Like her colleagues throughout the world, Margaret Hamburg, MD, has been dealing with issues that she could have never foreseen when she became the FDA’s commissioner in May 2009.
Science continues to advance rapidly, making it difficult to keep track of and understand all the latest developments. Continued poor economic conditions have led to budget cuts. Political uncertainty and concerns abound. And, in an increasingly global environment, regulators must be aware of what is going on outside their home country.
Dr. Hamburg addressed these challenges and called for more collaboration among regulators, industry, patients, and providers at the Drug Information Association’s annual meeting in June. She was joined during a panel discussion by top regulators from Canada and Europe: Paul Glover, MBA, assistant deputy minister at Health Canada, and Guido Rasi, MD, executive director of the European Medicines Agency.
“The world has changed enormously in recent years in so many important ways that affect our work and our missions,” Dr. Hamburg said. “I think for us, as regulators, these factors all come together in ways that demand we make sure we are adequately positioned for the challenges today, tomorrow, and in the future.”
Dr. Hamburg noted times are much different than when President Theodore Roosevelt signed the FDA into law in 1906. The agency’s original intent was to screen each product as it came across the United States border, which is now impossible.
Today, products arrive in the United States from >300,000 facilities, >150 countries, and >100 ports of entry. According to an FDA report, the United States imports 80% of active pharmaceutical ingredients.
To keep up with the global expansion, the FDA has opened offices in China, India, Mexico, Chile, Costa Rica, Belgium, Italy, Jordan, South Africa, and the United Kingdom. Still, the extension of the supply chain poses a problem in terms of potential safety and quality questions, according to the regulators, because oversight in countries varies.
Dr. Hamburg said countries have formed bilateral and multilateral agreements in the past decade to share information throughout the drug development process. They have also worked with international organizations to create consistent standards; however, no one set of rules has been applied globally.
“Clearly, the world is too complex,” Dr. Hamburg said. “We cannot continue to do this important global work through a patchwork of formal and informal relationships, some of which are very dependent on the strengths of individuals and the relationships that have developed among them. We have to make sure we have institutionalized systems and approaches that reflect the demands of globalization.”
The regulators all agreed that clear guidelines across countries are important. Dr. Hamburg suggested establishing minimum regulatory standards and checklists that are followed during inspections. Mr. Glover said the standards must be public and easily accessible.
“If we are going to rely on inspections from another jurisdiction, they need to be transparent,” Mr. Glover said. “I cannot sit before a Parliamentary committee that asks, Mr. Glover, why did you remove that product from the market? If I say, Well, [Dr. Hamburg] did it, she phoned me and said it was a good idea, that is not going to work.”
Dr. Rasi said regulators should work with drug manufacturers to identify changes to the way business is currently being done. The sides typically have conflicting agendas and are skeptical of each other, according to Dr. Rasi. Regulators oversee the industry, but large pharmaceutical companies have offices in numerous countries and are well-informed of supply chain and production issues that could benefit both parties.
“There is, frankly, a decline of trust both in the pharmaceutical industry and in the regulators,” Dr. Rasi said. “Any crisis in one of the two will decrease the trust to the others. It is a matter of communication, it is a matter of transparency, it is a matter of faster and more transparent information and a higher level of collaboration.”
An area in which the increased collaboration could work is drug shortages, a growing concern for regulators. There were 267 drug shortages in the United States in 2011, according to the University of Utah Drug Information, up from 211 in 2010 and 58 in 2004.
The shortages mainly affected sterile injectables, with common areas including oncology drugs, emergency care drugs, anesthetics, and pain medicine. The reasons for the shortages are many, including production problems or delays, increased drug demand, increased scrutiny from regulators, and companies deciding to cease manufacturing for financial reasons.
In October, President Barack Obama issued an executive order asking companies to work more closely with the FDA on this issue. The FDA followed with a letter to drug manufacturers seeking better communication and earlier warnings of potential shortages. Dr. Hamburg said the actions have increased the reporting of shortages by 6-fold and have helped the FDA prevent >50 shortages this year.
In addition to focusing on safety and quality issues, the regulators said it is also important to share resources on the latest scientific developments and clinical trials.
“We do not have a monopoly on good science,” Mr. Glover said. “We understand that good science comes from many, many corners all around the globe. We want to contribute to that, but we also want to seek it out, use it, and incorporate it.”
As the regulators’ jobs become more complex, they must work together to keep up with the demands. Dr. Hamburg noted that each year, tens of millions of shipments come to the United States, containing products whose safety she is responsible for ensuring. Nearly every drug the FDA regulates contains a component from another country.
“It is a whole new world,” Dr. Hamburg said. “We are just trying to make sure we are adequately positioned to address the needs and the implications of our agency to the American people by really engaging more globally.”