New Foreign Drug Trial Rule Coming

A new U.S. Food and Drug Administration final rule governing clinical trials held in foreign countries will spark painstaking legal review of pharmaceutical companies' protocols for trials. Although the FDA lacks authority to police clinical trials in other countries, it can and does regulate the types of clinical trial data it requires and accepts from companies applying for new drug approval or marketing approval for a drug or biological product.

The upshot is that pharmaceutical companies will need lawyers' help to design foreign trials to meet U.S. standards if they ever hope to sell drugs tested in those trials in the United States. The new rule, which takes effect on Oct. 27, standardizes the requirements across countries and adds requirements for trials in many countries, lawyers say.

The impact of the FDA's change is also likely to deepen during the next few years as drug companies increasingly embrace overseas clinical trials. An estimated 65% of the top pharmaceutical companies' FDA-regulated clinical trials will be staged outside the United States within three years, compared with 43% today, according to the Tufts Center for the Study of Drug Development Outlook 2008 report.

Raising the Stakes

The new rule raises the stakes for companies because failure to meet it carries significant consequences, said Philip Katz, a partner at Washington's Hogan & Hartson who specializes in FDA and other regulatory work for pharmaceutical and life sciences companies. 'The requirements used to be less specific and less burdensome, now they're more specific and more burdensome,' Katz said. 'Because the stakes are higher, I would expect to have more consultation than I have had in the past.' Katz also said the final rule meshes with the FDA's recent increased focus on safety issues. That includes the agency's recent announcement of plans to post full-time inspectors in China within 18 months.

Executive officials and Congress are also scrutinizing the agency's clinical trial oversight. Last September, the U.S. Department of Health and Human Services' Office of the Inspector General issued a report criticizing the agency's review of such trials. In May, House Energy and Commerce Committee members asked the Government Accountability Office to examine the FDA's disciplinary actions against clinical investigators.

According to the final rule, pharmaceutical companies doing drug studies abroad must now do more work to comply with FDA directives to adhere to so-called 'good clinical practices,' which requires documentation that the study is 'credible and accurate,' with information such as description of the research facilities, qualifications of the investigator and a detailed summary of the study's results and protocol. The FDA's rule explains that the good clinical practices mandate relies on principles similar to those outlined by The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.

Previously, the FDA's rules for foreign clinical studies were based on principals of ethical behavior for doctors and medical researchers working with human clinical subjects outlined by the Declaration of Helsinki issued by the France-based World Medical Association.

More Legal Work

The FDA's comments in the rule noted that 'standards for protecting human subjects have evolved over the past decade,' and that the agency wants good clinical practices to 'help ensure data quality and integrity' and 'proper conduct of trials.'

Adhering to the FDA's good clinical practices directives for studies done abroad means more work for clients and their attorneys, said Robert Nicholas, who heads McDermott, Will & Emery's FDA practice from its Washington office. 'We'll be working with companies trying to structure clinical studies that they'll be conducting outside the U.S.,' Nicholas said. 'There will be more specificity with respect to what the requirements are and additional requirements.'

The new rule is more stringent, but companies need a great deal of legal guidance because the International Conference on Harmonisation's clinical practice guidelines cited by the FDA are nonbinding, said Scott Bass, a partner in the Washington office of Sidley Austin who heads its global life sciences team. 'It makes it tougher to meet the standard and it shows the FDA is more open to accepting a globalized approach as to what could be used in drug applications,' Bass said.

Questions Remain

While the regulations seek to strike a careful balance between specificity and flexibility, a number of questions remain, said James S. Cohen, a shareholder and Washington-based FDA lawyer at Pittsburgh's Buchanan Ingersoll & Rooney. 'Investors and product developers will need to consider which good clinical practices standards are acceptable, what will be the nature and scope of inspections, and how the provisions will be applied and enforced by the FDA,' Cohen said.

However the rule is interpreted, lawyers agree that international law firms will play an expanded role as foreign clinical trials become even more popular and legitimate. Sidley Austin's pharmaceutical clients who are interested in conducting clinical trials in China, for example, would get advice from the firm's China office and U.S. attorneys on how to structure the trials, Bass said. 'It's more likely that companies would explore a global strategy in setting up clinical trials even if they originally were going to use them for one [country's] approval,' Bass said. 'It adds to the value of having foreign [law] offices who can evaluate local requirements.'

The usability of foreign clinical data for U.S. drug applications has been a bit of a puzzle for drug developers, and the new regulations will help companies assess whether foreign trials makes sense for them, said Suzanne M. O'Shea, a former Food and Drug Administration attorney who is now counsel to Baker & Daniels in Indianapolis.

Sheri Qualters is a reporter with the National Law Journal, a sister publication of this newsletter, in which this article first appeared.

