Monthly Archives: April 2012

FDA Voice Interviews Jesse Goodman, M.D., M.P.H., on the DARPA and NIH Project Collaboration: Human on a Chip

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FDA Voice: FDA has embarked on an exciting collaboration with the Defense Advanced Research Projects Agency (DARPA) and NIH—to develop a groundbreaking tool that could help bring new treatments to patients faster, more cheaply, and more safely. Can you talk about this new technology?

Dr. Goodman:  Yes, it’s what we’re calling Human on a Chip. This is an ambitious project to create a tool that could revolutionize toxicology testing and it’s something I’m really excited to talk about.  Scientists have relied largely on animal studies to determine if a drug is toxic before testing it in humans.  And while animal testing is useful, it’s also expensive, time consuming, and has drawbacks. For example, it doesn’t always detect toxic effects specific to humans and doesn’t usually provide information about the role that genetic differences within human populations play in toxicity. It can also generate false alarms, showing an effect in animals that doesn’t predict an actual effect in people, which leads us to abandon promising new drugs. FDA is collaborating with DARPA, NIH, and the scientific community to spur innovation in this field by exploring how tools like Human on a Chip can be integrated into our development tool box to improve testing for toxicity and potentially reduce the need for animal testing.

FDA Voice:  Can you describe Human on a Chip?

Dr. Goodman: Researchers are developing microsystems using human cells to test the effects of drugs or other substances. For example, scientists have developed a micro machine chip with human lung cells that grow on a surface to form a lung-like tissue that has both air spaces and blood circulation. FDA is supporting the coupling of this chip to a heart-like chip that beats and pumps blood. We can use this type of system to evaluate, with human cells, how specialized organs like the lung and heart react to a specific chemical.

The Human on a Chip builds on this approach. FDA’s collaboration with NIH and DARPA aims to create a 3D representation of 10 different human organ systems that mimic the processes and activities of those systems, potentially linking them to form a system with major features of human biology. For instance, in a living human, the interactions of heart, lung, kidney, and liver are crucial in the functioning of all 4 organs, and all are common targets of toxicity. A tool that creates and links organ-like systems will enable scientists to observe a substance’s effects on several interacting systems simultaneously. This can make it possible to test for beneficial effects as well as for toxicity. 

Once these systems are refined, if successful, they could not only improve testing beyond currently available tools, but could also be engineered to mimic disease states or be implanted with cells with a specific genetic background that is involved in specific diseases or drug interactions.

FDA Voice:  Why transform toxicology testing?

Dr. Goodman: Toxicity has been a major challenge in medical product development and in assessing environmental hazards. Technologies like Human on a Chip could help shrink the time frame it takes for new treatments to move to human testing and approval. These new tools can help identify toxicity earlier in product development, thus protecting patients, lowering development costs, and speeding new treatments to patients in need.

Human on a Chip could also contribute to developing medical countermeasures because the diseases and conditions we might need to treat in a public health emergency—like anthrax, smallpox, pandemic influenza, and radiation and toxin exposure—rarely occur naturally, often making animal models the only available tools for evaluating a new treatment’s effectiveness.

FDA Voice:  What makes FDA essential to this collaboration?

Dr. Goodman:  Our FDA scientists have vast experience using available tools to make tough scientific decisions about the safety and effectiveness of a multitude of products. They’ve seen what works and what doesn’t, and thus can provide insights and help solve challenges in defining how best to develop and evaluate new tools. Before accepting a new tool for use, FDA scientists must have the needed scientific data on how it performs to ensure that it is as safe and effective as possible. Once FDA accepts a scientific tool, industry can use it for its qualified purpose during product development.

FDA Voice:  In what other ways has FDA worked to drive innovation in toxicology testing?

Through the Critical Path and Advancing Regulatory Science initiatives, we are working to harness the use of new science and technology to transform regulatory science and help get needed products to people quickly and safely. FDA identified transforming toxicology as one of the eight priority areas where collaborative regulatory science research is essential and offers huge opportunities. In addition to Human on a Chip, FDA is collaborating with other Federal agencies, academia, and industry to bring new science to toxicology, such as on the cell-based Tox-21 project with EPA and NIH, and on FDA grants to evaluate cell-based approaches to evaluate risks of reproductive and developmental toxicity. 

My office has also formed a new FDA-wide council, together with scientists from across the agency, to explore, promote, and coordinate efforts concerning chemical and toxicology-related issues. FDA’s partnership throughout the development and evaluation cycle is critical to ensuring that exciting new tools and approaches like Human on a chip speed the delivery of safe and effective new treatments to people who need them.

