FDA’s Janet Woodcock, M.D., recognized by the Institute for Safe Medication Practices: Receives Lifetime Achievement Award for her career in public service

By: Margaret A. Hamburg, M.D.

FDA’s mission is to protect and promote the health of the American public. The FDA employees who dedicate their careers to this worthy goal do so not for personal reward or public recognition but because of an extraordinary commitment to improving public healthcare. Which is why it is even more special when these employees receive public acclaim.

Margaret Hamburg, M.D.

Margaret A. Hamburg, M.D., Commissioner of the Food and Drug Administration

One such individual is Dr. Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research (CDER). Janet recently was awarded the Institute for Safe Medication Practices (ISMP) Lifetime Achievement Award, recognizing “an individual who has had a significant career history of making ongoing contributions to patient safety and has had a major impact on safe medication practices.” This award is well deserved.

During her nearly 30 year career with FDA she has served in several different capacities in addition to her current position, including Director of the Office of Therapeutics Research and Review in the Center for Biologics Evaluation and Research (CBER) and as FDA’s deputy commissioner and chief medical officer. Throughout her career, Dr. Woodcock has helped the Agency elevate and transform its approach to medical product safety, personally leading the way on many key safety initiatives from their beginning to implementation.

During her distinguished career Dr. Woodcock:

  • Conceived and oversaw creation of the Adverse Event Reporting System (AERS) system, to manage the increasing number of spontaneous reports of adverse drug reactions submitted to FDA;
  • Co-led the FDA Task Force on Risk Management, one of the Agency’s first efforts to clearly delineate pre- and postmarket safety surveillance and management of medical product risks;
  • Chaired the Council on Pharmaceutical Quality, launched in 2007, presaging many of the Agency’s subsequent safety initiatives;
  • Led the launch of Safety First, a program created to help ensure alignment between premarket drug safety review and postmarket surveillance;
  • Led the creation of the Sentinel Initiative, a data-driven national system that allows active—close to “real time”—safety surveillance using electronic data from healthcare information holders;
Janet Woodcock

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

Through all of these accomplishments, and many others, Janet Woodcock has helped ensure that FDA can fulfill its mission effectively. She has championed the use of innovative new tools and approaches, and she has forged and enriched many partnerships with industry, academia, healthcare providers, patients and colleagues in government, including across the FDA.

Her work has helped lead FDA into a new century, an extraordinary time of transformation and opportunity in medical science. With these changes, FDA’s responsibilities have also grown enormously. We must continue to ensure that our capabilities for drug product evaluation, oversight, and regulation keep pace with these developments. Thanks to Janet’s vision and hard work, along with many of her colleagues at FDA, I am confident that FDA is up to the task.

I want to thank Dr. Woodcock for her years of dedicated service to the American public, and congratulate her on this most recent recognition of her many contributions.

Margaret A. Hamburg, M.D., is Commissioner of the Food and Drug Administration

Protecting the Public from Unsafe Compounded Drug Products

Margaret A. Hamburg M.D.

In 2012, a devastating outbreak of fungal meningitis linked to a contaminated compounded drug product tragically resulted in the loss of 64 lives and caused more than 751 illnesses, many of which were very serious. These events were a powerful reminder of the potential harm that could be caused by unsafe compounding products.

Margaret Hamburg, M.D.FDA is moving aggressively on many fronts to protect the public from such threats.

For example, we have conducted more than 175 inspections of compounding facilities in the past two years. Some of these inspections were for cause and were performed after we received reports of serious adverse events related to drugs made by compounding pharmacies or when states requested our assistance. Other inspections were proactive, targeted at facilities identified through a risk-based model. Our proactive inspections were conducted in coordination with state officials from around the country and focused on each firm’s sterile drug production, because drugs labeled as sterile are used in ways that could greatly compromise patient care and safety if they aren’t actually sterile.

Our findings uncovered a variety of problems with sterile drug production practices at these facilities. As a result of these inspections, numerous firms stopped making sterile drugs and many recalled drug products that had been made under substandard conditions. In some cases, we worked with state officials to revoke or suspend pharmacy licenses. We also issued warning letters to firms that were producing drugs under inadequate conditions, notifying them of violations of the law and the need to take steps to correct the violations and prevent their recurrence.

