FDA’s 2015 Science Forum attracted more than 800 people from the scientific community. Here’s what some attendees said about the innovative research going on at the agency and why FDA can be a valuable collaborator in research aimed at transforming food safety and medical product development. If you couldn’t attend the FDA science forum, you can still see all the presentations on our web site.
By: Howard Sklamberg, J.D., George Karavetsos, J.D., and Cynthia Schnedar, J.D.
Unfolding earlier this month was a global cooperative effort, which included the Food and Drug Administration, to combat the online sale and distribution of potentially counterfeit and illegal medical products. Operation Pangea VIII was a project of massive scope, a lightning move by 115 countries that resulted in more than 2,400 websites being taken offline and the seizure of $81 million worth of potential dangerous illegal medicines and medical devices worldwide.
It’s a sad and cruel fact that drug and device counterfeiting and adulteration pose serious threats to public health. Unapproved and misbranded prescription drug products and unapproved/uncleared medical devices offered for sale on the Internet are potentially dangerous. The illegal sale of these medicines and devices bypasses both the existing safety controls required by the FDA and the protections provided when these products are used under a licensed practitioner’s supervision.
FDA is dedicated to sustaining and expanding the fight against counterfeits as part of our global strategy that leverages resources and expertise, engages the private and public sectors, and is data-driven and risk-based.
We have developed a Global Strategic Framework for counterfeit and substandard medical products (sometimes known by the acronym SSFFC, for Substandard, Spurious, Falsely-Labeled, Falsified, Counterfeit) to help protect consumers by reducing their exposure to counterfeit and substandard medical products.
The framework is focused on three pillars: Prevention, Detection, and Response.
What’s needed is better prevention of market entry of counterfeit and substandard products. Better detection of these products. And, more efficient response when counterfeit and substandard products are found.
FDA developed this framework in order to lay out a strategic vision of what is needed and how these needs can be met globally. There are areas where our expertise can and does contribute to prevention, detection, and response, but there are other areas where other U.S. federal and local government agencies, foreign counterparts, industry, healthcare professionals, consumer and patients, non-governmental organizations, procurement and donor organizations, standards bodies, and others have a role.
It is important for all players fighting to combat counterfeit and substandard drugs and devices to understand exactly how to best use our resources, knowledge, and experience, and leverage the work of others. This framework helps shape what roles we can play, minimize duplication of effort, and strengthen our global might in this fight against the criminals.
FDA has many ongoing activities and initiatives that support the framework goals. To better prevent counterfeit and substandard products from entering the market, we are working on improving the transparency, accountability, and integrity of the supply chain. Specifically, we are focusing on good manufacturing, distribution, and pharmacy practices, and we’re working for a convergence of global standards to create a more level playing field for the legitimate supply chain.
We are also implementing the new track and trace law (the Drug Supply Chain Security Act), which outlines steps to build an electronic, interoperable system to identify and trace certain prescription drugs as they are distributed in the United States, no matter where they originate. This is a collaborative effort whereby FDA is working with drug manufacturers, wholesale drug distributors, repackagers and dispensers (primarily pharmacies) to implement the law and develop the new system over the next eight years. Some of the key goals of this system will be to trace the path of drugs at the package-level through the drug supply chain, help ensure they are legitimate products, and enhance the detection of illegitimate drugs.
To better detect potentially harmful products before they enter the supply chain on their way to patients, we are focusing on improving information-sharing and communication. Also, as part of our effort for better detection, we are improving our surveillance through more efficient investigations of suspect incidents, and more quickly confirming that products are counterfeit. To this end, we have developed new detection technologies, specifically the handheld device, CD3, which uses wavelength detection to detect counterfeit drugs and packaging at our ports of entry.
Lastly, to better respond to incidents in the most efficient manner, FDA’s Center for Drug Evaluation and Research is developing more effective ways to notify the public of confirmed incidents and quicker removal of counterfeit products from the marketplace.
As for enforcement, we will continue to rely on our skilled professionals in FDA’s Office of Criminal Investigations (OCI) to lead domestic and global investigations to combat counterfeits. For example, OCI’s involvement in the past seven years of Operation Pangea has resulted in the seizure of more than $172 million in unlawful medical products — a real testament to effective international partnership.
