International Harmonization Should Focus On Post-Marketing Activities - HRG

International harmonization efforts should include an emphasis on post-marketing activities, Public Citizen's Health Research Group Deputy Director Peter Lurie, MD, commented at an FDA public meeting on the future of the International Conference on Harmonization May 16.

The same level of emphasis ICH devotes to pre-market technical requirements should be given to activities following drug approval, Lurie maintained.

Marketing, advertising, labeling, information for patients and post-marketing studies would be appropriate targets for harmonization, he suggested.

Drug withdrawal is one area where harmonization efforts should be applied, Lurie said, noting drugs deemed "too dangerous" in one region should be regarded likewise in other markets.

Lurie speculated that issues such as post-marketing concerns do not make it onto the ICH agenda because industry and government control what is addressed.

Center for Biologics Evaluation & Research Associate Director for Medical & International Affairs and CBER ICH Steering Committee Member Elaine Esber, MD, noted the upcoming ICH 5 conference to be held in San Diego Nov. 9-11 will feature discussion on post-marketing surveillance and the use of ICH standards in adverse event reporting.

Esber cautioned, however, that ICH might not be an appropriate forum for post-marketing issues because of industry's presence at the table. These are traditionally regulator responsibilities, she added.

HRG also is concerned that harmonization promotes standards that act as a "ceiling rather than floor." An illustration of declining standards is the move toward carcinogenicity studies that use only one species of rodent as opposed to both rats and mice, even though some drugs may have carcinogenic potential in only one of the species, Lurie said.

Another example of potentially declining standards is in the area of controls for trials, Lurie maintained. HRG is concerned "the ICH is being used as a battering ram to push the agenda that the FDA has long had" of promoting the use of placebo-controlled trials "onto Europeans."

Approval should not be granted if a drug is not known to be as effective as an already marketed drug, Lurie advised. FDA is working on methodology for evaluating efficacy in active-control trials without placebo.

Lurie also argued for increased consumer participation in ICH, including involvement in the steering committee.

In the last few years, FDA has ceased to see itself as representing the interest of patients and consumers, preferring to focus on "partnerships with industry," Lurie asserted.

"What is interesting to me is how the energy that is expended upon harmonization on issues of interest to industry is not expended on harmonizing issues that might be of importance to consumers," he said.

As a result, "ICH has done a good job in identifying the needs of government and industry but a much poorer job of protecting the needs of patients," he noted.

Esber indicated many countries and organizations have expressed interest in participating in ICH. She noted the excipient industry and pharmacopoeias have requested to join the steering committee and that biotech, vaccines, blood, plasma and tissue organizations are interested in participating in ICH.

The interest in some of the topics has broadened because the guidances involve more than the industries and governments around the table, she said.

The original ICH steering committee was composed of six parties, with a government and an industry representative from the U.S., Europe and Japan. Reps from Switzerland, China, India, pharmacopoeias and the OTC and generic drug industries have since been added to the expert working groups.

The FDA official noted the need to be responsive to impacted parties, but cautioned "if you get too big the process will topple by the enormity of the membership."