Jesse L. Goodman, M.D., M.P.H., is FDA’s Chief Scientist and Deputy Commissioner for Science and Public Health

FDA’s Commitment to Reducing Prescription Drug Abuse and Misuse

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By: Douglas C. Throckmorton, M.D.

We hear tragic stories in the news about prescription medications ending up in the wrong hands and accidental deaths from overdoses. It’s become an epidemic. Today, FDA Commissioner Hamburg participated in a briefing with the White House Office of National Drug Control Policy to address startling new statistics about the abuse of prescription drugs, especially painkillers. While society as a whole has a role to play – the majority of new or occasional nonmedical users of pain relievers obtained the drug from family or friends for free or took them without asking – I’d like to tell you what FDA is doing to address this public health crisis.

Douglas C. Throckmorton, M.D.First of all, FDA is strengthening educational efforts in the use of opioids medicines. Through our work on the Opioid Risk Evaluation and Mitigation Strategy (REMS), FDA has created an outline of the information prescribers and patients need to know to balance the benefits of these drugs against the risks of serious outcomes including addiction, unintentional overdose, and death. Once finalized, this outline will be made available for use by educational providers to assist efforts to educate prescribers.

FDA is also strengthening the tools available to improve the use of opioid medicines. As a part of the President’s Prescription Drug Abuse Prevention Plan, FDA has convened a panel of outside experts to create a model Patient-Provider Agreement (PPA) to help guide the ongoing use of these powerful medicines while reducing the development of addiction and their misuse. In addition, FDA is supporting the Prescription Drug Monitoring Program Center of Excellence at Brandeis University. This program is working to improve prescriber utilization of state Prescription Drug Monitoring Programs (PDMPs) and also to examine the impact of strategies to reduce misuse and abuse of opioid medicines.

FDA is strengthening the science behind the use and misuse of opioid medicines. Last week FDA worked with National Institute on Drug Abuse (NIDA) and the Centers for Disease Prevention and Control (CDC) to convene an important public meeting on the use of naloxone as a treatment for deadly overdoses. The goal of the meeting was to find ways to reduce the thousands of unnecessary overdose deaths occurring in the US every year, including deaths due to prescription opioids. FDA has also announced plans to hold a two-day meeting to review the scientific data on the use of opioid drugs for the treatment of chronic pain.

Additionally, FDA is coordinating with Federal partners in programs like the Analgesic Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION). This partnership has been designed to streamline the discovery and development process for new analgesic medications and to more generally accelerate the development of pain treatments with improved efficacy and safety

FDA has been working to strengthen the science for assessing the abuse potential of new drugs. In October, 2011, FDA participated in a public workshop to discuss the science of abuse liability assessment. The public workshop was co-sponsored by FDA, the National Institute on Drug Abuse (NIDA) and the College on Problems of Drug Dependence (CPDD) at the Temple University School of Medicine. Feedback from this workshop has been instrumental in determining FDA guidance and necessary pathways for assessing the abuse potential for new drugs.

And, FDA has been working to speed the development of new medicine with reduced potential for abuse. FDA intends to issue an industry guidance on the development of new formulations of opioid medicines that are harder to abuse and misuse, a guidance that will also outline how the FDA will assess such formulations. 

Finally, we know that one part of the solution to preventing misuse and abuse of medicines is to dispose of them promptly once they’re no longer used. On Saturday April 28, the Drug Enforcement Agency has scheduled National Prescription Drug Take-Back Day at sites across the country, to help dispose of all types of unneeded medicines. We recently communicated about the importance of this activity and are proud to support this effort through a site at FDA’s headquarters facility at White Oak, in the Maryland suburbs of Washington, D.C. Additionally, for a small number of potent medicines, mostly pain medicines, FDA recommends flushing them down the toilet or sink, to keep them away from children and pets. You will find a list of these medicines on FDA’s website.

Science and innovation have allowed us to develop sophisticated prescription medications for public health and wellness needs. When we find out they are being diverted to inappropriate uses or not disposed of properly we must do all we can to solve the problem. FDA is committed to making a difference in this epidemic, and we will actively continue our work with other Federal agencies to implement the Administration’s goal to reduce prescription drug misuse, abuse and addiction.

Douglas C. Throckmorton, M.D., is FDA’s Deputy Director for Regulatory Programs in the Center for Drug Evaluation and Research.

Remembering Krebiozen: Why We Have Access to Unapproved Drugs and Why We Need Scientific Evidence

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By: Richard Pazdur, M.D.

I was in the third grade in the early 1960’s when my mother hung up the receiver of our old rotary dial telephone on the kitchen wall and broke down in tears. Dorothy, the mother of my close friend Fred, had just died of breast cancer. Dorothy and my mother worked together on various PTA and Cub Scout projects at my elementary school in Calumet City, a southeast suburb of Chicago. When my mother ended the phone call, she lamented “if only she received Krebiozen.”

