Form 483 un­masks man­u­fac­tur­ing is­sues at Alvotech be­fore its CRL, and one for Au­robindo too

Ear­li­er this month, the Ice­landic biotech Alvotech re­ceived a re­sponse let­ter from FDA sur­round­ing its po­ten­tial in­ter­change­able biosim­i­lar to Ab­b­Vie’s Hu­mi­ra, which dis­cussed sev­er­al de­fi­cien­cies at a Reyk­javik fa­cil­i­ty.

On Tues­day, the FDA un­veiled the 483 for that fa­cil­i­ty, find­ing sev­er­al is­sues re­lat­ed to pro­ce­dur­al and qual­i­ty con­trol, among 13 ob­ser­va­tions.

The FDA found that Alvotech’s fa­cil­i­ty, in­spect­ed in March, lacked the pro­ce­dur­al con­trols to en­sure that in­com­ing ma­te­ri­als were prop­er­ly qual­i­fied, as an in­ter­nal in­ves­ti­ga­tion in­to the fa­cil­i­ty’s de­vi­a­tion man­age­ment sys­tem was not con­duct­ed.

The reg­u­la­to­ry agency al­so ob­served that the man­u­fac­tur­ing site could not pre­vent bac­te­ria and mold, with a high num­ber of mold re­cov­er­ies in the site’s clas­si­fied rooms. In ad­di­tion to is­sues with in­ven­to­ry and raw ma­te­ri­als, writ­ten pro­ce­dures didn’t have enough de­tails to en­sure prod­uct qual­i­ty, the 483 says.

Alvotech CEO Mark Lev­ick said in a state­ment last week that the com­pa­ny is work­ing with the FDA to ad­dress the is­sues be­fore its De­cem­ber PDU­FA date.

Mean­while, an­oth­er In­dia-based gener­ic man­u­fac­tur­ing com­pa­ny that has fre­quent­ly popped up on the FDA’s radar re­ceived an­oth­er Form 483.

Au­robindo Phar­ma has got­ten the slap this time over an in­spec­tion of its API man­u­fac­tur­ing site in the vil­lage of Py­dib­hi­mavaram in the coun­try’s east.

The in­spec­tion, which took place from late Ju­ly to ear­ly Au­gust of this year, found sev­er­al is­sues, in­clud­ing de­fi­cient clean­ing and main­te­nance of equip­ment. The re­port not­ed that re-clean­ing of equip­ment did not take place mul­ti­ple times. A build-up of white pow­der and brown rust was ob­served in equip­ment used to man­u­fac­ture API batch­es.

The short, 3-ob­ser­va­tion Form 483 not­ed that from Ju­ly to Au­gust, Au­robindo logged 6,337 er­ror mes­sages for high-per­for­mance liq­uid chro­matog­ra­phy and gas chro­matog­ra­phy equip­ment, which were used for API batch­es man­u­fac­tured for the US mar­ket.

How­ev­er, no in­ves­ti­ga­tions were car­ried out or cor­rec­tions made to pre­vent the er­ror mes­sages. Mes­sages that were logged in­clud­ed “in­stru­ment fail­ure,” “se­quence stopped be­cause of er­ror,” and “se­quence stopped by the user,” among oth­ers.

The Form 483 al­so not­ed that pro­ce­dures sur­round­ing the qual­i­ty con­trol unit were not fol­lowed. This in­clud­ed that lab­o­ra­to­ry da­ta were not al­ways be­ing record­ed, as per re­quire­ments.

This is not the first time this year that Au­robindo has re­ceived a 483, as in Ju­ly, sev­er­al ob­ser­va­tions were made at Au­robindo’s Unit VII for­mu­la­tion plant in the vil­lage of Polepal­ly, In­dia dur­ing an in­spec­tion in ear­ly May. In­ves­ti­ga­tors found an un­ex­plained dis­crep­an­cy and fail­ure of a batch of its com­po­nents to meet any of its spec­i­fi­ca­tions, along with oth­er is­sues re­lat­ed to qual­i­ty con­trol.

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Dave Marek, Myovant CEO

My­ovant board balks as ma­jor­i­ty own­er Sum­it­o­mo swoops in with a $2.5B deal to buy them out

Three years after Sumitomo scooped up Roivant’s 46% stake in the publicly traded Myovant $MYOV as part of a 5-company, $3 billion deal, they’re coming back for the whole thing.

But these other investors at Myovant want more than what the Japanese pharma company is currently offering to pay at this stage.

