FDA hands a warn­ing let­ter to a Lupin sub­sidiary af­ter fail­ing to main­tain clean­li­ness once again

From In­dia to NJ, the core of the FDA’s in­struc­tions to Lupin sub­sidiary Nov­el Lab­o­ra­to­ries were the same: es­tab­lish prop­er clean­ing and process val­i­da­tion guide­lines at your man­u­fac­tur­ing sites. And af­ter fail­ing to do so for the third time in four years, the com­pa­ny has re­ceived a warn­ing let­ter.

Drug residue on tablet press­es and a fail­ure to val­i­date the man­u­fac­tur­ing process af­ter equip­ment changes were just two of the is­sues raised by the FDA af­ter an in­spec­tion of a Nov­el Lab­o­ra­to­ries plant that led to the June 11 let­ter.

The FDA said that Nov­el Lab­o­ra­to­ries’ Som­er­set, NJ plant had vi­o­la­tions of cur­rent good man­u­fac­tur­ing prac­tice reg­u­la­tions such as an in­ad­e­quate clean­ing pro­ce­dure and qual­i­ty con­trol pro­ce­dures. It’s the first vi­o­la­tion at this site, but the third in four years for sites with­in the com­pa­ny’s net­work.

Nov­el Labs is a sub­sidiary of Lupin. Two of the com­pa­ny’s sites in In­dia, one in Goa and an­oth­er in Man­dideep, were is­sued warn­ing let­ters in 2017 and 2019, re­spec­tive­ly, for sim­i­lar cGMP vi­o­la­tions. Those two fa­cil­i­ties made prod­ucts that, at the time, made up more than 40% of Lupin’s sales. The com­pa­ny did not re­spond to a re­quest for com­ment by the time of pub­li­ca­tion Thurs­day.

“This is a big neg­a­tive for the com­pa­ny … The warn­ing let­ter will not on­ly de­lay new ap­provals, thus im­pact­ing US rev­enues, but al­so in­crease re­me­di­a­tion cost that will put pres­sure on mar­gins,” bro­ker­age firm Edel­weiss Se­cu­ri­ties said in re­gards to the pre­vi­ous two let­ters.

“Re­peat­ed vi­o­la­tions at mul­ti­ple sites demon­strate that your com­pa­ny’s cor­po­rate over­sight and con­trol over the man­u­fac­ture of drugs is in­ad­e­quate,” the let­ter stat­ed. “You should fur­ther com­pre­hen­sive­ly as­sess your com­pa­ny’s glob­al man­u­fac­tur­ing op­er­a­tions to en­sure that sys­tems and process­es, and ul­ti­mate­ly, the drug prod­ucts man­u­fac­tured, con­form to FDA re­quire­ments at all your sites.”

The qual­i­ty unit failed to es­tab­lish and fol­low writ­ten pro­ce­dures to en­sure the drug was up to stan­dards. The FDA said the clean­ing pro­to­col didn’t have ad­e­quate over­sight, and the com­pa­ny failed to com­plete the re­quired an­nu­al prod­uct re­view. While the com­pa­ny pre­vi­ous­ly made com­mit­ments to strength­en op­er­a­tions and ac­knowl­edged a need for more qual­i­ty unit over­sight, it failed to pro­vide a com­pre­hen­sive as­sess­ment of all writ­ten pro­ce­dures, the let­ter said.

Nov­el Labs is re­quired to fol­low up with re­spons­es to the FDA for the fol­low­ing:

  • A com­pre­hen­sive as­sess­ment and re­me­di­a­tion plan to en­sure its qual­i­ty con­trol unit is giv­en the au­thor­i­ty and re­sources, in­clud­ing a de­ter­mi­na­tion of whether pro­ce­dures used by the firm are ro­bust and ap­pro­pri­ate.
  • A de­ter­mi­na­tion of whether the com­pa­ny’s qual­i­ty con­trol unit has the ad­e­quate ed­u­ca­tion, train­ing, and ex­pe­ri­ence to per­form its du­ties.
  • Pro­vi­sions for qual­i­ty con­trol unit over­sight through­out op­er­a­tions to eval­u­ate ad­her­ence to ap­pro­pri­ate prac­tices
  • A com­plete and fi­nal re­view of each batch and its re­lat­ed in­for­ma­tion be­fore the qual­i­ty con­trol unit dis­po­si­tion de­ci­sion.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Marianne De Backer (L) and Jeff Hatfield

Bay­er nabs star biotech Vi­vid­ion with a $2B buy­out and an ‘arms-length’ pact, pulling a part­ner out of the IPO con­ga line

Vividion is canceling that IPO it filed. Instead of following the industry-wide migration to Nasdaq, the biotech that has captured considerable attention for its still-preclinical work finding cryptic pockets to bind to on proteins is going to work for Bayer now.

The pharma giant is putting out word today that it has bought out Vividion for $1.5 billion in cash and another half-billion dollars in milestones.