We have also worked with the Department of Justice (DOJ) to hold facilities accountable if they harm patients or engage in serious violations of federal requirements that put patient safety at risk. Working with DOJ, FDA has initiated investigations and enforcement actions against compounding facilities that violate federal law – and we intend to continue this work with DOJ.

In addition to our inspection and enforcement efforts, FDA has taken many steps to implement the compounding provisions of the Drug Quality and Security Act (DQSA) — legislation enacted by Congress last year in response to the fungal meningitis outbreak.

To implement the compounding statutory provisions, FDA is establishing a policy framework to address compounding by state-licensed pharmacies as well as the new category of outsourcing facilities, which was created under the DQSA. Among other things, outsourcing facilities are facilities that compound sterile drugs and choose to register with FDA as outsourcing facilities, and they must comply with current good manufacturing practice requirements and are subject to FDA inspection on a risk-based schedule.

Two years after the fungal meningitis outbreak our hearts continue to go out to the victims of the tragedy and their families. Our work on behalf of all patients who want and deserve medicines that do not subject them to undue risk is far from being done. FDA will continue to work with the states, the Department of Justice and others to enable Americans to have greater confidence in their compounded drugs.

Margaret A. Hamburg, M.D., is Commissioner of the Food and Drug Administration

2014 Drug Approvals: Speeding Novel Drugs to the Patients Who Need Them

By: Margaret A. Hamburg, M.D.

Preliminary data announced earlier today shows that 2014 is shaping up to be another strong year for novel drug approvals, which is certainly good news for many patients and their families.

Margaret Hamburg, M.D.With a few weeks left in December, our Center for Drug Evaluation and Research (CDER) has so far approved 35 novel new drugs in 2014 compared to 27 in 2013. These numbers include both new molecular entities (NMEs), submitted to CDER in New Drug Applications (NDAs) and new therapeutic biologics submitted to CDER in Biologics License Applications (BLAs).

But the numbers don’t tell the full story. What really matters is that many of these new products offer significant clinical value to the care of thousands of patients with serious and life-threatening diseases. That’s certainly the case for patients with rare diseases that affect 200,000 or fewer Americans. So far this year we’ve reached a milestone with a record 15 approvals for rare diseases. The previous high was 13 drugs in 2012. These results are all the more significant because patients with rare diseases often have few or no drugs available to treat their conditions.

And here’s another point of interest – to date, 15 of the approvals have been first in their class drugs, another indicator of their potentially strong clinical impact.

To ensure that 2014’s novel drugs get to patients as quickly as possible, CDER effectively employed a variety of regulatory tools including FDA’s expedited development and review programs – fast track, priority review, accelerated approval and our new breakthrough therapy designation. Early and repeated communications with sponsors have also been helpful in speeding these products to market.

Consider for example, Blincyto, approved just last week to treat Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia. CDER employed all of its expedited review programs to help get this drug to market as early as possible, five months ahead of its review goal date. The sponsor also benefited from incentives for drugs that treat rare diseases.

Another example is Harvoni, the first combination pill approved to treat chronic hepatitis C virus genotype 1 infection and the first approved regimen that does not require administration with interferon or ribavirin. With this and other recent approvals, we are helping to change the treatment paradigm for patients living with hepatitis C. Harvoni received breakthrough therapy designation and was assigned priority review.

One of the more challenging areas of drug development has been the rather barren field of antibacterial drugs. Among our 2014 approvals to date are three new antibacterial drugs – Dalvance, Sivextro and Orbactiv—to treat skin infections, specifically acute bacterial skin and skin structure infections (ABSSSI). These drug approvals represent a welcome but modest increase in activity in this product area. Prior to 2014, only five new systemic antibacterial drugs were approved during the period from 2004 – 2013.

I want to congratulate the management and review staff at CDER for these very impressive preliminary numbers. Thanks in large part to CDER’s hard work and dedication, 34 of the 35 drugs approved so far in 2014 were approved before or on their Prescription Drug User Fee Act (PDUFA) review goal date and 23 of the 35 drugs were available to patients in the United States before they were available to patients in Europe.

In this holiday season of joy and reflection, we have much to be grateful for in the work that CDER does every day on behalf of patients.