Richard Pazdur, M.D.Dorothy was a proud, tall woman with jet black hair, wearing it upswept in a bun, and always appearing with bright red lipstick. She had undergone all the medical therapies available in the early 1960’s for advanced breast cancer, which would appear primitive in the light of today’s advances – including the now infamous Halsted radical mastectomy, large doses of searing cobalt radiation therapy, and surgery to remove her ovaries and adrenal glands to control painful bone metastases.

In discussing Krebiozen years later with my mother, she noted that Dorothy had received chemotherapy drugs. The doctors “had just given up on her” since the drugs didn’t work and there was “nothing else to do and that’s why she wanted to try Krebiozen.”

In the late 1950’s and early 1960’s, Krebiozen was touted as an active drug for cancer, especially in Chicago. The drug, initially developed from the blood of horses that had been injected with bacteria, was touted in written articles by a University of Illinois researcher extolling its benefits as an anti-cancer drug. Dozens of patients provided testimonials about the drug’s benefits to local media. My mother heard these accounts and desperately wanted my friend’s mother to have access to this promising, yet unproven drug: “she’s a young mother and is leaving behind two small children.”

Years later, I still frequently recall this story and its lessons. Patients with cancer, especially those who have exhausted currently available treatment options, and their friends and families search for a drug, possibly a drug that is not yet FDA-approved, and are willing to “take chances” in the hope that it may work. However, access to unapproved drugs needs to be balanced with both the protection of patients against a drug that may ultimately prove to be ineffective, and the need for clinical trials. These trials will demonstrate the drug’s safety and efficacy, ensuring a foundation for the drug’s use for future patients.

In 1987, the FDA first established rules that allowed patients with serious and life-threatening diseases access to investigational drugs outside of clinical trials, even though the safety and effectiveness of the drug has not been fully established. In August 2009 FDA changed its rules to clarify and broaden them for patients and treating physicians.  This is often referred to as “expanded access.”

Expanded access refers to the use of an investigational drug when the primary purpose is to treat a patient rather than to obtain information about the drug that is generally derived from clinical trials. There are different types of expanded access programs, ranging from single patient access to those providing access to hundreds or even thousands of patients. Information regarding the unapproved drug’s safety and efficacy required for use in a single patient is far less than information for trials that might provide access to hundreds of patients.

Some patients, who have not received standard therapies, especially if those therapies have been shown to improve survival, may not be candidates to receive unapproved drugs through an expanded access program. FDA has coordinated educational efforts with the American Society of Clinical Oncology (ASCO) to educate health care professionals and patients regarding appropriate patients for expanded access programs, as well as procedures to obtain expanded access to unapproved drugs.

Patients and healthcare providers seeking expanded access to unapproved drugs need to understand that drug companies must agree to provide these drugs to patients. FDA cannot mandate or require a drug company to provide an unapproved drug to patients. In fact, FDA oncologists have agreed with patients and their physicians that an unapproved drug could be used, only to find later that a drug company is unwilling to provide the drug. 

There are a variety of explanations that drug companies have offered for not providing patients expanded access to promising, yet unapproved drugs. These include cost, the perception that this access would interfere with the drug’s development and approval, or simply “corporate policy.” Other issues may be more opaque and involve manufacturing problems that companies may be unwilling to disclose and FDA cannot publicly comment on, in the context of an unapproved drug. 

In June, ASCO will be holding its annual conference and many abstracts will probably provide preliminary data on breakthrough drugs for patients with limited treatment options. Many patients will believe they cannot wait for the drug’s further development or its approval. FDA has provided clear guidance on the appropriate avenues to access promising, yet unapproved drugs; however, the success of these programs depends on the alignment of the FDA, an informed patient and healthcare provider, and ultimately, a willing drug company. 

Whatever happened to Krebiozen? A 1973 review by an independent committee of 24 scientists of over 500 “best cases” found it had no anti-cancer activity. The NCI director at the time noted “….from a scientific standpoint we regard the case closed.”

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

FDA’s Dr. Roberta Hammond: On the Trail of a Salmonella Outbreak

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Bringing a wealth of experience in food safety work — from fresh foods to inspecting restaurants — and years of experience coordinating investigations of food and waterborne disease outbreaks for the Florida Department of Health, Roberta Hammond, PhD, RS, joined FDA’s Center for Food Safety and Applied Nutrition (CFSAN) almost two years ago. At the time of this interview, Dr. Hammond was into her third week as Agency Incident Coordinator for the Salmonella Bareilly Incident Management Group (IMG), tracking the source of a recent outbreak of Salmonella infections.

