Califf seeks new authorities to approve opioids, mum on mifepristone
April 28, 2023
The US Food and Drug Administration (FDA) should be given the authority to approve new opioid drugs based on superior safety compared to currently marketed products, said Commissioner Robert Califf at a 19 April hearing before a Senate Appropriations subcommittee. However, he refused to comment on a recent court ruling that nullifies the agency’s approval of mifepristone.
Califf made these remarks at a hearing to discuss the FDA’s FY 2024 budget request on Wednesday. Yet much of the discussion veered to other areas, including the recent mifepristone ruling, drug shortages, cell and gene therapies, Medicare coverage of Alzheimer’s drugs and opioids.
While Califf enjoyed mostly broad support during the hearing, especially from senators on the panel who were sympathetic to FDA’s plight after the Texas district court’s recent ruling on mifepristone, he did come under criticism for having industry representatives on FDA advisory committees discussing opioids, as well as the rising number of clinical holds for cell and gene therapies.
Califf told the committee he appreciates the funding increases provided in the FY 2023 budget, as well as “expanded and new regulatory authority included in the legislation to address cosmetics and medical device cybersecurity.” He added that the funding requested in the FY 2024 budget request “builds upon this funding while also acknowledging additional needs and future challenges.”
FDA’s FY 2024 budget requests $7.2 billion, an increase of $524.4 million from FY 2023. Much of the increase, $210.6 million, is for investments in food safety, nutrition and cosmetics.
Califf avoids commenting on mifepristone
After testifying on the budget, Califf was asked to discuss the impact of the mifepristone ruling on FDA decision making by Sen. Martin Henrich (D-NM), who asserted the ruling “represents a danger to women’s reproductive rights” and “a very dangerous precedent for women’s reproductive rights” as well as FDA drug reviews.
At issue is the ruling by Judge Matthew Kacsmaryk of the Norther District of Texas, who declared FDA’s approval of the abortion drug mifepristone. The decision was partially stayed by the Fifth Circuit Court of Appeals, whose verdict the Department of Justice has appealed to the Supreme Court.
Califf avoided answering the question directly, stating only that “the matter is pending before the Supreme Court.” He added, “I will say that we are concerned about the potential impact of this case, as reflected in the extensive briefs filed by the Department of Justice on our behalf. The considerations are extensive.”
Sen. Patty Collins (D-WA) told the panel that “the determination of whether drugs are safe and effective needs to be left to the experts at FDA, not politicians and certainly not judges, we got a reminder of that this week.”
Yet not everyone was in FDA’s corner. The agency’s approval of the drug did come under attack from Sen. Cindy Hyde-Smith (R-MS) who told Califf that she supports the Texas court’s ruling, adding that mifepristone should not have been approved to begin with since it posed safety risks to women, particularly for those with ectopic pregnancies.
Califf responded that “we are confident that the law is on our side. We have appealed to the lower court decision to the Supreme Court.” He added that “FDA a does intend to comply with any court orders.”
Califf addresses recent actions on opioids
Califf was also asked by Henrich to discuss how the agency plans to tackle the opioid crisis, noting that two-thirds of overdose deaths involve opioids.
Califf said the agency has taken several actions to address the crisis: one is requiring drug companies provide pharmacies with mail-back envelopes so patients can mail back unused opioids. FDA recently mandated new safety labeling updates to warn of the risk of opioid-induced hyperalgesia with immediate-release and extended-released/long-acting opioids. (RELATED: FDA to require mail-back envelopes for unused opioids, Regulatory Focus 3 April 2023; FDA to require new safety warnings for opioids, Regulatory Focus 17 April 2023)
He further noted that the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) was meeting the same day to address the design of clinical trials for opioids.
Yet Califf said that to tackle the problem more directly, FDA should be given the statutory authority to approve only those opioids that can demonstrate “safety superiority” to those currently on the market.