Margaret A. Hamburg, M.D., is Commissioner of the Food and Drug Administration

Helping patients and health care professionals better understand the risks and benefits of medications for pregnant and breastfeeding women

By: RADM (Ret.) Sandra L. Kweder, M.D., F.A.C.P.

Good news for moms and expecting moms across the country. We have a new way of helping health care professionals and patients better understand the effects of medicines used during breastfeeding and pregnancy.

Sandra KwederToday, after years of careful consideration — and listening to public feedback — FDA has published a final rule that sets standards for providing a consistent way for drug manufacturers to provide information about the risks and benefits of prescription drug and biological products used during pregnancy and lactation (the medical term for producing milk). It also includes requirements for ways of communicating relevant information for women and men of reproductive potential.

The new rule eliminates an old and possibly confusing way of communicating risk during pregnancy and breastfeeding, which used letter categories of A, B, C, D, and X, to classify various types of risks. It may look simple, but this system was anything but. As a result, the letter categories that have been a familiar presence in drug labeling since the 1970s were often misinterpreted as a sort of grading system of risks, which gave an overly simplified view of product risks.

Our new method provides for explanations, based on available information, about the potential benefits and risks for the mother, the fetus, the breastfeeding child, and women and men of reproductive age.

Here’s a quick overview: Prescribing information for health care professionals provided by manufacturers will now contain required subheadings within the Pregnancy and Lactation subsections: risk summary, clinical considerations, and data. These subsections will provide more detailed information regarding, for example, human and animal data on the use of the drug, specific adverse reactions and information about dose adjustments needed during the pregnancy and post-partum (after giving birth) periods. It will apply not just to new drugs approved from now on, but also to older drugs approved since 2001 that have been marketed for years without their labeling being updated to incorporate important new information related to pregnancy and lactation.

Also today, FDA is issuing what we call a “draft guidance” for industry, to assist drug manufacturers in including information about pregnancy and lactation in their prescribing information according to the requirements of the new rule. We’ll finalize that draft guidance after receiving and incorporating input from the public. To provide comments on this draft guidance, visit this link.

There are more than 6 million pregnancies in the United States every year, and pregnant women take an average of three to five prescription drugs during pregnancy, so we’re excited about this rule, which will provide an extra layer of safety and informed decision making for patients and health care professionals.

Protecting pregnant women and children of breastfeeding mothers from adverse reactions from medications and informing patients and health care providers about their benefits is an ongoing effort we must constantly update and advance. This new rule is one of many steps along the way — and we believe it will help make a strong and positive difference in safeguarding the American public.

Sandra L. Kweder, M.D., is the Deputy Director of the Office of New Drugs at FDA’s Center for Drug Evaluation and Research

For an AIDS-Free Generation: Access to Drugs and Diagnostics Is Essential

By: FDA Commissioner Margaret A. Hamburg, M.D. and HHS Assistant Secretary Jimmy Kolker

Margaret Hamburg, M.D.On World AIDS Day this year, tens of millions of people with HIV are now living healthy, productive lives because of access to safe and lower priced medicines. We rejoice in this achievement, because all people, no matter how rich or poor, deserve to have the medicines they need to live their lives in the best health possible.

We can truly see in our future an AIDS-Free generation because of the wide availability of prevention and treatment tools. But the availability of these drugs and diagnostic tools, especially in Africa, was never a given. Ten years ago, in 2004, the U.S. Food and Drug Administration (FDA) committed to support the President’s Emergency Plan for AIDS Relief (PEPFAR) by introducing an expedited review process to make generic and low-cost treatment more readily available for the most affected countries. PEPFAR requires antiretroviral drugs to be safe, effective, and of high quality and supports their distribution to people needing treatment around the globe. But meeting these requirements can be costly and time-consuming. Those suffering from AIDS cannot wait. The FDA, an agency that is part of the Department of Health and Human Services (HHS), applied the tentative approval process in order to increase dramatically the number of products approved for purchase and distribution by PEPFAR.

Thanks to the commitment of FDA scientists, as of today FDA has issued expedited approval decisions for 179 products, including 39 formulations specifically designed for children that allow flexible dosing across multiple weight bands and many innovative formulations, such as fixed-dose combinations and co-packaged products that improve adherence to treatment and reduce the risk of developing resistance. The 179 tentative approvals allowed PEPFAR to purchase products at a lower cost, leading to cost savings of hundreds of millions of dollars. These savings contributed to additional patients being able to receive treatment.

