FDA’s Manufacturing Designation Could Derisk Mid-Development Manufacturing Changes

 

The status could support staged transitions to new manufacturing processes, potentially mitigating some risks of high-stakes switches.

Cell and gene therapy experts agree it is optimal to pick a manufacturing platform in preclinical and keep using it as a candidate advances through human trials and to the market. Yet that advice is of little use to sponsors who learn after trials are underway that their processes aren’t as scalable as they’d believed. Those companies have faced the prospect of landing themselves in a regulatory thicket in trying to get the green light for a switch. But that may be changing—at least for those sponsors who’ve secured an Advanced Manufacturing Technology (AMT) designation from the FDA.

The challenges faced by manufacturers of approved cell and gene therapies, many of which fail to achieve commercial success, show the risks of coming to market with a suboptimal production process. Manufacturing processes that work well enough for small, early phase trials can suffer from inefficiencies that make it hard to achieve commercial viability. Seeking to launch with scalable processes that enable profitable production at a price that is appealing to payers, companies may be tempted to rethink manufacturing between entering the clinic and winning approval.

Switching brings risks, though. Don Fink, a regulatory expert at Dark Horse Consulting, told BioSpace it is simplest to adopt technologies before a candidate enters clinical trials. By using a technology from the start of development, companies can build chemistry, manufacturing and control strategies around it from day one. Anna McMahon, director of regulatory affairs at cell therapy manufacturer Cellares, agreed, telling BioSpace that the optimal time to settle on a process is before a company files an IND to study a treatment in humans.

Fink said switching manufacturing platforms mid-development poses unique challenges. A sponsor that has generated early-phase data and is moving toward a larger efficacy trial will need to show that products made using the old and new manufacturing platforms are comparable. Fink said making comparisons without the baseline of an approved drug is problematic from a regulatory perspective.

The later a sponsor waits before making a change, the harder it is to manage the transition, according to the consultant. That means spending more time and money on the switch, Fink said, “and time and money in this day and age are pretty critical to whether or not you’re going to succeed.”

Yet these risk calculations may be evolving. Encouraged by the opportunities created by the FDA’s launch of its AMT program, McMahon said sponsors now have a blueprint for how to change manufacturing technologies while keeping their R&D programs on track.

Changing the Risk Equation

McMahon, whose company won an AMT designation for its platform in April and has had talks with the FDA under its auspices, is more bullish than Fink on the options available to companies that miss the optimal, pre-IND window. AMT designations give users of technologies that substantially improve manufacturing processes more opportunities to engage with the FDA, potentially smoothing the switch to technologies that have the status.

According to McMahon, the AMT designation “fundamentally changes the risk equation for cell therapy developers” and provides “a clear, repeatable path to engage FDA on manufacturing early.” Regulators understand switching manufacturing platforms is a complex change, she said. The FDA’s guidance on AMTs says that drug developers using designated technologies will benefit from additional communication “during both early drug development and subsequent application assessment.”

Through the AMT framework, the FDA is allowing “staged, evidence-led transitions” rather than viewing platform switching as all-or-nothing, McMahon said. The framework thus allows mid-trial switches to AMT-designated manufacturing platforms to be executed without interrupting studies, the Cellares director explained.

McMahon named multiple ways companies can use AMT designations to support transitions. She advised sponsors to validate comparability in parallel with ongoing trials using the designated platform by running side-by-side lots with pre-agreed readouts while dosing continues. She also recommended maintaining clinical continuity through bridging strategies that are discussed in advance with regulators to keep dosing on schedule.

Sponsors can use AMT-specific interactions to align on acceptance criteria before manufacturing clinical material, McMahon said. The interactions also offer chances to “plan future phases with confidence in the manufacturing foundation, including identity controls and data expectations.”

“This keeps trials on schedule and sets up a process that can be repeated across sites after approval,” McMahon added.

