Washington Editor

WASHINGTON - Early clinical testing could get easier, or at least more accessible, if product sponsors take note of recent FDA communications.

New guidance documents released by the agency detail its willingness to let researchers evaluate new drugs in humans with fewer regulatory hurdles - or with more flexibility - before filing an investigational new drug application. According to Karen Mahoney, a spokeswoman for the FDA's Center for Drug Evaluation and Research (CDER), the documents clarify existing regulations and make no changes.

"Everything is the same," she told BioWorld Today, adding that the central message explains "ways to do early studies."

The FDA's "Exploratory IND Studies" guidance explains a process for beginning human studies before Phase I, the standard period for safety testing. The result, the agency believes, will lead to more efficient drug development because ineffective candidates would wash out more quickly, while those with better efficacy would move forward.

As Acting FDA Commissioner Andrew von Eschenbach said in a teleconference, the new recommendations "can more rapidly establish whether or not a new compound truly has a real clinical benefit for people."

The exploratory studies, which involve very limited human exposure and have no therapeutic or diagnostic intent, can help researchers determine whether a preclinically observed mechanism of action also is observed in humans, provide pharmacokinetic information and allow for the selection of the most promising lead product.

Also, the exploratory studies can begin with less preclinical support than that required for traditional IND studies, because they produce fewer potential risks than Phase I studies that look for dose-limiting toxicities.

The guidance was developed by CDER's Office of New Drugs and is in line with an overarching FDA push these days to modernize regulations and therefore streamline development, the Critical Path Initiative. That broad effort, Mahoney added, is "something the FDA has been involved in for the past one and a half years."

A related draft guidance outlines the agency's suggested approach to complying with current good manufacturing practice (CGMP) requirements for drugs intended solely for Phase I. Titled "INDs - Approaches to Complying with CGMP During Phase I," it essentially removes cumbersome regulations that required researchers conducting very early studies to follow the same manufacturing procedures as companies that mass-produce drugs for broad distribution.

Once finalized, the guidance should aid researchers in implementing manufacturing controls that are appropriate for early stages of development.

The FDA soon is expected to release a second Critical Path report and its Critical Path Opportunities White Paper.

Private Firms Seek Tighter IRS Regulations

A pair of private biotech company executives came calling on the Treasury Department and the IRS last week to seek clarification on a stock option provision in the Internal Revenue Code, section 409A, which Congress approved in 2004 as a revenue offset in the American Jobs Creation Act.

As representatives of the Biotechnology Industry Organization, which is primarily composed of privately held businesses, they stressed the industry's reliance on such deferred compensation "in order to attract and retain the most talented people," said Richard Fitzgerald, the vice president of finance and administration for Horsham, Pa.-based Nucleonics Inc. He told BioWorld Today that as much as 15 percent to 20 percent of early stage biotech companies are held in stock options, so the staff-level meeting provided a chance to "move as a group and industry."

Section 409A is aimed at stopping abuses of deferred compensation, such as setting artificially low values on stock options, and BIO does not oppose its intent. But given the statute's overly broad language, biotech companies could unintentionally find themselves in default, a "rear-view mirror" analysis they shouldn't be exposed to, Fitzgerald said.

He found those at the meeting receptive to the industry's concerns, which arise from the fact that valuations "cascade" on companies, as their futures are "event-driven." Therefore, because stock option values ebb and flow, privately held biotech firms fear that the IRS could question such values and instead set them higher.

Fitzgerald said the industry simply wants "clarity around the parameters," and called last week's meeting the beginning of a continuing dialogue. BIO has submitted its opinions to the IRS, which is scheduled to hold a public hearing on the matter later this month.

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