Jimmy KolkerAccording to UNAIDS, by June 2014, 13.6 million people around the world had access to antiretroviral therapy. This is an important success, but many more people still need access.

Unfortunately, too many countries lack the regulatory capacity to conduct product registrations in a timely manner. This makes it difficult for these countries to provide high-quality rapid HIV tests and treatment.

The FDA and the HHS have been working with the Department of State Office of the Global AIDS Coordinator (S/GAC); the World Health Organization; the Global Fund to Fight AIDS, Tuberculosis, and Malaria; and other organizations to help countries build both their health care systems and regulatory capacities.

Importantly, FDA has partnered with host country health ministries to help strengthen regulatory capacities in support of their public health programs. PEPFAR recently contributed $1.5 million in support of this FDA partnership to further regulatory system strengthening in the East African community.

With these improvements, countries battling HIV and AIDS can build the systems necessary to ensure that patients get the high-quality treatment they need, which one day will lead to the realization of an AIDS-free generation.

Margaret A.  Hamburg, M.D., is the Commissioner of the Food and Drug Administration

Jimmy Kolker is Assistant Secretary for Global Affairs in the U.S. Department of Health and Human Services

China Journal: strengthening relationships to protect public health

By: Margaret A. Hamburg, M.D.

I am just about to wrap up a jam-packed five-day visit to China, a fascinating country with a dramatically growing economy and with an increasingly significant impact on the products that Americans consume. Indeed, a key reason for my trip is the important and growing collaboration between FDA and our counterpart agencies in China to ensure the safety of the large volume of foods and medical products exchanged between our two nations.

Margaret Hamburg, M.D.Of the 200 countries that export their products to the United States, China ranks first in exports (in dollar value) to our nation. It is the sixth largest provider of food and the sixth largest provider of drugs and biologics. Only the United States has more FDA-registered drug establishments than China. And these numbers are growing. Between 2007 and 2013, China’s annual exports of FDA-regulated products to the U.S. nearly quadrupled, reaching 5.2 million “lines” (portions of a shipment) of imported goods in 2013.

Ensuring the safety and quality of these and other U.S.-destined FDA-regulated goods is a major challenge. To meet it, FDA has transformed itself— from a domestic agency that focused primarily on products manufactured in the U.S. to a truly global agency grappling with the many challenges of globalization.

Among the many efforts in this area, an important component is the FDA’s establishment of permanent outposts staffed by FDA experts in all major exporting regions, including in China. We have 13 FDA staff members currently stationed in the country, primarily in Beijing. Their job is to help ensure that the food and medical products being exported from China meet our standards. FDA’s China Office does this by providing significant support for the Agency’s inspections in China, by strengthening our relationships with Chinese regulators, by working with industry and other stakeholders, by providing important information and technical assistance to all interested parties, and by analyzing trends and events that might affect the safety of FDA-regulated products exported from China to the United States.

Given the volume of U.S. trade with China, we are working to more than triple the number of American staff we place in China. Placing more FDA experts in China will allow FDA to increase significantly the number of inspections it performs in this dynamic, strategic country, as well as to be more effective partners with our colleagues here in China. Such dramatic staffing increases will also allow FDA to enhance its training efforts and technical collaboration with Chinese regulators, industry and others.

This week, we took an important step forward in strengthening our relationship with China when we signed an Implementing Arrangement with the China Food and Drug Administration (CFDA). We expect to sign a similar Implementing Arrangement with the General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ) in the coming weeks. These documents, which build on 2007 agreements with the same two agencies, help to frame the work our inspectors will do in China and create mechanisms for collaboration on inspections.

FDA is also engaging with other stakeholders to create sustainable models for training future champions of regulatory science and quality. Here in China, we helped to create a world-class graduate degree program in international pharmaceutical engineering management (IPEM) at Peking University (PKU), an institution renowned for educating Chinese leaders and thinkers.

This partnership with PKU began in 2005 with just two courses on current good manufacturing practices. These proved hugely successful, and drew attention from Chinese drug companies and regulatory agencies, as well as industry and regulators in neighboring countries. The following year, PKU established a master’s degree program in IPEM, with support from FDA and multinational pharmaceutical companies. The program was formally launched in March 2007, with courses in regulatory science, pharmaceutical science, engineering, and more.

