New Drug Attacks Resistant TB

By: Margaret A. Hamburg, M.D.

Having seen first-hand the threat to public health posed by multi-drug resistant tuberculosis (MDR TB), which cannot be cured by many of the most powerful drugs usually used to treat the disease, I’m pleased that another weapon has been added to the arsenal for fighting this deadly, contagious disease.

Margaret Hamburg, M.D.TB is a disease caused by germs that are spread from person to person through the air. TB usually affects the lungs, but it can also affect other parts of the body, such as the brain, the kidneys, or the spine. A person with TB can die if they do not get treatment.

The critical need for new interventions is real and fortunately we now have a new drug—approved in only six months through an expedited pathway — to treat this. Bedaquiline, sold under the brand name Sirturo, is the first drug developed specifically to treat multi-drug resistant tuberculosis involving the lungs — Mycobacterium tuberculosis. It will be used in combination with other drugs when other TB drug treatment regimens will not be effective.

Sirturo has a new mechanism of action: It inhibits an enzyme needed for replication of the M. tuberculosis bacteria and represents an important new development for some patients with particularly difficult to treat forms of tuberculosis

TB is one the world’s deadliest diseases, and is more prevalent now than at any time in history. Last year, nearly 9 million people worldwide became sick with TB, and 1.4 million died. A total of 10,528 cases were reported in the U.S. last year, according to the Centers for Disease Control and Prevention.

People with active TB must take several drugs on a regular basis for 6 to 12 months; for drug resistant TB the treatment regimens are longer and more complicated. If treatment is inadequate or incomplete, the disease can become resistant to certain drugs, meaning those medications don’t work anymore. It then becomes more difficult or sometimes impossible to treat or cure these patients, putting them and others at serious health risk.

Of course, drugs have risks too. Given the significant potential risks of Sirturo, a boxed warning will be included in the label for the drug alerting patients and health care professionals about the increased rate of mortality observed in patients who received bedaquiline compared to patients who received treatment of their resistant TB with other drugs. The boxed warning will also describe the risk of Sirturo’s effects on the heart that can infrequently result in abnormal heart rhythms, leading in some instances, to death.

There is no question that we need more and better treatments for drug-resistant TB. And we’ll continue to need new drugs as the disease mutates or changes.  Meanwhile, Sirturo is a welcome addition to the drugs that we have available to treat patients who have multi-drug resistant TB who need this drug as part of their treatment regimen.

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


FDA Writing New Chapters in Food Safety History

By: Michael R. Taylor, J.D.

Yesterday, Sunland Inc. entered into a court ordered agreement imposing requirements that must be complied with if the company is to operate. This consent decree follows FDA’s suspension of Sunland’s food facility registration in November as a result of evidence linking Sunland to an outbreak of Salmonella Bredeney that sickened 42 people in 20 states, as well as the company’s history of violations. The company was barred from distributing food in intrastate or interstate commerce while its registration was suspended. 

Mike Taylor, J.D.Yesterday’s consent decree may be seen by some as a final step in the process, but at FDA we see it as a beginning. Certainly, it is a new beginning for the company, which must correct the problems identified during recent FDA inspections before being allowed to market its nut butter products. More broadly, though, it is the beginning of a new chapter in FDA history.

With the suspension of Sunland’s food facility registration, for the first time FDA was, in effect, able to independently prevent a company from distributing food that could have caused harm to consumers. This was our first use of this new authority granted by the FDA Food Safety Modernization Act (FSMA), and it will be an important tool for FDA to use in the future to ensure the accountability of companies for the safety of the food they produce. 

Under the decree, Sunland must hire an independent sanitation expert to develop a program to ensure products are produced in a sanitary way and according to good manufacturing practices. The company must also conduct environmental testing to ensure that disease-causing bacteria aren’t present in its facility or in its final food products. FDA will evaluate the programs Sunland sets up, and will not allow the company to operate its peanut butter plant until we determine that its products can be safely produced. 