FDA Voice:  Dr. Hammond, thank you for meeting with us during your hectic day.  Can you tell us about this recent salmonella outbreak?  How are things going?  Do you know what caused it yet?  How many people have been affected?

Roberta Hammond, PhD

Dr. Hammond:  Well, we began tracking this outbreak in early April.  So far, we are aware of 148 affected individuals, with 21 hospitalizations.  We’re always concerned when food makes someone sick, but so far in this outbreak there have been no deaths, thank goodness.  Our field investigators have led us to frozen, raw, ground tuna that was used in sushi and possibly other sushi-related dishes.  The source appears to be a company in India that supplies mostly restaurants with this product.  We had a real breakthrough on this investigation — sometimes they are inconclusive, or we never find the source. 

Nevertheless, the outbreak has presented its own set of challenges.  Most of the identified cases were along the Eastern seaboard of the US, with a few in Texas and a few as far west as Missouri.  Strangely, there is no evidence of Salmonella Bareilly on the West Coast or in Hawaii, which is interesting because in the past, we’ve found those areas to have the highest concentration of people who eat sushi.

FDA Voice: You are the Agency Incident Coordinator for this particular Incident Management Group. What does that entail?

Dr. Hammond:  FDA has an excellent incident management process, with an established structure, a clear set of procedures, and an established chain of command. The Office of Crisis Management (OCM) is our focal point for coordinating responses to natural emergencies or emergencies like the Gulf Oil Spill.  FDA’s Coordinated Response and Evaluation Network, what we call CORE, is an agency outbreak-related activities network that was launched in 2011.  CORE typically receives the first news of a human or animal food incident.  CORE begins the investigation, and if the incident begins to escalate through a broader scope, greater severity, increased number of illnesses, or rise in deaths, we have the option to establish an Agency Incident Management Group, or IMG — this is the first IMG activation since CORE’s launch.  If OCM’s Emergency Operations Center approves the formation of the IMG, most of the staff in CORE who have been working on the issue move into the Agency’s IMG center.  Having the multidisciplinary team members working together in the same room enhances rapid information exchange and provides the group with additional operational support so the investigators can focus on their individual tasks.

We start by looking at the places where people think they may have eaten food that made them ill.  From there, we use invoices and other records to trace the suspect food back to suppliers and then to where the food was produced.  State and local health officials and FDA field staff do this work.  They also collect samples of the suspect products that are tested for the presence of the pathogen –the infectious agent suspected of making people sick. For Salmonella Bareilly, we drew on the expertise of more than 60 trained and experienced investigators in 7 FDA district offices and 20 states and the District of Columbia.

The investigation involves close coordination with FDA partners, with Federal partners like the Centers for Disease Control and Prevention, with our State partners, and anyone else who needs to be pulled into the collaboration. FDA’s response is a well-oiled machine, if I may use a well-worn analogy. 

FDA Voice:  What is your specific role during this emergency?

Dr. Hammond:  I help set up the IMG investigative team and then get out of the way.  This is the first time I have coordinated a major outbreak within the Agency IMG structure, and I’m very impressed — the staff at the Emergency Operations Center are outstanding at what they do as are the CORE staff.  I try to stay in the background, making sure the information gets to everyone who needs it.  I see to it that people have what they need to do their jobs.  And I watch for burn-out.  I am also the primary IMG spokesperson on any calls with other Federal agencies and States, and I provide information to FDA leadership. I’d say one of my most important roles is to listen.

FDA Voice:  Can you tell us what a typical IMG day looks like, if there is such a thing?

Dr. Hammond:  First comes the daily kick-off meeting.  I then meet with the section chiefs — planning, operations, logistics, and others.  Then we watch over the work of the nearly 30 people who are tracking down clues about what might be the cause of the outbreak and identifying the steps we need to take to keep the food supply safe.  I attend meetings and conference calls whenever needed, including meeting with the Agency Executive Group and FDA’s senior leadership to consider strategic options for the short and the long term.

FDA Voice:  Dr. Hammond, when does an IMG deactivate?

Dr. Hammond:  You can tell when things begin to wind down. People are no longer working at breakneck speed.  Once the IMG has slowed and no longer requires the intense level of activity, it is transferred back to the CORE staff who tie up the loose ends.  I will sit down with the IMG Section Chiefs and do what’s commonly referred to as a “hot wash.”  We carefully go over everything that has happened — the planning, the logistics, the operations, the communications.  We hope to glean any new understandings that can help us the next time.  And, whether another foodborne illness or a natural disaster, we know there will always be a next time.

Succeeding on Produce Safety

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By: Michael R. Taylor, J.D.

