Cristiano Ronaldo scores a stunning goal as he targets a sixth World Cup

MANCHESTER, England (AP) — Cristiano Ronaldo's quest to play in a record sixth World Cup began in spectacular fashion with two goals as Portugal made a winning start to its qualifying campaign by routing Armenia 5-0.

Ronaldo's goals extended his record as the highest scorer in men's international football to 140 and underlined his enduring motivation to keep setting benchmarks before his storied career comes to an end.

The 40-year-old soccer great has recently signed a new contract with Saudi Arabian club Al Nassr and led Portugal to victory at the UEFA Nations League last summer. The World Cup is the one major trophy that eludes him — leaving him behind his great rival Lionel Messi, who lifted soccer's biggest prize with Argentina in 2022.

Next year would likely be Ronaldo's last chance to win it when the tournament is staged in the United States, Canada and Mexico. Like him, Messi would also be playing at a sixth World Cup — setting the pair apart from any other player, with a host of names having appeared in five.

Ronaldo — a five-time Champions League winner, who also lifted the European Championship trophy with his country — struck in each half at the Vazgen Sargsyan Republican Stadium as Portugal made a flying start in Group F on Saturday.

His second saw him roll back the years with a thunderous shot from around 25 meters (yards). He wheeled away in celebration with his arms outstretched.

Joao Felix also scored twice and hit the opening goal after just 10 minutes. Joao Cancelo was also on target.

"It was a near-perfect performance,” said Portugal midfielder Vitinha.

England maintained its 100% record in qualifying with a 2-0 win against Andorra at Villa Park.

Thomas Tuchel's team is top of Group K with four straight wins after an own goal from Christian Garcia and a Declan Rice header.

While Ronaldo further gilded his record, Harry Kane was left frustrated as England failed to convince again under Tuchel.

A 1-0 win against Andorra in June was described by one British newspaper as England's “worst ever.” It was followed by a 3-1 home loss against Senegal in a friendly before the end of the season.

Tuchel made 10 changes to his squad and while there was an improvement, England still had to toil against the 174-ranked Andorrans.

It took Garcia to open the scoring when inadvertently glancing Noni Madueke's inswinging cross into his own net in the 25th.

England created more chances after the break, with Andorra goalkeeper Iker Alvarez making two fine saves from close range to deny Eberechi Eze and Elliott Anderson.

Rice headed in at the far post in the 67th from Reece James' cross.

“The energy was right, quality was there. We should have scored more,” Tuchel said.

England's all-time leading scorer Kane could not extend his record, with his best chance coming when failing to connect with James's first half cross with an open net to aim at.

Also in Group K, Serbia beat Latvia 1-0 to move up to second in the table.

England plays Serbia on Tuesday in what is likely to be its biggest test in the group.

“We know what’s coming. It’s a difficult away game, but it’s a crucial game for us because we can make a huge step into the qualification, and we are well aware of it,” Tuchel said.

Portugal played its first match since the death of former player Diogo Jota and his brother Andre Silva in a car accident in July.

Ronaldo pointed up to the sky after after his first goal, while Cancelo recreated Jota's trademark celebration by sitting with his legs crossed and mimicking playing a video game.

“Diogo will always be with us. Celebrating Joao Cancelo was a beautiful moment,” midfielder Joao Neves said.

“It was about winning, giving everything,” teammate Vitinha added.

Paris Saint-Germain confirmed France forwards Ousmane Dembele and Desire Doue will be sidelined for weeks after picking up injuries while playing for their country.

Dembele will be out for up to six weeks with a “serious injury” to his right hamstring after limping off against Ukraine on Friday.

Doue strained his right calf — ruling him out for around four weeks, PSG said.

Ireland fought back from two goals down to secure a 2-2 draw against Hungary.

Adam Idah leveled the game in the third minute of stoppage time at the Aviva Stadium after the visitors had raced to a 2-0 lead inside 15 minutes.

Barnabas Varga put Hungary ahead in the second minute and the lead was doubled by Roland Sallai.

Evan Ferguson pulled a goal back for Ireland shortly after halftime and Hungary was soon down to 10 men when Sallai was shown red in the 52nd for a foul on Dara O’Shea.

Hungary looked like holding on in the face of increased pressure until Idah’s late header.

Bosnia and Herzegovina and Austria maintained their perfect records in Group H.

Veteran striker Edin Dzeko scored twice as Bosnia routed 10-man San Marino 6-0 to top the group on 12 points after four games.

Austria has played a game less and is second after Marcel Sabitzer’s penalty sealed a 1-0 win against Cyprus.

