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Tight FDA deadlines increase drug safety concerns; FDA Defends Itself
 
 
  28 March 2008
www.pharmatimes.com
 
Drugs fast-tracked by the US Food and Drug Administration are three times more likely to be withdrawn later than medicines approved at normal speed, according to a Harvard University study.
 
Manufacturing revisions and forced label changes are also much more common in drugs that get faster-than-normal approval by the US regulator, the legal and medical experts warn in this week's New England Journal of Medicine. The authors say that federal law requiring the FDA to complete a certain proportion of licence applications within 12 months is to blame for the growing number of fast-track approvals.
 
Under the controversial Prescription Drug User Fee Act (PDUFA) of 1992, the FDA must act on 90% of all drug candidates within 12 months of submission or face funding cuts. The time-line was even tightened to 10 months as part of the 1997 Food and Drug Administration Modernization Act.
 
Some observers have suggested these deadlines lead to the rushed approval of medications, a theory that the team by Professor Daniel Carpenter tested by examining data on the timing of FDA approvals dating back to 1950. He found that following the enactment of PDUFA in 1992, there appeared to be a disproportionate number of approvals coming in the two months immediately before deadlines. In effect, the US regulator was processing applications as quickly as possible in order to avoid fines.
 
Prof Carpenter said: "We found that while these deadlines speed up the approval process, many drugs are approved right up against the deadline, which might lead to unintended consequences with regard to drug safety. He added: "This suggests that drug safety might improve under an FDA approval protocol that is more flexible and less driven by deadline pressures and more by stable growth in FDA resources."
 
His study found that drugs rushed to approval just before the deadline were two to three times more likely to eventually be pulled off shelves due to safety concerns, two to seven times more likely to receive added label warnings known as 'black box revisions' and twice as likely to experience changes in manufacture. In addition, fast-tracked products were between two to seven times more likely to be voluntarily discontinued by manufacturers due to lack of clinical demand.
 
He predicted that due to "high-profile regulatory mistakes in recent years", the US Congress was likely to scrutinise the deadlines very carefully when they were next reviewed in 2012. "While we are not arguing that these deadlines should be abandoned, our research indicates that mechanisms other than strict deadlines may better balance the need for expeditious yet rigorous drug approval," Prof Carpenter said.
 
PhRMA defends PDUFA
Nevertheless, Pharmaceutical Research and Manufacturers of America senior vice president Ken Johnson defended the PDUFA, however. "While the Act does carry timeframes for the completion of a review, the FDA can, and often does, go back to the sponsor with further questions about safety or efficacy that ultimately lengthen the review time," he told PharmaTimes World News.
 
He noted too, that other studies had come to different conclusions. "As the authors acknowledge, their findings are inconsistent with previous, high-quality analysis," he said. "What's more, therapies approved by the FDA since PDUFA have become more sophisticated. The newer products, such as biotech cancer therapies, often offer enhanced benefits and a different risk profile than medicines approved prior to the user fee Act, complicating direct comparisons," Mr Johnson concluded.
 
By Michael Day
 
...while CDER chief rejects claims agency is over-cautious
 
28 March 2008
 
One of the most senior members of the FDA has presented a stout defence of the agency's work to the Financial Times. She told the newspaper that when the FDA rejected new medicines, it did so based on safety and efficacy, not as a result of political pressure or greater conservatism.
 
She said: "We have a different story from the companies. We understand that [they] have productivity issues but [we] stick to the same safe and effective criteria as our bedrock. Pharma is having a difficult time but we are seeing drugs that have a lot of questions." Ms Woodcock added that the FDA would unveil proposals this autumn on reducing drug development costs by standardising the format and content of clinical trial data. "We need to learn from Henry Ford. Companies collect too much information because they are worried that the FDA will ask for it," she said.
 