One of the highlights of my trip this week was speaking to more than 200 PKU students, future leaders who will help to accelerate the modernization of this nation’s pharmaceutical industry. I discussed not only FDA’s growing regulatory cooperation with China but the importance of strengthening regulatory science in China to ensure that the highest standards are used to support the development, review, and approval of new medical products, as well as the manufacturing and safety monitoring of medical products. All of this can make an enormous difference in the lives of patients in China, the U.S. and beyond.

Also this week, I met with top Chinese regulatory officials, toured CFDA’s mobile laboratories that test for counterfeit drugs and contaminants in food, and attended the 9th International Summit of Heads of Medicines Regulatory Authorities in Beijing.

Throughout the week, we addressed tough problems that require global solutions. Our discussions ranged from how best to advance biomedical product innovation, expand access to important pharmaceuticals through generic and biosimilar regulatory pathways, and how coordinated action, along with using new, state-of-the art technologies and analytical methods, will more effectively protect the public from substandard or counterfeit products. We are also making tangible progress in strengthening FDA’s partnership with our Chinese counterparts to better oversee the increasingly complex international supply chain and to prevent problems before they occur.

As I prepare for the journey home, I am encouraged by what we accomplished. And all of this bodes well for our ability to promote and protect protect public health in the future.

Margaret A. Hamburg, M.D., is the Commissioner of the Food and Drug Administration

View Photos from China:

Commissioner Margaret A. Hamburg, M.D., tours an FDA China Office mobile lab that tests for counterfeit OTC drugs and contaminants in food

Commissioner Margaret A. Hamburg, M.D., meets with Chinese pharmaceutical executives

Commissioner Margaret A. Hamburg, M.D., with students of Peking University

 

Additional progress on reducing the abuse of opioid pain relievers

By: Janet Woodcock, M.D.

FDA’s approval today of the extended-release opioid pain medicine Hysingla ER (hydrocodone bitartrate) marks additional progress in the fight against the ongoing misuse and abuse of prescription opioids. Hysingla ER’s approval provides prescribers with another option for managing pain severe enough to require daily, around-the-clock, long term opioid treatment in patients for whom alternative treatment options are inadequate, while potentially reducing hydrocodone abuse.

Janet WoodcockIn pre-approval testing, Hysingla ER exhibited properties that we expect will reduce the likelihood users could abuse the drug by chewing the tablet and ingesting it orally, or crushing it into powder for snorting or injecting. This is important because immediate-release combination products containing hydrocodone are among the most frequently abused opioid products. Hysingla ER is the fourth prescription opioid approved with product labeling that is consistent with the FDA’s 2013 guidance on abuse-deterrent opioids. The drug’s abuse-deterrent properties are expected to reduce – but not totally prevent – abuse by these routes.

While Hysingla ER has the same active ingredient (hydrocodone) as Zohydro ER, the only other approved extended-release hydrocodone product, there are important differences between the two. Hysingla ER has approved abuse-deterrent labeling, while Zohydro ER does not. Also, Zohydro ER is taken every 12 hours, and so comes in lower dosage strengths than Hysingla ER, which is taken every 24 hours. FDA has not yet determined whether Hysingla ER will prove to be safer than Zohydro ER.

It’s important to address some potential misperceptions about these extended-release hydrocodone products.

First, it would be misleading to suggest these products are stronger than other opioids on the market. Both Zohydro ER and Hysingla ER contain larger amounts of hydrocodone compared to immediate-release hydrocodone combination products because they need to be taken much less frequently. The range of tablet strengths for Hysingla ER is comparable to the strengths of existing approved extended-release opioids. The highest tablet strength of Hysingla ER, 120 mg, is comparable in potency to the currently marketed highest tablet and capsule strengths of extended-release morphine and hydromorphone products which, like Hysingla ER, are taken once daily.

Second, we do not expect these drugs to increase the number of patients treated with opioids. FDA is monitoring the use of all opioid products carefully and has been monitoring Zohydro ER prescribing since it was approved. In July 2014, Zohydro ER’s sixth month of marketing, there were 3,588 outpatient retail prescriptions dispensed. This represents 0.23% of the 1.6 million extended release, long acting (ER/LA) opioid analgesic prescriptions and only 0.02% of the nearly 18 million prescriptions dispensed for all opioid analgesics during the same month.

