A big step to help the patients most in need

By: Peter Lurie, M.D., M.P.H.

Today, I had the pleasure of announcing an important measure intended to help streamline expanded access to investigational drugs. We heard concerns from patients and physicians that the process for gaining access to investigational drugs was too difficult, and pulled together a team to find a way to make that process simpler. Today, we’re introducing a much simpler draft form for comment that, when finalized, should accelerate patient access to investigational drugs. We know what an important tool this will be for physicians who treat those patients with serious or immediately life-threatening diseases or conditions for which there are no comparable alternative treatments.

Dr. Peter LurieThe new draft document, entitled “Individual Patient Expanded Access Applications: Form FDA 3926,” includes a simplified application form that, when finalized, will be used for requesting the medications, and is designed to greatly simplify and accelerate the process by which a physician can request that FDA permit the use of an experimental — so-called “investigational” — drug or biological product while it’s still being tested to establish its safety and effectiveness.

The draft guidance and draft form continue a policy that started in the early years of the AIDS epidemic when FDA authorized, in certain cases, “compassionate use” of unapproved investigational drugs. In 2009, FDA made these rules broader and clearer. However, concerns persisted that the existing application form was too complex: it called for 26 separate types of information and seven attachments. In fact, it was originally designed for manufacturers seeking to begin human testing, not for physicians seeking use by single patients.

FDA authorizes the vast majority of expanded access requests, typically within days or even hours. However, FDA is committed to streamlining its processes wherever possible. The agency therefore tasked a special working group with designing a form more suitable for use by a physician not necessarily familiar with the IND process. The revised process, when finalized, will not change the agency’s rigorous requirement that all medical products on the market be studied in clinical trials in order to be FDA-approved as safe and effective. As before, expanded access to an investigational medication may be available when there is no other product that can diagnose, monitor, or treat the patient’s disease or condition, and the patient is not and cannot be enrolled in a clinical study testing it.

But we know why patients want access to these drugs and we know how busy their treating physicians can be. So we streamlined the new draft form to be shorter and simpler for physicians to fill out. The new draft form, when finalized, will require only eight elements of information and a single attachment. We estimate that physicians will be able to complete the finalized version of the form in just 45 minutes, as compared to the 100 hours listed on the previous form.

Additionally, to further assist the physician seeking access to an experimental therapy, we have redesigned our website to make it easier to navigate and to explain the new proposed process in detail.

For years, FDA has maintained a staff dedicated to assisting physicians and patients to navigate our system. These efforts will continue. The new draft guidance and draft form are the latest examples of FDA’s determined effort to minimize unnecessary red tape, increase efficiency and better serve patients in need.

Peter Lurie M.D., M.P.H. is associate FDA commissioner for public health strategy and analysis.

Making the Case for Critical FSMA Funding

By: Michael R. Taylor

Over the past two years, my colleagues and I have written here about what FDA is doing to create the preventive, risk-based food safety system mandated by the FDA Food Safety Modernization Act (FSMA). We’ve taken you along on our visits to farms and food facilities to get input on the FSMA rules we have proposed. We’ve described the changes we’re making within FDA and the framework we’re building to implement those rules after they become final in late 2015 and early 2016.

Michael Taylor

Michael Taylor

Now we’re at a critical juncture as Congress considers the funding that will help transform all the plans and preparations we’ve shared with you into protections that will greatly reduce the number of illnesses caused by contaminated foods and greatly increase consumer confidence in the safety of our food supply. President Obama’s FY 2016 budget request, released to Congress yesterday, would provide an additional $109 million for FSMA implementation. In the current fiscal year, FDA received an additional $27.5 million.

Why do we need this money? Because a lot of work must be done right now to ensure that the FSMA rules are implemented smoothly and effectively in late 2016 and 2017. Let me give you a few examples of areas in need of additional funding that, through FSMA, will transform the food safety system into one that prevents hazards instead of just responding to them.

Under FSMA, our approach to food safety inspections and compliance will be fundamentally different. FDA will deploy inspectors who are specialized in specific food commodities, rather than covering a broad range of FDA-regulated products. Backed by technical experts, they will assess the soundness and performance of a facility’s overall food safety system. Achieving this will require a major reorientation and retraining of more than 2,000 FDA inspectors, compliance officers and other staff involved in food safety activities.

While FSMA has given us new enforcement tools to use against those who flout safety requirements, the vast majority of food producers want to comply and keep their products safe. FDA will be issuing guidance documents that will be essential to helping industry meet FSMA requirements. Funds are needed now for FDA to recruit additional experts who can ensure that guidance development is based on the best science and knowledge of industry practices. These experts will also collaborate with industry, academia, and state extension services to ensure that their concerns are heard, that their advice is sought and used, and that the guidance documents reflect the most cost-effective solutions.