The short history of the AMT program, which the FDA finalized in January, means Cellares, Oribiotech and the other companies with designations are still determining the impact of the regulatory status. While the scientific challenge of proving comparability will remain, the AMT program may offer a way to simplify the regulatory path, McMahon said.

Whether companies are willing to take that path and what happens to those that do may become clearer over time. For now, the program at least offers a potential way forward for sponsors that fear they may risk future commercial failure by coming to market with a costly, unscalable process.

https://www.biospace.com/fda/fdas-manufacturing-designation-could-derisk-mid-development-manufacturing-changes

https://www.zerohedge.com/geopolitical/seattles-woke-world-cup-agenda-implodes-pride-match-set-between-countries-anti-gay

Pritzker's Sanctuary Policies Freed 1,700 Criminal Aliens Since January

 Illinois sanctuary policies have allowed more than 1,700 criminal illegal aliens to slip back onto the streets since President Trump took office on January 20, and the Department of Homeland Security is now calling out state officials for putting politics ahead of public safety. Among those released are individuals charged with or convicted of homicide, sexual assault, and kidnapping—crimes that should have kept them locked up and handed over to federal immigration authorities.

ICE Director Todd Lyons sent a letter to Illinois Attorney General Kwame Raoul urging him to honor ICE detainers for over 4,000 criminal illegal aliens currently sitting in state custody. The letter marks the second attempt by federal officials to get cooperation from Illinois—the first, sent in September, was completely ignored. 

The numbers are staggering. According to the Department of Homeland Security, “Illinois' failure to honor ICE detainers has resulted in the release of 1,768 criminal illegal aliens since January 20. The crimes of these aliens include five homicides, 141 assaults, 23 burglaries, four robberies, 24 dangerous drugs offenses, 15 weapons offenses, and 10 sexual predatory offenses.”

And that's just the ones who've already been let go. The 4,015 criminal illegal aliens still in Illinois custody with active ICE detainers have even grimmer records: 51 homicides, 1,134 assaults, 107 burglaries, 36 robberies, 275 dangerous drug offenses, 120 weapons offenses, and 813 sexual predatory offenses.

BREAKING - It has been revealed that since the beginning of 2025, Illinois Governor JB Pritzker has released over 1,700 known criminal aliens who were charged with murder and rape in other countries in an attempt to hide them from ICE detainers. pic.twitter.com/9rsmuOHmYS

— Right Angle News Network (@Rightanglenews) December 8, 2025

ICE reached out to Illinois Attorney General Kwame Raoul in September, urging him to work with the agency and honor detainers on criminal illegal aliens, but Raoul’s office ignored the letter

"Gov. Pritzker and his fellow Illinois sanctuary politicians are releasing murderers, pedophiles, and kidnappers back into our neighborhoods and putting American lives at risk," DHS Assistant Secretary Tricia McLaughlin said in a statement. “We are calling on Governor Pritzker and his administration to stop this dangerous derangement and commit to honoring the ICE arrest detainers of the more than 4,000 criminal illegal aliens in Illinois’ custody. It is common sense. Criminal illegal aliens should not be released back onto our streets to terrorize more innocent Americans.”

The Department of Homeland Security highlighted several cases of criminal illegal aliens who were released from custody and put back on the streets because of Prtizker’s sanctuary policies. 

Under Governor Pritzker, Illinois’ sanctuary policies have led to the release of some of the most dangerous illegal immigrants, even when ICE had detainers and the offenders clearly threatened public safety: Victor Manuel Mendoza-Garcia, a Mexican national convicted of three counts of aggravated kidnapping for ransom and sentenced to 18 years. Cook County ignored ICE’s detainer, which meant that federal agents had to arrest him after his release. 

Then there’s Juan Morales Martinez of Guatemala, who killed two people in a car crash and was found with ammunition and an extended magazine. Clark County also refused to work with ICE, so federal agents had to wait outside the jail to catch him the moment he walked free. He has since been removed from the country.

