There are signs that the Food and Drug Administration could berelaxing a controversial position on drug approval criteria forcontrast agents. Although the shift may be temporary, it comesas welcome news for two contrast developers whose product
There are signs that the Food and Drug Administration could berelaxing a controversial position on drug approval criteria forcontrast agents. Although the shift may be temporary, it comesas welcome news for two contrast developers whose product marketingplans were delayed for months while the FDA sorted out its position.
The FDA hinted last year that it would begin requiring approvalapplications for new contrast agents to include information aboutthe diseases the agents were intended to help diagnose (SCAN 1/27/93and 9/16/92). FDA regulations state that all drugs approved bythe agency must contain information in their labeling insertsabout the diseases for which they are intended. The FDA had notenforced the regulation with respect to contrast agents, but decidedto change its interpretation last year, according to the agency.
The change initially affected two companies with agents inthe FDA's drug review process: Alliance Pharmaceutical, whoseGI oral MRI agent Imagent was under review by an FDA advisorycommittee, and Advanced Magnetics, which was preparing to filea new drug application (NDA) for Gastromark (ferumoxsil), an MRIbowel marker.
The agency's policy shift was first communicated to industryat the advisory committee meeting for Imagent GI. After the meeting,the FDA asked Alliance to review its data for the product, andthe company changed the wording in its labeling insert to moreclosely correspond to the agency's new interpretation.
A short time later, the FDA refused to accept Advanced Magnetics'NDA for Gastromark. The company went back to the drawing boardto rewrite its submission to include more disease-specific information.
In both cases, the FDA's new interpretation contradicted advicethe agency had given the companies in designing clinical trialsfor the products. The agency specifically told Advanced Magneticsnot to include disease-specific criteria in its protocols, accordingto president and CEO Jerome Goldstein.
"Our original protocol had elements of pathology delineationand they made us change it," Goldstein said. "It's avery straightforward product, and they didn't want to see thousandsof pages of data."
In addition to revising the insert for Imagent GI, Alliancetook up its case with the FDA, pointing out that the company hadbeen advised not to include disease-specific information in itsindication.
"We maintained that we did what was required of us,"said Theodore Roth, Alliance executive vice president. "Ourposition was that we did what they told us to, and that's what'sright."
The company's efforts apparently paid off. In August the FDAcleared Imagent for marketing (SCAN 8/25/93) without requiringthe company to conduct new clinical trials. The product's labelinginsert was modified from the earlier version, but did not containdisease-specific criteria.
Further signs that the FDA had softened its position came lastmonth, when the agency accepted Advanced Magnetics' NDA filingfor Gastromark. Advanced Magnetics revised the application toinclude more disease-specific data, but the product's indicationdoes not mention a specific disease state.
Both firms, and the contrast industry in general, remain inthe dark about the FDA's current interpretation of drug approvalregulations. The agency may have decided to compromise on theissue by withdrawing the disease-specific requirement for NDAfilings that were developed based on the FDA's previous rule interpretation.
"For companies going through process who were adviseda certain way, (the FDA) recognized how (the companies) had beenadvised and they knew they had a responsibility to have some consistencyin their actions," Goldstein said.
Contrast agents now under development could be held to themore stringent interpretation, however. For its part, the FDAdeclined to comment about the status of the policy, and contrastagent firms must resort to guesswork to determine the agency'sposition.
The FDA's vacillation on the issue added months to the productdevelopment time line of Gastromark and Imagent GI. Gastromark'sNDA filing was delayed a year and a half, and Imagent GI's approvalwas put off by at least six months.
Meanwhile, Gastromark has already been approved in Europe underthe trade name Lumirem and Advanced Magnetics has begun initialshipments to its European licensee, Guerbet S.A. of France.
"Companies have been looking to Europe to launch products,"Goldstein said. "The clinical process is taking the sameamount of time, but the approval process takes less time in Europe."