However some drugmakers are adamant that the FDA is too cautious and over-concerned about what the policymakers in Washington think of its efforts. Novartis seems to have all but given up on getting approval in the USA for its new diabetes drug Galvus (vildagliptin), which received the green light in Europe last month, and James Shannon, outgoing head of drug development at the firm, pulled no punches when speaking to the Wall Street Journal.
 
He said that "the scientists and physicians who are reviewing the products are looking over their shoulder at Capitol Hill". He added that "I think it results in them taking decisions which are conservative".
 
Back to Ms Woodcock who told the FT that FDA staffing and funding, specifically for the inspection of foreign manufacturing sites, remained "thin", and the funding issue was also brought up by the FDA's Commissioner Andrew von Eschenbach. Speaking at a conference in Washinton, he said that the increase in funding has not kept pace with the agency's increasing responsibilities. He added that as a result, the FDA "may fail in its mission to protect and promote the health of every American''.
 
The view that more funding is necessary is backed in most circles but Commissioner Eschenbach has come under fierce criticism from politicians and pressure groups who have claimed that requests for more funds have not been more specific.
 
Tight FDA deadlines increase drug safety concerns
 
28 March 2008
 
Drugs fast-tracked by the US Food and Drug Administration are three times more likely to be withdrawn later than medicines approved at normal speed, according to a Harvard University study.
 
Manufacturing revisions and forced label changes are also much more common in drugs that get faster-than-normal approval by the US regulator, the legal and medical experts warn in this week's New England Journal of Medicine. The authors say that federal law requiring the FDA to complete a certain proportion of licence applications within 12 months is to blame for the growing number of fast-track approvals.
 
Under the controversial Prescription Drug User Fee Act (PDUFA) of 1992, the FDA must act on 90% of all drug candidates within 12 months of submission or face funding cuts. The time-line was even tightened to 10 months as part of the 1997 Food and Drug Administration Modernization Act.
 
Some observers have suggested these deadlines lead to the rushed approval of medications, a theory that the team by Professor Daniel Carpenter tested by examining data on the timing of FDA approvals dating back to 1950. He found that following the enactment of PDUFA in 1992, there appeared to be a disproportionate number of approvals coming in the two months immediately before deadlines. In effect, the US regulator was processing applications as quickly as possible in order to avoid fines.
 
Prof Carpenter said: "We found that while these deadlines speed up the approval process, many drugs are approved right up against the deadline, which might lead to unintended consequences with regard to drug safety. He added: "This suggests that drug safety might improve under an FDA approval protocol that is more flexible and less driven by deadline pressures and more by stable growth in FDA resources."
 
His study found that drugs rushed to approval just before the deadline were two to three times more likely to eventually be pulled off shelves due to safety concerns, two to seven times more likely to receive added label warnings known as 'black box revisions' and twice as likely to experience changes in manufacture. In addition, fast-tracked products were between two to seven times more likely to be voluntarily discontinued by manufacturers due to lack of clinical demand.
 
He predicted that due to "high-profile regulatory mistakes in recent years", the US Congress was likely to scrutinise the deadlines very carefully when they were next reviewed in 2012. "While we are not arguing that these deadlines should be abandoned, our research indicates that mechanisms other than strict deadlines may better balance the need for expeditious yet rigorous drug approval," Prof Carpenter said.
 
PhRMA defends PDUFA
Nevertheless, Pharmaceutical Research and Manufacturers of America senior vice president Ken Johnson defended the PDUFA, however. "While the Act does carry timeframes for the completion of a review, the FDA can, and often does, go back to the sponsor with further questions about safety or efficacy that ultimately lengthen the review time," he told PharmaTimes World News.
 
He noted too, that other studies had come to different conclusions. "As the authors acknowledge, their findings are inconsistent with previous, high-quality analysis," he said. "What's more, therapies approved by the FDA since PDUFA have become more sophisticated. The newer products, such as biotech cancer therapies, often offer enhanced benefits and a different risk profile than medicines approved prior to the user fee Act, complicating direct comparisons," Mr Johnson concluded.
 
By Michael Day
 
 
 
 
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