Paving the way for this new beginning of accountability for food safety was the work of the many employees from FDA and CDC, and state and local governments, who responded to and investigated this outbreak. The work done on this investigation was outstanding. Within days of being notified of the outbreak, our Coordinated Outbreak Response and Evaluation (CORE) network was making headway on the investigation. A link was made between the illnesses and the product and its manufacturer, and our investigators in the field ramped up their on-going investigation of Sunland’s facility to find the source of the outbreak.  

I also think that FDA’s first use of the suspension authority provided by FSMA demonstrates the promise that FSMA itself holds in all its aspects. The suspension of Sunland’s registration demonstrates FDA’s new enforcement tools, but we are also working on other new preventative tools as well. 

As I said earlier, we are writing new chapters in the history not just of FDA, but of food safety. Our response to the recent Salmonella Bredeney outbreak related to peanut butter was a fine example of our newest innovations, like CORE, and using our authority to suspend a registration. But there is still more to come.

Michael R. Taylor, J.D., is Deputy Commissioner for Foods and Veterinary Medicine


Strategies for More Successful Drug Trials

By Bob Temple, M.D.

Bob Temple, M.D.  is Deputy Director for Clinical Science in FDA’s Center for Drug Evaluation and Research

Bob Temple, M.D., Deputy Director for Clinical Science

In recent months, drug developers have succeeded in bringing important drugs to market for cystic fibrosis, cancer and other conditions by employing strategies for achieving greater clinical trial success.

Today FDA is issuing a draft guidance that spells out how drug developers can use such strategies, known as clinical trial enrichment, to greatly increase the likelihood that data collected during a clinical trial will demonstrate that an effective drug is effective. These are potentially powerful strategies for the pharmaceutical industry because appropriate use of enrichment could result in smaller studies, shortened drug development times, and lower development costs.

Here’s how it works. Before any promising drug can come to market in the United States, drug developers must provide sufficient evidence that the product is safe to use on patients (that is, that the benefits of the drug outweigh its known risks), and is effective in treating a specific disease or medical condition.

Evidence is typically collected by enrolling patients in a clinical trial and then randomly assigning them to two groups: one group that will receive the drug and the other group that doesn’t.

Those who employ an enrichment strategy enroll patients who are likely to demonstrate an effect, based on their demographics, clinical histories or other characteristics.

Anyone familiar with clinical trial selection knows that rudimentary enrichment strategies have long been common. After all, investigators don’t simply study a random sample of the overall population. Instead they try to find a population most suitable for studying the drug.

One way to do this is to decrease what might be called “noise.” For example, including people who don’t really have the disease being studied, or including people who won’t take the medicine or complete the study, will make an effect harder to show.

There are two other kinds of enrichment: prognostic enrichment and predictive enrichment. Prognostic enrichment involves choosing patients for a study who will have the disease manifestations the drug is intended to prevent. For example, a study of a lipid-lowering drug intended to decrease the rate of heart attacks might choose a population likely to have an increased risk of heart attacks, such as being diabetic. Choosing patients of that kind makes it more possible to see an effect if there is one.

Predictive enrichment is particularly exciting and involves use of some aspect of the patient’s physiology, genetics or past responses to identify patients who can respond to the treatment.

Conducting a clinical study in a patient population that has a larger than average response to treatment can greatly reduce the number of patients needed in the study and can direct the treatment to the patients in whom the drug actually works.

The cystic fibrosis drug Kalydeco (ivacaftor) is an example of this successful strategy. The drug works only in the 4 percent of CF patients with a specific genetic abnormality. If the drug had been studied on the entire CF population, it would have been impossible to detect the drug’s effect.

An enrichment strategy was also used successfully in studies of of Xalkori (crizontinib) for patients with a late-stage form of lung cancer.

While enrichment won’t save a drug that doesn’t work, it will help find one that will.

Bob Temple, M.D., is Deputy Director for Clinical Science in FDA’s Center for Drug Evaluation and Research

Improving the World through Improved Food Safety

By: Margaret A. Hamburg, M.D.