We fully recognize that there are sophisticated, global criminal networks engaged in money laundering and the preparation and transportation of illegal products around the world. Importantly, we are meeting this global threat with international collaboration. FDA’s Office of International Programs has engaged with the World Health Organization’s Global Surveillance and Monitoring System, the World Bank, and the U.S. Agency for International Development in securing drug supply chains, reducing the threat of substandard drugs and strengthening regulatory systems.
We also collaborate with many foreign law enforcement organizations. For example, we have an OCI agent permanently assigned to Europol, based in The Hague, Netherlands. We also have a longstanding and solid partnership with the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA). More recently, OCI signed with the French National Gendarmerie a Letter of Intent to increase law enforcement collaboration.
Moreover, the stakes have grown higher in the U.S. as judges around the country recognize the risks of unapproved drugs in the U.S. marketplace. In January 2015, for example, a Turkish exporter of illegal drugs was sentenced to 30 months in federal prison for his part in the scheme.
As underscored by Operation Pangea last week, our actions to protect the health of Americans from the online sale of potentially dangerous illegal medical products will continue. In the longer term, our focus will be prevention, detection and response. We will need a more coordinated, domestic and global approach that leverages resources, expertise, tools, and trainings, and engages stakeholders, other regulators, and law enforcement.
Through our framework for strategically safeguarding supply chain security and integrity and combatting counterfeit and substandard drugs and devices, we know we are on the right path with the right goal: Protecting public health by helping to ensure that the prescription medications and devices used by health care professionals and patients are safe, effective and of high quality.
Howard Sklamberg, J.D., is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy
George Karavetsos, J.D., is FDA’s Director, Office of Criminal Investigations
Cynthia Schnedar, J.D., is FDA’s Director, Office of Compliance, Center for Drug Evaluation and Research
By: Margaret A. Hamburg, M.D.
The tragic Ebola epidemic is an extraordinary global public health crisis, and FDA is taking extraordinary steps to be proactive and flexible in our response – whether it’s providing advice on medical product development, authorizing the emergency use of new diagnostic tools, quickly enabling access to investigational therapies, or working on the front lines in West Africa.
FDA has an Ebola Task Force with wide representation from across FDA to coordinate our many activities. We are actively working with federal colleagues, the medical and scientific community, industry, and international organizations and regulators to help expedite the development and availability of medical products – such as treatments, vaccines, diagnostic tests, and personal protective equipment – with the potential to help bring the epidemic under control as quickly as possible.
These efforts include providing scientific and regulatory advice to commercial developers and U.S. government agencies that support medical product development, including the National Institutes of Health (NIH), the Office of the Assistant Secretary for Preparedness and Response (ASPR), the Centers for Disease Control and Prevention (CDC), and the Department of Defense (DoD). The advice that FDA is providing is helping to accelerate product development programs.
Our medical product reviewers have been working tirelessly with sponsors to clarify regulatory requirements, provide input on manufacturing and pre-clinical and clinical trial designs, and expedite the regulatory review of data as it is received. FDA has been in contact with dozens of drug, vaccine, device, and diagnostic test developers, and we remain in contact with more than 20 sponsors that have possible products in pipeline.
We also have been collaborating with the World Health Organization and other international regulatory counterparts—including the European Medicines Agency, Health Canada, and others—to exchange information about investigational products for Ebola in support of international response efforts.
Investigational vaccines and treatments for Ebola are in the earliest stages of development and for most, there are only small amounts of some experimental products that have been manufactured for testing. For those in limited supply, there are efforts underway to increase their production so their safety and efficacy can be properly assessed in clinical trials.
As FDA continues to work to expedite medical product development, we strongly support the establishment of clinical trials, which is the most efficient way to show whether these new products actually work. In the meantime, we also will continue to enable access to investigational products when they are available and requested by clinicians, using expanded access mechanisms, also known as “compassionate use,” which allow access to such products outside of clinical trials when we assess that the expected benefits outweigh the potential risks for the patient.
In addition, under the FDA’s Emergency Use Authorization (EUA) authority, we can allow the use of an unapproved medical product—or an unapproved use of an approved medical product—for a larger population during emergencies, when, among other reasons, based on scientific evidence available, there is no adequate, approved, and available alternative. To date, FDA has authorized the use of five diagnostic tests during this Ebola epidemic: one was developed by DoD, two were developed by CDC, and this week FDA issued EUAs for two new, quicker Ebola tests made by BioFire Defense.
