New CDER Report Highlights Ongoing Drug Safety Initiatives and Priorities

By: Janet Woodcock, M.D.

At FDA’s Center for Drug Evaluation and Research (CDER), drug safety is among our highest priorities. Before we approve a drug, we make every effort to ensure its benefits outweigh its risks. After approval, we keep a careful watch for new safety issues that can arise once new therapies are prescribed for a broad population of patients.

Janet WoodcockIt’s a complex and ever-changing responsibility. As drug therapies become increasingly advanced, so too must our methods to prevent and/or manage risks related to their use. These risks come in many forms – including adverse events (side effects), problems arising from inappropriate or incorrect use, manufacturing issues related to sophisticated new production techniques, criminal tampering or counterfeiting, and the devastating effects of addiction, like that of the opioid epidemic. And, as innovative study methods provide new information, new safety issues can emerge for drugs that have been on the market and widely used for decades. For these reasons, we focus our efforts both on newly approved drug therapies and those already on the market.

Our annual report, Drug Safety Priorities 2017, provides updates on our ongoing initiatives, discusses new work, and highlights last year’s safety-related milestones and achievements.

Protecting the American public from risks associated with medications requires teamwork from many scientific and medical specialists at FDA working together to inform decisive regulatory action. Key efforts include the Safe Use Initiative to reduce preventable harm from medications; the FDA Adverse Event Reporting System (FAERS), which collects vast amounts of data about side effects and medication errors from medical products reported by patients, health care professionals, and manufacturers; and the Sentinel System, our state-of-the-art electronic drug safety surveillance system. We also collaborate with health care professionals, academia, researchers, and other health and science agencies in studying the effects of medications before and after approval to help ensure that the benefits of these therapies outweigh their risks.

Our report describes many ways CDER worked in 2017 to enhance drug safety for the American public. These include:

  • Safety surveillance and oversight of marketed drug products: In 2017, CDER’s Office of Surveillance and Epidemiology (OSE) conducted 7,446 safety reviews. Of those, 2,860 were initiated as a result of ongoing OSE surveillance.
  • The importance of real-world evidence to help advance drug safety science: Although randomized clinical trials (RCTs) are the gold standard for medical and scientific evidence needed to support FDA drug product approval decisions, they are often conducted in specialized and controlled research settings and are time-consuming and costly. And at the end of a drug development program, RCTs can leave critical questions unanswered, particularly about the effects or impacts of a drug after it gets into the “real world,” and is used by hundreds of thousands of people over an extended period. CDER safety scientists are using powerful new scientific computing and data storage technologies to enhance our capabilities of gaining valuable information from “real world evidence.”
  • New tools and new approaches for fighting our Nation’s opioid crisis: Our report emphasizes that in 2016, an estimated 11.5 million people misused prescription opioids — and that each day of that year, an estimated 116 people died from an opioid-related overdose. FDA actions taken in 2017 in response to the opioid epidemic align with our current four key priorities in this area: 1) decreasing exposure and preventing new addiction, 2) safely treating those with opioid addiction, 3) developing safe and effective novel alternative therapies to opioids, and, 4) improving enforcement of safety measures and assessing benefit-risk ratios.
  • Safety oversight for generic drugs: The report explains how we evaluate generic drugs to ensure they meet quality standards and deliver the necessary amount of active ingredient, and how we monitor generic drug use in the marketplace to flag early safety concerns. CDER’s Clinical Safety Surveillance Staff (CSSS) is addressing post-marketing safety concerns related to complex generic drug-device combination products. In 2017 a generic drug had two intravenous (IV) bag ports (rather than a single IV bag port used by the brand name drug). This difference raised concerns for potential confusion, risk of incompatibility issues, and potential adverse events in patients. The CSSS’s collaboration activities led to the development of a new process for managing review of similar IV bags with different port configurations.
  • Efforts to reduce preventable harm from medications: More than a million Americans are injured or killed each year due to preventable medication errors. FDA’s Safe Use Initiative works to reduce preventable medication-related errors, such as medicines dispensed in error, medicines taken for too long or not long enough, or medicines inappropriately mixed with other medicines or with foods that can increase risks of side effects. Among many other efforts, our work through the Safe Use Initiative in 2017 included making recommendations to enhance the safety of fluoroquinolone antibiotics, identifying “high-risk” prescribers (those who write prescriptions for high doses or co-prescribe with medications which increase the risk of adverse events) and educating them about safer prescribing practices, and identifying which diabetic patients may be at high risk of hypoglycemia (low blood sugar).
  • Compounded drugs – continuing regulatory and oversight efforts: FDA has taken many steps to strengthen safety measures for compounded medications since the 2012 outbreak of fungal meningitis associated with contaminated compounded drugs. Among other actions, the agency conducted 140 inspections, sent 55 warning letters, and issued 40 recalls related to compounding.
  • Diverse strategies, tools, and services for communicating drug safety: Effectively communicating what we do is an essential component of our work to protect the public. In 2017, we responded to 57,094 inquiries from the public (39,883 by phone, 16,269 by e-mail, and 942 via written letters), each an opportunity to help a patient ensure they are safely using their medication. Our Drug Safety Podcasts reached an estimated 350,000 listeners each week. These and many other communication efforts, such as our Drug Safety Communications that alert consumers and health care professionals about new or potential safety issues, serve to keep the public informed of important drug safety concerns that may impact them.

The report also details a variety of ways we keep pace with the rapid evolution of technology. For instance, we are evaluating the use of technologies, such as machine learning methods and other advanced computation techniques, to help our analytics systems contribute to more predictive safety and risk data. We are also exploring ways to leverage mobile apps, social media, and electronic prescribing data while ensuring patient privacy. As we pursue a wide-ranging safety agenda, CDER Drug Safety Priorities 2017 offers a deeper dive into FDA’s drug safety research, surveillance, and regulatory activities. We hope this report serves to demonstrate CDER’s ongoing commitment to protect the American public.

Janet Woodcock, M.D., is the Director of FDA’s Center for Drug Evaluation and Research

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