Food safety may seem an unusual issue for a lending institution created to encourage growth and reduce poverty in developing countries.

Photo courtesy of the World Bank

The World Bank, however, rightly notes that food safety is not only about public health, as important as that is. It is also critical for economic development, expanded market access and trade, and ultimately for the alleviation of poverty. This week in Paris, the World Bank held its first Global Food Safety Partnership Conference and I was immensely pleased to be able to participate.

The Global Food Safety Partnership (GFSP) is a major milestone on the road to protecting the health of all people in our increasingly interconnected world. Participants represent governments, industry, academia, international organizations and technical bodies.  Among other things, both public and private members are committed to working collectively for stronger food safety systems and strategies.

FDA’s primary mission is to protect the supply of food and medical products in the United States. Increasingly, though, that mission cannot be carried out completely within our borders. Given that we import half of the fresh fruits and 80 percent of the seafood we consume, to name just two commodities, our efforts must be global.

As I noted during a keynote address, the overarching theme of the FDA Food Safety Modernization Act is prevention. The law acknowledges the global movement toward stronger food safety standards and higher assurances that standards are being met, which is a driver of FDA’s transformed import strategy. For FDA, it is essential that we contribute to and rely on capable foreign food safety oversight. Strengthening these food safety systems is the key to maintaining the integrity of the global supply chain. 

Serendipitously, our self-interest coincides with a humanitarian imperative.

Photo courtesy of the World Bank

Up to a third of people in the developing world suffer food and water-borne illnesses every year. More than 2.2 million each year, mostly children, die of those illnesses. Farmers and other food-related enterprises in those countries have little hope of competing in the marketplace as long as their products are suspect.

GFSP is an innovative example of the kind of cooperation we need around the world. It is bringing together food producers and manufacturers, academics, regulators and industry representatives, as well as lenders and borrowers. We all have a collective interest in food safety, and a shared responsibility. When any country improves, everyone wins.

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

A New Partnership with New Zealand

By: Deborah M. Autor, J.D. and Michael R. Taylor, J.D.

This week, for the first time, FDA and New Zealand’s Ministry for Primary Industries recognized each other’s food safety systems as providing a comparable degree of food safety assurance at a signing ceremony at the Embassy of New Zealand in Washington, D.C.

One practical result of this arrangement is enhanced information exchanges to avoid duplication of efforts: for example, if the two food-exporting countries decide that their food safety programs and practices provide a comparable level of food safety assurance, they can take this into account as appropriate in determining the type and frequency of inspections to conduct of foreign manufacturing establishments and of imported food shipments.

This means the comparable nations can concentrate more resources, including inspections, on foods that present a greater risk, providing for improved food safety overall.

The arrangement with New Zealand is part of an overall strategy for strengthening the global food safety net through closer collaboration with regulators around the world, highlighted in FDA’s report “Pathway to Global Product Safety and Quality.”

Mike Taylor, J.D.FDA recognizes that, while import examinations are an important tool in helping to ensure that imported foods are safe, we can’t examine every food headed for or arriving at our borders. Instead we make risk-based decisions about which shipments need the least and the most scrutiny at the border. Under the new Food Safety Modernization Act (FSMA), FDA is mandated to expand its import tool kit beyond FDA’s border screening to include stronger importer accountability for verifying the safety of food imports, a much strengthened system of private audits, more FDA inspections overseas, and importantly, greater collaboration with foreign regulatory authorities.

Globally, however, there are major differences in the strength of food safety regulatory systems. For years, we have conducted reviews of various food safety policies and programs in place in other countries to provide assurances of the safety of individual products. The systems recognition process that we completed with New Zealand goes beyond our previous commodity-specific evaluation strategy, covering the overall food safety system that is in place, and how it is implemented, and extending to all FDA-regulated food products.


