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

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.

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