Reflecting on our steps to give Americans more informed food choices

By: Michael R. Taylor

Michael R. Taylor is FDA’s Deputy Commissioner for Foods and Veterinary Medicine.Yesterday we released final rules to make it easier for Americans to make informed choices about the foods they buy at major chain restaurants and similar retail food establishments and from vending machines. Every day, for years to come, millions of consumers will see and benefit from ready access to calorie information they would otherwise lack.

In evaluating public health issues, FDA must often make difficult decisions and strike delicate balances. For an issue like menu labeling that touches so many people and must address the complexities of our modern food system, it is natural that there would be a wide range of views. So we appreciate the very positive reactions to our rules from the restaurant industry, the vending industry, consumer groups and public health experts, including the following:

We also know that, while our FDA team worked long and hard on these final rules, crafting them after carefully reviewing more than 1,000 comments on our original proposals, our work is not done. We will continue to work with all affected industries to answer questions about the rules and facilitate compliance in a practical way that can benefit the health of Americans for many years to come.

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

Providing Consumers More Information with Menu and Vending Labeling

By: Margaret A. Hamburg, M.D.

Increasingly, Americans are paying more attention to the foods we eat – the kinds, the quantities, the sources, and the individual ingredients that go into our meals. We know that when we have more information about the nutritional content of our food, we have the opportunity to make more informed choices.

Margaret Hamburg, M.D.Increased awareness about the choices we make certainly does not mean that we always eat what is healthy. But whether we choose to eat french fries or a tuna sandwich, those selections should reflect informed decision-making. That can only happen if the right information is available to make those choices. That’s why the two new rules FDA issued today on menu and vending machine labeling are so valuable for consumers.

Some states, localities and big restaurant chains are already doing their own forms of menu labeling. The new rules will require calorie information to be listed in a consistent, direct and accessible manner on menus in chain restaurants and similar retail food establishments, and on vending machines. Under the menu labeling rule, certain additional nutrition information will need to be available in writing when customers ask for it.

This is especially important, because about one third of the calories Americans eat and drink come from foods and beverages consumed away from home. In addition, research shows that when we eat out we often consume less nutritious foods and underestimate the number of calories we are taking in.

People can clearly benefit by knowing more, and the new FDA rules will help to do just that. They are not requirements about what people should eat or what restaurants should serve, but rather they will place more information in the customer’s hands so that they can make more informed choices for themselves and their families.

After considering more than 1,100 comments on the proposed versions of these rules, the rules create a consistent approach that will establish a level playing field for larger chain restaurants, while not being overly burdensome on small businesses or individual food establishments. The menu labeling rule applies to restaurants and similar retail food establishments only if they are part of a chain of 20 or more locations and satisfy other criteria.

Few decisions are as critical to our health and our daily lives as those involving the foods we eat. With these new rules on menu and vending machine labeling, Americans can be more certain that those choices are informed ones.

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

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

FDA Approves a Vaccine to Address a Critical Public Health Need – Trumenba– for Prevention of Serogroup B Meningococcal Disease

By: Karen Midthun, M.D.

Over the last year and a half, there have been numerous reports about outbreaks of bacterial meningitis on several college campuses. Invasive meningococcal disease is a life-threatening illness caused by the bacterium Neisseria meningitidis that infects the bloodstream (sepsis) and the lining that surrounds the brain and spinal cord (meningitis). N. meningitidis is a leading cause of bacterial meningitis, which can have devastating consequences. Between 10 and 15 percent of people who develop meningococcal disease die from the infection, and another 10 to 20 percent suffer permanent complications, such as brain damage or limb loss.

Dr. Karen MidthunThere are five main serogroups of meningococcal bacteria that cause illness: A, B, C, Y and W. FDA has previously approved other vaccines to prevent invasive disease caused by serogroups A, C, Y and W, but they do not protect against meningococcal disease caused by serogroup B, which is the serogroup responsible for the recent outbreaks.  These outbreaks underscore why it’s so important to have vaccines that can prevent meningococcal disease.

FDA recently used several strategies to approve Trumenba, the first vaccine licensed in the United States to prevent invasive meningococcal disease caused by serogroup B. This included use of the accelerated approval regulatory pathway, which allows the agency to approve products that provide meaningful therapeutic benefit to patients over existing treatments for serious or life-threatening diseases, based on evidence that the product has an effect that is reasonably likely to predict clinical benefit. The use of this pathway reduces the time it takes for needed medical products to become available to patients.

Trumenba also received breakthrough therapy designation. This designation facilitated the development, scientific evaluation, and approval of the vaccine. In particular, it provided the manufacturer with more intensive FDA guidance on an efficient vaccine development program, and an organizational commitment involving senior FDA managers. It also provided for a “rolling” submission of the Biologics License Application, which allows for sections of the application to be submitted to FDA for review as they are completed, without waiting to submit the complete application at one time.

FDA also designated this application to receive priority review. I am very proud of the extraordinary effort by FDA review staff to thoroughly evaluate the safety and effectiveness of Trumenba and approve it in record time. Our scientific staff worked tirelessly to complete their evaluation in well under the usual six-months timeframe for priority reviews. My colleagues worked closely with Pfizer, the manufacturer, to address this critical public health need.

We are committed to making important medical products available to people who need them. The approval of Trumenba is just one example of the outstanding work by dedicated FDA staff.

Karen Midthun, M.D., is the Director of FDA’s Center for Biologics Evaluation and Research

FDA and Asia-Pacific Colleagues Focus on Food Safety

By: Camille Brewer, M.S., R.D., and Christopher Hickey, Ph.D.

