Two CRLs lat­er, Illi­nois-based CD­MO hit with FDA warn­ing let­ter over 's­pore-form­ing' bac­te­ria and fun­gi

Dupo, IL-based con­tract man­u­fac­tur­er Ster­ling Phar­ma­ceu­ti­cals has had a long, tough year.

Last Sep­tem­ber, part­ner Ver­ri­ca Phar­ma­ceu­ti­cals’ NDA for a po­ten­tial skin dis­ease treat­ment was hit with a sec­ond CRL, with the com­pa­ny pin­ning the prob­lems on Ster­ling. Eight months lat­er, Ver­ri­ca was hit with a third CRL due to fur­ther is­sues at Ster­ling, fol­low­ing a Feb­ru­ary rein­spec­tion by FDA of the Ster­ling site.

Now, de­tails of that rein­spec­tion are com­ing to light in a new warn­ing let­ter pub­lished this week by FDA which rais­es ma­jor con­cerns about the way the site is de­signed and how it op­er­ates.

Chief among them were con­t­a­m­i­na­tion-re­lat­ed risks and “rou­tine­ly iden­ti­fied poor asep­tic be­hav­ior by per­son­nel,” with FDA find­ing that the com­pa­ny’s in­ves­ti­ga­tions in­to con­t­a­m­i­na­tion is­sues “were in­ad­e­quate be­cause they did not thor­ough­ly ad­dress the per­sis­tent ad­verse trend of mi­croor­gan­isms re­cov­ered from ISO 5 ar­eas, in­clud­ing spore-form­ing bac­te­ria and fun­gi.”

While Ster­ling told FDA that it con­duct­ed a ret­ro­spec­tive eval­u­a­tion of all mi­cro­bi­o­log­i­cal mon­i­tor­ing re­sults be­tween Jan­u­ary 2021 and March 2022, “and con­clud­ed that there was no im­pact to the lots pre­vi­ous­ly re­leased,” the FDA says the re­sponse was not ad­e­quate and that the firm

failed to con­sid­er that per­sis­tent­ly de­fi­cient en­vi­ron­men­tal con­trols are like­ly root­ed in fun­da­men­tal fa­cil­i­ty or equip­ment de­sign flaws. In ad­di­tion to line de­sign haz­ards that fun­da­men­tal­ly com­pro­mise asep­tic pro­cess­ing, you per­formed makeshift line mod­i­fi­ca­tion with­in the ISO 5 ar­eas us­ing ma­te­ri­als that can har­bor biobur­den.

On a more ba­sic lev­el, Ster­ling iden­ti­fied its asep­tic pro­cess­ing lines as Re­strict­ed Ac­cess Bar­ri­er Sys­tems (RABS), but the FDA says those lines lacked “fun­da­men­tal el­e­ments of a valid RABS de­sign in­clud­ing glove ports which are em­ployed to re­duce or elim­i­nate di­rect op­er­a­tor in­ter­ven­tions in­to the ISO 5 crit­i­cal area.”

The agency al­so notes how on Ju­ly 7, 2021, Ster­ling de­tect­ed a steril­i­ty fail­ure, with a lot of a redact­ed prod­uct con­t­a­m­i­nat­ed with the gram-neg­a­tive bac­teri­um, Herbaspir­il­lum aquaticum.

“Non-ster­ile oph­thalmic drugs pose un­ac­cept­able risks to pa­tients,” FDA adds. “We ac­knowl­edge that you re­ject­ed this lot, how­ev­er your in­ves­ti­ga­tion failed to con­sid­er that this steril­i­ty fail­ure, in con­junc­tion with your ad­verse EM [en­vi­ron­men­tal mon­i­tor­ing] trends, may be in­dica­tive of con­t­a­m­i­na­tion risks from the ba­sic de­sign of your pro­cess­ing lines and could im­pact oth­er batch­es.”

The FDA al­so sought to make clear that while steril­i­ty tests are crit­i­cal for qual­i­ty con­trol when it comes to asep­ti­cal­ly processed prod­ucts that pur­port to be ster­ile, the tests

can­not be sole­ly re­lied up­on as jus­ti­fi­ca­tion to re­lease drug prod­uct batch­es as the test is on­ly the last in a se­ries of de­sign pro­vi­sions and con­trols in­tend­ed to pro­tect the con­sumer from dis­tri­b­u­tion of an un­safe batch. Any fin­ished prod­uct pos­i­tive steril­i­ty test re­sults rep­re­sent a se­ri­ous CGMP is­sue re­quir­ing prompt and com­pre­hen­sive in­ves­ti­ga­tion. Fur­ther­more, your firm’s ab­sence of strict ad­her­ence to prop­er de­sign, asep­tic meth­ods, and en­vi­ron­men­tal con­trols un­der­mine your dai­ly as­sur­ance of con­sis­tent ster­ile man­u­fac­tur­ing.”

Tom Riga, Spectrum Pharmaceuticals CEO

Spec­trum im­plodes af­ter a harsh pub­lic slap­down and now a CRL from Richard Paz­dur

The FDA has gone out of its way several times to flatten any expectations for Spectrum’s lung cancer drug poziotinib, including slamming the regulatory door in the biotech’s face four years ago when the their executive crew came calling for a breakthrough drug designation and encouragement from the oncology wing of the FDA.