To further augment diagnostic capacity, we have contacted several commercial developers that we know are capable of developing rapid diagnostic tests and have encouraged them to work with us to quickly develop and make available such tests. Several entities have expressed interest and have initiated discussions with FDA.
We also are monitoring for fraudulent products and false product claims related to the Ebola virus and taking appropriate action to protect consumers. To date, we have issued warning letters to three companies marketing products that claim to prevent, treat or cure infection by the Ebola virus, among other conditions. Additionally, we are carefully monitoring the personal protective equipment (PPE) supply chain to help ensure this essential equipment continues to be available to protect health care workers.
And at least 12 FDA employees are being deployed to West Africa as part of the Public Health Service’s team to help with medical care. We are proud that they are answering the call.
As you can see, FDA has been fully engaged in response activities and is using its authorities to the fullest extent possible to continue its mission to protect and promote the public health, both domestically and abroad. Our staff is fully committed to responding in the most proactive, thoughtful, and flexible manner to the Ebola epidemic in West Africa.
I could not be more proud of the dedication and leadership that the FDA staff involved in this response has shown. I therefore want to take this opportunity to thank more than 250 staff, including those soon to be on the ground in West Africa, who have already contributed countless hours to this important effort, and who will continue to do so in the coming days and weeks as we address this very serious situation. I am hopeful that our work and the coordinated global response will soon lead to the end of this epidemic and help reduce the risk of additional cases in the U.S. and elsewhere.
Margaret A. Hamburg, M.D., is Commissioner of the Food and Drug Administration
By: Luciana Borio, M.D.
The world is witnessing the devastating effects of the Ebola virus outbreak in West Africa, the worst Ebola outbreak in recorded history. To date, more than two thousand people in Guinea, Liberia, Nigeria and Sierra Leone have become infected, and more than twelve hundred have died. The stories of so many lives lost, and those of so many others fighting for their lives, are heartbreaking and tragic. We at the Food and Drug Administration are dedicated to helping end this outbreak as quickly as possible. And we are working hard to accelerate the development and production of treatments and vaccines to help prevent future outbreaks like this.
The primary approaches to contain the current outbreak remain standard public health measures. However, this outbreak presents complex challenges, in part because there are no FDA-approved treatments or vaccines for the Ebola virus. FDA has an important role during situations like this.
For example, we are working closely with U.S. government agencies that support medical product development – including the National Institutes of Health, the Biomedical Advanced Research and Development Authority, and the U.S. Department of Defense (DoD) – to speed the development and production of medical products that could help mitigate outbreaks like this. And we are working interactively with medical product sponsors to clarify regulatory and data requirements in order to move investigational products forward in development as quickly as possible. We also are in close contact with the World Health Organization and several of our international regulatory counterparts to exchange information about these investigational products for Ebola treatment, and to exchange information about how FDA works to facilitate development of and access to these products.
The experimental vaccines and treatments in development are in the earliest investigational stages and have not been fully tested for safety or efficacy. Only small amounts of some experimental products have been manufactured for testing, which means few courses, if any, are available for companies to make available for compassionate use in response to this outbreak. We are working closely with our U.S. government colleagues to have experimental treatments and vaccines available for clinical evaluation in the next few months. We are hopeful that, in the future, we will have medical products approved and manufactured for wide-scale use to address the Ebola outbreak. However, these products are not at that stage yet.
In the meantime, FDA is doing all we can to alleviate the situation. FDA has one of the world’s most flexible regulatory frameworks, which includes mechanisms to enable access to available investigational medical products when, based on certain criteria such as the balance between expected risk and benefit to the patient, it would be appropriate to use such products.
For example, under certain circumstances, clinicians may request the use of an Emergency Investigational New Drug (EIND) application under the FDA’s Expanded Access program to access investigational products outside of clinical trials for their patients. And under the FDA’s Emergency Use Authorization (EUA) authority, we can allow the use of an unapproved medical product – or an unapproved use of an approved medical product – for a larger population during emergencies, when there are no adequate, approved and available alternatives.
This month, we authorized the use of an Ebola diagnostic test, developed by DoD, under an EUA to detect the Ebola virus in DoD-designated laboratories. This test can help facilitate an effective response to the ongoing outbreak in West Africa by helping to rapidly identify patients infected with Ebola virus and facilitate appropriate containment measures and clinical care.
