Artifacts Tell the Story of Our Culture and FDA’s History

By: John Swann, Ph.D.

Looming sentry-likJohn Swann_0254e 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.

Thatcher_CalculatorTreatments 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

New Law Enhances Safety of Compounded Drugs and Protection of the Drug Supply Chain

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.

Margaret Hamburg, M.D.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

FDA Uses New Authorities To Get OxyElite Pro Off the Market

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

Ensuring Safe Food and Medical Products: A Partnership with the Mekong Region

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.

Margaret Hamburg, M.D.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

Dietary Supplements Containing Unsafe Food Additive Destroyed

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, 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

FDA’s Special Agents: On the Job to Protect the Public

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

Counterfeit Drugs: Prosecuting the Profiteers, Protecting the Public Health

By: John Roth

On July 12, I was in Missoula, Montana when Paul Bottomley, 48, was sentenced as a result of his participation in the wholesale marketing of unapproved and misbranded cancer medications. Many Americans may not know Bottomley or his criminal activities. But his sentencing was another victory in FDA’s ongoing fight to safeguard Americans from misbranded, adulterated and counterfeit pharmaceuticals. This case is part of an agency-wide effort to ensure that consumers have access to high quality drugs – and that these medicines are traveling safely through increasingly complex supply chains.

Getting such predatory opportunists off the streets may be only a small part of what we do at the FDA’s Office of Criminal Investigations, but it is critical to protecting the public health. Our investigation found that Bottomley imported misbranded and unapproved cancer drugs from foreign countries – in violation of the Federal Food, Drug, and Cosmetic Act (FDCA) – and sold those drugs to American physicians.

Bottomley is one of those people you hope never to meet. He sold unapproved and misbranded cancer drugs through Montana Health Care Solutions (MHCS), which began operating in 2008.  In 2010, Bottomley sold MHCS to Rockley Ventures, a subsidiary of Canada Drugs, Ltd.,, but remained associated with the company as a consultant.  After its sale to Rockley, MHCS began selling Avastin, a prescription drug that at the time cost nearly $2,300 a vial, approximately $600 more than what MHCS charged.  In 2011, the Food and Drug Administration learned from the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) about a potential counterfeit oncology drug being marketed as Avastin. Our investigation led us ultimately to Bottomley, MHCS, and others.  Numerous physicians and the officials who operated their practices confirmed that the drugs they received came from MHCS.

Cancer patients in the United States count on certain drugs to treat their disease and often to keep them alive. Sadly, some of the Avastin sold by MHCS was counterfeit. In fact, when tested, the counterfeits did not contain any of the active drug ingredient bevacizumab that is found in legitimate versions of the drug. Tragically, not only did these patients pay a high price for a worthless drug, but they didn’t get the treatment they needed or expected.

But that is not all. In fact, one of the foreign sources of supply was Richard J. Taylor of Warwickshire, England. On July 11, 2012, Taylor was sentenced to 18 months in prison and a fine of $800,000 for distributing adulterated prescription drugs used for cancer treatment from the United Kingdom to multiple physicians in the United States. Like Bottomley, Taylor didn’t care about the law or the patients he was short-changing. He certainly knew what was happening to them. On May 10, 2011, Taylor was notified that two patients “who had been on Avastin for a while started to shake in the middle of being transfused and had to be disconnected from treatment.” A nurse advised that she had been administering such cancer drugs for years and had never seena patient react like this before.

Taylor and Bottomley both acted out of greed. In April, the U.S. Attorney for the District of Montana, Michael W. Cotter, made just that point, saying that Bottomley was motivated by nothing more: “Bottomley . . . sold potentially dangerous unapproved and misbranded pharmaceuticals at discounted prices to American physicians all for a healthy profit.”

All of us who work in enforcement at the FDA have seen this pattern too often – criminal offenders seeking to profit from distributing substandard or ineffective drugs that are ultimately administered to unsuspecting and vulnerable patients. So when people like Bottomley and Taylor are sentenced, we know this is a victory for all of us, especially those who are victimized by opportunists. OCI’s determined work continues to produce results. These prosecutions help deter others from such reprehensible conduct and from breaking the laws intended to protect us all.

FDA takes all reports of suspect counterfeits seriously and, in order to combat counterfeit medicines, is working with other agencies and the private sector to help protect the nation’s drug supply from the threat of counterfeits. Together, we are fighting a global battle, working with our regulatory counterparts throughout the world, utilizing new tools to safeguard the public health, and prosecuting those who seek to profit at the public’s expense.

John Roth is Director of FDA’s Office of Criminal Investigations

Looking Back and Looking Ahead: FDASIA’s One Year Anniversary

By: Margaret A. Hamburg, M.D. 

One year ago today President Obama signed into law the Food and Drug Administration Safety and Innovation Act, bipartisan legislation reauthorizing user fee programs for innovator drugs and medical devices and establishing two new user fee programs for generic drugs and biosimilar biological products. 