Amilcar Waldo Gonzalez-Jimenez, another Mexican national, had convictions for DUI, domestic battery, and multiple counts of criminal sexual assault. ICE’s detainer was ignored, and agents had to track him down on their own. The same story played out with Juan Alberto Caro Marin, convicted of aggravated criminal sexual abuse of a family member. Cook County let him walk despite ICE’s request to hold him.

Jose Manuel Fuentes-Vargas, also from Mexico, had a criminal history including domestic violence and the sexual assault of a child under 13. His detainer wasn’t honored either. Repeat border crosser Leonardo Ignot-Osto had been convicted of theft, child abduction, and had entered the U.S. illegally at least four times. Cook County still released him. ICE eventually found him and removed him.

The list continues with offenders like Jaime Mandujano-Nunez, convicted of predatory criminal sexual assault of a child and sentenced to 17 years. The Illinois Department of Corrections (IDOC) released him without notifying ICE. Federal agents later located and removed him. Alfonso Batalla Garcia had one of the most alarming records: attempted murder, aggravated sexual assault with bodily harm, and aggravated kidnapping. IDOC freed him anyway, ignoring ICE’s detainer, and ICE had to step in to clean up the mess.

And then there’s Guillermo Garcia-Porcayo, convicted of attempted murder with intent to kill. IDOC released him despite an active detainer. ICE finally apprehended him weeks later and removed him from the country.

These cases represent only a handful of the worst offenders. 

Governor Pritzker is widely viewed as a likely contender for the Democrats’ 2028 nomination, and his sanctuary policies fit neatly with what the party activists want. They want a standard-bearer who treats resistance to President Trump as a defining principle, and Pritzker has been trying to position himself as that champion, even at the expense of the safety of his constituents.

https://www.zerohedge.com/political/governor-pritzkers-sanctuary-policies-freed-1700-criminal-aliens-january

Immigration Gone Wild

 by Victor Davis Hanson via American Greatness,

It is hard now even for Democrats to defend illegal immigration, given that the Biden administration allowed in more than 10 million entrants. Among them were an estimated 500,000 criminals. No one believes that was wise or should ever be repeated.

Worse, the message went out that there would be few, if any, deportations and no real ICE kinetic activity beyond the border.

The world’s poor, sick, both law-abiding and criminal, young and old, understood that anyone could now enter the U.S. at will. Deterrence and legality were lost.

In its place, the message went out that if it was permissible to cross the border unlawfully, then, by extension, it would be seen as equally fine to reside illegally as well—and perhaps further to ignore laws, on the theory that the host had sanctioned all such exemptions.

During the lockdown hysteria, some 8,000-8,500 U.S. soldiers were expelled from the military for refusing the experimental mRNA vaccine. State employees nationwide were being fired for refusing the government vaccines. Nevertheless, illegal aliens would have no such mandates or worries. They simply walked in without worries over vaccinations and current COVID status and surmised correctly that illegal aliens were part of a Biden-administration-protected and privileged category.

Indeed, between 2021 and 2025, in one of the most bizarre episodes in U.S. immigration history, the border simply disappeared. There were to be no background checks, no health audits, and no identification of the greatest influx in any four-year period in U.S. history.

No one knew why. All had their explanations.

Was the Biden handlers’ plan for more poor to grow the welfare state and expand liberal government?

Was it misplaced idealism to welcome in millions of the world’s poorest, who would soon make it even more difficult for the nation’s citizen poor to find affordable housing and health care?

Was the agenda to create future dependencies and constituencies for an otherwise ossified Democratic Party?

Or was it an effort to ensure, in DEI terms, that the oppressed and victimized would outgrow the inert white oppressors and victimizers?

Oddest of all has been the attitude of the left toward the past destruction of the border. They went mum about the rampant illegality as the border disappeared and as millions filtered throughout the nation. Americans had no idea who the newcomers were, or even where or why they were here.

Given that it is much easier to destroy the border and allow millions to enter than to restore it and find the millions who entered illegally, the Democrats’ response has been Orwellian. After assuming the law did not apply to illegal alien entrants, they now insist its full force must apply to each of 10 million aliens before they can be sent home.

