FDA slaps Flori­da's Al­lay Phar­ma­ceu­ti­cals with warn­ing let­ter over vague re­spons­es to drug po­ten­cy is­sues

In­ad­e­quate re­spons­es to find­ings of po­ten­cy dis­crep­an­cies, blend­ing is­sues and out-of-spec­i­fi­ca­tion sam­ples dur­ing a May 2020 in­spec­tion re­cent­ly land­ed tablet man­u­fac­tur­er Al­lay Phar­ma­ceu­ti­cals with a scorch­ing FDA warn­ing let­ter.

In a heav­i­ly-redact­ed ver­sion of the Jan 27 let­ter that was made avail­able this week, the FDA chid­ed the Hialeah, Flori­da man­u­fac­tur­er for vague and in­suf­fi­cient re­spons­es across the board to three ma­jor ob­ser­va­tions dis­cov­ered dur­ing the May 5 to 15, 2020 site in­spec­tion. Those ob­ser­va­tions were com­mu­ni­cat­ed through a Form 483 let­ter, and Al­lay’s re­spons­es to the FDA on June 6 clear­ly irked the agency.

Most no­tably, the FDA took is­sue with the fact that Al­lay ei­ther doesn’t have, or didn’t pro­vide, suf­fi­cient da­ta that could ex­plain why the tablet sam­ples of an un­named drug that were tak­en dur­ing the site in­spec­tion last year were be­low nec­es­sary po­ten­cy stan­dards and var­ied in what po­ten­cy they had.

“Your man­u­fac­tur­ing fail­ures in­di­cate that you do not have an ad­e­quate on­go­ing pro­gram for mon­i­tor­ing process con­trol to en­sure sta­ble man­u­fac­tur­ing op­er­a­tions and con­sis­tent drug qual­i­ty,” the FDA wrote, lat­er urg­ing the com­pa­ny to con­sult with a cGMP ex­pert to bring its stan­dards up to code.

While it’s un­clear ex­act­ly how many drugs the FDA ob­ser­va­tions are re­lat­ed to, Al­lay is un­der con­tract to pro­duce at least one tablet with a com­pa­ny whose name is al­so redact­ed. Re­gard­less of what oth­er terms the two groups agreed to, the FDA made clear to Al­lay that it is re­spon­si­ble for meet­ing qual­i­ty stan­dards, which it hasn’t done or in­ves­ti­gat­ed in a thor­ough man­ner.

“In the qual­i­ty agree­ment with the prod­uct own­er, you have the pri­ma­ry re­spon­si­bil­i­ty for in­ves­ti­gat­ing (out-of-spec­i­fi­ca­tion) re­sults,” the let­ter reads. “Your in­ves­ti­ga­tion in­to the OOS sam­ple re­sult was in­ad­e­quate and did not iden­ti­fy (Cor­rec­tive Ac­tion and Pre­ven­tive Ac­tion). Fur­ther­more, an in­ves­ti­ga­tion was not per­formed to en­sure that pre­vi­ous­ly re­leased lots met your re­vised as­say spec­i­fi­ca­tions. FDA in­ves­ti­ga­tors found 13 lots with­in ex­piry that ex­ceed­ed your new as­say spec­i­fi­ca­tion dur­ing re­lease or sta­bil­i­ty test­ing. These lots should have been iden­ti­fied in your in­ves­ti­ga­tion.”

The FDA al­so high­light­ed test­ing er­rors and dis­crep­an­cies for ac­tive phar­ma­ceu­ti­cal in­gre­di­ents, call­ing out test­ing re­sults that didn’t match up to those quot­ed by a new API man­u­fac­tur­er used by Al­lay. In one in­stance, the com­pa­ny’s tests on an API lot dif­fered by 7.8% com­pared to the rate quot­ed by the in­gre­di­ent mak­er, but Al­lay went ahead with man­u­fac­tur­ing its drug any­way, the FDA said.

Al­lay is now re­quired to pro­vide the FDA with a re­view of all oth­er prod­ucts it man­u­fac­tures, re­gard­less of whether the prod­ucts were iden­ti­fied in the Form 483 ob­ser­va­tions, as well as a “com­pre­hen­sive and in­de­pen­dent” as­sess­ment es­sen­tial­ly of its en­tire sys­tem for ad­dress­ing de­vi­a­tions from cGMP man­u­fac­tur­ing process­es.

Al­lay has 15 busi­ness days (Feb. 18) to re­spond to the FDA’s warn­ing let­ter. The com­pa­ny did not im­me­di­ate­ly re­turn a re­quest from End­points News seek­ing com­ment.