Sumitomo is bidding $22.75 a share for the outstanding stock, which now represents 48% of the company after Sumitomo bumped its ownership since the original deal with Roivant. Myovant, however, created a special committee on the board, and they’re shaking their heads over the offer.

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Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

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Vlad Coric, Biohaven CEO

Vlad Coric charts course for new Bio­haven with neu­ro­science push and Big Phar­ma vets on board

What’s Biohaven without its CGRP portfolio? That’s what CEO Vlad Coric is tasked with deciding as he maps out the new Biohaven post-Pfizer takeover.

Pfizer officially scooped up Biohaven’s CGRP assets on Monday, including blockbuster migraine drug Nurtec and the investigational zavegepant, for $11.6 billion. As a result, Coric spun the broader pipeline into an independent company on Tuesday — with the same R&D team behind Nurtec but about 1,000 fewer staffers and a renewed focus on neuroscience and rare disease.

In AstraZeneca's latest campaign, wild eosinophils called Phils personify the acting up often seen in uncontrolled asthma

As­traZeneca de­buts an­noy­ing pur­ple ‘Phil’ crea­tures, per­son­i­fied asth­ma eosinophils ‘be­hav­ing bad­ly’

There are some odd-looking purple creatures lurking around the halls of AstraZenca lately. The “Phil” character cutouts are purple, personified eosinophils with big buggy eyes and wide mouths, and they’re a part of AZ’s newest awareness effort to help people understand eosinophilic asthma.

The “Asthma Behaving Badly” characters aren’t only on the walls at AZ to show the new campaign to employees, however. The “Phils” are also showing up online on the campaign website, and in digital and social ads and posts on Facebook and Instagram.

Mar­ket­ingRx roundup: No­var­tis re­cruits NFL coach for Leqvio cam­paign; Pfiz­er pro­motes ‘Sci­ence’ merch on so­cial me­dia

Novartis is turning to a winning coach to talk about Leqvio and the struggles of high cholesterol — including his own. Bruce Arians, the retired NFL head coach of the Arizona Cardinals and Super Bowl-winning Tampa Bay Buccaneers, is partnering with the pharma for its “Coaching Cholesterol” digital, social and public relations effort.

In the campaign, Arians talks about the potential for “great comebacks” in football and heart health. Once nicknamed a “quarterback whisperer,” he is now retired from fulltime coaching (although still a front-office consultant for Tampa Bay), and did a round of media interviews for Novartis, including one with People and Forbes.

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Amy West, Novo Nordisk head of US digital innovation and transformation (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: No­vo Nordisk dig­i­tal in­no­va­tion chief Amy West dis­cuss­es phar­ma pain points and a health­care 'easy but­ton’

Amy West joined Novo Nordisk more than a decade ago to oversee marketing strategies and campaigns for its US diabetes portfolio. However, her career path shifted into digital, and she hasn’t looked back. West went from leading Novo’s first digital health strategy in the US to now heading up digital innovation and transformation.

She’s currently leading the charge at Novo Nordisk to not only go beyond the pill with digital marketing and health tech, but also test, pilot and develop groundbreaking new strategies needed in today’s consumerized healthcare world.

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Benjamine Liu, TrialSpark CEO

Paul Hud­son and Tri­alSpark's mu­tu­al de­sire to speed up de­vel­op­ment con­verges in three-year, six-drug goal

A unicorn startup that originally set out to hasten clinical studies for biopharma partners dug further into its revised path of internal drug development by linking arms with Sanofi in a pact that the biotech’s CEO said originated from the top.

TrialSpark and the Big Pharma on Tuesday committed to in-licensing and/or acquiring six Phase II/Phase III drugs within the next three years.

“I’ve known Paul Hudson for a while and we were discussing the opportunity to really re-imagine a lot of different parts of pharma,” TrialSpark CEO Benjamine Liu told Endpoints News, “and one of the things that we discussed was this opportunity to accelerate the development of new medicines in mutual areas of interest.”

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Take­da to pull key hy­poparathy­roidism drug from the mar­ket af­ter years of man­u­fac­tur­ing woes

Takeda on Tuesday morning made an announcement that almost 3,000 people with the rare disease known as hypoparathyroidism were fearing.

Due to unresolved supply issues and manufacturing woes, Takeda said it will cut its losses and discontinue its hypoparathyroidism drug, known as Natpara (parathyroid hormone), halting all manufacturing of the drug by the end of 2024, but the entire inventory will be available until depleted or expired, a company spokesperson said via email.