I cannot say enough about the importance of education and technical assistance to help farmers, processors and importers—especially small businesses—implement the new standards. Approximately 300,000 entities could be subject to the final FSMA rules. FDA wants to make a substantial investment in providing such assistance and making training materials widely available. In addition to direct technical assistance, FDA would use a large portion of these resources to provide financial support to state agencies and public-private-academic collaborative entities, such as the Produce Safety Alliance and the Preventive Controls Alliance. FDA has also joined with the U.S. Department of Agriculture’s National Institute of Food and Agriculture (NIFA) in providing grants that will fund food safety training for small, sustainable and organic farm owners and food processors.

We cannot make FSMA a reality without our state partnerships. There are more than 3,000 state, local and tribal government agencies involved in food safety. To align state programs with FDA’s new facility inspection and compliance approach, the agency will provide states with funds for inspector training, information sharing capacity with FDA and other states, state laboratory coordination, and inspector certification programs. These preparations have already begun but they must be accelerated in 2016 if the states are to be prepared to conduct sound, consistent inspections when industry must comply with the new prevention standards starting in late 2016. In addition, to successfully implement the produce safety rule, FDA must build state partnerships and capacity in 2016 to provide education and technical assistance to growers.

About 50 percent of fresh fruits, 20 percent of fresh vegetables, and 80 percent of seafood consumed by Americans comes from other countries, so it is clearly essential to modernize how we ensure the safety of imported foods. The Foreign Supplier Verification Program (FSVP) mandated by FSMA, will require importers to implement supplier verification plans to help ensure food produced overseas meets U.S food safety standards. This shift presents an enormous challenge for both FDA and food importers, given that last year there were approximately 88,000 consignees receiving food shipments and, in 2013, 12 million entries for FDA to oversee. FSVP will require a substantial regulatory development process, increased staffing and the training of more than 400 investigative and compliance personnel within FDA to enforce the regulation. It will also require extensive training and technical assistance for importers.

Those are just the highlights; there’s much more to be done. The bottom line is that without investment now, and sustained funding afterwards, there is the risk that the implementation of FSMA will be uneven or even delayed. This would be bad for everyone, including those who must meet the new standards and those who must enforce them. Most importantly, it would be bad for consumers, who want to be sure that the foods they are eating and serving their families are safe.

Michael R. Taylor is FDA’s Deputy Commissioner for Foods and Veterinary Medicine

FDA’s FY 2016 Budget Request

By: Margaret A. Hamburg, M.D.

Margaret Hamburg, M.D.FDA oversees products that represent more than 20 cents of every dollar that American consumers spend. Today, FDA presented its FY 2016 budget to Congress.This sensible budget request will help ensure that FDA can continue to fulfill its vast responsibilities to protect the public health, safety, and quality of life of the American public.

I want to share the cover letter that I wrote to Congress outlining some of our specific proposals.

 

Letter from the Commissioner

I am pleased to present the FY 2016 Food and Drug Administration (FDA) Budget.

FDA fulfills its important mission to promote and protect health in an increasingly complex and globalized world in many ways.  The scope of our work includes assuring that foods are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drugs, vaccines and other biological products, and medical devices intended for human use are safe and effective; and regulating tobacco products.  We also play a lead role in protecting the public from electronic product radiation and assuring that cosmetics and dietary supplements are safe and properly labeled.  Finally, we have devoted – and will continue to devote – substantial resources to advancing the public health by helping to speed product innovations.

FDA’s responsibilities continue to expand as we work to fulfill the mandates of groundbreaking legislation passed in recent years, including the Family Smoking Prevention and Tobacco Control Act of 2009, the Patient Protection and Affordable Care Act of 2010, the Food Safety Modernization Act (FSMA) of 2011, the FDA Safety and Innovation Act (FDASIA) of 2012, and the Drug Quality and Security Act of 2013.  Further, with so many FDA-regulated products manufactured in whole or in part outside of our borders, FDA is keenly focused on the complexities of regulating in a global marketplace.

In FY 2014, we took important steps to finalize a key set of proposed food safety rules; worked to improve the safety of compounded pharmaceutical products by conducting more than 90 inspections and implementing compounding legislation through proposed regulations, guidances, and other actions; published the “deeming rule” to extend FDA’s tobacco authority; and collaborated with federal, international, and industry partners to expedite the development and availability of medical products.  In addition, FDA has worked intensively to respond to the Ebola epidemic in West Africa by facilitating the development and availability of investigational diagnostics, therapeutics, and vaccines with the potential to help combat the epidemic.