It is an unfortunate fact that, during outbreaks like this, fraudulent products that claim to prevent, treat or cure a disease rapidly appear on the market. FDA has learned of several fraudulent products that claim to prevent or treat this Ebola virus infection, including so-called natural remedies. Consumers who have seen these fraudulent products or false claims should report them to us. For our part, we will remain vigilant for fraudulent products and false product claims related to the Ebola virus, and will take enforcement actions as warranted to protect public health.
FDA stands ready to work with companies and healthcare providers to speed product development and to facilitate access to investigational products to treat patients when appropriate. We are fully committed to helping end this outbreak as quickly as possible and to sustaining our efforts to help prevent such outbreaks in the future.
Luciana Borio, M.D., is the Assistant Commissioner for Counterterrorism Policy and Acting Deputy Chief Scientist.
By: John Swann, Ph.D.
Looming sentry-like over the collection of artifacts that document FDA’s history, the products we regulate, and our interactions with the public is a rather large and curious figure. It is a green velvet head with bulbous, languid eyes and two upper teeth in an otherwise large and empty mouth. It doesn’t have ears or hair, but is marked by a few bright green pustules. This is part of a life-size costume, an element of a public education campaign called Fight Bac! in which FDA was a major participant. It began in the 1990s to alert the public, young and adult alike, to the dangers of food-borne diseases and how to avoid them.
Countless objects in our collection tell the decades-long tale of FDA’s educational activities. For example, the agency still has a cabinet and some of its contents from the “Chamber of Horrors” exhibit that traveled around the country in the early 1930s to alert citizens, legislators, the press and others of the need for a stronger consumer protection law, drawn from egregious examples of how the law then in place fell short. FDA officials also communicated through a variety of other displays for Congressional testimony and other purposes.
Much of the collection captures the problems that gave rise to the laws and regulations we have today, a regulatory arc often originating with a problem product—sometimes of disastrous proportions. Thus one can find specimens of:
- Elixir Sulfanilamide, a poisonous preparation of a wonder drug in 1937;
- thalidomide, the globally marketed sedative that caused thousands of grave birth defects in the 1950s and 1960s;
- Bon Vivant vichyssoise, a botulism threat in the early 1970s;
- the ill-designed Dalkon Shield intrauterine device that caused thousands of pelvic infections; and
- ephedra-containing dietary supplements from the 1990s that killed several users.
These are among the objects that eerily illustrate why we have the laws and regulations we do.
Decision-making in the agency depends to a considerable extent on investigations and analyses, some of the tools of which are documented here. These artifacts of the growth of regulatory science include:
- balances and early calculating devices used in the laboratories of the Bureau of Chemistry from the 1900s to 1920s to analyze questionable foods and drugs;
- triers, tools used for routine sampling of various foods to ensure compliance with the law, from the mid-20th century; and
- advanced analytical devices from the 2000s to detect sophisticated counterfeiting of medicinal products.
Treatments of dubious value for both serious and non-serious diseases make up a significant part of the collection as well. There are hundreds of fraudulent medications, primarily up to about World War II, as well as hundreds of medical devices from the 1950s and 1960s that offered hope with no scientific underpinning.
In addition, how the public came to engage FDA and its work, especially from the 1970s forward, can be seen in a number of objects, including protest buttons and placards from the past two decades.
Artifacts like these tell the story of how our many laws and regulations came to be, how FDA has carried them out, and how the public and FDA have engaged each other in the interest of the public health.
John Swann, Ph.D., is an Historian at FDA
By: Margaret A. Hamburg, M.D.
Since last year’s tragic meningitis outbreak and subsequent events involving compounded drugs, Congress has been hard at work to pass new legislation to provide FDA with the appropriate authorities for regulating compounded drugs to help make these products safe for the American public.
Over a much longer period of time, efforts have been made in Congress to enhance the security of the drug supply chain and protect consumers from exposure to counterfeit, stolen, contaminated or otherwise harmful drugs.
I am pleased that the Drug Quality and Security Act can help FDA protect public health in both of these critical areas.