We get our fresh produce from all over the place – from the broad lettuce fields of Salinas, the smaller truck farms of North Carolina and Delaware, and the road side produce operations that dot Long Island. And just about everywhere in between.

But, as much as we all enjoy locally-grown produce bought at a nearby farmer’s market, our quest for abundant supplies of fresh fruits and vegetables year round has turned our eyes and our markets outward. We now import 50% of our fresh fruit and 20% of our fresh vegetables, with Mexico being our largest source of both. In fact, two-thirds of imported fresh vegetables and almost 30% of imported fresh fruit comes from Mexico.

Michael R. Taylor, J.D.I recently spent a day in Tubac, Arizona, participating in the America Trades Produce conference. Tubac is near Nogales, which is the site of the highest volume port of entry for produce coming into the United States from Mexico – sometimes over 1,000 truckloads per day.

The conference brought together people on both sides of the border with a stake in this trade – growers and shippers of produce, importers, federal and state officials from the United States, and our regulatory counterparts from Mexico. I went to the meeting to talk about FDA’s progress in implementing the Food Safety Modernization Act (FSMA), which will transform how we oversee the safety of fresh produce, whether grown in Mexico or the United States.

I came away with some strong impressions. First, food safety is a front-of-mind topic for the produce industry. Those trading across the border of course have trade concerns, such as avoiding logistical delays in entering goods at the port of entry. But the people I spoke with consider food safety central to their business. That’s why they wanted to hear from me about FSMA implementation and why the conference program included exercises using realistic scenarios to share knowledge about how to manage recalls and other food safety incidents.

Second, they know that managing problems after they occur is not nearly enough.  Significant outbreaks of illness affecting major produce commodities have harmed consumers and consumer confidence and cost millions in lost sales. That’s why many in the industry have invested in growing and handling practices they know can prevent contamination and illness. And it’s why they voice strong support for implementing FSMA, which will create a level playing field of modern, prevention-oriented standards to ensure wider adoption of sound food safety practices.

Finally, they want to get on with building the new import safety system mandated by FSMA. In addition to new produce safety standards, FSMA requires importers to have a verification program that provides assurances that the food they import is as safe as domestic produce, strengthens the private audit system, mandates more foreign inspection by FDA, and directs FDA to partner more closely with foreign governments to ensure food safety. These reforms respond directly to concerns reflected in a 2011 food-industry sponsored survey showing that only 50% of Americans have confidence in the safety of the food supply and 61% consider imported food less safe due to the lack of adequate government oversight.

Building the new import system can be a win-win for consumers and industry. By building in prevention and verification from the point of production, the system can make produce safer, bolster public confidence, and streamline the border entry process, which is crucial for the shelf life and quality of perishable fruits and vegetables.

People often say to me “You folks at FDA must really have your hands full implementing FSMA.”  That’s true, and even an understatement. The day in Tubac reminded me, however, why we’ll succeed. Modernizing the food safety system is a community effort.  We have broad common interests that motivate our individual and collaborative efforts.  By working together, we make success the only possible outcome.

Michael Taylor is Deputy Commissioner for Foods at FDA

The Triage Pilot: Increasing Efficiencies for Device Review

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By: Alberto Gutierrez, Ph.D.

In the next few months, manufacturers of certain in vitro diagnostic and radiology products may start to notice they are getting decisions on their premarket notification (510(k)) submissions sooner than expected. This will be due to a six-month pilot program called Triage, launched recently by FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety, a part of the Center for Devices and Radiological Health (CDRH).

The goal of Triage is to improve efficiencies in the review process. Reviewers will focus more of their time and attention on higher-risk and novel devices, like companion diagnostics, and less time on devices that are lower-risk and have well-known and well-understood safety and effectiveness profiles. 

Alberto Gutierrez, Ph.D.As the name “Triage” suggests, when certain 510(k) submissions are submitted, reviewers will make an assessment of the level of resources needed to complete a review, based on a quick assessment of the submission’s content and completeness. High-quality submissions that meet certain criteria and contain all of the information needed for a substantial equivalence evaluation will be slated for a 30-day Quick Review. Those 510(k) submissions not meeting these criteria would receive the standard review (generally 90 days) consistent with user fee performance goals.

To qualify for a 30-day Quick Review, the 510(k) submission must:

  • be well-written, organized and contain all expected data and information to support substantial equivalence claims;
  • be for a device that is well-known to FDA;
  • be for a device that does not have existing or unresolved postmarket issues;
  • not require an extensive review by a subject matter expert other than the reviewer assigned to the submission; and
  • contain a 510(k) Summary, which is a summary of the information used to support the substantial equivalence determination.