“Right now, by law we do not have the authority to make that decision. It would really help us if we had that authority,” he said.
Califf said it would also help if industry developed non-addictive pain medicines. “It is a tough job, but we are not successful in having nonaddictive pain medicines coming through the pipeline. We need to do everything we can do to push industry and make this happen.”
In the meantime, Sen. Joe Manchin (D-WV) opposed the agency’s move to allow industry members to participate on advisory committees addressing opioids.
“I previously raised concerns about the pay to play, [industry] would pay to be at an advisory committee meeting, the speakers today had not been disclosed nor have they disclosed their involvement” in the opioid industry,” said Manchin in referring to the AADPAC meeting. He noted that an industry member was speaking at the meeting and asserted that industry “does not have the expertise” to address these issues.
He added that “my state is ground zero on this.”
In response, Calif said “to be clear about it the most important thing you can do is to give us statutory authority with opioids so that if anything comes on the market, it has to demonstrate clear superiority.” He added that “this was the same conversation that we had in 2016.”
Rising clinical holds on cell and gene therapies
In other areas, concerns were expressed that FDA is placing a growing number of cell and gene therapy applications on clinical holds.
“What I am frequently hearing is that CBER has put clinical holds without explanation on some promising cell therapies. Do you agree that there are problems in this area?” asked Sen. Susan Collins (R-ME).
In response, Califf said “I do think there are some issues there that have to be worked out.” He added that CBER is going to be hiring 150 to 200 people in this area.”
Califf added that sometimes FDA places clinical hold on applications because something is wrong with the manufacturing. He said a lot of cell and gene therapy companies “are start-ups without robust manufacturing facilities.” He agreed though that “we have to move in this area a lot more quickly.”
Senators opposed CMS refusal to cover Alzheimer’s drugs
Some senators criticized the decision of the Center for Medicare and Medicaid Services (CMS) to restrict reimbursement for Alzheimer’s drugs.
Califf said that while FDA approves a drug based on its safety and effectiveness, CMS’s standard is different, and considers whether a drug is “reasonable and necessary” for reimbursement. “I am confident that we will get this resolved in a positive way and let’s see the data as it comes in,” Califf said.
Califf made these remarks at a hearing to discuss the FDA’s FY 2024 budget request on Wednesday. Yet much of the discussion veered to other areas, including the recent mifepristone ruling, drug shortages, cell and gene therapies, Medicare coverage of Alzheimer’s drugs and opioids.
While Califf enjoyed mostly broad support during the hearing, especially from senators on the panel who were sympathetic to FDA’s plight after the Texas district court’s recent ruling on mifepristone, he did come under criticism for having industry representatives on FDA advisory committees discussing opioids, as well as the rising number of clinical holds for cell and gene therapies.
Califf told the committee he appreciates the funding increases provided in the FY 2023 budget, as well as “expanded and new regulatory authority included in the legislation to address cosmetics and medical device cybersecurity.” He added that the funding requested in the FY 2024 budget request “builds upon this funding while also acknowledging additional needs and future challenges.”
FDA’s FY 2024 budget requests $7.2 billion, an increase of $524.4 million from FY 2023. Much of the increase, $210.6 million, is for investments in food safety, nutrition and cosmetics.
Califf avoids commenting on mifepristone
After testifying on the budget, Califf was asked to discuss the impact of the mifepristone ruling on FDA decision making by Sen. Martin Henrich (D-NM), who asserted the ruling “represents a danger to women’s reproductive rights” and “a very dangerous precedent for women’s reproductive rights” as well as FDA drug reviews.
At issue is the ruling by Judge Matthew Kacsmaryk of the Norther District of Texas, who declared FDA’s approval of the abortion drug mifepristone. The decision was partially stayed by the Fifth Circuit Court of Appeals, whose verdict the Department of Justice has appealed to the Supreme Court.