One part of the new law offers a step forward in FDA’s oversight of certain entities that prepare compounded drugs. The new law will enable these compounders to register with the FDA to become “outsourcing facilities,” making them subject to certain other requirements including Federal quality standards, known as current good manufacturing practice. These facilities will also be subject to inspection by FDA on a risk-based schedule. If compounders register with FDA as outsourcers, hospitals and other health care providers will be able to provide their patients with drugs that were compounded in facilities that are subject to FDA oversight and federal requirements for current good manufacturing practice, among others. To that end, we will be encouraging healthcare providers and health networks to consider purchasing compounded products from facilities that are registered with FDA and subject to risk based inspections.
Drugs produced by compounders that are not registered as outsourcing facilities must meet certain other conditions described in the law, or they will be regulated by FDA as conventional drug manufacturers.
Generally, the state boards of pharmacy will continue to have primary responsibility for the day-to-day oversight of state licensed pharmacies, including traditional pharmacy compounding. And FDA will continue to cooperate with state authorities to address pharmacy compounding activities that may be in violation of the Federal Food Drug and Cosmetic Act.
Another part of the new law enables certain prescription drugs to be traced as they move through the U.S. drug supply chain. The goal is to protect the public from exposure to counterfeit, stolen, or otherwise harmful drugs. This will require manufacturers, repackagers, wholesale drug distributors, and dispensers (other than most licensed health care practitioners) to provide product and transaction information with each sale and notify the FDA and other stakeholders of illegitimate products, which will result in improved detection and removal of potentially dangerous drugs from the supply chain.
Starting four years after enactment of the law, manufacturers, followed by repackagers, will be required to affix a unique product identifier to each drug package that contains the drug’s national drug code (NDC), serial number, lot number, and expiration date. Starting six years after enactment of the law, wholesale drug distributors, followed by dispensers, may only trade products that are encoded with product identifiers and will be able to verify the product identifier if they determine that they have suspect product. Ten years after enactment, supply chain stakeholders and FDA will benefit from an electronic, interoperable system which will facilitate the efficient exchange of product and transaction information for prescription drugs at the individual package level. The system, when fully implemented, will enable verification of the legitimacy of the drug product identifier down to the package level, enhanced detection and notification of illegitimate product, and improved efficiency of recalls.
The Drug Quality and Security Act is a significant step toward having new and stronger drug quality and safety laws. While the law does not provide FDA with all the additional authorities sought, these provisions are a sign of progress.
We are committed and prepared to implement the new law that will help us to further protect public health.
Margaret A. Hamburg, M.D., is the Commissioner of the Food and Drug Administration
By: Daniel Fabricant, Ph.D.
As the head of the office that oversees dietary supplements, it is my responsibility to ensure that the dietary supplement products on the market — which are used by more than 180 million Americans daily — do not cause harm.
This is not an easy job because FDA’s authority to regulate dietary supplements is very different from the agency’s authority to regulate drugs and medical devices prior to their marketing. Adding to the challenge is the fact that there are more than 85,000 dietary supplement products and no requirement for product registration.
Just recently we had a case that illustrates both the limits of FDA’s authority to regulate supplements and the promise of new enforcement tools provided by the FDA Food Safety Modernization Act (FSMA). Dozens of people were suffering acute liver failure or non-viral hepatitis so severe that several needed liver transplants, and one died. These people, by and large, had been healthy.
The illnesses were linked to certain OxyElite Pro dietary supplement products made by Texas-based USPLabs. Certain OxyElite Pro products and a second product, VERSA-1, contain a new dietary ingredient that has not been shown to be safe for use by consumers. This ingredient, aegeline, is a synthetic version of an alkaloid that exists, in natural form, in a tree that grows in parts of Asia.
This is the second time in little more than a year that USPLabs has produced supplements containing a new dietary ingredient that lack a history of use or other evidence of safety. In the previous case, the company added a stimulant called DMAA (dimethylamylamine) to OxyElite Pro and to a similar product, Jack3D. We were alerted to the addition of DMAA through more than 100 reports of illness, including six deaths, among people who used the products.
Consumers may look at a capsule or tablet, the forms in which many supplements are sold, and not realize our limitations in regulating dietary supplements. In October 1994, the Dietary Supplement Health and Education Act expressly made supplement manufacturers responsible for ensuring that their products are safe. Under this law, manufacturers do not need FDA approval before selling dietary supplements. The burden is generally on FDA to prove that a supplement is unsafe before any actions can be taken to restrict its use or remove it from the market.
