauterine device, an ill-designed product that left thousands of women sterile during the 1970s, and encouraged Congress to craft legislation that specifically addressed the safety and efficacy of medical devices, and,
  • the Relaxicisor, a passive electric muscle stimulation “exercise” device first made famous during the 1950s, and again, more recently, thanks to the television show “Mad Men.”

Artifacts like these tell the story of the origins of many of our laws and regulations, the ways in which the FDA works to carry out its responsibilities to uphold them, and the interactions between the agency, its stakeholders, consumers, patients, and Congress in the interests of public health and product safety.

Other artifacts in our vault  illustrate how FDA’s essential tools, which once seemed pioneering in their time, are eventually superseded as FDA adopts new approaches in response to continuing advances in science and technology.

The first video released today harkens back to the time of the Bureau of Chemistry, the organization that preceded the FDA, when data on foods and drugs was analyzed using a novel early calculating device.

It’s worth noting that like other federal agencies, FDA also hired women to be human “computers,” an important role that was brought to greater attention in the recent movie “Hidden Figures,” which depicted three such women who worked at NASA. By the 1940’s and 1950’s, women at the FDA regularly used statistical methods to distinguish products with therapeutic merit from those “which merely had good copywriters.” Their work played an important role in the analysis of the earliest “cooperative” clinical drug trials. Of course, just like NASA, data analysis at FDA is now made possible by computers and supercomputers.

The series of videos we begin today are designed to be entertaining, informative, fun, as well as highlight some of the items in our collection securely stored in our White Oak facility. We plan to release them once a month, always on Thursday, as part of the popular social media tradition of “Throwback Thursday.” The goal is to educate and increase the understanding of the ways that the FDA has, for more than 100 years, embraced scientific advances to ensure the well-being of the American public.

We hope you enjoy your visit to “the FDA’s History Vault.”

Suzanne Junod, Ph.D., and John Swann, Ph.D., are FDA Historians.

FDA’s Commitment to Women’s Heart Health Research

By: Marsha B. Henderson, MCRP

FDA research has been especially important in helping FDA better understand cardiovascular diseases in women and the effects of drugs on women’s heart health.

Marsha HendersonKnowing that heart disease is the leading cause of death for women, our Office of Women’s Health (OWH) has been committed to using a significant portion of our limited funds to support cardiovascular research from the very beginning of our research program in 1995. We’ve accomplished that by working across several FDA Centers to support studies on issues ranging from sex differences in cardiac interventions to the cardiotoxicity of breast cancer drugs.

One of our earliest funded projects examined the connection between certain drugs and Torsade de Pointes (TdP) – a rare but dangerous heart arrhythmia that can lead to sudden death. Women are more likely than men to have this heart rhythm problem. FDA has been leading an effort to evaluate better ways to screen drugs for their potential to cause this rhythm problem. This is made possible in part because drugs that cause TdP almost always prolong the QT-interval on the electrocardiogram (ECG), which measures the heart’s electrical cycle.

On the heels of Heart Health Month, I wanted to highlight the history of FDA research on QT prolongation and demonstrate the ways ongoing collaborations across FDA research programs are helping to advance policies and projects to protect women’s heart health.

Early Years: Understanding the Sex Differences

The exact reason for the higher rate of drug-induced TdP in women is unknown. OWH funded studies to help FDA better understand the mechanism of the sex differences in drug-induced QT prolongation. OWH also funded research within the Center for Drug Evaluation and Research (CDER) enabling post-market drug analysis to better recognize drug safety effects in women.

Supporting the Development of FDA Guidance

FDA QT Story GraphicBuilding on the previous studies, OWH partially funded additional research on metabolic drug-drug interactions that contribute to QT prolongation. This research contributed to FDA guidance on the assessment of the QT prolongation potential of drugs for both men and women. As part of this guidance, FDA recommended that drug sponsors conduct a comprehensive study, called the Thorough-QT (TQT) study when seeking FDA approval of a new drug. The TQT study, implemented in 2005, has been an effective screening tool. Although certain commonly used drugs, such as antihistamines and antibiotics, had to be withdrawn from the US market because of drug-induced QT prolongation concerns, no such withdrawals have been necessary since 2005.