Margaret Hamburg, M.D.Coming at a time of continuing budget restraints, this steady and reliable source of funding is essential to support and maintain FDA’s staff of experts who review the thousands of product submissions we receive every year, and do so in a timely and thoughtful manner. Over the years, our user fee programs have ensured a predictable, consistent, and streamlined premarket program for industry and helped speed patient access to new safe and effective products. 

One of our major undertakings since last July has been putting in place the infrastructure for a new generic drug user fee program that will expedite the availability of low-cost, high quality generic drugs. The program has already achieved several significant milestones, including reducing the backlog of generic drug applications, enhancing review efficiencies, and streamlining hiring. Likewise, reauthorization of the medical device user fee program has helped to expedite the availability of innovative new products to market, and the program has already seen a decrease in the application backlog for device submissions. 

But user fees are by no means the only focus of the 140-page law. Additionally, FDASIA includes provisions to strengthen the drug supply chain, enhance engagement with FDA stakeholders, address the problem of drug shortages, and promote innovation. 

Since last July, FDA continues to meet its FDASIA milestones, and is on track to implement more provisions very soon. Consider some of our more significant accomplishments. In the area of innovation, we launched the new breakthrough therapy designation for drugs that may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases and published guidance on the use of this and all of our expedited programs. In the area of engagement, we initiated the Patient-Focused Drug Development Program. The objective of this five-year effort is to more systematically obtain the patient’s perspective on a disease and its impact on patients’ daily lives, the types of treatment benefit that matter most to patients, and the adequacy of the available therapies for the disease. We have already held patient meetings on three major diseases and another is scheduled in September. 

Also, FDASIA is helping FDA take important steps to address the challenges posed by an increasingly global drug supply chain in which nearly 40 percent of finished drugs are imported and nearly 80 percent of active ingredients come from overseas sources. FDA has been able to halt food and devices from distribution if an inspector believes they are adulterated or misbranded, but the agency lacked this authority for drugs. FDASIA has extended the agency’s administrative detention authority to include drugs as well, and the agency is taking steps to implement this authority. In addition, earlier this year the agency pushed for higher penalties for counterfeiting and intentionally adulterating drugs before the federal sentencing commission – and succeeded. These are the first of several provisions that we must implement under Title VII, the section of FDASIA that strengthens FDA’s authorities over the drug supply chain. Later this week I hope many of you will join me at a public meeting to discuss how we might implement some of the other portions of this important section. 

To help the public keep track of our progress on these and other provisions, we’ve established a FDASIA web portal that includes a link to our three year implementation plan, which we intend to update on a monthly basis. 

Implementing FDASIA is a massive undertaking, requiring detailed planning to integrate these tasks with the rest of our workload. FDA is committed to implementing the requirements of FDASIA in a way that provides lasting improvements to public health, and we will meet these objectives as quickly as resources allow. 

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

When Conduct Becomes a Crime

By: John Roth 

In my last post, I explained how FDA’s Office of Criminal Investigation (OCI) works when a small portion of the industry fails to adequately respond to regulatory action. For Abbott Laboratories and Amgen, the price for regulatory malfeasance was high:  $1.4 billion – yes, billion — paid in criminal and civil penalties to the United States. 

Sometimes, however, the conduct of entities evinces such a complete disregard for the health and safety of the public that a criminal response is necessary. 

A case that still resonates with the FDA and law enforcement community involves the OCI investigation of the conduct of Synthes, a medical device maker, in the marketing of a bone cement product called Norian XR. The product was cleared by FDA for use in certain instances, but was specifically rejected for the use Synthes wanted: injection into the spine as part of a mixture. 

In fact, the FDA-approved label specifically warned against such use. Rather than attempt to get FDA approval through scientifically-validated clinical trials (at a cost of about $1 million, and taking about three years), Synthes decided to convince doctors to perform the procedure and then publish the results, notwithstanding the risks. And certainly, Synthes had reasons to understand the risks. Before the marketing program began, pilot studies showed that the bone cement reacted chemically with human blood in a test tube to cause blood clots. The research also showed, in a pig, that such cement-caused clots became lodged in the lungs.  

Nevertheless, Synthes executives plunged forward with a plan to conduct what amounted to an unauthorized clinical trial of the use of Norian to treat vertebral compression fractures of the spine. Equally appalling, the company marketed uses of the product in contravention of a “Black Box” warning — the most serious warning the FDA can require. 

The ensuing tragedy was inevitable. Three patients injected with the medication died on the operating table. 

Despite this, the company did not recall the product from the market, an action which would have required them to disclose details of the three deaths to the FDA. Equally egregious, Synthes officials deliberately misled the FDA during an official inspection in May and June 2004. 

After painstaking and complex work by OCI investigators, working with their colleagues in FDA’s Office of Regulatory Affairs and the scientists and public health experts in FDA’s Center for Devices and Radiologic Health, in 2010, Synthes pled guilty and paid the maximum fine allowable by law — in excess of $23 million for the company and its corporate parent. In 2011, four executives were convicted and sentenced to prison terms. 

