Reducing Preventable Harm from Medications: Too Big for FDA to Do Alone

By: John J. Whyte, M.D., M.P.H.

Sometimes a drug can be used exactly as FDA approved it, taken just the way a doctor prescribed it, and a patient can still experience adverse events. When it comes to drugs, not all risks are known – even after approval.

John WhyteSadly, however, harm from medications also may come from known risks that could have been prevented. The Institute of Medicine (now called the National Academy of Medicine) estimated that at least 1.5 million preventable adverse drug events occur within our health care system each year. It’s a complex system where safety issues can arise at any turn.

Among the many challenges, prescribers and other providers often struggle with the intricacies of today’s health care system, patients can have difficulty following detailed directions, and manufacturers must carefully package and label their products to avoid confusion and misunderstanding for how they are used.

Even giving a child a dose of acetaminophen, the commonly-used over-the-counter pain reliever and fever reducer, can lead to tragic results. The product is available in a strongly concentrated form for infants so they can take a very small amount, as well as a much weaker form for older kids to swallow by the teaspoonful. Unfortunately, over the years, some parents have accidentally given their infants a full teaspoonful of the stronger concentrated form, resulting in serious liver damage and even death.

Safe Use blog imageReducing preventable harm from medications is a big part of FDA’s mission. It requires teamwork across all of health care and the medication manufacturing, distribution, and delivery system.

As one of many ways we facilitate that teamwork, FDA’s Center for Drug Evaluation and Research’s Professional Affairs and Stakeholder Engagement Staff is hosting a one-day public meeting on June 15, 2017, called “Safe Use Symposium: A Focus on Reducing Preventable Harm From Drugs in the Outpatient Setting.”

We’ll gather with patients, caregivers, prescribers, pharmacists, manufacturers, distributors, and others to discuss sources of preventable harm from drugs in the outpatient setting. Attendees will consider situations such as the use of inappropriate medications in certain age groups, the use of drugs that interact with one another, and unintended exposures of dangerous medications to children.

Those attending will include representatives from:

  • Federal agencies such as the Drug Enforcement Agency, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, and the Centers for Medicare and Medicaid Services;
  • State regulatory bodies, including professional licensure and oversight boards;
  • Healthcare insurers; and
  • Patient advocacy organizations.

During this symposium, we want to generate ideas for specific solutions to reduce preventable harms and discuss how to evaluate the ideas’ effectiveness. These new ideas for future research can be funded by grants from FDA’s Safe Use Initiative. A variety of important research projects have been completed and FDA offers new opportunities on an ongoing basis.

There is no registration fee but early registration is recommended because seating is limited. More information about registration is available online.

We encourage all parties interested in the safe use of medications to attend. Some jobs, such as reducing the many forms of preventable harms from medication, are too big for one organization. It truly requires a communal and collaborative effort for success.

John J. Whyte, M.D., M.P.H., is Director of Professional Affairs and Stakeholder Engagement at FDA’s Center for Drug Evaluation and Research

FDA and NIH Release Final Template for Clinical Trial Protocols

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

A little more than a year ago, FDA and NIH announced the availability of a draft template for investigators to use when organizing clinical trial protocols, which are essentially roadmaps for conducting a clinical trial.

Peter MarksToday, we are excited to announce that the NIH-FDA Joint Leadership Council has issued a final version of the template, a development which is likely to contribute important efficiencies to the process of protocol development, saving medical product development time and money.

The final version is intended for clinical investigators who are writing protocols for phase 2 and phase 3 NIH-funded studies requiring investigational new drug or investigational device exemption applications, but could also be helpful to other investigators conducting studies of medical products that are not regulated by FDA. It provides both instructional and sample text and reflects input from the public, consisting of nearly 200 comments from over 60 individuals. Importantly, it also has been harmonized with a separate protocol template that was recently developed by the private sector organization, Transcelerate Biopharma, for industry-sponsored research.

Clinical trial protocols are critical components of any medical product development program, describing trial objectives, trial design, methodology, statistical considerations, and trial organization.

Having a standard protocol format will facilitate review of protocols by regulators and others (e.g., institutional review boards). We believe that the template will help investigators prepare protocols that are consistent and well organized, contain all the information necessary for the clinical trial to be properly reviewed, and follow the International Conference on Harmonisation (ICH) E6 Good Clinical Practice guidelines. By clarifying expectations, the template will contribute important time and money-saving efficiencies.

Guidance is available from FDA on the content that should be included in a protocol to help ensure human subject protection and high data quality, but the guidance does not describe a standardized format for presenting this information. Placing relevant information in a standardized location in a clinical trial protocol can expedite the development and review of protocols thus enabling a quicker start of a clinical trial, potentially leading to more timely completion of studies and getting important new treatments to patients more quickly. What’s more, with the increased complexity of clinical development, such as use of combinations of different medical products, it is more important than ever that investigators understand protocol development expectations and capture important components right from the start.