That stinging early rebuke pointed straight down the path to a corrosive in-house agency review of Spectrum’s attempt to land an accelerated approval for the oral EGFR TKI and a public whipping that included a classic takedown by none other than Richard Pazdur, who slammed the company for “poor drug development” that led to confusion over the dose needed for a slice of NSCLC patients harboring HER2 exon 20 insertion mutations.

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Sta­da to place $50M+ in­vest­ment in a new fa­cil­i­ty in Ro­ma­nia

While Romania may conjure up images of vast mountain ranges and tales of medieval kings, one generic manufacturer has broken ground on a new facility there.

German pharma company Stada said Monday that it has placed a €50 million ($51.9 million) investment into a 100,000 square-meter (1.08 million square-foot) site in Turda, Romania, a city in the Southeast of the country. According to a Stada spokesperson in an email to Endpoints News, the company has developed only 281,500 square feet of the site so far.

Vac­cine doc­u­ments, young lead­ers and mar­ket tur­moil: End­points' 10 biggest sto­ries of 2022

It’s been a volatile year in the world of biopharma. Market declines reset M&A valuations, and may be beginning to tempt bigger buyers back into dealmaking. Russia’s war in Ukraine disrupted drug sales and clinical trials. A new generation of young biotech leaders emerged in the Endpoints 20(+1) Under 40. And as capital runs dry in a tough environment for raising new funds, companies big and small are taking a look at their headcounts and operations for ways to make it through lean times.

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FDA tells Catal­ent to fix is­sues at two man­u­fac­tur­ing sites on its own

The CDMO Catalent will have to fix issues at two manufacturing plants in the US and Europe that were subject to inspections by the FDA this summer, giving the company room to correct the issues without facing further regulatory action.

The FDA gave Catalent a “voluntary action indicated” response to two inspections at the contract manufacturer’s site in Bloomington, IN, and Brussels, Belgium. Fixing the issues on its own is a preferable outcome to facing an “official action indicated” response, meaning that an official warning would be sent out or a sit-down with the FDA would be required.

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Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; 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.

As you start planning for #JPM23, we hope you will consider joining Endpoints News for our live and virtual events. For those who are celebrating Thanksgiving, we hope you are enjoying the long weekend with loved ones. And if you’re not — we’ll see you next week!

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Albert Bourla, Pfizer CEO (John Thys/POOL/AFP via Getty Images)

Pfiz­er CEO un­der fire from UK watch­dog over vac­cine com­ments — re­port

Pfizer CEO Albert Bourla told the BBC last December that he had “no doubt in my mind that the benefits, completely, are in favor” of vaccinating 5- to 11-year-olds for Covid-19. Almost a year later, those comments have reportedly landed him in trouble with a UK pharma watchdog.

Children’s advocacy group UsForThem filed a complaint with the UK’s Prescription Medicines Code of Practice Authority (PMCPA) last year accusing Bourla of making “disgracefully misleading” statements during the BBC interview, including one that “Covid in schools is thriving.” At the time, UK regulators had not yet cleared the vaccine for the 5 to 11 age group, though the vaccine did have a positive opinion from the EMA’s human medicines committee.

In­dus­try groups, CVS pick apart FDA's pro­posed path­way for gener­ics to carve out OTC in­di­ca­tions

Pharma industry groups like the Association for Accessible Medicines (AAM) and PhRMA are raising pointed questions about an FDA plan to create a new pathway for marketing prescription drugs with an additional condition for nonprescription use (ACNU), which would require more safeguards than the current OTC pathway but essentially carve out new OTC uses for some generic drugs.

Chief among the concerns were: Insurance companies dropping coverage for the Rx version, new ACNU patents to block competition, and industry essentially governing the pathway.

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Robert Califf, FDA commissioner (Jose Luis Magana/AP Images)

Fourth ac­cel­er­at­ed ap­proval in Duchenne? Sarep­ta gets pri­or­i­ty re­view for gene ther­a­py amid FDA scruti­ny

Sarepta is once again on the accelerated approval path for a Duchenne drug, picking up a priority review Monday morning.

The FDA granted the accelerated review to SRP-9001, Sarepta announced Monday, which would become the biotech’s fourth Duchenne drug if approved. Much like SRP-9001 will do, each of the previous three therapies went through the accelerated approval pathway. But unlike the others, SRP-9001 is a gene therapy.

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Sanofi's new headquarters, La Maison Sanofi, in Paris (Credit: Luc Boegly)

Sanofi wel­comes 500 staffers to new Paris HQ af­ter €30M ren­o­va­tion

When Paul Hudson took the helm at Sanofi back in 2019, he promised to reinvent the pharma giant — including its Paris headquarters. This week, the company set up shop in new “state-of-the-art” digs.

La Maison Sanofi, as the new HQ is called, is officially open for business, Hudson announced on Monday. The 9,000-square-meter (just under 97,000-square-foot) space accommodates 500 employees across the company’s government and global support functions teams, including finance, HR, legal and corporate affairs — and it was built with environmental sustainability and hybrid work in mind.