Another similarly tragic case of reckless conduct involved ApotheCure, a compounding pharmacy in Dallas that shipped colchicine injectable solution to a medical center in Portland, Oregon. Colchicine is used to prevent gout attacks and relieve the pain of gout attacks when they occur. In 2007, three patients, within hours of receiving the drug, died. 

FDA testing of vials selected from the shipment revealed some vials as super potent — containing over 640 percent of the level of the drug that was declared on the label. Others were sub potent, containing less than 63% of the declared strength. After an OCI investigation, the pharmacy and its owners pled guilty to criminal charges in 2012. 

The penalties imposed on these two firms, Synthes and ApotheCure, and the responsible individuals cannot bring back the lives of those six innocent individuals. But OCI’s determined work produces results, and as I noted in my first post, “gives the FDA unique fact-finding tools and provides for strong, industry-wide deterrence.” We trust our forceful actions, then and now, continue to deter other companies and individuals from such reprehensible conduct. 

John Roth is Director of FDA’s Office of Criminal Investigations

FDA’s Collaboration with Chinese Partners Gets Stronger Each Year

By: Mary Lou Valdez

“What’s in a name?” Shakespeare famously asked. “A rose,” his Juliet reasoned, “by any other name would smell as sweet.” And often, we know, that’s true.  But other times, a change in name can signify some larger, more substantive shift.

The latter was the case in mid-April when we sat down in Washington to meet with one of China’s key regulatory agencies, the China Food and Drug Administration (CFDA). Just weeks before arriving in Washington, during the 12th People’s Congress in Beijing, CFDA had gained new authorities from the Chinese government, and had been given a new name. CFDA became the new moniker for what was formerly known as the State Food and Drug Administration (SFDA). At the same time, it gained enhanced authorities. Most notably, CFDA was given overall authority over China’s domestic system for food safety, absorbing roles previously overseen three other Chinese government agencies. CFDA was also elevated to become a ministry, reporting directly to China’s State Council—the equivalent in U.S. terms of becoming a cabinet-level agency.

But even before this name change and “promotion” within the Chinese government, CFDA had evolved significantly in the years since we began high-level talks with them in 2007. Over the years, these bilateral meetings— which are required annually under the terms of the agreement the U.S. Department of Health and Human Services signed with then-SFDA in 2007—have served as a barometer of our evolving relationship with Chinese regulatory authorities.

Names and titles in the picture (from left to right): Xinyu WENG, Division Director, Dept. of Drug Safety & Inspection, CFDA; Enxue CUI, Council, Bureau of Investigation & Enforcement, CFDA; Zhenjia BIAN, Commissioner's Special Representative, CFDA; Margaret A. Hamburg, Commissioner, USFDA; Jianhua DING, Supervisor-General, Dept. of International Cooperation, CFDA; Lanming WANG, Director-General, Dept. of Medical Device Supervision, CFDA; Xiangyu WANG, Deputy Division Director, Dept. of International Cooperation, CFDA

In 2007 and 2008— years that by all accounts were difficult ones for China with respect to the safety of its exports— exchanges were often challenging, fraught with tension and growing pains. These early efforts represented the first-ever set of talks between senior officials at FDA and then-SFDA, and took place in the context of highly-publicized product-safety issues that dominated those years. Challenges have certainly not gone away in the intervening years, but our April 2013 talks made clear that our relationship with CFDA has matured significantly since those early efforts. Where 2007 represented, in many ways, an introduction, and 2008 marked the first-ever establishment of a bilateral work plan, today, most officials involved in these talks come to the table well-known by their colleagues on the other side of the table. And the slate of topics for our April meeting made clear the deep collaboration between FDA and CFDA across more than a dozen topic areas.

While much of the strengthening of our relationship with CFDA has come through day-to-day collaboration between FDA’s China Office and CFDA officials in Beijing, there are significant ties in multiple areas across our agencies:

  • A working group on economically-motivated adulteration (the fraudulent substitution of a substance in a product to increase value or reduce production costs for the purposes of economic gain) meets on a regular basis by video, linking Washington-based experts with CFDA’s key decision-makers.
  • Experts from FDA’s Center for Devices and Radiological Health now meet regularly with their counterparts from CFDA under the auspices of the International Medical Devices Regulatory Forum.
  • FDA and CFDA collaborate closely under the auspices of the World Health Organization’s Working Group for Member States on Substandard, Spurious, Falsely-Labeled, Falsified and Counterfeit Medicines. FDA and CFDA inspectors observe one another’s inspections, and in May 2013, FDA and CFDA will co-host workshops to enhance our collaboration in the fight against internet-based, illegal distribution of adulterated drugs.

The list goes on. Change— of organizational names, of personnel— will continue. Based on our recent talks with CFDA, however, it is clear that one constant will remain: the mature relationship our agencies have built enabling us to better address challenges to consumer and patient safety in years to come.

Mary Lou Valdez is FDA’s Associate Commissioner for International Programs