NIH, which supports and conducts biomedical research, and FDA, which evaluates the safety and effectiveness of medical products and depends on high-quality research to inform its decisions, agreed that developing a protocol template would be an excellent opportunity to help improve the design of clinical trials. Our agencies believe that the availability of this template and accompanying instructional information will be very useful to investigators in creating well-organized, high-quality protocols — a benefit to everyone involved in medical product development.

Peter Marks, M.D., Ph.D., is the Director of FDA’s Center for Biologics Evaluation and Research

Working to Raise Awareness and Reduce Health Disparities

By: Jonca Bull, M.D.

Minority Health Month imageApril is National Minority Health Month and this year’s theme is “Bridging Health Equity Across Communities.”

FDA’s Office of Minority Health (OMH) is committed to the HHS mission of advancing health equity, and our office works year-round to advance FDA’s message of ensuring the safety and efficacy of our nation’s food supply and medical products to all communities, but with a focus on minority groups. The first HHS Office of Minority Health was established nearly three decades ago and FDA’s own office came into being in 2010.

Jonca Bull, M.D., is Director of FDA’s Office of Minority HealthIn the intervening years, we have made significant progress. But we are reminded daily that there is still more to be accomplished in the fight to reduce and eliminate health disparities.

Today, minority communities and those at the lower socioeconomic rungs still remain disproportionately burdened by chronic disease and are much more likely to succumb to certain illnesses.

Within the past year, we have worked diligently to connect our communities to resources to help educate and raise awareness about these issues. Highlights from our two programmatic teams include:

Outreach and communications –

Released English and Spanish language videos to encourage minority participation in clinical trials, with the most recent video being released this month;

  • Worked closely with the health fraud team in the Office of Regulatory Affairs to raise awareness about tainted and fraudulent products that target some ethnic groups;
  • Exhibited and presented at nearly a dozen conferences throughout the year; and,
  • Spearheaded the agency’s Language Access plan to help ensure that FDA materials are available to all consumers in their native language.

Research and Collaboration –

  • Worked with FDA centers and external partners to support research studies around minority health and health disparities. Projects included: Racial Disparities in Multiple Myeloma, Underutilization of Generic Medications in Underserved Patients, and Advertising and Promotional Labeling in Adult Immunization Disparities.
  • Funded multiple Centers for Excellence in Regulatory Research Science and Innovation (CERSI) projects with Georgetown University (Targeting triple negative breast cancer in African American women), University of California San Francisco/Stanford (Safer Labeling of Pediatric Medications: Reducing Literacy-related Health Disparities among Chronically Ill Adolescents), Johns Hopkins University (Workshop Clinical Trials: Assessing Safety and Efficacy for a Diverse Population);
  • Supported a genomics and health disparities fellow at Harvard University School of Medicine; and,
  • Hosted more than half a dozen fellows and pharmacy students from Howard University, the University of Washington, and Florida Agricultural and Mechanical University, among others.

In addition, last fall, OMH issued a draft guidance document titled, Collection of Race and Ethnicity Data in Clinical Trials-Guidance for Industry and FDA Staff with the goal to ensure that subpopulation data is collected consistently by industry. This document outlines FDA’s expectations for, and recommendations on, the use of a standardized approach for collecting and reporting race and ethnicity data in submissions for clinical trials for FDA regulated medical products conducted in the United States and abroad. We also hosted a webinar to walk through the document.

Working collaboratively within FDA and with external stakeholders, we will continue promoting and protecting the health of diverse populations through research and communicating of science information that addresses health disparities.

Jonca Bull, M.D., is FDA’s Assistant Commissioner for Minority Health, Office of Minority Health

For more information read: The FDA Supports Research to Reduce Health Disparities

FDA Takes Action Against Fraudulent Cancer Products

By: Donald D. Ashley, J.D., and Douglas Stearn, J.D.

A cancer diagnosis often provokes a sense of desperation. Unfortunately, rogue operations exploiting those fears peddle untested and potentially dangerous products, particularly on the internet. FDA responds in two ways: with compliance and enforcement actions against unscrupulous companies and with consumer education to decrease demand.

Donald Ashley

Donald D. Ashley is director of the Office of Compliance in FDA’s Center for Drug Evaluation and Research

Every one of FDA’s product centers and the FDA’s Office of Regulatory Affairs (ORA) has staff devoted to rooting out health fraud scams. These teams regularly investigate consumer complaints and monitor the stores and online marketplaces where such products are advertised. Recently the Center for Food Safety and Applied Nutrition and the Center for Drug Evaluation and Research teamed up with ORA to search the Internet and social media for bogus products that falsely claim to diagnose, treat or cure cancer, a violation of federal law.

It was a challenging assignment.

Those marketing fraudulent products – primarily or exclusively on the internet – attempt to subvert compliance and enforcement efforts by changing the names of their products, their companies, and/or their websites.