There were no protests when an errant Biden ICE became dysfunctional due to massive illegality. But there is now outrage when it attempts to restore legality and follow the law.

The result, however, of such a massive nullification of immigration laws has been that the nation’s outrage over illegal immigration has now extended to legal immigration as well. At the current level of frustration, all legal immigration will likely soon be put on hold.

Why?

One, we are currently in a great experiment: never has the U.S. foreign-born resident population approached 50-55 million or 16 percent of the population.

Two, never has the once-time-tried melting-pot creed of assimilation, integration, and acculturation been under greater assault and ridicule—just when it is most needed.

The canon of DEI—the nation is divided between a mostly white oppressor class and the non-white oppressed—has served to amplify the effects of giving up on civic education and melting-pot assimilation.

Somehow, the left advanced the absurd notion that the salad bowl of immigrants, chiefly and permanently identified by tribal ethnicities, races, religions, and nationalities, and only secondly as new Americans, would radically change America for the better. And so ended the ancient notion of assimilation, now to be known as “cultural appropriation.”

Three, if millions of legal immigrants are not asked to assume fully American identities, and further, if they feel that there are exemptions and largesse to be had by emphasizing their tribal and victimized status, then will they also feel they are not subject to any American customs and laws?

Instead, immigrants under these new protocols will seek to carve out their own tribal communities, based both on ethnic chauvinism and a sense of exemption from accountability. And if they insist on identifying as collectives rather than unique individuals, they will become increasingly unpopular not just as ingrates, but as hypocrites whose greater affinity with the nation they abandoned does not extend to returning to it.

Indeed, they will appear to have arrived in America only to craft a cocoon of security, freedom, and prosperity lacking in their homeland, but otherwise not to become fully American or see their former homeland as incidental, not essential, to their new identities.

The logical result of such tribal immigration is now upon us. Somali immigrants, both legal and illegal, have pulled off a likely multi-billion-dollar welfare fraud in Minnesota—perhaps the greatest single heist of welfare funds in the nation’s history. They were empowered by the usual DEI boilerplate rhetoric from their Minnesota champions, Rep. Ilhan Omar (who claimed the U.S. was now “one of the worst countries in the world”), Governor Tim Walz, and Attorney General Keith Ellison.

The more criminality, theft, and fraud were uncovered, the more the Somali leadership screamed “racism,” with the Democrat apparat blaming everyone but the perpetrators themselves.

Meanwhile, California has issued at least 17,000 commercial driver’s licenses to illegal alien truck drivers, the majority of them non-residents with little if any prior trucking expertise or English facility. The result is a sort of road-warrior new atmosphere on the nation’s freeways, as a new generation of truckers ignores the norms of the past and rightly concludes that if they were given exemption to enter the U.S. illegally and further to drive without proper audits, then naturally no authorities would mind if they also violated American traffic laws.

There are roughly one million foreign students in the U.S., the majority from China, India, and the Middle East. After October 7, protests, often violent and in violation of campus rules, spread nationwide.

There was never much pushback from either campus official or law enforcement. Within a few months, our liberal bastions of higher education had become saturated with anti-Semitic rhetoric, protests, and occasional violence against Jews.

Middle-East guest students often openly cheered on Hamas, called for the destruction of Israel, and, despite being non-citizens, often declared campus areas as no-go zones for American Jews. They did so because they could and had fully absorbed the DEI mantras of exemption.

So often they screamed “Islamophobia” when called out on their anti-Semitism, damning their critics with slurs of “nativism,” “racism,” and “xenophobia.” Thousands of foreign students felt contempt for their hosts and rhetorically attacked the U.S. as much as they fought in reality to remain in America.

As for the millions who crossed the southern border, almost daily, a national news story relates that a DUI driver has killed an American family, or a U.S. citizen has been murdered or raped, by an “undocumented immigrant,” usually with a criminal record, several deportations, and revolving-door arrests.