FDA continues to seek new ways to obtain the most public health value for the federal dollar as we implement expanded authorities.  The products that FDA regulates are essential to public health, safety, and quality of life and represent over 20 cents of every consumer dollar spent on products in the United States.  Yet, in terms of our FDA budget, each American taxpayer contributes approximately $8 per year for the vast array of protections and services provided by FDA.

In FY 2016, we are requesting essential and timely resources to address critical food and medical product safety issues.  Mindful of the fiscal environment, we have identified targeted reductions where possible and identified long-term needs for additional user fees to balance budget authority growth.  FDA is requesting a total of $4.9 billion to support our various mandates to protect the American people.  This includes a $148 million budget authority increase to focus on the following:

  • delivering a farm-to-table system of prevention, including improved oversight of imported foods, through effectively implementing the final rules required by FSMA;
  • combating the growing threat of antibiotic resistance – in which drugs become less effective, or ineffective, against harmful bacteria;
  • promoting the development and appropriate use of reliable molecular and genetic diagnostics – precision medicine tools – to “personalize” the diagnosis, treatment, and prevention of disease;
  • implementing key FDASIA requirements to improve medical product review and inspections;
  • addressing the safety of compounded drugs;
  • continuing implementation of new requirements for review of sunscreen ingredients under the Sunscreen Innovation Act; and
  • supporting modern facilities to provide the laboratories and office space needed to meet FDA’s expanded legislative mandates.

As a science-based regulatory agency with a public health mission, FDA plays a unique and essential role in promoting and protecting public health and safety.  We are committed to meeting the needs and expectations of the American people.

Margaret A. Hamburg, M.D.

Commissioner of Food and Drugs

Listening to Patients’ Views on New Treatments for Obesity

By: Kathryn O’Callaghan and Jeffrey Shuren, M.D., J.D.

The world was a very different place in 1976, when the Food and Drug Administration launched its medical device program.

Kathryn O'Callaghan

Kathryn O’Callaghan, Associate Director for Science and Strategic Partnerships (Acting), FDA’s Center for Devices and Radiological Health

Since Steve Jobs and Steve Wozniak were just that year launching a computer company called Apple, doctors weren’t yet able to view X-ray images or look up drug prescribing information on their iPhones. Moreover, patients couldn’t Google treatments for heart disease, nor were they able to instantly find all open U.S. clinical trials for breast cancer. Not only was patients’ access to health care information much more limited, so was their role in making their own health care decisions.

Doctors diagnosed. Doctors made treatment decisions. Patients followed directions.

It’s different now.

Patients are more empowered today. Driven in part by a need to address emerging or neglected illnesses, such as HIV/AIDS and rare disorders, patients over the past three decades have increasingly banded together, creating organizations that advocated for their interests and generated public awareness of their diseases, their needs, and the lack of effective therapies. This activity produced legions of informed and empowered patients, who today urge us to take a more active role in our own health and urge clinicians to engage patients in shared health care decision-making. Patients are now not only partners in their health care but active consumers who make choices about their doctors, treatments, diagnostics, and health care experiences, an empowerment that is affecting the development of innovative therapies and new clinical solutions.

Today, there are no health care debates, discussions and decisions without considering the patient perspective.

Jeffrey Shuren

Jeffrey Shuren, M.D., J.D., Director of FDA’s Center for Devices and Radiological Health

At FDA’s Center for Devices and Radiological Health (CDRH), we have been systematically involving patients in our regulatory decision making process. Since 1999, CDRH has included a patient representative on each of our advisory panels of outside experts, giving us a better understanding of patient concerns about particular technologies. And in 2012, we began focusing our medical device approval decisions on incorporating the patients’ perspective.

Under this benefit-risk framework for high-risk and innovative, lower-risk medical devices, CDRH’s health care professionals, scientists, and engineers consider the patients’ perspective on both a product’s benefits and their tolerance for any risks when weighing the evidence to determine whether or not to approve a product.

In the past, CDRH experts may have determined that a device should not be approved because its probable risks outweighed its probable benefits. However today, under a patient-centric assessment of risk, if adequate evidence indicates that a subset of well-informed patients with a particular illness or condition would value the product’s benefits more than its risks, CDRH may approve the device for that particular group. However, if we were to approve such a device we may require appropriate product labeling that clearly defines the patient sub-population and their benefit-risk preference. That information would be included in the product’s “Indications for Use” section of the label to ensure that patients and health care practitioners are able to make well-informed decisions.