Nevertheless, today we are announcing that 14 companies peddling bogus cancer cures have received warning letters from FDA. Warning letters are a primary compliance tool that FDA uses to address violations of the Federal Food, Drug and Cosmetic Act.

Douglas Stearn

Douglas Stearn is director of the Office of Enforcement and Import Operations within FDA’s Office of Regulatory Affairs

These companies used slick ads, videos, and other sophisticated marketing techniques, including testimonials about miraculous outcomes. Often a single product was promoted as a treatment or cure for multiple diseases in humans and animals. Hoping to skirt the law on a technicality, some sellers made false claims and then in small print provided a disclaimer that their products are not intended to diagnose, treat, cure or prevent any disease.

Making such obvious claims and then saying later that you are not doing so might seem clever, but the technique does not comply with federal laws intended to protect public health.

Each of these companies has 15 working days to respond with a plan to come into compliance with the law.

If necessary, FDA also has authority to take further action, including criminal prosecutions, product seizures, and injunctions. Companies that fail to come into compliance after receiving a warning letter can for example, face criminal prosecution and court-ordered decrees that require them to recall products and get written permission from FDA before resuming operations. The violations identified in the warning letters, if not corrected, are punishable by up to one year in federal prison, five years’ probation and a fine of either $100,000 or twice the gain from the offense.

FDA works diligently to monitor and take action against companies marketing unsafe products online and has issued more than 90 warning letters over the past decade to companies marketing fraudulent cancer products.

image of fake cancer curesConsumer education is critical in combating the dangers posed by these types of products. Thus, our recent cancer fraud initiative includes a push to raise consumer awareness and thereby decrease demand. Efforts include contacting media outlets that reach millions of consumers, posting a Consumer Update article at FDA.gov, and encouraging consumer groups, trade associations, and others to help us spread this important “buyer beware” information.

The message to consumers is this: These products are untested. Some contain ingredients that may be a direct risk to your health. The ingredients may interact in a dangerous way with professionally-prescribed treatments. They are not a substitute for appropriate treatments. Using these products can waste your money, and, more importantly, endanger your health.

Donald D. Ashley is director of the Office of Compliance in FDA’s Center for Drug Evaluation and Research

Douglas Stearn is director of the Office of Enforcement and Import Operations within FDA’s Office of Regulatory Affairs

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 

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

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

FDA Drug Trials Snapshots and Diversity When Testing New Drugs

By: John J. Whyte, M.D., M.P.H.

Did you know that some drugs affect men and women differently? For instance, women are often prescribed only half the dose that men take of the sleep medication, Ambien (zolpidem). Race and ethnicity also make a difference. One type of drug commonly used to treat high blood pressure, angiotensin-converting enzyme (ACE) inhibitors, has been shown to be less effective in African American patients than in white patients.

John WhyteThese are just two examples of why it’s important to test drugs on the appropriate patient populations. This is especially true for drugs we call “novel drugs,” new medicines that have never been used before in the U.S. marketplace. Over the past two years, FDA’s Center for Drug Evaluation and Research (CDER) approved 67 novel drugs. So it’s no surprise that in recent years, representation in clinical trials of certain subgroups, such as people of different ages, races, ethnic groups, and genders, has become of growing interest.

To help keep the public better informed, CDER piloted the Drug Trials Snapshots program two years ago to provide easily accessible information about patient representation in clinical trials. Snapshots show who participated in the studies used to approve a novel drug and organize information from the studies by sex, race, and age subgroups. Further, they provide a brief narrative on whether there were any reported differences in how the drug worked by subgroup and whether there were any reported differences in side effects among the different groups. Since January 2015, CDER has published a Drug Trials Snapshot within a month of each novel drug’s official approval date.

Just this week, we released our Drug Trials Snapshots Summary Report, which provides a yearly average of the diversity of participants in the clinical trials for novel drugs approved in 2015 and 2016. It shows for example, that women were represented at a rate of 40 percent in 2015 and 48 percent in 2016 and African Americans were represented at a rate of 5 percent in 2015 and 7 percent in 2016. The report also lays out the extent to which safety and effectiveness data are based on demographic factors such as sex, age, and race. At its heart, this report is an effort to be transparent – to provide information to the public, and actually show the number and participation of men and women, of various races and age groups within the clinical trials. Being able to share more information and facts will help us to facilitate a thorough and robust discussion about clinical trial demographics. Now, anyone can go to the site and see the numbers for themselves in a quick snapshot.

Until the late 1980s, clinical trials were conducted predominantly on men. Much has changed since then. Our Drug Trials Snapshots program and Summary Report underscore FDA’s commitment to enhancing transparency and better understanding of patient representation in clinical trials.

John J. Whyte, M.D., M.P.H., is Director of Professional Affairs and Stakeholder Engagement at FDA’s Center for Drug Evaluation and Research