Sus­pend­ed Cal­i­for­nia cell ther­a­py man­u­fac­tur­ing site hit with FDA warn­ing let­ter over ma­jor qual­i­ty con­cerns

A cell ther­a­py out­fit in Cal­i­for­nia that man­u­fac­tures a hu­man um­bil­i­cal cord de­rived cel­lu­lar prod­uct and ex­o­some prod­ucts is fac­ing a warn­ing from the FDA over sev­er­al ma­jor ob­ser­va­tions re­lat­ed to qual­i­ty.

The FDA notes the site’s “de­fi­cient donor screen­ing prac­tices, in­ad­e­quate asep­tic prac­tices, un­val­i­dat­ed man­u­fac­tur­ing,” and the “risk that your prod­ucts may be con­t­a­m­i­nat­ed with mi­croor­gan­isms or have oth­er se­ri­ous prod­uct qual­i­ty de­fects.”

In­vit­rx Ther­a­peu­tics re­ceived the warn­ing let­ter ear­li­er this month for its site in Lake For­est, CA, which was in­spect­ed in March and lat­er halt­ed some man­u­fac­tur­ing.

The let­ter, which had 10 ma­jor ob­ser­va­tions, states that In­vit­rx had failed to de­ter­mine and doc­u­ment the el­i­gi­bil­i­ty of a cell or tis­sue donor based up­on the re­sults of screen­ing and test­ing and not­ed that it had not re­viewed “rel­e­vant med­ical records” it re­ceived from the um­bil­i­cal cord tis­sue sup­pli­ers to de­ter­mine el­i­gi­bil­i­ty.

The let­ter al­so re­vealed that since op­er­a­tions be­gan, In­vit­rx has “failed to de­ter­mine and doc­u­ment the el­i­gi­bil­i­ty of hun­dreds of tis­sue donors.” Tis­sues from these donors were re­port­ed to be used to man­u­fac­ture prod­ucts.

The agency al­so not­ed that In­vit­rx had failed to val­i­date the asep­tic process to man­u­fac­ture sev­er­al of its prod­ucts, with in­ves­ti­ga­tors al­so ob­serv­ing “pri­ma­ry prod­uct con­tain­ers” for items that are sup­posed to be ster­ile be­ing stored on a shelf in an “open bag” in the clean­room. Caps that are re­ceived in bulk al­so did not have fur­ther clean­ing or ster­il­iza­tion.

As for the site’s en­vi­ron­men­tal mon­i­tor­ing pro­ce­dures, the let­ter said that In­vit­rx did not per­form en­vi­ron­men­tal mon­i­tor­ing of its asep­tic pro­cess­ing area or have writ­ten pro­ce­dures in place at the time of in­spec­tion.

Two-year ex­pi­ra­tion dates for some prod­ucts were set with­out sup­port­ing da­ta and in­cu­ba­tors used for “steril­i­ty test­ing” were al­so not qual­i­fied for that use. Sev­er­al oth­er QC is­sues in­volv­ing writ­ten pro­ce­dures and oth­er test­ing were al­so not­ed.

The FDA said that “cor­rec­tive ac­tions” had been tak­en and sus­pend­ed all clin­i­cal drug sub­stance man­u­fac­tur­ing and drug prod­uct batch­es at the Lake For­est fa­cil­i­ty “in­tend­ed for use in do­mes­tic clin­i­cal tri­als.” How­ev­er, this is not en­tire­ly sat­is­fac­to­ry for the FDA.

“It is un­clear from this state­ment whether you have sus­pend­ed the man­u­fac­tur­ing of all prod­ucts iden­ti­fied in the FDA-483. Fur­ther, it is un­clear, based on your re­sponse, whether you will man­u­fac­ture your prod­ucts at any of your oth­er lo­ca­tions for dis­tri­b­u­tion. Your re­sponse al­so de­scribes ‘in­ter­im con­trol[s]’ you plan to im­ple­ment pri­or to com­plet­ing cer­tain cor­rec­tive ac­tions, which sug­gests that In­vit­rx will re­sume man­u­fac­tur­ing pri­or to ad­e­quate­ly ad­dress­ing the ex­ist­ing de­fi­cien­cies,” the let­ter said.