The top 100 bio­phar­ma VCs, Bob Brad­way places $2B bet in can­cer, gene edit­ing pi­o­neer's new big idea, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Before diving in, we had some news to share: Endpoints is launching a premium weekly report focusing on all things regulatory. Coverage will be led by our new senior editor, Zachary Brennan, who joins us from POLITICO. Arsalan Arif has more details in his Publisher’s Note.

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Robert Bradway (Photographer: Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Am­gen snaps up can­cer drug play­er Five Prime, adding PhI­II-ready FGFR2b drug in $2B M&A play

Amgen is making a long-awaited move on the M&A side, buying South San Francisco-based Five Prime $FPRX for close to $2 billion and adding a slate of new cancer drugs to the pipeline.

Amgen is paying $38 a share, putting the deal value at $1.9 billion. The stock closed at $21.26 last night, giving investors a 78% premium.

The jewel in the crown of this deal is bemarituzumab, which Amgen describes as a first-in-class, Phase III-ready anti-FGFR2b antibody. Amgen was drawn to the bargaining table by Five Prime’s mid-stage data on gastric cancer, satisfied by PFS and OS data helping to validate FGFR2b as a target. Amgen researchers will now expand on the R&D program in other epithelial cancers, including lung, breast, ovarian and other cancers.

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David Liu (Casey Atkins Photography courtesy Broad Institute)

David Liu has a new big idea: pro­teome edit­ing. It could one day shred tau, RAS and some of the worst dis­ease-caus­ing pro­teins

Before David Liu became famous for inventing new forms of gene editing, he was known around academia in part for a more obscure innovation: a Rube Goldberg-esque system that uses bacteria-infecting viruses to take one protein and turn it into another.

Since 2011, Liu’s lab has used the system, called PACE, to dream up fantastical new proteins: DNA base editors far more powerful than the original; more versatile forms of the gene editor Cas9; insecticides that kill insecticide-resistant bugs; enzymes that slide synthetic amino acids into living organisms. But they struggled throughout to master one of the most common and powerful proteins in the biological world: proteases, a set of Swiss army knife enzymes that cut, cleave or shred other proteins in everything from viruses to humans.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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In the lat­est big in­vest­ment in gene ther­a­py man­u­fac­tur­ing, Bio­gen com­mits $200M to a ma­jor new fa­cil­i­ty in NC

You’d be forgiven for thinking that the only R&D effort of any consequence at Biogen belongs to aducanumab, its controversial Alzheimer’s drug. But behind the uproar around that drug, the big biotech has a full scale pipeline in play that includes a growing focus on developing gene therapies.

Now Biogen plans to build up the kind of manufacturing muscle that will give it an advantage in gaining FDA approvals — where CMC is always key — and then marketing them around the world.

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As Brain­Storm con­tin­ues to tout ‘clear sig­nal’ on ALS drug, the FDA of­fers a rare pub­lic slap­down on the da­ta

A little more than a week after BrainStorm acknowledged that regulators at the FDA had informed them that the biotech needed more data before it could expect to gain an approval for its ALS treatment NurOwn — while still touting a “clear signal” of efficacy and not ruling out an application — the agency has decided to clarify the record in a most unusual statement.

The FDA statement amounts to a straight slapdown, offering a different set of efficacy numbers from the company’s public presentation last November and ruling out any chance of statistical significance.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

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Bruce Cozadd, Jazz CEO (Jazz Pharmaceuticals)

Jazz CEO Bruce Cozadd cam­paigned for 6 months to buy GW Phar­ma. A 90% pre­mi­um sealed the deal — along with $17.6M in ‘re­ten­tion’ in­cen­tives

Jazz CEO Bruce Cozadd didn’t beat around the bush.

In his first video meeting with GW Pharma chief Justin Gover last July 8, he offered to pay $172 a share to get the company, which had beaten the odds in getting its remarkable cannabinoid drug Epidiolex across the regulatory finish line for epilepsy. GW’s stock closed at $129 that day.

Cozadd had already done his homework on the financing to make sure he could swing it the way he wanted. He just needed to do some due diligence before making the non-binding bid firm.

UP­DAT­ED: Not 3 weeks af­ter tak­ing Hu­ma­cyte pub­lic, Ra­jiv Shuk­la launch­es an­oth­er blank check com­pa­ny

One of biotech’s earliest SPAC investors is back with another blank-check company, less than a month after his last effort announced its intent to merge.

Rajiv Shukla is intending to take a third lucky winner public with Alpha Healthcare Acquisition III, filing to go public Thursday with a $150 million raise penciled in. The move comes just a couple of weeks after Shukla’s second SPAC said it would jump to Nasdaq in tandem with Laura Niklason’s Humacyte in a $255 million new investment.

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