In the past, New Zealand and the U.S. had certain commodity-specific arrangements in place such as ones for seafood and dry dairy products. A scheduled review of these arrangements coincided with the time FDA was starting to consider ways to expand the global safety net through enhanced cooperation with other nations. Both countries thought: Why not try to expand beyond these products to include every product regulated by FDA and its counterpart in New Zealand?

Carol Barnao, Deputy Director General Standards, New Zealand Ministry for Primary Industries, and Mike Taylor, FDA Deputy Commissioner for Foods and Veterinary Medicine, at the signing ceremony.

That was the start of intense work which began in 2010. FDA, working with New Zealand regulators, comparing every facet of each country’s food safety system—the training of inspectors, procedures for identifying and responding to food safety issues, and legal authority, to name a few.

Once we had confidence in the system on paper, we conducted on-site reviews of the implementation of their programs, to give us an understanding of how their programs worked in practice.

Both countries retain the right to conduct inspections of each other’s products as appropriate. But assured about each other’s competency and commitment, both are more likely to focus their resources on higher risks. Importantly, if a problem does occur, each country intends to work cooperatively on follow up.

The process for conducting systems recognition is still being pilot tested with Canada. FDA will continue to update and refine our process as we work through the pilot with Canada. Systems recognition is voluntary and not required in order for a country to export FDA-regulated foods to the U.S., but any country that believes it can meet the very high bar will have the option of seeking recognition. Meanwhile, we will continue working to foster a global food safety net for all.

Deborah M. Autor, J.D., is Deputy Commissioner for Global Regulatory Operations and Policy

Michael R. Taylor, J.D., is Deputy Commissioner for Foods and Veterinary Medicine

U.S. and Canada Working Together To Provide Access to Needed Veterinary Drugs

en  français

By: Bernadette Dunham, D.V.M, Ph.D. and Murray M. Lumpkin, M.D., M.Sc.

Bernadette Dunham, D.V.M, Ph.D., Director of FDA’s Center for Veterinary Medicine

The first simultaneous review and approval of a veterinary drug by the United States and Canada marks a successful start to a collaboration aimed at providing quicker access to needed veterinary medicines. The collaboration is also intended to remove trade barriers and reduce costs for consumers, regulators and manufacturers.

Here’s the background: Last year, President Obama and Canada’s Prime Minister Stephen Harper announced the creation of the U.S.-Canada Regulatory Cooperation Council (RCC). The council’s goal is to better align several regulatory approaches, to remove duplicative requirements, and to better share regulatory resources.

Eliminating overlapping efforts is expected to result in reduced costs and more timely access to products while encouraging trade and investment.

Murray M. Lumpkin, M.D., M.Sc., FDA Commissioner's Senior Advisor and Representative for Global Issues


After the agreement to create the council was signed, one of the first projects was to have drug regulators in both countries simultaneously review the same effectiveness data for approval of Elanco’s new animal drug, Comfortis, used to kill fleas and prevent flea infestation in cats. That effort culminated in this week’s announcement that FDA’s Center for Veterinary Medicine and Health Canada’s Veterinary Drugs Directorate had simultaneously approved the drug.

Regulators in both countries have determined that several other veterinary drugs are also potentially eligible for simultaneous review by both countries under the RCC action plan.


Because of this successful initial collaboration, there is much potential opportunity going forward to continue to improve our review efficiency and the use of our review resources to improve access to safe and effective products on both sides of the border.

Bernadette Dunham, D.V.M, Ph.D., is Director of FDA’s Center for Veterinary Medicine.

Murray M. Lumpkin, M.D., M.Sc., is FDA Commissioner’s Senior Advisor and Representative for Global Issues.


China Takes Steps to Strengthen Food Safety

By: Camille Brewer, M.S., R.D.

An important message came through loud and clear during FDA’s whirlwind visit to China this month: China is determined to strengthen its food safety system. I had not visited China in nearly 10 years and I was struck by the extraordinary progress in the cities we visited. The towering skyscrapers, tree-lined boulevards, and the obvious signs of a rising middle class demonstrate the reality of an economy that has grown by leaps and bounds. That growth has led to rising consumer expectations, and China is clearly working hard to meet consumer and global expectations for safe food. 