Moving Forward: Improving Prediction and Prevention

Although the current FDA guidelines are very useful for identifying QT prolonging drugs, not all QT prolonging drugs cause TdP. OWH is currently partnering with CDER to sponsor studies to better screen for the subset of QT-prolonging drugs that have lower or no risks for TdP. This new research has the potential to enhance drug development and safety for both women and men by improving the accuracy of the evaluation of a drug’s potential to cause heart rhythm problems, and by providing this information earlier in drug development.

Improving women’s heart health is an ongoing challenge. So, I encourage you to visit FDA’s website to learn about the research OWH is currently funding and other FDA research programs.

Marsha B. Henderson, MCRP, is FDA’s Assistant Commissioner for Women’s Health

2016: A Record-setting Year for Generic Drugs

By: Kathleen “Cook” Uhl, M.D.

Over the last 10 years, generic drugs have saved the U.S. healthcare system about $1.68 trillion. I’m pleased to report that 2016 was a record-setting year for FDA’s generic drug program, a result that will help generate further cost savings for American consumers, while assuring the quality of these generic products.

Kathleen "Cook" UhlAnd the timing couldn’t be better amid concerns about rising drug prices.

Last year, FDA’s Office of Generic Drugs (OGD) in the Center for Drug Evaluation and Research generated the highest number of approvals in the history of FDA’s generic drug program – more than 800 generic drug approvals, including both full approvals and tentative approvals. (Tentative approvals are granted to applications ready for approval from a scientific perspective, but cannot be fully approved due to patents or exclusivities on the brand-name drug.) Last year’s performance surpassed 2015’s previous record of 726. Many of these approvals were for “first-time generic drugs,” meaning the introduction of a generic counterpart for a brand-name product for which there was previously no generic. That’s typically the first step towards lower drug prices because multiple generic versions of brand-name drugs drive price competition, leading to more affordable drugs.

An important factor in OGD’s record-setting performance has been the Generic Drug User Fee Amendments (GDUFA) of 2012, a landmark legislation negotiated with the generic drug industry, which completely reshaped the generic drug program at FDA. Among other things, it authorized funds for FDA to hire additional reviewers, modernize the review of generic drug applications, expand facility inspection capabilities, advance IT infrastructure for generic application review, and perform other regulatory actions. This is the first time Congress has authorized a user fee program specifically for generic drugs. It’s a five-year program, up for renewal October 1, 2017. GDUFA I has challenged OGD to reach a variety of goals while maintaining or improving the quality of the review process.

2016 Office of Generic Drugs Annual Report CoverWith the assistance of many other offices throughout FDA, OGD is on track to meet, or has already met, all of our GDUFA commitments. In addition to increased approvals and tentative approvals, FDA improved communications processes to alert industry to deficiencies in their applications, which reduces the number of review cycles and supports faster approvals.

We also are making a significant effort to spur generic drug development. For example, GDUFA Regulatory Science priorities contribute valuable research to generic drug development. Our efforts are geared to helping the generic drug industry develop validated scientific methods for demonstrating bioequivalence and assuring therapeutic equivalence to the brand-name counterpart. We are translating the results of these scientific efforts into generic drug product development via recommendations for specific drug products, which assist the generic drug industry during product development.

These are just a few of the exciting developments for 2016. Our annual report tells the rest of the story.

Despite these developments in 2016, a lot remains to be done as we approach the end of our first-ever five-year GDUFA program. We look forward to working with industry, the research community, physicians, lawmakers, and other stakeholders to help American consumers and advance use of generic drugs in our nation’s health care system.

Kathleen “Cook” Uhl, M.D., is FDA’s Director, Office of Generic Drugs in the Center for Drug Evaluation and Research