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Tadataka Yamada (Photographer: Kiyoshi Ota/Bloomberg via Getty Images)

Sci­ence pi­o­neer, phar­ma re­search chief, glob­al health ad­vo­cate and biotech en­tre­pre­neur Tadata­ka ‘Tachi’ Ya­ma­da has died

Tadataka Yamada, a towering physician-scientist who made his name in academia before transforming drug development at GlaxoSmithKline and developing vaccines for malaria and meningitis at the Gates Foundation, died unexpectedly of natural causes at his home in Seattle Wednesday morning.

He was 76. Frazier Healthcare Partners’ David Socks confirmed his death.

Known widely by the mononym “Tachi,” Yamada had a globetrotting career and arrived in industry relatively late in life. A 2004 Independent article noted GSK had asked Yamada to stay on beyond his approaching 60th birthday, the company’s usual retirement age. Yamada would continue working for the next 17 years, steering the Gates Foundation’s global health division for 6 years, funding Jim Wilson’s gene therapy work when few would touch it, launching Takeda Vaccines and co-founding a series of high-profile biotechs.

UK re-in­ves­ti­gates Pfiz­er's eye-pop­ping price goug­ing on an epilep­sy drug

When a drugmaker raises the price of a drug in the US by more than 2,000% overnight, and without any particular reason for that increase, nothing typically happens to the company. No fines, no court orders, just business as usual.

Martin Shkreli’s decades-old anti-parasitic drug Daraprim was the perfect example — massive price spike on an old drug, lots of media attention, public outcry, Congressional committees dragging his former company through multiple hearings, and at the end of it? Nothing happened to the price or the company (until generic competition came).

Thomas Lingelbach, Valneva CEO

A small vac­cine de­vel­op­er fa­vored by the UK gov­ern­ment in Covid-19 touts a PhI­II first in chikun­gun­ya

Before Valneva garnered the favor of the UK government as a potential supplier of Covid-19 vaccines, the French biotech prided itself on being the first company to bring a chikungunya vaccine into Phase III.

It now has positive pivotal results to back up the breakthrough therapy designation the FDA granted just weeks ago.

There are currently no approved jabs to prevent chikungunya virus infection despite decades of R&D efforts, a fact that underscores just how arduous traditional vaccine development can be, particularly for neglected tropical disease. In a absence of a major commercial market, the US government and NGOs such as CEPI have deployed various grants and incentives to spur on a small crew of academics and industry players, with Merck, via its acquisition of Themis, claiming a spot in that race.

Josh Hoffman, outgoing Zymergen CEO (Zymergen)

UP­DAT­ED: Syn­bio uni­corn Zymer­gen jet­ti­sons found­ing CEO, cuts guid­ance as cus­tomers re­port lead prod­uct does­n't work

Zymergen, just months off a $500 million IPO that put the synthetic bio firm in rarified air, has now ejected its founding CEO and downgraded its revenue forecasts after customers reported its lead film product doesn’t work as advertised, the company said Tuesday afternoon.

CEO Josh Hoffman will leave his role and sacrifice his board seat immediately in favor of Jay Flatley, the former CEO of Illumina who will take the lead role on an interim basis as the company conducts a search for its next leader.

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Zymergen co-founders Zach Serber, Josh Hoffman, and Jed Dean (Zymergen via website)

Zymer­gen's sud­den im­plo­sion shocked biotech. A lin­ger­ing loan could make things even worse

As former synbio unicorn Zymergen picks up the pieces from its spectacular implosion Tuesday, an outstanding loan from Perceptive Advisors — the only blue-chip biotech crossover investor to touch Zymergen’s fundraising efforts — could make the situation worse, according to public documents.

In December 2019, more than a year before Zymergen filed for what would eventually become a $500 million IPO, the “biofacturing” firm signed a $100 million credit facility with Perceptive to help supplement the nearly $700 million the company had raised across four VC rounds.

Am­gen adds new NC plant to the list as part of $1B man­u­fac­tur­ing ex­pan­sion plans state­side

What can $1 billion buy? If you’re Amgen, it’s good for two manufacturing facilities in the US.

The California-based drug giant will invest close to $550 million in a drug substance plant in Holly Springs, NC, adding itself to an ever-growing list of biotech companies that have decided to call North Carolina home, and marking its second drug manufacturing announcement in a little more than a month.

Bio­gen, Ei­sai are push­ing for an­oth­er ac­cel­er­at­ed Alzheimer's OK — this time for BAN2401

Now that the door at the FDA has been opened wide for Alzheimer’s drugs that can demonstrate a reduction in amyloid, Biogen and its partners at Eisai are pushing for a quick OK on the next drug to follow in the controversial path of aducanumab.

In a presentation to analysts, Eisai neurology chief Ivan Cheung outlined some bullish expectations for their newly-approved treatment and set the stage for what he believes will be a fast follow for BAN2401 (lecanemab) — after a dry spell in new drug development that’s lasted close to 20 years.

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