In Los Angeles, we were treated to street scenes of immigrants, apparently both legal and illegal, waving the Mexican flag while occasionally burning the American flag, sending the message that they would resist returning to the country whose flag they chauvinistically waved but demanded permanent residence in the nation whose flag they trashed and burned.

The net result was that our recent generations of immigrants have done the impossible: turned the most generous nation in the world from the most welcoming to increasingly resistant to mass immigration of any sort.

Again, why the change? They have read the news of one too many horrendous semi-truck accidents, one too many horrific murders, one too many anti-Semitic screams, and one too many massive abuses of a generous welfare state.

In sum, Americans now believe that the current generation of immigrants interprets their magnanimity and generosity as weakness and stupidity to be manipulated and scorned, and rarely as generosity to be appreciated and reciprocated in kind.

https://www.zerohedge.com/political/immigration-gone-wild

DEI Doctors and Nuclear Engineers

 by Adam Sharp

In recent newsletters, we’ve been critical of aspects of President Trump’s foreign policy.

But he does deserve significant credit here at home. We’ve already covered his important work in streamlining the permitting process for drilling and mining projects.

Today we’re going to discuss another area where the President has made good progress. Reversing the negative effects of DEI, and putting America back on track towards a merit-based system.

A few years back I remember seeing the chart below, and being absolutely blown away. I had no idea it had gotten this bad.

The chart shows the U.S. medical school acceptance rate by race. It is broken into groups by scores on the MCAT (med school acceptance test) and GPA.

Source: AEI

In the first group, we see that only 6% of Asians and 8% of White people who score 24-26 on their MCAT are accepted into med school. Meanwhile 31% of Hispanic and 56% of Black applicants with those same scores are admitted.

And even in the highest-scoring bracket, only 58% of Asians and 63% of Whites get in, while 83% and 94% of Hispanics and Blacks gain acceptance.

Is this the kind of society we want? One where race matters more than merit? Especially when it comes to life and death careers?

This is no small issue. It affects the very incentives that make our economy and society work. If we don’t fix this issue, and re-orient towards a merit-based system, the outlook is bleak.

DEI Nuclear Workers

Over in the U.K., DEI is also wreaking havoc.

For example, the country is attempting to build small modular nuclear reactors (SMRs) to meet growing power demand.

But DEI requirements are mucking up the process. From The Times:

Previously hailed as the fastest plan of its kind in the world, the bidding process to develop small modular reactors (SMR) took two years and saw firms face extra requirements to prove their “social value”.

Companies were told to fill out up to 350 pages solely dedicated to how they would give jobs to groups of disadvantaged people — including asylum seekers, who generally cannot work while their claim is being processed.

…Companies were asked how they would create jobs for those “who face barriers to employment”, which included “refugees, people who have recently immigrated or are seeking asylum”.

The British government is forcing companies building nuclear reactors to hire people “who face barriers to employment”?! These dolts never even considered how dangerous their little social experiment could prove to be.

Companies were also instructed to outline plans to maintain a 50% female workforce, which is completely unrealistic. Women are not as naturally drawn to industries like construction and nuclear as men are. These DEI campaigners refuse to recognize that there are inherent differences between the sexes and their differing interests in careers.

If there was a nuclear plant being built upwind of your house, would you want anyone but the most qualified and motivated people building it? Of course not.

And can you imagine hiring asylum seekers (refugees with little screening and questionable skills) to build a nuclear plant? It’s absolute madness.

Due to all this red tape, just the bidding process for a few SMRs took 2 years and cost £22 million.

Here in the U.S., nuclear firms were also committed to DEI goals before Trump came into office. Thankfully they have mostly closed their DEI offices since. As we enter this nuclear renaissance, I want absolutely zero DEI involved in the process.

I use the examples of medical and nuclear careers because they show how dangerous DEI can be. But realistically, this applies to the entire economy.