Better tools are needed to more reliably and scientifically characterize patient preferences about benefit and risks, so we launched our Patient Preferences Initiative, to identify and develop methods for assessing patient valuations of benefit and risk related to specific device types and specific illnesses and conditions.

The goal is to ensure we have sufficient confidence in these methods to rely on them to inform product approval decisions.

Earlier this month, a team of FDA scientists led by Telba Irony, PhD, Chief of General and Surgical Devices Branch in the Division of Biostatistics, published an article in Surgical Endoscopy with leading behavioral economists at RTI Health Solutions, a business unit of RTI International, illustrating how this paradigm can inform medical device approval decisions. The authors successfully tested a new method for capturing patient sentiment and translated it into a decision-making tool for incorporating patient preferences into clinical trial design for obesity treatments. They were able to estimate the tradeoffs in risks that obese patients are willing to accept in exchange for a certain amount of weight loss, and the minimum number of pounds they would have to lose to tolerate the risks of a weight loss device.

Shortly after the study was published, FDA approved a new weight loss device – the Maestro Rechargeable System, an important therapeutic option for obese patients. The decision to approve the device was based in part on the data from Irony’s study that showed a substantial portion of obese patients would accept the risks associated with a surgically implanted device if they lost a sufficient number of pounds. Maestro is the first FDA-approved obesity device since 2007.

Our Patient Preferences Initiative is testing other ways to reach out to patients and capture their views through public workshops, websites, and a new patient-focused advisory committee. CDRH is also participating in related research as a member of the Medical Device Innovation Consortium (MDIC), a non-profit partnership between the FDA, National Institutes of Health, Centers for Medicare & Medicaid Services, and 43 medical device companies, patient groups and other non-profit organizations. MDIC is developing a framework for incorporating patient preferences into the device development and assessment process, and compiling a catalog of methods for collecting patient preference information that can be used to develop, design, and market devices that meet the needs of patients. Simultaneously, CDRH is developing draft guidance outlining how data from patient preference assessment tools can inform device approvals and other regulatory decision making.

As patient groups, industry sponsors, and others conduct more patient preference studies, we will better understand the tradeoffs that patients with medical device-treatable diseases and conditions are willing to make. This research, along with actions taken by CDRH, MDIC and others will drive more patient-centered device development and assessment. As a result, patients will play an influential role in determining which treatments and diagnostics are available in the U.S. market.

It may have taken more than 30 years, but patients are finally having their say.

We should take care to listen.

Kathryn O’Callaghan is Associate Director for Science and Strategic Partnerships (Acting), FDA’s Center for Devices and Radiological Health

Jeffrey Shuren, M.D., J.D., is Director of FDA’s Center for Devices and Radiological Health

A CDRH Priority: Clinical Trials in the U.S.

By: Owen Faris, Ph.D., and Jeffrey Shuren, M.D., J.D.

At the Center for Devices and Radiological Health (CDRH), clinical trials are the foundation for our decisions to approve the most important medical devices—products that have the potential to save or sustain life, but that also present the greatest risk to patients.

Owen Faris

Owen Faris, Ph.D., Clinical Trials Director (acting), Office of Device Evaluation in FDA’s
Center for Devices and Radiological Health

Over the past year, we saw several exciting new medical devices reach U.S. patients, including devices to treat heart disease and diabetes and diagnose cancer. Just last week, we approved a new device to treat obesity. None of these products would have come to market without clinical trials.

CDRH is committed to improving U.S. patient access to new devices by strengthening and streamlining the process of testing complex medical devices so that their clinical trials are conducted in the U.S. in a safe, efficient and cost-effective manner. In fact, this is so important for us that we made it one of our three 2014-2015 Center Strategic Priorities, along with striking the right balance between premarket and postmarket data collection and improving our customer service. Please visit our website for an update on our Strategic Priorities.

Innovative medical products begin with clinical trials – and before a clinical trial of a significant risk device begins in the U.S., a researcher, among other things, must apply for and receive FDA’s approval through the Investigational Device Exemption (IDE) process.  The FDA reviews IDE applications to determine whether the sponsor has provided enough information to be sure that the study does not present an unreasonable risk to its participants. FDA takes into account the qualifications of the clinical investigators, information about the device, the design of the clinical investigation, the condition for which the device is to be investigated, and the health status of the participating patients.