This message was repeated in meeting after meeting that Mike Taylor, Deputy Commissioner for Foods and Veterinary Medicine, and I had with Chinese officials. We saw a clear recognition of the scope and complexity of the challenge as well as a resolve—indeed, an enthusiasm—to take on the challenges head-on, and develop a modern, effective, and efficient food safety system.

Make no mistake: this will not be easy for China.  It has considerable catching up to do in the science and daily practice of food safety and in its legal system.  But the enthusiasm and commitment we saw seems real, and is backed up by action.

China is now implementing its first comprehensive food safety law, which established a Food Safety Committee to oversee all ministries responsible for food safety. The law also calls for the establishment of a national center to focus on risk assessment and risk monitoring to strengthen the scientific underpinnings of food safety regulations.

Earlier this year, China issued a five-year plan for national food safety supervision.  The plan directs the Food Safety Committee and its working office to oversee improvements intended to strengthen China’s food safety regulatory system, emergency response capabilities, supply chain management, surveillance systems, standard-setting activities, and third-party testing. It also calls for improved risk communication and interagency coordination among regulators at central, provincial, and local levels. This plan is testimony to the resolve of the Chinese government to elevate the importance of food safety.

FDA has been working very closely with China for some time to enhance cooperation and address food safety issues of concern. Today, FDA and Chinese food safety authorities renewed an agreement originally signed in 2007. Under the agreement, FDA has helped China to strengthen its regulatory system and better understand FDA’s food safety requirements. This cooperation was made much easier when FDA established offices in China in 2008, enabling us to dramatically increase our inspections and conduct workshops for Chinese government and industry representatives.

On our trip, we also noticed increased consumer interest in food safety. We met with a professor and blogger from China Agricultural University who emphasized Chinese consumers’ concern about economic fraud.  A representative from the Shanghai State FDA and Shanghai Food Safety Committee told us that they have established a consolidated consumer hotline for food safety concerns. 

Michael R. Taylor, Deputy Commissioner for Foods and Veterinary Medicine

This consumer focus dovetailed well with the presentation made by Mike Taylor at the China International Food Safety and Quality Conference in Shanghai. He noted that consumer confidence in the food supply is an important goal, and what is needed to improve food safety is also what is needed to strengthen consumer confidence in the food they eat. That’s an industry commitment to food safety, credible and effective government oversight, public-private collaboration and partnership, and transparency on the part of industry and government.

He noted that countries other than China are pursuing similar food safety initiatives. In addition to the United States, which is implementing the FDA Food Safety Modernization Act, the Canadian Senate recently passed the Safe Food for Canadians Act, and the Dominican Republic, Madagascar and Vietnam are among countries pursuing modernized food safety laws.

During our trip, we also met with representatives of multinational corporations doing business in China and visited a canned food facility in operation in the Huairou District, a suburb of Beijing.

We know there is still a lot of work ahead to improve food safety worldwide, and efforts by our trading partners must be combined with strong oversight by U.S.government agencies. The FDA Food Safety Modernization Act gives us new tools to improve that oversight, so the elements that are necessary to improve both food safety and consumer confidence are coming together.

The speech presented by Mike Taylor can be accessed at the following link:

The text of the 2007 agreement, which was officially renewed on December 11, 2012, is available at:

Camille Brewer is Director of International Affairs at FDA’s Office of Foods and Veterinary Medicine


Patients to Benefit from Novel Medicines

By: Margaret A. Hamburg, M.D.

At FDA, we face a careful balancing act between the need to bring innovative new drugs to patients quickly while taking care that these medicines are safe and effective.

Margaret Hamburg, M.D.A new FDA report shows that in the case of 35 novel drugs, called new molecular entities, we were able to strike that balance. These innovative drugs, many of which target devastating diseases, were approved by the agency in FY 2012, which ended September 30. That’s the same number of novel drug approvals as in FY 2011.  