And even with time saved, the Triage pilot program will preserve the quality and transparency of the normal 510(k) review process. Reviewers will still assess the same elements as they would in a standard review, but instead will accomplish it within 30 days. If the device is found to be substantially equivalent to a legally marketed predicate device, the 510(k) Summary will be posted online, allowing the public to see FDA’s basis for the substantial equivalence determination.

At the end of six months, FDA plans to evaluate and refine the program. The evaluation will provide us with some simple metrics on 510(k) review times and use of resources, but the impact, we hope, will go beyond the numbers.

For manufacturers, healthcare practitioners and patients, faster reviews will mean some products will be available sooner. For FDA staff, the time saved by using Quick Review can be devoted to reviewing submissions for higher-risk devices and novel technologies and to expanding their knowledge and expertise in new and emerging science. Depending on the pilot’s outcome, CDRH may consider expanding the Triage program to other device types besides in vitro diagnostics and radiology products.

Facilitating access to safe and effective devices is a goal shared by FDA, manufacturers, the healthcare community, and the public. We’re optimistic that our innovative Triage pilot program can help us meet that goal and that industry will see the possibility of a 30-day review as additional incentive to submit high quality 510(k) submissions.

Alberto Gutierrez, Ph.D., is Director of FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety, a part of the Center for Devices and Radiological Health

Collaboration for a Global Product Safety Net

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By: Mary Lou Valdez

If it takes a village to raise a child, in today’s economy it takes the support and commitment of a global community to ensure the safety of the food we eat and the medications we rely on.

This point was made clear in an Institute of Medicine report released on April 4. The report was commissioned by the FDA as the agency addresses the challenges of global supply chains, international trade, and foreign sourcing of foods, feeds, and medical products. It complements the FDA Commissioner’s Report on Global Pathway to Product Safety and Quality released last summer.

Mary Lou ValdezImports of food and drug products regulated by FDA have increased by more than 13 percent per year since 2002, resulting in a four-fold increase of products produced outside of the United States. Approximately 50% of the fresh fruits and 20% of fresh vegetables, as well as 80% of seafood consumed in America comes from abroad. Similarly, more than 80 percent of the active pharmaceutical ingredients used to make medicines are imported. To ensure that the vast array of products Americans depend on are safe, FDA focus can no longer be solely domestic – it must be global.

Since many of the products imported are from emerging and developing countries, the FDA asked the IOM to take a look at the regulatory systems in those countries to identify major gaps and to design a strategy for how the FDA, along with other regulators and stakeholders, can help to strengthen their regulatory systems and build capacity.

Not surprisingly, the IOM found that the hurdles are great in some countries where there is inadequate clean water, electricity, transportation, communication systems and Internet access. Their regulatory agencies often operate with a skeletal staff, outdated equipment and limited or non-existent surveillance systems. In some of the least resourced countries there are weak or no laws governing product safety while product safety is not a high priority in others.

The IOM Committee’s strategy was to focus on the nexus of public health, product safety, development and trade, while recognizing that regulatory systems play an important role. The IOM identifies several core elements of a regulatory system: they must be responsive, outcome-oriented, predictable, risk-based or proportionate and independent. Other important commonalities include an enterprise risk management approach to regulation; focus on securing the entire supply chain; develop a profession of regulators – an “esprit de corps”; and make accountability an essential element of their system. The IOM also acknowledges that industry must play a role in ensuring the safety of its imported products.

To help build regulatory capacity, the IOM recommends that the FDA, other federal agencies and international organizations provide technical expertise, training and tools to strengthen the surveillance system in developing countries.

We take pride in the efforts FDA already has undertaken to support and collaborate with regulatory systems across the globe, such as our foreign training programs on good clinical practice inspections and low acid canned food inspections; a medical products information “hub” for the Americas in collaboration with the Pan American Health Organization; our interagency agreements with the US Agency for International Development to better understand pharmacovigilance systems in Africa and Asia; and our involvement with the World Bank’s Global Food Safety Fund, a partnership of public and private organizations intended to boost food safety capacity around the world. And this is only a short list of our activities.

We welcome the IOM’s call to international and intergovernmental organizations to invest more in strengthening the capacity of regulatory systems in developing countries, and to track progress as a priority of development banks, regional economic communities and public health institutions.

We were pleased that the IOM supports the agency’s risk-based strategy for monitoring and inspecting imported products and recommends that the agency extend this approach by working with strong regulators in other countries to plan inspections and pool data.

However, additional legal authorities would be helpful to accomplish this goal. FDA currently is barred from sharing certain non-public information with other regulatory agencies that might lead to timely identification, prevention, and resolution of emerging threats. Nor do we have the authority to use foreign audit data collected by our foreign regulatory counterparts with strong regulatory systems that would better leverage our limited resources.