Jeffrey Shuren

Jeffrey Shuren, M.D., J.D., Director of FDA’s Center for Devices and Radiological Health

FDA reviews an IDE submission within 30 days, but the review often results in questions which the study sponsor needs to answer, or changes that are needed before the study can be approved. Just a few years ago, it was therefore not uncommon for a year or more to pass before FDA could grant approval to a medical device developer to begin the trial. This type of delay was one factor that led developers to seek approval in other countries.

Over the past year, CDRH has taken a number of actions to expedite the safe initiation of clinical trials in the U.S., and we believe these policies will result in conducting clinical studies in the U.S. earlier in the device development process than was the case in the past.

Our improvements started with establishing a formal Clinical Trials Program within the Office of Device Evaluation. This program provides consistency in decision-making and encourages more interaction between FDA and the device industry during the IDE process. We also provided extensive training to CDRH review staff and the device industry. In addition, we issued numerous guidance documents, including one explaining IDE Decisions and one introducing CDRH’s new Early Feasibility Study program.

We’re excited to report that these changes have greatly shortened the time for an IDE to reach approval, so that a clinical trial can begin. From 2011 to 2014, the median number of days to full IDE approval has decreased from 442 to only 101. This cuts the time it takes to bring a new medical device to market by nearly a full year.

To learn more about CDRH’s clinical trials program, please join us for a webinar on January 22, 2105, where we will discuss the implementation of the IDE processes, our 2015 performance goals, early feasibility studies and our future plans. More information, including how to attend, is on the CDRH Webinar webpage.

The FDA is charged with the enormous task of protecting and promoting the health of the American public. To do this, we must ensure that the medical products on which Americans rely every day have been rigorously tested and are safe and effective. We are committed to making U.S. patients the first in the world to have access to safe and effective medical devices. And we’ve taken the first step to that, by helping ensure that clinical trials take place here, in the U.S.

Owen Faris, Ph.D., is Clinical Trials Director (acting), Office of Device Evaluation in FDA’s Center for Devices and Radiological Health

Jeffrey Shuren, M.D., J.D., is Director of FDA’s Center for Devices and Radiological Health

Australia, Brazil, Canada, Japan, and the US: Safeguarding Medical Devices

By: Kim Trautman, M.S.

The FDA and its regulatory counterparts abroad have the weighty responsibility of ensuring the safety of the thousands of regulated medical devices imported in their countries each year. To make this task more manageable, FDA and regulatory agencies in Australia, Brazil, Canada, and Japan embarked in 2014 on a pilot called the Medical Device Single Audit Program (MDSAP). Its goal is to develop a process that allows a single audit, or inspection to ensure the medical device regulatory requirements for all five countries are satisfied, in an efficient yet thorough manner.

Kim TrautmanOn January 1, 2015 the MDSAP pilot reached a major milestone – manufacturers around the globe interested in marketing medical devices in Australia, Brazil, Canada, and the U.S. were invited to participate in the program. This summer, when Japan enters the MDSAP as a full member, the same invitation will be issued also to medical device manufacturers interested in marketing in Japan.

Under this pilot, audits will be conducted by recognized third-party organizations, and medical device regulators in the participating countries will be able to use these inspection reports when making their regulatory decisions. Not only does this program reduce the participating regulators’ need to individually perform routine inspections; it allows them all to have the same reliable information about inspectional findings.

Manufacturers, too, can benefit from the MDSAP pilot by cutting down on the number of regulatory audits they have to host, thereby minimizing manufacturing plant and personnel disruptions. This form of international and standardized oversight lessens the burden on manufacturers by bringing more consistency and transparency to the regulatory process.

The MDSAP pilot does not increase regulatory requirements for medical device manufacturers – the audits cover only existing requirements of the regulatory authorities participating. In many cases, these requirements are already harmonized or very similar to one another, such as the international standard for medical devices quality management systems (ISO 13485:2003), the Brazilian Good Manufacturing Practices (RDC ANVISA 16/2013), the U.S. Quality System Regulation (21 CFR Part 820), and other specific pre- and post-market regulatory requirements of the authorities participating in the MDSAP pilot.

The FDA will accept MDSAP audits as a substitute for routine FDA inspections, typically done every two years for all classes of medical devices and including in vitro diagnostic devices. Pre-approval inspections for devices requiring premarket approval applications (PMAs) and “for cause” compliance inspections will not be part of the MDSAP pilot.

Manufacturers that choose to participate in the pilot program will help to shape the policies and procedures of the fully operational MDSAP, which is scheduled to begin in 2017. We expect that the MDSAP pilot will enhance confidence in third party audit programs, increasing the footprint of this global endeavor.