As with all extended release opioid medicines, FDA will carefully monitor and assess the use of Hysingla ER over time, and we are requiring the manufacturer to conduct studies to measure the effects of the abuse-deterrent features on abuse in the community.

Third, FDA has heard concerns about whether there is a need for additional prescription opioids. Given what we know about the needs of doctors and patients for additional choices of medicines, we believe having an additional choice of pain medicine like Hysingla ER, the first once daily hydrocodone product, is beneficial overall when treating patients in pain.

This latest approval also marks an important reminder of the limitations of today’s abuse-deterrent formulations. The reality is that opioids with abuse-deterrent properties can still be abused. Currently available abuse-deterrent technologies are important and offer a step in the right direction, but the science in this area is still evolving.

Prescription opioids with abuse-deterrent properties will not completely fix the prescription opioid abuse problem, but they can be part of a comprehensive approach to combat the epidemic. And the development of abuse-deterrent opioids is only one of many elements of FDA’s overall approach, which includes provider and patient education, close monitoring of approved opioids, and review and approval of drugs to treat addiction and prevent overdose. We will continue to work hard to address the serious problem of opioid abuse while providing needed pain medicines for patients.

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

Mind the Gap: Strengthening relations with the European Medicines Agency to the benefit of public health

David Martin, M.D., M.P.H.

Cars driving on the left side of the road and exhortations to “mind the gap” when exiting the underground became a part of my daily routine when I joined the FDA Office of International Programs as the Acting FDA Liaison to the European Medicines Agency (EMA) in London. EMA is an important partner for the FDA: It coordinates a network of 4,500 European scientists and evaluates and supervises human and animal medicines for more than 500 million people in 31 countries.

Sabine Haubenreisser and David Martin

EMA’s Sabine Haubenreisser, MSc, Ph.D., and David Martin, M.D., M.P.H., who served as the Acting FDA Liaison to the European Medicines Agency from June through September 2014.

On my first day at the EMA, I learned that its Pharmacovigilance Risk Assessment Committee (PRAC) was debating a suspension of the European marketing authorization for a product approved in the United States by FDA. Moreover, PRAC was seeking urgent action within a week, which required quick response by FDA. Without it, suspension of a marketing authorization by Europe for an FDA-approved product could be confusing to patients, medical care providers, and industry in the U.S.

Consulting with management, review team members, and the international team from the FDA Center for Drug Evaluation and Research (CDER), I described the decision points to be addressed by the Europeans. The CDER team was already conducting a preliminary epidemiologic analysis of the possible relationship between the product and the adverse event in a large U.S. medical claims database. EMA had been already made aware of the ongoing CDER analysis, but needed formal detailed information to include in its benefit/risk assessment. PRAC had to be briefed on the broad outlines of the FDA evaluation within 48 hours, and needed access to FDA’s interim analysis within two weeks.

After a quickly arranged briefing under the auspices of an FDA-EMA confidentiality arrangement, CDER completed and shared the analysis in less than one week. At a follow-up meeting, FDA, EMA, and PRAC experts reviewed all data sources. The information indicated that the benefits of the product outweighed the low potential risk of adverse events. This information was included in the formal review by the PRAC, and a majority of PRAC members voted to maintain the product’s marketing authorization.

This episode showed  the importance of reciprocal FDA and EMA representation at each agency, which is currently carried out by EMA’s Sabine Haubenreisser, MSc, Ph.D. in FDA’s headquarters in White Oak and FDA’s Amy Egan, M.D. in London. Contacts between the liaisons and host agency leadership facilitate strategic dialogue that informs future policy making. And through close observation of the U.S. and European regulatory agencies in action, the FDA and EMA liaisons can help both sides find common ground when they are faced with regulatory decisions that could impact global public health.

David Martin, M.D., M.P.H., served as the Acting FDA Liaison to the European Medicines Agency from June through September 2014. He is the Director of the Division of Epidemiology within FDA’s Center for Biologics Evaluation and Research.