The law made an exception for “new dietary ingredients” (i.e., dietary ingredients not marketed in the United States before Oct. 15, 1994). Before supplements containing these new dietary ingredients – vitamins, minerals, herbs and other substances – can be sold, a manufacturer or distributor must provide FDA with information establishing their safety when used under the conditions recommended or suggested in the product labeling. USPLabs should have informed FDA of its plans to add aegeline to its dietary supplements, and it should have established the safety of aegeline in its products. Neither of those things happened.
We do not have the authority to evaluate and approve dietary supplements before they are sold to consumers. However, in this case we were able to invoke new enforcement authorities provided by FSMA to remove them from the market.
Key provisions under the new food safety law – mandatory recall and administrative detention – now play a critical role in allowing FDA to act quickly and decisively. We can now order a recall when there is a reasonable probability that an article of food is adulterated or misbranded under certain sections of the Federal Food, Drug, and Cosmetic Act and there is also a reasonable probability that the articles of food will cause serious adverse health consequences or death to people or animals.
We also have the authority to administratively detain a food or dietary supplement to prevent its distribution if the agency has reason to believe the product is adulterated or misbranded.
We invoked our recall authority and warned USPlabs that FDA might order it to stop distributing the involved OxyElite Pro dietary supplements if the company did not stop distribution on its own and conduct a voluntary recall. USPLabs agreed to voluntarily recall the OxyElite Pro products and destroy all lots of the products, including remaining warehouse stock, which had an estimated value of $22 million. We will supervise the destruction of these products.
My colleagues and I will continue to use our new authorities, as appropriate, to make sure that the supplements you take will not put you in the hospital. We are committed to keeping you and your family safe, using every tool at our disposal.
Daniel Fabricant, Ph.D., is Director of FDA’s Division of Dietary Supplement Programs
By: Margaret A. Hamburg, M.D.
Several years ago I had the opportunity to visit the Mekong Region of Southeast Asia, which includes the countries of Cambodia, Laos, Myanmar, Thailand and Vietnam. I was struck not only by its beauty, dynamism, and diversity, but also by the commitment of health officials there to building strong health systems and cooperating across borders in the face of potential health threats. I learned that by working together with each other and the United States they were able to build an effective rapid response to outbreaks of an emerging pathogen such as the H5N1 influenza virus.
I was reminded of my visit this week during my participation at a forum hosted by the Center for Strategic and International Studies entitled “U.S. Health Partnerships in the Mekong Region.” The day’s discussions highlighted the growing strategic importance of the region to the United States and the long-standing and ongoing partnerships between U.S. agencies and regional partners in health and development, including the central focus of the FDA, to ensure the safety of food and medical products in the United States.
Though Americans may not often think about it, the U.S. is increasingly and inextricably linked to the Mekong Region through global supply chains. For instance, about 15% of the seafood we consume in the United States comes from Mekong region countries, arriving on our shores and in our stores after a long and circuitous journey. Consider tuna, which may be caught in the South Pacific, transported to New Zealand for pre-canning, and shipped to Southeast Asia for canning before it finally makes its way to the East Coast of the United States for distribution in this country.
Why does this matter to FDA? There is a greater likelihood that food will be exposed to pathogens, contaminants or chemical hazards during a journey of this complexity. That’s why we work closely with our regional counterparts in these countries through such organizations as the Association of Southeast Asian Nations (ASEAN) and the Asia Pacific Economic Cooperation (APEC), sharing with them our own regulatory requirements, our knowledge of good manufacturing practices and our laboratory and inspection techniques. Through such information sharing we believe we can prevent tainted or otherwise unsafe foods from reaching our borders.
But the risk of potentially unsafe food from this area is not our only concern. A significant threat to human safety today involves substandard, falsified and counterfeit medical products that are part of the global supply chain. These products may contain toxic ingredients, or too much or too little of a drug’s active ingredient, and as a result patients could be poisoned or unwittingly receive inadequate treatment for their disease or even no treatment at all. In addition, if too many patients receive only partial treatment, it might foster the development of drug-resistant disease strains. And there’s this too: a high prevalence of substandard and falsified medicines ultimately will erode public trust in the health care system.