The FDA is pleased to be part of this MDSAP pilot. International cooperation promotes global alignment of regulatory approaches and technical requirements, expanding the safety net that protects patients world-wide.

New information about how countries will participate in the MDSAP pilot is available on the FDA’s MDSAP pilot web page.  Manufacturers can find additional information on the MDSAP web pageThis MDSAP page provides information on the auditing organizations involved in the pilot for interested manufacturers to contact directly.

Kim Trautman is Associate Director of International Affairs at the FDA’s Center for Devices and Radiological Health

CDER Approved Many Innovative Drugs in 2014

By: John Jenkins, M.D.

Each year, FDA’s Center for Drug Evaluation and Research (CDER) will typically approve more than 100 new medications. A portion of those are novel new drugs, medications that have not previously been approved by FDA and are often among the most innovative products serving previously unmet medical needs or otherwise significantly helping to advance patient care and public health.

John JenkinsThis year, the news media has been concentrating on the number of novel new drugs – either new molecular entities or new therapeutic biologics – approved by CDER in 2014. And that’s understandable because we approved 41 novel drugs this year, the most in nearly 20 years. But instead of looking at the approval tally, we prefer to focus on the significant benefits that many of these drugs bring to patients and the steps that CDER took to get these products to market in a timely manner while maintaining FDA’s standards for safety, effectiveness, and quality.

Many of the 41 new drugs have the potential to add significant clinical value to the care of thousands of patients with serious or life-threatening diseases. They include eight new drugs for treating patients with various types of cancer, four new drugs to treat type-2 diabetes, four new antibiotics to treat serious infections, and two new products to treat patients with hepatitis C.

Moreover, consider these facts:

  • Seventeen (41%) of the 41 novel new drugs were approved to treat rare diseases that affect 200,000 or fewer Americans. This is the highest yearly total of such drugs ever — surpassing the previous high of 13 from 2012. These approvals are particularly significant because patients with rare diseases often have few or no drugs available to treat their conditions.
  • Seventeen (41%) of the 41 novel new drugs are identified by CDER as “First-in-Class,” one indicator of a drug’s degree of innovation. The total for First-In-Class approvals in 2014 approaches the highest yearly total of 20 reported in 2012.

To expedite the development and review of these products, CDER used a number of regulatory programs, including Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval.

  • Fast Track and Breakthrough Therapy designations are designed to speed the development of promising new drugs intended to treat serious conditions with unmet medical needs. Almost half – 19 or 46% of the 41 novel new drugs approved in 2014 — were designated as Fast Track, Breakthrough, or both.
  • Twenty-five (61%) of the 41 novel new drugs were designated for Priority Review. These are drugs in which CDER sees potential for providing a significant advance in medical care, and sets their review target to within six instead of the standard 10 months.
  • Six (20%) of the 41 novel new drugs were approved under FDA’s Accelerated Approval program, which allows early approval of a drug for a serious or life-threatening illness that offers a benefit over current treatments. Accelerated Approval is based on a “surrogate endpoint” or an intermediate clinical endpoint that is thought to be “reasonably likely to predict clinical benefit.” Additional clinical trials are required after approval to confirm the predicted clinical benefit. A surrogate endpoint is a marker of drug effect (e.g., an effect on a lab value or tumor size) that does not directly represent an improvement in how a patient feels or functions, but is expected to predict such a benefit.

Here are a few other ways we assess our contributions to last year’s approvals:

  • Under the Prescription Drug User Fee Act (PDUFA), sponsors pay fees when they submit a product application. This money is used to provide FDA with additional resources to meet performance goals, such as a goal date for completing its review of the application. In 2014, CDER acted on or before the PDUFA goal date for 40 (98%) of the 41 novel new drugs approved.
  • CDER approved more than three-quarters — 32 (78%) — of the 41 novel new drugs on the “first cycle” of review, meaning without requests for additional information that would delay approval and lead to another cycle of review.
  • Nearly two-thirds of the novel new drugs – 26 (63%) — were approved in the U.S. before approval in another country.

It’s been another strong year for approval of novel new drugs for patients in need. We are proud of our role in helping to safely and efficiently bring important new medications to the American public.

Our Novel New Drug Summary for 2014 provides more details. A current list of CDER’s 2014 novel new drug approvals is available on our Web site.

John Jenkins, M.D., is Director of the Office of New Drugs in FDA’s Center for Drug Evaluation and Research

Protecting Susceptible Populations from Chemical Contaminants in Food

By: Suzanne Fitzpatrick, Ph.D., DABT

Anyone who regularly eats food containing low levels of certain chemical contaminants may be adversely affected over time. But some groups of people are more sensitive to chemical contaminants than others and thus are more likely to be harmed by long-term exposure. We call these groups “susceptible populations.”