James Robson is at https://twitter.com/jamesalanrobson

AP soccer: https://apnews.com/hub/soccer

Armenia's goalkeeper Henri Avagyan fails to save the shot from Portugal's Cristiano Ronaldo during a World Cup 2026 group F qualifying soccer match between Armenia and Portugal at the Vazgen Sargsyan stadium in Yerevan, Armenia, Saturday, Sept. 6, 2025. (AP Photo/Hakob Berberyan)

England's Anthony Gordon heads the ball during the World Cup Group K qualifying match between England and Andorra at Villa Park stadium in Birmingham, Saturday, Sept. 6, 2025 . (AP Photo/Dave Shopland)

England's head coach Thomas Tuchel reacts during the World Cup Group K qualifying match between England and Andorra at Villa Park stadium in Birmingham, Saturday, Sept. 6, 2025 . (AP Photo/Dave Shopland)

England's Declan Rice celebrates after his team scored their side's first goal during the World Cup Group K qualifying match between England and Andorra at Villa Park stadium in Birmingham, Saturday, Sept. 6, 2025 . (AP Photo/Dave Shopland)

Portugal's Cristiano Ronaldo celebrates after scoring his side's second goal during a World Cup 2026 group F qualifying soccer match between Armenia and Portugal at the Vazgen Sargsyan stadium in Yerevan, Armenia, Saturday, Sept. 6, 2025. (AP Photo/Hakob Berberyan)

Portugal's Cristiano Ronaldo celebrates after scoring his side's second goal during a World Cup 2026 group F qualifying soccer match between Armenia and Portugal at the Vazgen Sargsyan stadium in Yerevan, Armenia, Saturday, Sept. 6, 2025. (AP Photo/Hakob Berberyan)

WASHINGTON (AP) — The Food and Drug Administration commissioner's effort to drastically shorten the review of drugs favored by President Donald Trump's administration is causing alarm across the agency, stoking worries that the plan may run afoul of legal, ethical and scientific standards long used to vet the safety and effectiveness of new medicines.

Marty Makary's program is causing new anxiety and confusion among staff already rocked by layoffs, buyouts and leadership upheavals, according to seven current or recently departed staffers. The people spoke to The Associated Press on the condition of anonymity because they were not authorized to discuss confidential agency matters.

At the highest levels of the FDA, questions remain about which officials have the legal authority to sign off on drugs cleared under the Commissioner’s National Priority Voucher program, which promises approval in as little as one month for medicines that support “U.S. national interests.”

Traditionally, approval decisions have nearly always been handled by FDA review scientists and their immediate supervisors, not the agency’s political appointees and senior leaders.

But drug reviewers say they've received little information about the new program's workings. And some staffers working on a highly anticipated anti-obesity pill were recently told they can skip certain regulatory steps to meet top officials' aggressive deadlines.

Outside experts point out that FDA drug reviews — which range from six to 10 months — are already the fastest in the world.

“The concept of doing a review in one to two months just does not have scientific precedent,” said Dr. Aaron Kesselheim, a professor at Harvard Medical School. “FDA cannot do the same detailed review that it does of a regular application in one to two months, and it doesn’t have the resources to do it.”

On Thursday Reuters reported that FDA officials have delayed the review of two drugs in the program, in part due to safety concerns, including the death of a patient taking one of the medications.

Health and Human Services spokesman Andrew Nixon said the voucher program prioritizes “gold standard scientific review” and aims to deliver “meaningful and effective treatments and cures."

The program remains popular at the White House, where pricing concessions announced by the Republican president have repeatedly been accompanied by FDA vouchers for drugmakers that agree to cut their prices.

For instance, when the White House announced that Eli Lilly and Novo Nordisk would reduce prices on their popular obesity drugs, FDA staffers had to scramble to vet new vouchers for both companies in time for Trump's news conference, according to multiple people involved in the process.

That’s sparked widespread concern that FDA drug reviews — long pegged to objective standards and procedures — have become open to political interference.

“It’s extraordinary to have such an opaque application process, one that is obviously susceptible to politicization,” said Paul Kim, a former FDA attorney who now works with pharmaceutical clients.

Many of the concerns around the program stem from the fact that it hasn't been laid out in federal rules and regulations.

The FDA already has more than a half-dozen programs intended to speed up or streamline reviews for promising drugs — all approved by Congress, with regulations written by agency staff.

In contrast, information about the voucher program is mostly confined to an agency website. Drugmakers can apply by submitting a 350-word “statement of interest.”

Increasingly, agency leaders such as Dr. Vinay Prasad, the FDA’s top medical officer and vaccine center director, have been contacting drugmakers directly about awarding vouchers. That’s created quandaries for FDA staffers on even basic questions, such as how to formally award a voucher to a company that didn’t request one.