Trump’s Efforts to Fix It

DEI may have started out as a good-natured attempt to remove prejudice in hiring. But as it stands today, it’s a disaster.

A society that isn’t based on merit loses its moral compass. It becomes a nepotistic mess. Of course our society shouldn’t discriminate based on race, but these nutjobs have taken it way too far.

I don’t believe DEI is doing the people who are “benefitting” any favors, either. The incentive structures get all mixed up. If certain groups feel like they have a free pass, they’ll be less motivated to work hard and expect to get by anyway. So while DEI might “help” in the short-term, in the long run it creates a nightmare of incentive structures. And bad outcomes.

Thankfully DEI is one of the first items Trump addressed once in office. He instructed all government offices to dismantle their diversity, equity, and inclusion infrastructure.

He essentially required the same of any institution or company that gets significant funding from the government (which is most universities, non-profits, and companies).

This is a huge development. It will take time to show up, but the effects of re-instituting a merit-based system will be extremely positive.

There’s more work to be done, but this is a good start.

So whenever I get frustrated with something the Trump administration does, I have to remind myself that they’re doing important work in certain areas. And that is something to be thankful for.

https://dailyreckoning.com/dei-doctors-and-nuclear-engineers/

Florida labels Muslim Brotherhood, CAIR terrorist groups

 Florida Governor Ron DeSantis announced he is designating the Muslim Brotherhood and the Council on American-Islamic Relations (CAIR) as foreign terrorist organizations in the state, effective immediately.

"Florida agencies are hereby directed to undertake all lawful measures to prevent unlawful activities by these organizations, including denying privileges or resources to anyone providing material support," DeSantis wrote on X, detailing the order.

The designation is akin to the one imposed by Texas Governor Greg Abbott, who branded the two groups as "foreign terrorist organizations and transnational criminal organizations" in November.

https://breakingthenews.net/Article/Florida-labels-Muslim-Brotherhood-CAIR-terrorist-groups/65317382

'Retail investors pushing gold out of safe haven role to more speculative asset, BIS says'

 Retail investors drove the latest rise in gold prices, pushing bullion out of its traditional safe haven pattern to a more speculative asset, the Bank of International Settlements said Monday in its quarterly report on market developments.

While the rally may have begun from institutional traders seeking safe haven exposure as doubts rose about stretched equity valuations, BIS pointed to evidence that it was amplified by retail investors trying to take advantage, which prompted a shift away from usual safe-haven patterns.

"Gold has become much more of a speculative asset," Hyun Song Shin, head of the BIS Monetary and Economic Department, told Bloomberg.

BIS said the past few quarters are the only time in at least the last 50 years in which gold and equities have entered "explosive territory" simultaneously.

"Following its explosive phase, a bubble typically bursts with a sharp and swift correction," BIS wrote, pointing to the case of gold in 1980, while also noting that corrections can occur over variable and potentially long time frames.

Gold and silver futures fell Monday as bond yields moved higher, ahead of the U.S. Federal Reserve's near-certain rate reduction for cues on monetary policy next year.

"The market is waiting for the Fed decision and for more guidance on policy," Zaner Metals senior metals strategist Peter Grant said in a note, adding that gold remains attractive as fundamentals stay strong and central bank buying continues, with a move toward $5,000/oz in mext year's Q1 within reach.

Front-month Comex gold (XAUUSD:CUR) for December delivery closed -0.6% to $4,187.20/oz, snapping a three-session winning streak, and front-month Comex December silver (XAGUSD:CUR) ended -1.1% to $57.779/oz, its fourth loss in five sessions.

ETFs: (GLD), (GDX), (GDXJ), (IAU), (NUGT), (PHYS), (GLDM), (AAAU), (SGOL), (RING), (BAR), (OUNZ), (SLV), (PSLV), (SIVR), (SIL), (SILJ)

https://www.msn.com/en-us/money/markets/retail-investors-pushing-gold-out-of-safe-haven-role-to-more-speculative-asset-bis-says/ar-AA1RXP5L