About EMA: European Medicines Agency

EU facts and figures: European Union

EMA/FDA confidentiality agreement: International Programs

Partnerships Are the Key to Keeping Foods Safe Worldwide

By: Michael R. Taylor

The success or failure of our efforts to keep foods safe all over the world rests on the strength of our global partnerships and the work we can do together to verify that food safety standards are being met. That’s why, today, after two days of meetings in Beijing with Chinese regulators, I am speaking at the China International Food Safety and Quality Conference and Expo in Shanghai about meeting the food safety challenges that all nations face.

Mike Taylor speaks in China

Deputy FDA Commissioner Michael R. Taylor giving the keynote address at the China International Food Safety and Quality Conference and Expo.

No matter where we live, we all want to feed our families with the confidence that the foods we are enjoying are safe to eat. Food safety is thus a goal that transcends international borders, and the food supply has never been so global. In the United States, 15 percent of our food supply is imported from other countries, including nearly 50 percent of fresh fruit and 20 percent of fresh vegetables. And last year, the U.S. exported a record $136 billion in foods, feed and beverages.

Congress recognized this when it enacted the FDA Food Safety Modernization Act (FSMA) and established a new regulatory paradigm for food safety, drawing on widely accepted international practices. The paradigm is simple. No matter where food comes from, we will achieve the best food safety results if we define—in workable, science-based standards—the approaches to managing food safety systems that we know are effective in preventing food safety problems AND if we achieve high rates of compliance with those standards.

Verification is key to the success of the FSMA paradigm and our global understanding of how to make food safe. It is also key to the consumer confidence that makes robust trade in food possible. Verification begins with what food producers do in their operations to verify, on an ongoing basis, that they are successfully implementing proper controls to prevent safety problems. But verification is also a public responsibility and a challenge that all nations face in our global food system.

FDA Staff at China Event

From left, Christopher Hickey, director of FDA’s China offices, Deputy Commissioner Michael Taylor and Roberta Wagner, co-chair of FDA’s FSMA Operations Team Steering Committee, visiting the China Food and Drug Administration.

Domestically, we will use inspections and other means, including sampling and testing, to verify that private food safety management systems are working effectively to prevent problems. This is a shift from our historic focus on enforcement of adulteration standards, although we will continue to act swiftly and forcefully when violations are putting consumers at risk.

In FDA’s oversight of imported foods, FSMA’s new Foreign Supplier Verification Programs (FSVP) will make importers accountable to FDA for documenting that their foreign suppliers have taken preventive measures to help ensure the safety of their food products. And we will inspect importers to verify that they are doing their job with regard to FSVP.

But we know that is not enough. Congress also mandated that we work more closely with foreign governments to verify that food safety standards are being met, so we are investing heavily in new forms of partnership with major trading partners with the goal of relying on each other’s verification activities as an element of the overall assurance system.

A prime example and model for collaboration is our joint initiative with Mexico to build a full operational partnership on produce safety, based on a strongly shared commitment to food safety as a public health goal. We are working directly with SENASICA and COFEPRIS – the agencies in Mexico that are responsible for produce safety – to expand the sharing of information, personnel and best practices, and to improve laboratory and other technical harmonization. Our goal is mutual reliance on each other’s oversight work. This initiative includes an important public-private partnership component.

Another model for building verification partnerships is our pursuit of what we call “systems recognition agreements” with countries whose overall food safety systems are comparable to ours. We have one with New Zealand and are working on agreements with Canada and Australia.

We also believe that being present in foreign countries is important to our own verification work and to building partnerships with foreign governments. That’s why we have increased our foreign inspections and have FDA offices in China, India, Europe, and Latin America. China, with its size and complexity, poses unique challenges as we seek to build food safety partnerships, so we are working to increase our China-based staff as a way to improve verification and foster mutual understanding and confidence.

The challenge of implementing the FSMA food safety paradigm on a global scale is huge, but I’m convinced from all the dialogue we’ve had around the world that we are on the right track. We have a long way to go, of course, but I have no doubt we’ll get there with the continued collaboration and commitment of our trading partners.

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

Getting Potentially Life-Saving Drugs to High-Risk Breast Cancer Patients Faster

By: Tatiana Prowell, M.D. and Richard Pazdur, M.D.