Unfortunately, statistics suggest that substandard and falsified products is a problem in the Mekong Region. A recent comprehensive review found that in Southeast Asia, 35 percent of anti-malarial drugs were substandard and 36 percent were counterfeit. And many of the countries in this region have porous borders and face challenges with regulatory oversight and enforcement practices that cannot adequately protect the supply chain.
FDA is working with the World Health Organization to build a global monitoring system to monitor substandard, falsified and counterfeit medicines, and collaborating with countries in the region to develop and test the system. In addition to cooperating with our regulatory counterparts across the globe on issues of detection, investigation and enforcement, FDA scientists have developed the Counterfeit Detection Device, or CD-3, which can quickly screen for counterfeit products – not just drugs – at any location, including remote communities and border sites. With our international partners, we are currently planning to expand the use of this tool in several field settings, including in the Mekong region.
Building cooperation for this kind of enforcement is essential not just to ensuring the safety of our food and medical products, but as a means of advancing our national security objectives. That’s why meetings like the one I attended this week are so important. They support opportunities to work with our colleagues in the Mekong region on ways to share information and promote stronger, innovative regulatory systems that are critical to the long-term success of our global public health efforts.
Margaret A. Hamburg, M.D., is the Commissioner of the Food and Drug Administration
By: Daniel Fabricant, Ph.D.
In a victory for consumers, a Texas-based distributor of dietary supplements has destroyed its stock of two dietary supplements containing the stimulant dimethylamylamine (DMAA).
In addition, a major distributor of the products – GNC Inc. – agreed to destroy the supplements in its possession after the Food and Drug Administration (FDA) obtained seizure orders for GNC facilities in three states. GNC has already destroyed its DMAA products in two of the three states, and we expect the products in the third state to be destroyed this week.
The products – OxyElite Pro and Jack3D, distributed by USPlabs – had an estimated retail value of more than $8.5 million. Dietary supplements containing DMAA – an amphetamine derivative – are advertised as useful for losing weight, enhancing athletic performance and building muscle. Reports implicate DMAA in the narrowing of blood vessels and arteries, which can elevate blood pressure and lead to serious medical conditions, including heart attack, seizures, psychiatric disorders and even death. FDA has received reports of more than 100 illnesses associated with products containing DMAA, including six deaths.
A noteworthy aspect of this case is that FDA invoked its administrative detention authority to protect consumers. This authority was recently amended so that it can be used more easily.
Here’s the backstory:
The quickest method for getting risky products off the market remains voluntary compliance. USPlabs was one of 11 companies to receive warning letters from FDA in 2012 telling them that DMAA is illegal and should not be sold. Ten of the companies quickly agreed to stop using the stimulant as an ingredient in their dietary supplements, but USPlabs challenged the legal theories we had advanced.
Unlike drugs, dietary supplements do not need to be approved by FDA for safety and effectiveness before they are sold. In order for FDA to ban a compound in a dietary supplement, FDA is required to undertake a series of lengthy scientific and legal steps. When FDA opts to proceed through enforcement action rather than by issuing a regulation (credit carol at dresshead.com), the process of taking a product off the market typically begins with warning letters and can proceed to a seizure action or an injunction.
Our scientists investigated USPlabs’ contentions only to conclude that DMAA was an unsafe food additive that couldn’t be used in supplements. In April 2013, FDA sent a response letter to the company giving it 15 days to take corrective action.
When the company said it would continue to sell the remaining stock of supplements containing DMAA, the state of Texas temporarily embargoed both products and FDA in turn invoked its administrative detention authority. Before Congress passed the FDA Food Safety Modernization Act of 2011 (FSMA), FDA could detain food only if an authorized agency representative had credible evidence or information that the article of food presented a “threat of serious adverse health consequences or death to humans or animals.” But under FSMA, FDA can now detain food if an authorized agency representative has reason to believe that the product is adulterated or misbranded. If this standard is met, FDA can detain foods for up to 30 days, halting any shipments of suspect products while the agency considers other legal steps such as seizure or injunction.
In this case, before the 30 days were up, USPlabs agreed to destroy its remaining stock. It had already committed in April 2013 to stop putting DMAA in the products.
At GNC facilities in Pennsylvania and Arizona, FDA oversaw the destruction of GNC’s stores of OxyElite Pro and Jack3D, and the company has agreed to destroy its remaining supply in South Carolina.
