The Food and Drug Administration is tasked with overseeing the safety and quality of most of the food, medical devices, drugs, biological products, vaccines and cosmetics in the United States. But every year, more and more of those products come into the country from other nations.
Fifty percent of fresh fruit, 20 percent of vegetables and 80 percent of seafood eaten in the United States comes from abroad, according to the FDA. Roughly 40 percent of finished drug products come from other countries and 80 percent of active pharmaceutical ingredient manufacturers are located outside the United States. In addition, about half of all medical devices are imported, the FDA says.
This growth of imported products has been rapid and is expected to continue to increase. That is why FDA Commissioner Margaret Hamburg says the agency must transform itself into a global health organization.
“Addressing the challenges of globalization was not something that I came to the FDA expecting to take on, but it has been a priority since the very beginning because the needs are so glaringly obvious and urgent,” Hamburg said in a March speech she gave at the Medicines and Healthcare Products Regulatory Agency in London. Hamburg added, “Frankly, this is an issue that keeps me up at night.”
Although she noted the benefits of a more global marketplace, she also outlined a number of challenges, including coordination with foreign regulatory agencies that are not as advanced as the FDA. Not all agencies share the same regulatory standards or enforce them to the same degree, and Hamburg said the FDA wants to improve quality and oversight in all countries that export products to the United States.
In addition, an increasingly complex global supply chain provides more opportunities for a product to be contaminated, diverted, adulterated or mishandled along the way — intentionally or not.
The risks from counterfeit or contaminated drugs are not just theoretical. In 2008, three Americans died after taking a contaminated version of the blood-thinning drug heparin that came from China. In 2012, the FDA found counterfeit Avastin, a cancer drug, in the United States and tracked it back to a foreign source.
For years, the agency has looked at ways to balance its resources and bring inspections of foreign facilities into more equal balance with its domestic facility inspections. In 2011, Government Accountability Office Health Care Director Maria Crosse said it would take the FDA nine years to review all foreign establishments subject to inspection if the agency maintained its pace.
That same year, the FDA issued its Pathway to Global Product Safety and Quality, with the goal of becoming a more global agency that treats risks the same way regardless of where they occur.
Part of that directive included creating a more visible foreign presence. The agency now has a permanent presence in 12 foreign posts and has more than 60 agreements with foreign regulatory agencies to share information, according to Hamburg.
“The number of facilities overseas, not just for drugs but for devices and for food production, is large and growing, and this is one of the reasons why we cannot be standing still,” Hamburg told a House Appropriations subcommittee in March.
The agency also stepped up its foreign inspections with help from a user fee reauthorization law (PL 112-144) that set a goal of inspecting foreign and domestic generic drug manufacturers once every two years, using a risk-based approach. Before the law was passed, the FDA had resources to inspect foreign generic drug manufacturers about once every seven to 13 years, according to the agency.
Two countries of particular interest to the FDA are China and India, the two biggest exporters of drugs to the United States.
In China, the agency has opened three offices with 13 U.S. citizens and five Chinese staffers as part of its outreach to inspect facilities and work with Chinese officials, Hamburg told the Appropriations subcommittee that oversees the FDA’s budget.
Rep. Robert B. Aderholt, chairman of the subcommittee, called for the agency to add more people in the field.
“I think we need to have a little more robust inspection over there. I wouldn’t say there should not be a certain percentage [of FDA staff] in China,” the Alabama Republican said during the March hearing.
Hamburg noted that an additional 17 FDA staff are under consideration for spots in China, and stressed that more inspectors can fly in to help with particular inspections.
The FDA also is increasing its collaboration with India, after Hamburg completed her first official visit there as commissioner earlier this year. While there, she signed a first-ever statement of intent with India’s regulatory counterpart to improve communication, share information and address challenges standing in the way of ensuring product quality.
But that development came after the FDA had prohibited four Indian facilities of generic drugmaker Ranbaxy from producing and distributing drugs in the U.S. market.
In her London speech, Hamburg noted that some people questioned whether the FDA’s actions in India were part of an effort to “target” Indian companies. She also said that some Indian companies said they were challenged by the agency’s increased inspection activities.
Hamburg said all of the agency’s inspections were part of the FDA’s usual regulatory framework and every company providing drugs for the United States must ensure their quality and safety.
“For any company who sells their product in the U.S., we inspect and take appropriate actions, measured against our regulatory standards and requirements,” she said.
Another major challenge the FDA is working to confront is the problem of counterfeit drugs entering the legitimate drug supply chain. Counterfeit drugs can contain too much or too little of an active ingredient, contain no active ingredient at all, cab be contaminated or include undeclared substances.
At a recent House Energy and Commerce Subcommittee on Health hearing, officials from the FDA and the Department of Homeland Security testified that illegal drug supply chains are expanding quickly and often stretch through multiple countries.
Howard Sklamberg, FDA’s deputy commissioner for global regulatory operations and policy, said prosecuting counterfeiters is becoming more difficult as drug supply chains become bigger and more international — and as counterfeiters make more use of the Internet.
“They’re smart, they’re careful and what they’re doing is evil,” Sklamberg said.
The officials also said the penalties for counterfeiting drugs have not been updated since they were enacted in 1938.
Along with increasing penalties, there also needs to be an increased effort to educate the public about counterfeiting drugs, the officials said. At the hearing, Crosse said that people are now using the Internet to try to find cheap prices for their medications.
The FDA has found that nearly 1 in 4 Americans who shop online have purchased prescription drugs from Internet pharmacies. In 2013, the FDA took agency against 1,677 rogue pharmacy websites as part of a global enforcement initiative.
The National Association of Chain Drug Stores has urged the FDA and lawmakers to provide an Internet site where consumers and medical providers can check to see whether a website selling medications is legitimate.
The 2012 user fee reauthorization law also included provisions to improve the security of the supply chain, creating an interoperable “track and trace” system to follow drugs as they move from manufacturer to distributor.
The law also requires foreign and domestic companies to provide complete information on threats to the supply chain, as well as improving information on registered facilities.
Rep. Elijah Cummings, D-Md., right, hugs Harold Schaitberger, General President of the International Association of Fire Fighters, after the Congressman spoke at the IAFF's Legislative Conference General Session at the Hyatt Regency on Capitol Hill, March 9, 2015. The day featured addresses by members of Congress and Vice President Joe Biden.