Suzanne FitzpatrickThe FDA’s charge to ensure the safety of the food supply is not limited to the protection of the general public. We also have a responsibility to protect susceptible populations.

Pregnant women, infants, young children, and older adults have long been recognized as susceptible populations by the scientific community. In addition, people with cancer, diabetes, HIV/AIDS and transplant recipients may have weakened immune systems and thus may also be more vulnerable. In short, these groups may be at greater risk from a given amount of a chemical contaminant because of their age, genetics, sex, or health status.

Committed to protect susceptible populations as best we can, the FDA convened its Food Advisory Committee on December 16-17, 2014 to help shape our efforts to understand when and how risk assessments should integrate concern for susceptible populations.

Conducted and used by regulators, risk assessments are one of the most objective and scientific ways to understand the potential adverse health effects of chemical contaminants in the food we eat. They help regulators apply science in policy and decision-making. Think of them as a foundation for risk management, a bridge between data and decisions.

At times, however, susceptible populations may require special consideration. They may even warrant separate risk assessments under certain circumstances. If we evaluate their risk with the same broad brush that we apply to the general population, we might miss certain realities. In pregnant women, for example, metals like cadmium, lead and arsenic can cross the placenta and may harm the fetus while its neurological and immune systems are in their earliest stages of development. Similarly, senior citizens may have nutritional deficiencies or cardiovascular problems that make them more susceptible to certain contaminants.

We asked difficult questions of the Food Advisory Committee. To paraphrase a few, we asked what factors the FDA should use to define a susceptible population, what data and level of confidence are needed to initiate a separate assessment for any given susceptible population, and whether there are subpopulations or life stages of particular concern. We also asked several technical questions.

My colleagues and I hope to make meaningful inroads toward better understanding the risks faced by susceptible populations through our risk assessments, in part with the committee’s help. We are confident that we are on the right track. In fact, our effort aligns with a recent report by the National Academy of Sciences (on inorganic arsenic), which suggests that, depending on the chemical, separate risk assessments may be warranted for certain susceptible populations.

We will study the committee’s advice to consider how we can best incorporate susceptible populations into our risk assessments. Ultimately, we know that it might not always make sense to take a “one-size-fits-all” approach when it comes to food safety.

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

Another important step in FDA’s journey towards enhanced safety through full-scale “active surveillance”

By: Janet Woodcock, M.D.

They say the longest journey begins with a single step. In 2008, FDA launched the Sentinel Initiative and thus began a long journey toward the challenging goal of developing a full-scale medical product safety monitoring program using an important scientific technique called “active surveillance,” which complements our FDA Adverse Event Reporting System (FAERS). FAERS is already well developed and uses the equally important technique of “passive surveillance.” Today, I’d like to recognize our progress along the way.

Janet WoodcockAfter a successful five-year pilot program, which began in 2009, FDA’s Mini-Sentinel program is now transitioning, as planned, to the full-scale Sentinel System. I’d like to share with you the success of our Mini-Sentinel pilot program and some of FDA’s visions for our new leg of the journey toward full-scale “active surveillance” under the new Sentinel System.

First, a quick discussion of the importance of “active surveillance”: Over many years, FDA’s program that we now call FAERS has been our main tool for assessing the safety of medical products. This system relies on patients, medical professionals, and product manufacturers to report to us potential safety issues of the products FDA regulates.

FAERS is an invaluable asset, and we’re not seeking to replace it. However, the Sentinel System offers us the exciting possibility of not waiting for safety information to come to us in the form of reports, but rather it enables us to go out and get that information, adding greatly to our safety monitoring capability. This is active surveillance.

Over the past five years, the Mini-Sentinel pilot program has established secure access to the electronic healthcare data of more than 178 million patients across the country, enabling researchers to evaluate a great deal of valuable safety information. While protecting the identity of individual patients we can get valuable information from Mini-Sentinel that helps us better understand potential safety issues, and share with you information on how to use medicines safely. We have used Mini-Sentinel to explore many safety issues, helping FDA enhance our safety surveillance capabilities, and giving us valuable input in decision-making on drugs and vaccines.

We’re now well on our way to developing a nationwide rapid-response electronic active surveillance system, Sentinel System, for monitoring the safety of FDA-regulated drugs and other medical products.

So where does our journey take us from here?