Other authorities would be helpful to help us better manage risks. These include the ability to refuse admission of a product if inspection of the manufacturing facility is delayed, limited, or denied; and allow FDA to destroy the low value but large number of unsafe drugs that are coming into the country through international mail, typically purchased over the internet. In order to enhance our risk data, we would like additional information such as unique facility identifier as a condition of registration and import that would make it easier for FDA to properly follow a threat through the supply chain.

To ensure that industry assumes appropriate responsibility for their imported product, it would be helpful for manufacturers to account for the quality and origins of the materials that go into their products and require that manufacturers provide complete information to FDA on threats to the drug supply chain. Furthermore, the use of accredited third parties that meet prescribed standards could provide an additional set of eyes to help ensure the safety of the drug supply chain.

Ensuring the safety of imported food and medicines takes all countries working together, including governments, industry, academia, and other stakeholders. But marshalling the forces of this vast community may not be enough to provide the robust regulatory system we need in today’s global marketplace without new authorities to protect the health of the American public.

Mary Lou Valdez is FDA’s Associate Commissioner for International Programs and Director, Office of International Programs

A Strategy to Keep Antimicrobials Effective

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By: Michael R. Taylor, J.D.

Over the past century, few innovations have been as important to public health as the development and use of antimicrobial drugs to treat bacterial infections. They have been successfully used for more than 50 years to treat, control, and prevent diseases in both humans and animals. But over the years, while physicians, veterinarians, and the livestock industry have been putting these important medications to their many uses, we’ve also learned a critical lesson:  they have to be used judiciously to ensure they remain effective.

Michael R. Taylor, J.D.There are complex reasons for this development, including the overuse of antimicrobial drugs in human medicine – a problem FDA and the medical community are working to address. But we also know that an additional factor contributing to antimicrobial resistance is the use of medically important drugs for feed efficiency or growth promotion (so-called “production” uses) in food-producing animals. For the FDA, an agency that’s responsible for protecting the health of the public, this fact requires a response to help preserve the continued effectiveness of these drugs for both humans and animals.

So FDA has settled on a strategy to phase out production uses of medically important antimicrobials and provide that they be used only for targeted, FDA-approved animal health purposes under the supervision of a veterinarian. The important sea change that will enable us to implement this strategy efficiently and expeditiously has been the willingness of many drug companies, veterinarians and animal producers to work collaboratively with FDA to ensure that medically important antimicrobial drugs are used in food-producing animals only when necessary to ensure their health. Many animal producers already work in this way, and we look forward to working closely with the animal production community to make judicious use of antimicrobials standard practice throughout the industry.

In developing our strategy, FDA’s Center for Veterinary Medicine has consulted extensively with our colleagues at the U.S. Department of Agriculture, with the agricultural and veterinary communities, with the animal drug and feed industries, and with public health and consumer advocates. And, as a result of that work, we have released three documents that outline a collaborative approach to keeping antimicrobials effective by limiting their food animal use to specific medical needs.

First, we are publishing a final guidance for industry on The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals. This document establishes a framework for phasing out the use of these drugs for feed efficiency or growth promotion and phasing in veterinary consultation or oversight of their medical uses in food-producing animals.

Second, we are asking for public comments on a draft guidance to drug companies on how to revise their FDA-approved product labels for medically important antimicrobial drugs to no longer include use for feed efficiency or growth promotion, and include veterinary oversight or consultation.

And third, we are publishing a draft proposed regulation, also for public comment, to streamline and modernize the current regulation that governs veterinary authorization for the use of certain drugs in animal feed.

I know there will be those who question why we have not taken mandatory action to ban production uses of antimicrobials. The answer is that, with the willingness of drug companies and others in the animal production industry to collaborate in implementing our strategy, we can make changes more quickly than if we had to rely solely on a cumbersome regulatory process that would require us to seek change drug by drug, and labeled use by labeled use. Working together is how we will get good results in a timely manner.

In implementing our strategy, we want to avoid adverse impacts on animal health and disruptions to the agricultural industry. We anticipate that the phase out of production uses of antimicrobials and establishment of veterinary oversight of remaining ones will take three years. For that reason, in the draft guidance to drug companies we are proposing this timeframe for implementation. We intend to monitor progress after the three-year timeframe has elapsed to evaluate the rate of adoption of these changes. If progress is not what we expected, we will consider further action as warranted in accordance with existing provisions of the FD&C for addressing matters related to the safety of approved new animal drugs.

We know, and so do our colleagues at USDA, that change will be more challenging for small-scale and geographically remote animal producers. It will take time to ensure they have the veterinary support these changes will require and other technical assistance to adjust to the phase out. And we won’t forget about these unique needs.