Last month, researchers at an international oncology conference in Spain reported that pertuzumab, which was FDA-approved for treatment of HER2+ metastatic breast cancer in June 2012, improved survival by an average of nearly 16 months when added to standard treatment. This was yet another piece of good news, and one of unprecedented magnitude, for patients living with what was once the most dreaded type of breast cancer.

Tatiana Prowell and Richard Pazdur

Tatiana Prowell, M.D., Breast Cancer Scientific Lead, Division of Oncology Products 1,
Office of Hematology Oncology Products, and Richard Pazdur, M.D., Director of the Office of Hematology and Oncology Products, both of FDA’s Center for Drug Evaluation and Research

In the past, the next step would have been to wait for years while large clinical trials were conducted to determine if the drug also worked for earlier stages of breast cancer. This is beginning to change.

Although most women diagnosed with early breast cancer have surgery first to remove their tumor and then drug treatment to reduce risk of recurrence (as “adjuvant therapy”), it is also possible to give the same anti-cancer medicines before surgery (as “neoadjuvant therapy”) with equally beneficial results. Most breast cancers will shrink when drugs are given before surgery, and some will completely disappear by the time of surgery. This is called a pathological complete response, or pCR. Patients with a pCR at the time of surgery are at much lower risk of having their cancers “metastasize,” or spread, in the future.

To help speed drug approval for high-risk patients, in May of 2012, we proposed using pCR as a new endpoint that could support accelerated drug approval in high-risk early breast cancer. The basis for drug approval in early breast cancer to that point had generally been disease-free survival (how long patients survive without their cancer coming back) or overall survival. Such long-term outcomes remain tremendously important both to patients and regulators and will continue to be measured in clinical trials of every drug for early breast cancer. But relying exclusively on these outcomes for drug approval creates a gap of 5-10 years between approval for metastatic breast cancer and subsequent approval for use in patients with earlier stages of the disease.

Last month, we finalized FDA’s policy on use of pCR for accelerated approval in high-risk early breast cancer. Since we first proposed to rely on the endpoint for approval more than 2 years ago, we have learned a lot. FDA staff have spoken in conferences around the country, held webinars, and reviewed dozens of comments on the policy from academia, pharmaceutical companies, patients, and engaged citizens. We hosted an open public workshop that gathered breast cancer thought leaders, patient advocates, drug developers, and regulators, and produced consensus on use of pCR to support accelerated approval. To refine our understanding of pCR as a regulatory endpoint, FDA also led an international effort to pool data from more than 12,000 women enrolled in neoadjuvant trials.

So where are we in 2014? This pathway clearly has the potential to put the most promising drugs in the hands of the highest risk breast cancer patients years earlier than would ever have been possible previously, and in so doing, may increase their odds of cure.  Nonetheless, uncertainty remains about how well pCR rate can predict a drug’s ability to improve outcomes for patients with high-risk, early breast cancer, and what magnitude of increase in pCR rate is meaningful. For now, to make our decisions on accelerated approval in early breast cancer, we will rely on everything we know about a drug: the science behind how it works; how effective it is in other types of cancer or in more advanced stages of breast cancer; how well other drugs in the same class work; what side effects the drug causes, and how much it increases pCR rate compared to what can be accomplished with standard treatment.

Our first approval of a neoadjuvant drug for high-risk, early breast cancer occurred in September 2013. Pertuzumab was granted accelerated approval upon the basis of pCR rates and safety data from two neoadjuvant trials of the drug, as well as earlier efficacy and safety results from the metastatic breast cancer trial. At the time it granted accelerated approval, FDA required the sponsor to conduct a large adjuvant trial to confirm that pertuzumab does in fact reduce the risk of recurrence or death for women with earlier-stage tumors. The first results of that trial are expected in about 2 years.

There will always be uncertainty whenever we grant an accelerated approval for a neoadjuvant breast cancer drug, and this case is no exception. But, for the first time, women facing a new diagnosis of high-risk HER2+ breast cancer and their doctors will be able to decide whether the benefits and risks of pertuzumab make sense for them. There is still much to be done, but this is an important first step.

Tatiana Prowell, M.D., is Breast Cancer Scientific Lead, Division of Oncology Products 1, Office of Hematology Oncology Products, at FDA’s Center for Drug Evaluation and Research

Richard Pazdur, M.D., is Director of the Office of Hematology and Oncology Products at FDA’s Center for Drug Evaluation and Research