A new U.S. Food and Drug Administration final rule governing clinical trials held in foreign countries will spark painstaking legal review of pharmaceutical companies' protocols for trials. Although the FDA lacks authority to police clinical trials in other countries, it can and does regulate the types of clinical trial data it requires and accepts from companies applying for new drug approval or marketing approval for a drug or biological product.

The upshot is that pharmaceutical companies will need lawyers' help to design foreign trials to meet U.S. standards if they ever hope to sell drugs tested in those trials in the United States. The new rule, which takes effect on Oct. 27, standardizes the requirements across countries and adds requirements for trials in many countries, lawyers say.

The impact of the FDA's change is also likely to deepen during the next few years as drug companies increasingly embrace overseas clinical trials. An estimated 65% of the top pharmaceutical companies' FDA-regulated clinical trials will be staged outside the United States within three years, compared with 43% today, according to the Tufts Center for the Study of Drug Development Outlook 2008 report.

Raising the Stakes

The new rule raises the stakes for companies because failure to meet it carries significant consequences, said Philip Katz, a partner at Washington's Hogan & Hartson who specializes in FDA and other regulatory work for pharmaceutical and life sciences companies. 'The requirements used to be less specific and less burdensome, now they're more specific and more burdensome,' Katz said. 'Because the stakes are higher, I would expect to have more consultation than I have had in the past.' Katz also said the final rule meshes with the FDA's recent increased focus on safety issues. That includes the agency's recent announcement of plans to post full-time inspectors in China within 18 months.

Executive officials and Congress are also scrutinizing the agency's clinical trial oversight. Last September, the U.S. Department of Health and Human Services' Office of the Inspector General issued a report criticizing the agency's review of such trials. In May, House Energy and Commerce Committee members asked the Government Accountability Office to examine the FDA's disciplinary actions against clinical investigators.

According to the final rule, pharmaceutical companies doing drug studies abroad must now do more work to comply with FDA directives to adhere to so-called 'good clinical practices,' which requires documentation that the study is 'credible and accurate,' with information such as description of the research facilities, qualifications of the investigator and a detailed summary of the study's results and protocol. The FDA's rule explains that the good clinical practices mandate relies on principles similar to those outlined by The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.

Previously, the FDA's rules for foreign clinical studies were based on principals of ethical behavior for doctors and medical researchers working with human clinical subjects outlined by the Declaration of Helsinki issued by the France-based World Medical Association.

More Legal Work

The FDA's comments in the rule noted that 'standards for protecting human subjects have evolved over the past decade,' and that the agency wants good clinical practices to 'help ensure data quality and integrity' and 'proper conduct of trials.'

Adhering to the FDA's good clinical practices directives for studies done abroad means more work for clients and their attorneys, said Robert Nicholas, who heads McDermott, Will & Emery's FDA practice from its Washington office. 'We'll be working with companies trying to structure clinical studies that they'll be conducting outside the U.S.,' Nicholas said. 'There will be more specificity with respect to what the requirements are and additional requirements.'

The new rule is more stringent, but companies need a great deal of legal guidance because the International Conference on Harmonisation's clinical practice guidelines cited by the FDA are nonbinding, said Scott Bass, a partner in the Washington office of Sidley Austin who heads its global life sciences team. 'It makes it tougher to meet the standard and it shows the FDA is more open to accepting a globalized approach as to what could be used in drug applications,' Bass said.

Questions Remain

While the regulations seek to strike a careful balance between specificity and flexibility, a number of questions remain, said James S. Cohen, a shareholder and Washington-based FDA lawyer at Pittsburgh's Buchanan Ingersoll & Rooney. 'Investors and product developers will need to consider which good clinical practices standards are acceptable, what will be the nature and scope of inspections, and how the provisions will be applied and enforced by the FDA,' Cohen said.

However the rule is interpreted, lawyers agree that international law firms will play an expanded role as foreign clinical trials become even more popular and legitimate. Sidley Austin's pharmaceutical clients who are interested in conducting clinical trials in China, for example, would get advice from the firm's China office and U.S. attorneys on how to structure the trials, Bass said. 'It's more likely that companies would explore a global strategy in setting up clinical trials even if they originally were going to use them for one [country's] approval,' Bass said. 'It adds to the value of having foreign [law] offices who can evaluate local requirements.'

The usability of foreign clinical data for U.S. drug applications has been a bit of a puzzle for drug developers, and the new regulations will help companies assess whether foreign trials makes sense for them, said Suzanne M. O'Shea, a former Food and Drug Administration attorney who is now counsel to Baker & Daniels in Indianapolis.

Sheri Qualters is a reporter with the National Law Journal, a sister publication of this newsletter, in which this article first appeared.