Originally published June 1996
Inside the walls of the beleaguered FDA, officials are struggling to communicate to manufacturers the dynamics of FDA's structure, its priorities, and its role in both establishing and endorsing international standards. Shrinking resources have forced the agency to adopt a rigid stance in determining its priorities, complicating its participation in the harmonization process. To frustrated device companies outside its walls, the agency often appears as though it is dragging its feet or ignoring industry's need for the harmonization of requirements.
Although committed to harmonization, FDA also considers other factors when adopting standards, including whether a standard sets performance limits and whether it calls for sufficient evidence to demonstrate safety, said Donald Marlowe, director of FDA's Office of Science and Technology in the Center for Devices and Radiological Health, at the Association for the Advancement of Medical Instrumentation (AAMI)/FDA International Standards Conference on Medical Devices last March.
According to FDA, lack of resources is hampering the agency's ability to participate in international standards development. Because its resources will decline 23% over the next six to eight years, FDA has set priorities that put endorsing most international standards third on the list at best. "The priorities at the agency are first the revised GMP regulation and then the pilot programs. Reviewing specific standards and preparing guidances for them becomes tertiary when the agency allocates its resources," says Kim Trautman, GMP/quality systems expert in the device center's Office of Compliance.
But FDA's reduced resources are really not the issue, says Barry Page, convenor of International Organization for Standardization (ISO) technical committee (TC) 194 working group 11, which develops standards for ethylene oxide (EtO) sterilization process residuals. "It's really a matter of getting some people in FDA to recognize that there are issues outside their area of expertise that other experts in the agency understand. FDA's structure is devised so that individuals are empowered to raise questions if they have a concern, even if it's outside their specific area of expertise," he explains.
"If I were [CDRH director Bruce] Burlington," he says, "and my resources were declining as much as 23% and I were investing funds to support international standards, I'd be asking why we aren't supporting and using them once they are written and accepted."
Page concedes that FDA's structure differs from the regulatory scheme in Europe, making it more difficult to achieve consensus. He suggests that FDA's guidance documents could indicate that a given ISO standard should be the basis to meet a particular requirement. For example, he says, harmonized European Committee for Standardization (CEN) standards that correspond to an ISO standard are written to meet certain essential requirements of the medical device directives for safety and performance. In a CEN standard, the final annex will document how the European Union (EU) medical device directives will be addressed. Because the United States does not have an equivalent to the EU directives, FDA is caught between laws and regulations, Page says, and interpretation is left to individuals at the agency. He points out, however, that as part of ISO's consensus process, committees address all comments in the process of reconciliation.
He says device companies, especially small manufacturers, want access to guidance documents that can walk them through the requirements. "They want to know what FDA wants," Page says. Many small companies that lack the expertise to interpret standards look for documents from AAMI or FDA's Division of Small Manufacturers Assistance. They know it's FDA that decides whether they can market their products, says Page. He also notes, however, that manufacturers want to use the same information to get approval in Europe, Japan, and the United States.
Page adds that the ISO process of reaching consensus is designed to address committee members' concerns and to incorporate those that the majority endorse. For the EtO standard, this included addressing some member countries' and FDA's concern surrounding acute irritation effects from small devices. The standard states that a device must meet the biological requirements and limits in other parts of ISO 10993. The committee felt that these limits -- already required in ISO 10993-10 -- met this need.
Many individuals at FDA passionately support harmonization of medical device standards. Marlowe and Trautman are among them. They stress FDA's active participation in the process. But, once the ISO committees vote on a standard, FDA's voice is greatly diminished due to the voting structure, Trautman says. ISO committees, striving to achieve consensus, specifically define consensus as: "General agreement, characterized by the absence of sustained opposition to substantial issues by any important part of the concerned interests and by a process that involves seeking to take into account the views of all parties concerned and to reconcile any conflicting arguments. Note: Consensus need not imply unanimity."
Trautman suggests that this definition of consensus is not so easy to accept. For ISO TC 210 on global harmonization, for example, the United States has one vote. If FDA's view is slightly different from Europe's, its vote doesn't carry as much weight as Europe's 15 votes. FDA has a strong voice as a member of the global harmonization task force, she says, which enables the agency to have a greater effect on international standards than it would have as a member of a committee dealing with a specific issue.
"We try to find some middle ground. FDA may have only one of many votes on the U.S. ballot," Trautman says. To accept international standards as a matter of compromise, FDA may need to publish a guidance that interprets its requirements. That adds another step for U.S. manufacturers. But Trautman says the agency feels compelled to publish its own guidances. At the FDA/ AAMI conference, both Marlowe and Trautman reiterated FDA's desire to participate in the harmonization process and adapt agency policy as much as possible.
Trautman's explanations of an overstretched FDA may not reassure device manufacturers frustrated by the result. As the agency balances its priorities with its diminishing resources, the industry's need for harmonization and international standards continues to grow. -- Sherrie Steward