  • FDA will build on the successes of the Mini-Sentinel Pilot. We have a variety of safety assessments ongoing under Mini-Sentinel that will continue and we will seek to expand our reach and capabilities with the Sentinel System;
  • Mini-Sentinel gave us an important start, but it is essential to continue to develop and refine existing scientific methods to evaluate the data we access through the Sentinel System;
  • We see Sentinel as a potentially valuable national resource for other safety researchers, besides those at FDA. Looking even further ahead, our hope is that, working with other scientific groups, we will be able to create a National Data Infrastructure that would enable other users (e.g., other governmental agencies, researchers from academia or industry) to access the Sentinel infrastructure for multiple purposes (e.g., medical product research, quality improvement);
  • Not only will such access directly serve the public health, it will also help sustain these programs because stakeholders will have an incentive to provide support (financial and otherwise) for its maintenance and growth.

From the outset, the goals of the Sentinel Initiative have been large and of ground-breaking scale. We knew it would be years in the making, but Mini-Sentinel’s successful completion marks important progress. We look forward to continuing and expanding our active surveillance capabilities as we now transition to the full-scale Sentinel program.

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

Together: A Food Safe America

By: Michael R. Taylor

I recently had the pleasure of speaking at the Consumer Food Safety Education Conference convened by the Partnership for Food Safety Education (PFSE). The conference brought together food safety educators from across the country – people in state and local health departments, universities, extension services, and food businesses who are working every day on the front line, with consumers, to reduce food safety risks by improving consumer food handling practices.

Michael Taylor

Michael Taylor

The theme of the conference was “Together: A Food Safe America” – a theme that captures so well the sense of community, high purpose and energy that were present so abundantly at the conference. I shared the podium with two good friends and colleagues representing key FDA partners on food safety – USDA’s Acting Under Secretary for Food Safety Brian Ronholm, and Joe Corby, the Executive Director of the Association of Food and Drug Officials, which represents state and local food safety officials.

We regulators have a responsibility, through our oversight of the food industry, to do everything we reasonably can to make sure that the foods consumers bring into their homes are as safe as they can be. We are doing this by building into our food safety standards and compliance programs modern concepts and techniques for preventing the contamination that can make people sick.

Under the FDA Food Safety Modernization Act (FSMA), we at FDA have a new mandate to build a farm-to-table system of prevention, encompassing work that must be done to make food safe at four major stages of the commercial food system. These pillars of prevention include:

  • Production of produce on the farm,
  • Practices in food processing and storage facilities,
  • Transportation of food, and
  • Practices in grocery stores and restaurants.

But there’s a fifth pillar of prevention, and that’s the consumer. We all know that, even with the best of efforts by commercial food producers and handlers, consumers still must play a crucial role in preventing the introduction and spread of contamination – by keeping their hands and food surfaces clean, by keeping raw meat and produce separate, and by being sure to cook food to proper temperatures and chill food through prompt refrigeration.

It seems like common sense – and the basic ideas are – but food safety educators know that it’s far from simple to provide consumers the information, tools, and motivation they need to turn common sense into sustained behavior change. But they are out there, every day, doing the hard work.

We in government and the food industry need to better support our food safety educators.  FDA, USDA, and the Centers for Disease Control and Prevention (CDC) do some good work on food safety education. For example, at FDA, our current programs include targeting groups and individuals who are especially vulnerable to foodborne illness and partnering with the National Science Teachers Association to incorporate food safety into the science curriculum at the middle and high school levels. But there is more we can do to support food safety educators at the front line, in their daily work with consumers in clinics, in schools and in communities – where most of the food safety education, and all of the behavior change, takes place.

At FDA, we will be building food safety education into our risk-based priority setting paradigm, which means documenting better the contribution that education makes to reducing risk, evaluating what works to sustainably improve consumer practices, and targeting resources where they will make a real difference. Federal food safety agencies – and their finite resources – are overwhelmingly focused on the congressional mandate to prevent hazards arising from the commercial supply chain, which makes sense: that’s what we regulate. But, backed up by the right analysis, we can effectively target and increase our investment in consumer education in ways that will make a real difference for public health.

But the federal government can only do so much. And that’s where PFSE comes in. The Partnership brings together government, industry and consumer leaders to pool their expertise, share their perspectives, and collaborate on the hard work of food safety education. I applaud and thank the consumer groups, food companies, and trade and professional associations that are contributing their time, creative energy and resources to the work of the Partnership. And I salute the PFSE’s Executive Director Shelley Feist for her leadership and her sustained commitment to food safety and consumer education.

Working hard, and working together, we can have a Food Safe America.

Michael R. Taylor is FDA’s Deputy Commissioner for Foods and Veterinary Medicine