It is al­so not­ed that the FDA can­not ful­ly as­sess the com­pa­ny’s re­spons­es to sev­er­al of the ob­ser­va­tions as they do not pro­vide suf­fi­cient de­tails on the “cor­rec­tive ac­tions,” and they lack a time­line for the com­ple­tion of all the ac­tions. The re­sponse al­so does not prop­er­ly ad­dress the fail­ure to have an IND in ef­fect for clin­i­cal in­ves­ti­ga­tions of In­vit­rx’s prod­ucts. How­ev­er, In­vit­rx is com­mit­ted to re­call­ing dis­trib­uted prod­ucts.

In­vit­rx has been pulled in­to a “reg­u­la­to­ry meet­ing” with the FDA to dis­cuss the steps that have been tak­en since the March in­spec­tion. The meet­ing is on the books for the mid­dle of De­cem­ber.

End­points News reached out to In­vit­rx for a state­ment on the let­ter but did not re­ceive a re­sponse by press time.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; 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.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

CBER Director Peter Marks (Susan Walsh/AP Images)

FDA ad­vi­so­ry com­mit­tee votes unan­i­mous­ly in fa­vor of bi­va­lent Covid shots re­plac­ing pri­ma­ry se­ries

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all current vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

The vote marks an effort to clear up confusion around varying formulations and dosing schedules for current primary series and booster vaccines, as well as “get closer to the strains that are circulating,” according to committee member Paul Offit, professor of pediatrics at the Children’s Hospital of Philadelphia.

FDA re­ports ini­tial 'no sig­nal' for stroke risk with Pfiz­er boost­ers, launch­es con­comi­tant flu shot study

The FDA hasn’t detected any potential safety signals, including for stroke, in people aged 65 years and older who have received Pfizer’s bivalent Covid booster, one senior official told members of the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Thursday.

The update comes as the FDA and CDC investigate a “preliminary signal” that may indicate an increased risk of ischemic stroke in older Americans who received Pfizer’s updated shot.

FDA cuts off use for As­traZeneca’s Covid-19 ther­a­py Evusheld

The FDA has stopped use of another drug as a result of the new coronavirus variants. On Thursday, the agency announced that AstraZeneca’s antibody combo Evusheld, which was an important prevention option for many immunocompromised people and others, is no longer authorized.

The FDA said it made its decision based on the fact that Evusheld works on fewer than 10% of circulating variants.

Evusheld was initially given emergency authorization at the end of 2021. However, as Omicron emerged, so did studies that showed Evusheld might not work against the dominant Omicron strain. In October, the FDA warned healthcare providers that Evusheld was useless against the Omicron subvariant BA.4.6. It followed that up with another announcement earlier this month that it did not think Evusheld would work against the latest Omicron subvariant XBB.1.5.

Rodney Rietze, iVexSol CEO

Bris­tol My­ers, Charles Riv­er join Se­ries A fund­ing for iVex­Sol

Massachusetts-based iVexSol has secured funding to the tune of $23.8 million in its latest Series A round. The new investors include Bristol Myers Squibb, manufacturer Charles River Laboratories and Asahi Kasei Medical.

iVexSol is a manufacturer of lentiviral vectors (LVV), used in making gene therapies, and this latest round of fundraising brings its total Series A total over $39 million, which will be used to recruit more employees and bolster its technology.

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John Rim, Samsung Biologics CEO (Samsung/PR Newswire)

Sam­sung Bi­o­log­ics spells out ex­pan­sion plans in South Ko­rea and US

The CDMO arm of one of South Korea’s largest conglomerates has posted its year-end results and plans for 2023, which include new construction.

Samsung Biologics netted north of KRW 3 trillion ($2.4 billion) in 2022 revenue and an operating profit of KRW 983.6 billion ($799 million), which the company touted on Friday as “record-high earnings.” The revenue boost was 55% compared to 2021.