Nixon, the HHS spokesman, said that voucher submissions are evaluated by “a senior, multidisciplinary review committee,” led by Prasad.

Questions about the legality of the program led the FDA’s then-drug director, Dr. George Tidmarsh, to decline to sign off on approvals under the pathway, according to several people with direct knowledge of the matter. Tidmarsh resigned from the agency in November after a lawsuit challenging his conduct on issues unrelated to the voucher program.

After his departure, Sara Brenner, the FDA’s principal deputy commissioner, was set to have the power to decide, but she also declined the role after looking further into the legal implications, according to the people. Currently the agency’s deputy chief medical officer, Dr. Mallika Mundkur, who works under Prasad, is taking on the responsibility.

Giving final approval to a drug carries significant legal risks, essentially certifying that the medicine meets FDA standards for safety and effectiveness. If unexpected safety problems later emerge, both the agency and individual staffers could be pulled into investigations or lawsuits.

Traditionally, approval comes from FDA drug office directors, made in consultation with a team of reviewers. Under the voucher program, approval comes through a committee vote by senior agency leaders led by Prasad, according to multiple people familiar with the process. Staff reviewers don't get a vote.

“It is a complete reversal from the normal review process, which is traditionally led by the scientists who are the ones immersed in the data,” said Kesselheim, who is a lawyer and a medical researcher.

Not everyone sees problems with the program. Dan Troy, the FDA’s top lawyer under President George W. Bush, a Republican, says federal law gives the commissioner broad discretion to reorganize the handling of drug reviews.

Still, he says, the voucher program, like many of Makary’s initiatives, may be short-lived because it isn't codified.

“If you live by the press release then you die by the press release,” Troy said. “Anything that they’re doing now could be wiped out in a moment by the next administration.”

Initially framed as a pilot program of no more than five drugs, it has expanded to 18 vouchers awarded, with more under consideration. That puts extra pressure on the agency’s drug center, where 20% of the staff has left through retirements, buyouts or resignations over the past year.

When Makary unveiled the program in October there were immediate concerns about the unprecedented power he would have in deciding which companies benefit.

Makary then said that nominations for drugs would come from career staffers. Indeed, some of the early drugs were recommended by FDA reviewers, according to two people familiar with the process. They said FDA staffers deliberately selected drugs that could be vetted quickly.

But, increasingly, selection decisions are led by Prasad or other senior officials, sometimes unbeknownst to FDA staff, according to three people. In one case, FDA reviewers learned from GlaxoSmithKline representatives that Prasad had contacted the company about a voucher.

Access to Makary is limited because he does not use a government email account to do business, according to people familiar with the matter, breaking with longstanding precedent.

Once a voucher is awarded, some drugmakers have their own interpretation of the review timeline — creating further confusion and anxiety among staff.

Two people involved in the ongoing review of Eli Lilly's anti-obesity pill said company executives initially told the FDA they expected the drug approved within two months.

The timeline alarmed FDA reviewers because it did not include the agency's standard 60-day prefiling period, when staffers check the application to ensure it isn’t missing essential information. That 60-day window has been in place for more than 30 years.

Lilly pushed for a quicker filing turnaround, demanding one week. Eventually the agency and the company agreed to a two-week period.

Nixon declined to comment on the specifics of Lilly's review but said FDA reviewers can “adjust timelines as needed.”

Staffers were pushed to keep the application moving forward, even though key pieces of data about the drug's chemistry appeared to be missing, according to one person involved in the process. When reviewers raised concerns about some of the gaps during an internal meeting, the person said, they were told by a senior official: “If the science is sound then you can overlook the regulations.”

Former reviewers and outside experts say that approach is the opposite of how FDA reviews should work: By following the regulations, staffers scientifically confirm the safety and effectiveness of drugs.

Skipping review steps could also carry risks for drugmakers if future FDA leaders decide a drug wasn’t properly vetted. Like other experts, Kesselheim says the program may not last beyond the current administration.

“They are fundamentally changing the application of the standards, but the underlying law remains what it is,” he said. “The hope is that one day we will return to these scientifically sound, legally sound principles.”

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education and the Robert Wood Johnson Foundation. The AP is solely responsible for all content.

FILE - The Food and Drug Administration seal is seen at the Hubert Humphrey Building Auditorium in Washington, April 22, 2025. (AP Photo/Jose Luis Magana, File)

Dr. Marty Makary, commissioner of the Food and Drug Administration, speaks during a press briefing at the White House, Wednesday, Jan. 7, 2026, in Washington. (AP Photo/Jacquelyn Martin)