Most of these 35 drugs were approved in theUnited Statesbefore they were approved in other countries, and all but one was approved within its target review date. This is thanks in part to the use of several authorities designed to enable quicker-than-usual action for drugs that treat serious or life-threatening diseases and that may fill an unmet medical need. FDA also permitted shorter, smaller, or fewer clinical studies when justified, which can reduce the length and cost of drug testing and bring drugs to market sooner.

If you go beyond the statistics, you will find the reality: elderly men and women whose sight may be saved, children who will breathe more easily, and cancer patients whose lives may be extended.

One of these 35 medicines is the first drug available to treat advanced basal cell carcinoma, a form of the most common skin cancer. Another is the first for the bone marrow disease myelofibrosis, which impairs the body’s ability to produce normal blood cells.

The list of novel drugs demonstrates numerous scientific advances and innovative approaches. For example, one is the first approved drug made from the blood of the human umbilical cord.  Another groundbreaking treatment targets a gene defect in certain cystic fibrosis patients rather than just treating the symptoms of the life-threatening disease. Another helps the body process a commonly used chemotherapy drug that can cause kidney failure and death in high and sustained concentrations.

It is also important to note that these faster approval times do not mean that the agency relaxed its review standards regarding patient safety. FDA continued its focus on assuring drug safety prior to approval as well as monitoring their safety after approval.  This included the implementation of the new drug adverse event system, FDA Adverse Event Reporting System (FAERS), which has modernized the agency’s ability to process more than one million adverse event reports received each year. It also included the agency’s Sentinel Initiative—FDA has been using a pilot of that program called Mini-Sentinel—to access electronic health information from 159 million patients and perform rapid assessments when there is an early signal that there may be a safety problem with a drug on the market.

For more about the novel medicines approved this fiscal year see the report at Most importantly, these new drugs will offer hope to some of the millions of patients awaiting critical treatments.

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

Advancing “Breakthrough” Drug Therapies

By:  Janet Woodcock, M.D.

Thanks to a recent law that went into effect on July 9, 2012, FDA now has a new program to help expedite the development of new drugs that could potentially offer a substantial improvement over existing therapies for patients with serious or life-threatening diseases. The new law is designed to get “breakthrough” therapies developed as quickly and safely as possible so they can be available to treat the patients who need them. We’re excited about it!  In fact, although the law is only a few months old, we’re already putting it to use. Recently we identified the first therapy to receive this special designation. And it likely won’t be long before we have more. Several other drug developers have already made inquiries and there is lots of interest in the pharmaceutical industry in taking advantage of this new development tool.  

Janet Woodcock, M.D.The law is called the Food and Drug Administration Safety and Innovation Act, or FDASIA for short. It defines a “breakthrough” therapy as one that is “is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition and for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.” In other words, a breakthrough drug is one that may offer important new benefits for patients with serious or life-threatening disease who are especially in need of new safe and effective treatments. 

This new option will complement the three programs we have used for many years to help speed up the development and FDA review of especially important new drug therapies.  They’re called “expedited drug development and review” programs, named Fast Track, Priority Review and Accelerated Approval. Each one is different, but for simplicity, think of them as various ways of bringing potentially important new therapies to patients sooner.  These programs have been very successful and are part of the reason that FDA leads the world in first approvals of innovative new drugs.

We’re delighted now to have another tool to help expedite the development and approval of products with the “breakthrough” designation. We’ll continue to use our existing tools and the new “breakthrough” authority to make our expedited drug development process even more effective, with the ultimate goal of benefiting patients with unmet medical needs.

I’d like to assure the American public of one important aspect of all of FDA’s development and review programs and procedures. We always decide whether to approve a drug after evaluating whether its benefits outweigh its risks. Regardless of which development or review program we use, FDA never compromises its safety or efficacy standards in exchange for rapid approval. That means that those drugs approved under the new “breakthrough” designation will meet our usual rigorous standards for safety and effectiveness. We intend to continue to maximize the value of our new breakthrough therapy designation. So stay tuned!

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