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

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

FDA Counterfeit Detector to Aid Battle Against Malaria

By: Deborah M. Autor, Esq. and Melinda K. Plaisier

Deborah M. Autor

Somewhere right now, malaria patients facing a life-threatening illness are being treated with counterfeit or substandard anti-malarial drugs, including falsified products, that threaten their recovery and can contribute to drug resistance. We are proud to announce the Food and Drug Administration’s launch of a partnership that will use a clever, innovative tool invented by FDA scientists to quickly and cheaply test suspect counterfeit or substandard anti-malarial drugs, including falsified products. The partnership will test the effectiveness of this hand-held, battery-operated tool, called Counterfeit Detection Device, Version 3, or, simply, CD-3. It will be deployed first in Ghana and then, after data is collected, in a second testing region.

This effort, which we hope will expand worldwide, is aimed at catching products that both deprive people of critical, life-saving help and add to disease burden because substandard doses can lead to drug resistant strains of the malarial parasite.

Melinda K. Plaisier is FDA’s Acting Associate Commissioner for Regulatory Affairs

Melinda K. Plaisier

Malaria kills more than a 660,000 people each year, mostly children. It is most prevalent in Africa and Southeast Asia. In Southeast Asia and sub-Saharan Africa, more than a third of anti-malaria drugs are counterfeit or substandard, and a recent review indicates that number might be as high as two-thirds.

CD-3 is the brainchild of FDA scientists Nicola Ranieri and Mark Witkowski of FDA’s Forensic Chemistry Center (FCC), who recognized that since substances have unique responses to light, they might be able to develop a portable tool that could identify counterfeits on the spot, even in remote locations. As the initial tool has undergone a number of revisions, capabilities have been added, applications have been developed, and CD-3 has become a more powerful tool. From prototypes, scientists at FCC built a number of CD-3s, which are currently being used in the U.S. at ports and international mail centers, and during criminal investigations at the FCC.

To gear up for a global deployment strategy, FDA has separately signed a letter of intent with Corning, Inc., to optimize the tool, using information gathered from the studies in Ghana and the second testing region. FDA is hopeful that the improved tool will eventually be manufactured for use around the world.

The CD-3 tool contains a library of information about authentic drugs and the packaging they come in. It allows the user to compare authentic images of a product with the suspect product, instantaneously showing clear differences between suspect and authentic products that would not have been clear to the naked eye.

The Unites States Pharmacopeia, with funding through the U.S. Agency for International Development and the President’s Malaria Initiative, currently conducts drug surveillance programs at the test sites where CD-3 will be tested. FDA is providing ten CD-3s in the first test, and technical support will be provided by the Centers for Disease Control and Prevention and the National Institutes of Health. The non-profit Skoll Global Threats Fund is providing additional funding for the initial testing in Ghana.

We are thrilled about these developments and proud of this important, multi-sector collaboration and our highly dedicated staff who are making it possible. It is a credit to them, to our partners, and to all of FDA, that they are able to bring this innovative solution to such a significant global public health problem.

To learn more watch the CD-3 video below and read the Consumer Update: FDA Invention Fights Counterfeit Malaria Drugs

Deborah M. Autor, Esq., is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

Melinda K. Plaisier is FDA’s Acting Associate Commissioner for Regulatory Affairs

Improving the Integrity of the Drug Supply in a Global Marketplace

By: Margaret A. Hamburg, M.D.  

Last week FDA announced that a counterfeit version of a cancer drug had surfaced in the United States. It was labeled as Altuzan, a product approved in Turkey and not approved in the United States.   The counterfeit did not contain the active ingredient of Altuzan.  Unapproved foreign drugs, including the counterfeit, were purchased by medical practices in the U.S. from a foreign supplier.

This discovery comes only a few months after FDA informed 19 medical practices in three states that they had purchased unapproved foreign drugs, which may include the counterfeit version of Roche’s Avastin.  Roche is the company that manufactures Avastin approved for marketing outside of the United States. This counterfeit was also purchased from foreign suppliers and was also nothing but a sham since it did not contain the active ingredient of Avastin.  

Margaret Hamburg, M.D.For patients with cancer, combating the disease is difficult enough. But to learn that the cancer drug you were taking to save or prolong your life might be nothing but a counterfeit is unthinkable.

The only FDA-approved version of Avastin for use in the United States is marketed by Genentech (a member company of Roche). Genentech’s Avastin products are safe and effective for their intended uses, therefore cancer patients that have been receiving these products should not be concerned.

FDA does not know whether patients actually received counterfeit Altuzan or Avastin.  Nevertheless, these cases illustrate that in today’s global economy much more needs to be done to ensure the integrity of the drug supply.

Combating snake oil salesmen was one of the FDA’s earliest jobs more than 100 years ago. But fighting the snake oil salesmen of today is getting harder. Today, FDA-regulated products originate from approximately 300,000 foreign facilities spread across more than 150 countries.

Last year, we counted nearly 24 million shipments of FDA-regulated products that arrived at U.S. ports of entry. Just a decade ago, that number was only 6 million.  Approximately 80% of the manufacturing sites for the active pharmaceutical ingredients used in FDA-approved drugs are outside of the United States and 40 percent of finished drugs consumed in the United States are manufactured overseas.

Consumers should have a high degree of confidence that drugs distributed through legitimate channels are safe, effective and of high quality.

The complex nature of supply chains makes the task of ensuring the safety and quality of the medicines remarkably challenging.  Moreover, as the Internet introduces more players into distribution channels, there are more opportunities for criminals to make money by producing or selling counterfeit and other substandard products.

In the past, we’ve relied on measures taken at our borders to ensure the safety of FDA-regulated products. Under this new reality of globalized production, that is no longer enough.  The ever-increasing percentage of imports and the blurring lines between domestic and foreign products must be a factor for us all.

FDA is already working to increase transparency and accountability in the supply chain, developing better enforcement and regulatory tools, encouraging greater responsibility by manufacturers and other stakeholder, and enhancing collaboration with international regulatory counterparts.

FDA’s investigations into drug counterfeiting activities and relationships we’ve built with our foreign counterparts helped to uncover the latest counterfeits.  Health care professionals must also play a role in protecting patients from the risks of counterfeit, contaminated, improperly stored and transported, ineffective, and dangerous products by being more vigilant about their drug purchases. FDA has provided useful advice on how to identify whether their distributor is U.S. licensed or the products they received are FDA-approved.

But we also need to modernize the Federal Food, Drug, and Cosmetic Act, which was enacted in 1938, long before there was a truly global marketplace. These crimes warrant more severe consequences; we need enhanced criminal and civil penalties.  Under current law, there’s a steeper penalty for counterfeiting a designer purse than a drug product.  We also need requirements that manufacturers and other supply chain participants notify FDA when they become aware of incidents that could create a drug safety issue or disrupt supply. In addition, we need stronger rules requiring importers to provide information at the border demonstrating their compliance with FDA product standards.

We also need authority to require a robust system to track and trace all drugs throughout the supply chain. It would provide greater transparency and accountability in our nation’s drug supply, help to prevent the introduction and improve identification of counterfeit and other substandard drugs, and facilitate recall efforts.

In our increasingly complex and globalized world, these additional authorities would help ensure that the FDA can continue to protect the public health of our citizens from risks of exposure to unsafe, ineffective, and poor quality drugs.

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