In the alphabet soup of international affairs— UN, NATO, WTO— APEC is perhaps one of the lesser-known entities. In FDA’s world, APEC (Asia-Pacific Economic Cooperation), which focuses on facilitating economic growth, cooperation, trade and investment in the Asia-Pacific region, is a significant focus of collaboration in the area of food safety.

Camille Brewer

Camille Brewer, M.S., R.D., Director of International Affairs at FDA’s Office of Foods and Veterinary Medicine.

Food safety is one of the priority areas for APEC, as evidenced by the establishment of the Food Safety Cooperation Forum (FSCF), which has been co-chaired by China and Australia since the forum was formally established in April 2007. FSCF was founded to bring together APEC’s 21 member economies to make the region’s food standards consistent with those of the international food standards body (Codex Alimentarius Commission) – all for the ultimate purpose of improving public health while facilitating trade. (The word “economies,” rather than “nations,” is used to describe APEC members because of their focus on trade and economic issues.)

In September, FDA joined colleagues for APEC food safety meetings in Beijing. Because of the importance of building the capacity for food safety protections in China and the region, China hosted a “Special Session” of FSCF to consider progress from technical working groups on export certificates and maximum residue limits of pesticide in food products. There was also a meeting called the “High-Level Regulator Industry Dialogue” to spotlight numerous cooperative ventures between the private and public sectors. This overview of APEC projects gave us a sense of how well the regions’ economies function together.

Christopher Hickey

Christopher Hickey, Ph.D., FDA’s Country Director for the People’s Republic of China.

While FSCF aims to support dialogue among regulators, many of APEC’s food safety initiatives are built on collaboration with government, industry and academia. At the High-Level Regulator-Industry Dialogue session, the group discussed how working with partners is enhancing food safety by leveraging the benefits of our shared work. FDA talked about how the FDA Food Safety Modernization Act (FSMA) creates new tools to prevent food safety problems, and how FDA’s foreign offices are working with fellow regulators to bolster a coordinated approach.  It was especially heartening to see China present its challenges in the area of food safety as an opportunity to lead development of deeper food safety capacity in the APEC region.

The central role of partnerships was a predominant theme throughout, and when Pam Bailey, CEO and president of the Grocery Manufacturers of America (GMA), addressed participants, she implored delegates to “work together to create conduits for the private sector to interface with governments as they develop newfound safety regimes.”  Bailey highlighted the U.S. notice and comment rule-making process, and noted GMA’s proactive engagement in this process. She emphasized the transparency of the U.S. system, and spoke of GMA’s active engagement to provide constructive feedback on the rules that FDA has proposed to implement FSMA. The importance of transparency in regulatory operations was a message repeated by all representatives from private and public sectors.

Camille Brewer

Camille Brewer, M.S., R.D., at the APEC food safety meetings in Beijing.

There is exceptional collaborative work taking place. The value of these partnerships was evident in technical sessions of the meetings, which covered best practices in laboratory proficiency testing, pilot projects on export certificates in the wine industry, and the convergence of approaches to regulate maximum residue limits for pesticides in wine grapes. It was exciting for us to hear constructive proposals from both developing and developed countries, industry and academia, each with a vital role to play in addressing the challenges of a globalized food safety system. The candid exchange of views is a recipe for success.

Camille Brewer, M.S., R.D., is Director of International Affairs at FDA’s Office of Foods and Veterinary Medicine.

Christopher Hickey, Ph.D., is FDA’s Country Director for the People’s Republic of China.

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

FDA Now Collects Data for Tobacco User Fee Calculations

By: Bryan Walsh

The Family Smoking Prevention and Tobacco Control Act (FSPTCA) granted FDA the authority to regulate tobacco products and to collect user fees from tobacco manufacturers and importers to support FDA tobacco regulation activities. These fees provide the FDA with resources for building a regulation framework to reduce the impact of tobacco use on the nation’s health.

Bryan WalshOn July 10, 2014, FDA issued a final rule that changed some administrative aspects of the tobacco product user fee process. In the past, U.S. Department of Agriculture (USDA), under a separate tobacco assessment program, collected information from tobacco product manufacturers and importers and shared that information with FDA. FDA then used that information to calculate tobacco product user fees. However, the USDA program ended in September 2014, and FDA’s authority to collect the information directly from tobacco product manufacturers and importers began on October 1, 2014.

This change does not have a large impact on tobacco manufacturers and importers. The July rule applies only to domestic manufacturers and importers of four classes of tobacco products – cigarettes, snuff, chewing tobacco, and roll-your-own tobacco. They will submit essentially the same information to FDA as they did to USDA. The new Form FDA 3852 is very similar to the form manufacturers and importers have been sending to USDA. Thus, the new rule does not add additional administrative burdens to required data submissions.

The rule also addresses other issues related to tobacco product user fees. For example, it advises how manufacturers and importers might submit a dispute, explains FDA notification procedures and how to pay user fee assessments, and describes penalties for failure to report information or pay user fees.

The final rule will help ensure that FDA continues to have the information needed to assess and collect tobacco product user fees. You can find more information on our User Fees page, including the form FDA 3852 (which includes submission information).

If you are interested in learning more about user fees, please join us for a webinar on Nov. 5, 2014 at 2 p.m. EST.

Bryan Walsh is a Program Analyst, Office of Management, at FDA’s Center for Tobacco Products