Concerns about the use of antimicrobial drugs in humans and food-producing animals have been on FDA’s agenda for many years. We see the collaborative strategy we are announcing as a major step forward. It is designed to protect and promote the health of the American public while minimizing disruption to animal health and the animal agriculture industry. We look forward to the public’s comments and to the work ahead to achieve these important goals.

Mike Taylor is Deputy Commissioner for Foods at FDA

Making a Difference: Innovation Pathway and Entrepreneurs in Residence

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Interview with Todd Park Chief Technology Officer of the United States

Prior to becoming Chief Technology Officer of the U.S. in March 2012, and prior to that, CTO at the U.S. Department of Health and Human Services in 2009, Park co-founded three companies that developed web-based and telehealth solutions for doctors and consumers.

Q – Since you joined HHS, what have you learned about making innovation happen in the government?

Todd ParkI’ve learned that a lot of the same rules that drive success in private sector innovation also apply in the public sector.  The philosophy I used extensively in the private sector boiled down to what Eric Ries calls “lean startup” — the whole idea behind lean startup being  that you want to engage customers early and rapidly prototype solutions in collaboration with them in order to achieve maximum success.

We have successfully applied lean startup principles at HHS across a range of key initiatives.  We’ve emphasized the need to rapidly prototype solutions, engage customers in f those solutions as soon as possible, and then quickly and repeatedly iterate those solutions based on working with customers, until we arrive at both an optimal understanding of what customers really want and a solution that delivers what they want..

It’s a technique that a lot of private sector entrepreneurs have used to great effect, and that we’re now using to great effect in the public sector.

Q – How do you then ensure that a good idea or an innovative idea can be scaled up in a government setting, where the culture may be less receptive to something new?

Critical to the success of our growing array of lean startup projects is the following approach:  whenever we  consider an idea to make the government work differently and  better,  the first thing we do is find three to five people at HHS who had that idea a long time ago. They know a lot more about it than we do, and can make the change happen if they’re given the chance.

We band those folks together into a “virtual lean startup team,” and we give them the air cover they need and block down field for them, so they can actually do the thing they’ve always wanted to do.

In the case of FDA, through the Entrepreneurs in Residence Program, we’ve also brought in incredibly talented entrepreneurs and experts from the outside, to complement our best internal innovators. Together, they can make amazing things happen in an incredibly short time.

Q – What’s so great about the Entrepreneurs in Residence Program at FDA?

What’s phenomenal about the FDA’s Entrepreneurs in Residence Program is that it’s a living, breathing incarnation of lean startup within HHS.  FDA has taken its best internal innovators and put them to work together with entrepreneurs with highly complementary experiences and expertise. The result has been an amazing band of doers and thinkers who are rocking and rolling, and making terrific things happen terrifically fast.

Q – Somewhere, somebody has to give you the green light for these innovations. Where does that start?

In every organization, the tone is set at the very top. And since his first day in office, President Obama has been an incredibly enthusiastic champion of open innovation in government..  He supports the whole idea that government needs to partner with the private sector, the academic sector, and the citizen sector, help unleash the creativity of innovators across these sectors, and team up with them to jointly attack our biggest problems and exploit our biggest opportunities. That’s the overall tone that the President has set, and it provides massively fertile ground for innovation.

Q – What excites you most about FDA’s Innovation Pathway?

Two things:  First, the Innovation Pathway will help bring safe and effective medical devices to American patients faster. That will make a huge difference in many lives. And on top of it, the initiative will help medical device companies get their products to market faster and at a lower cost. That will help create jobs and grow the economy.

On another level, I’m enormously excited by the way that the Innovation Pathway project has been run, and by the whole Entrepreneur in Residence, lean startup mode of operation it has embodied. The fact that lean startup has been employed to such great success in the Innovation Pathway project, I think, bodes very well for the replication of this approach  more broadly across HHS and the government in general.

Q – What’s the main lessons you’ve learned from the success of FDA’s Innovation Pathway?

The Innovation Pathway at FDA is a phenomenal example of lean startup in action in the government.  It proves the success of the whole idea of rapid prototyping, engaging customers and stakeholders as soon as possible, co-inventing an optimal solution through hyper-rapid iteration, and doing all of this at warp speed.

Innovation Pathway exemplifies the power of collaboration.  Given the challenges and opportunities that we as a nation face, we’re really only going to be able to get optimal results if we team up as a country.

It’s not about government solving problems by itself.  It’s about the private sector, the research sector, the citizen sector, government, and the public in general, teaming up in truly innovative collaborations to deliver optimal results for the American people.