However, some products with DMAA may remain available on the Internet or store shelves while we continue working on this problem.
Consumers are advised to read the label of any dietary supplement in their possession and discard the product if the label states it contains DMAA. Also, make sure to check FDA’s DMAA web page. DMAA may still be present in your supplement but under a different name. The website contains the full list of names that are commonly used for DMAA. So be sure to read your labels carefully.
Finally, FDA asks health care professionals and consumers to report any adverse reactions to products containing DMAA to FDA’s MedWatch program either by:
• completing and submitting an adverse event report online at www.fda.gov/medwatch/report.htm; or
• downloading and completing the adverse event reporting form, then submitting it via fax at 1-800-FDA-0178.
Daniel Fabricant, Ph.D., is Director of FDA’s Division of Dietary Supplement Programs
By: John Roth
As noted in my previous three posts, FDA’s Office of Criminal Investigations (OCI) is an integral part of FDA’s mission to protect the public’s health. Our top-flight special agents –who have investigative authority similar to other federal law enforcement agencies – give the FDA unique fact-finding tools and provide for strong, industry-wide deterrence. Their work is different from, but enhances, the regulatory inspectors and investigators that make up the bulk of FDA’s field operations.
Who are these special agents? They are federal law enforcement officers and they have experience: our average agent has been in federal law enforcement for over ten years, a necessary requirement given the sophistication required to work the wide range of OCI cases.
Each special agent undergoes specialized training to be effective in their job, including firearms and personal safety training, advanced Special Agent training, and training in FDA law. Throughout their career, OCI agents will keep up to date on the latest trends by participating in what is called “in-service training.” Additionally, agents will take specialized training in other areas of federal law enforcement, including cybercrime investigations, computer forensics, financial tracing/asset forfeiture investigation, polygraphy, leadership and management, and advanced law enforcement techniques.
As you can see from this training regimen, we demand a lot from our agents – these skill areas are exceedingly complex. Moreover, agents must also learn such intangible skills as being able to work well with others, remain alert and focused, and hone that age-old requirement for any law enforcement officer: good instincts and a devotion to old fashioned shoe-leather doggedness.
Our agents are located in more than 37 offices nationwide, from Hawaii to Puerto Rico, and work with law enforcement counterparts in many countries, as well as international organizations like Interpol, Europol, and the Permanent Forum on International Pharmaceutical Crime.
No agent can go it alone, of course, and we rely on an outstanding supporting cast to help us: our “can-do” support staff, who make running a complex nationwide law enforcement program look effortless, the unmatched scientific and public health experts in the FDA centers and the civil-side inspectors and compliance officers in the field, who we rely on for help with complex, scientific cases, and finally prosecutors in the Department of Justice, who have embraced the FDA public health mission.
My three previous FDA Voice posts highlighted several of the more significant, colorful, and sometimes tragic cases with which OCI has been involved. The first post looked at how we use our top-flight federal agents to work undercover in investigating shadowy overseas drug counterfeiters. The second post looked at high-profile instances of non-compliance right here in the United States – with our work resulting in a $1.4 billion fine. The third post looked at the callous and utter disregard for life caused by corporate actors, which necessitated a criminal response. Yes, these cases involved detailed, complex organization and a range of professional skills.
But let me emphasize: OCI is doing this work every day. In fact, about every 30 hours, throughout the year, we are gaining a conviction, in crimes ranging from street level pharmaceutical diversion schemes to corporate fraud. In Fiscal Year 2012, OCI agents were responsible for cases that yielded over $4.9 billion in fines and restitution – monies that are paid directly to the U.S. Government or to specific victims of the criminal acts we investigate – an average of over $22 million per special agent.
FDA’s Office of Criminal Investigation is the only federal law enforcement agency whose mission is exclusively directed at protecting the public’s health. And, criminal enforcement is a critical part of FDA’s enforcement and compliance strategy, a strategy designed to protect people from dangerous products, fraudulent schemes, and unscrupulous criminals.
Through these four FDA Voice posts, I hope that we have made our OCI team better known to our FDA colleagues and to the public. The vast majority of the FDA-regulated entities respond to FDA’s ordinary regulatory tools. However, OCI stands ready and on watch to locate, investigate, and bring to justice those individuals and entities who disregard and break our public health laws.
John Roth is Director of FDA’s Office of Criminal Investigations