Califf avoided answering the question directly, stating only that “the matter is pending before the Supreme Court.” He added, “I will say that we are concerned about the potential impact of this case, as reflected in the extensive briefs filed by the Department of Justice on our behalf. The considerations are extensive.”
Sen. Patty Collins (D-WA) told the panel that “the determination of whether drugs are safe and effective needs to be left to the experts at FDA, not politicians and certainly not judges, we got a reminder of that this week.”
Yet not everyone was in FDA’s corner. The agency’s approval of the drug did come under attack from Sen. Cindy Hyde-Smith (R-MS) who told Califf that she supports the Texas court’s ruling, adding that mifepristone should not have been approved to begin with since it posed safety risks to women, particularly for those with ectopic pregnancies.
Califf responded that “we are confident that the law is on our side. We have appealed to the lower court decision to the Supreme Court.” He added that “FDA a does intend to comply with any court orders.”
Califf addresses recent actions on opioids
Califf was also asked by Henrich to discuss how the agency plans to tackle the opioid crisis, noting that two-thirds of overdose deaths involve opioids.
Califf said the agency has taken several actions to address the crisis: one is requiring drug companies provide pharmacies with mail-back envelopes so patients can mail back unused opioids. FDA recently mandated new safety labeling updates to warn of the risk of opioid-induced hyperalgesia with immediate-release and extended-released/long-acting opioids. (RELATED: FDA to require mail-back envelopes for unused opioids, Regulatory Focus 3 April 2023; FDA to require new safety warnings for opioids, Regulatory Focus 17 April 2023)
He further noted that the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) was meeting the same day to address the design of clinical trials for opioids.
Yet Califf said that to tackle the problem more directly, FDA should be given the statutory authority to approve only those opioids that can demonstrate “safety superiority” to those currently on the market.
“Right now, by law we do not have the authority to make that decision. It would really help us if we had that authority,” he said.
Califf said it would also help if industry developed non-addictive pain medicines. “It is a tough job, but we are not successful in having nonaddictive pain medicines coming through the pipeline. We need to do everything we can do to push industry and make this happen.”
In the meantime, Sen. Joe Manchin (D-WV) opposed the agency’s move to allow industry members to participate on advisory committees addressing opioids.
“I previously raised concerns about the pay to play, [industry] would pay to be at an advisory committee meeting, the speakers today had not been disclosed nor have they disclosed their involvement” in the opioid industry,” said Manchin in referring to the AADPAC meeting. He noted that an industry member was speaking at the meeting and asserted that industry “does not have the expertise” to address these issues.
He added that “my state is ground zero on this.”
In response, Calif said “to be clear about it the most important thing you can do is to give us statutory authority with opioids so that if anything comes on the market, it has to demonstrate clear superiority.” He added that “this was the same conversation that we had in 2016.”
Rising clinical holds on cell and gene therapies
In other areas, concerns were expressed that FDA is placing a growing number of cell and gene therapy applications on clinical holds.
“What I am frequently hearing is that CBER has put clinical holds without explanation on some promising cell therapies. Do you agree that there are problems in this area?” asked Sen. Susan Collins (R-ME).
In response, Califf said “I do think there are some issues there that have to be worked out.” He added that CBER is going to be hiring 150 to 200 people in this area.”
Califf added that sometimes FDA places clinical hold on applications because something is wrong with the manufacturing. He said a lot of cell and gene therapy companies “are start-ups without robust manufacturing facilities.” He agreed though that “we have to move in this area a lot more quickly.”
Senators opposed CMS refusal to cover Alzheimer’s drugs
Some senators criticized the decision of the Center for Medicare and Medicaid Services (CMS) to restrict reimbursement for Alzheimer’s drugs.
Califf said that while FDA approves a drug based on its safety and effectiveness, CMS’s standard is different, and considers whether a drug is “reasonable and necessary” for reimbursement. “I am confident that we will get this resolved in a positive way and let’s see the data as it comes in,” Califf said.
Source: News
About The Author
