FDA slaps warn­ing let­ter on Min­neso­ta API fa­cil­i­ty af­ter em­ploy­ee de­stroys clean­ing log

A man­u­fac­tur­ing fa­cil­i­ty be­long­ing to the Nether­lands-based API pro­duc­er Fa­gron Group has en­tered the FDA’s crosshairs af­ter an em­ploy­ee de­stroyed a clean­ing log, among oth­er vi­o­la­tions.

One of its plants in Saint Paul, MN re­ceived a warn­ing let­ter on June 14, fol­low­ing an in­spec­tion last No­vem­ber that un­cov­ered cross-con­t­a­m­i­na­tion con­cerns.

“In your re­sponse, you pro­vid­ed a fol­low-up clean­ing val­i­da­tion re­port in which you on­ly as­sessed the car­ry­over of niacin swab sam­ples but not prog­es­terone, which was in­clud­ed in your ini­tial clean­ing val­i­da­tion,” FDA says in the let­ter. “The lack of prog­es­terone (b)(4) [com­mer­cial­ly con­fi­den­tial in­for­ma­tion] is con­cern­ing con­sid­er­ing the fail­ing residue re­sults you pro­vid­ed to in­ves­ti­ga­tors would yield un­ac­cept­able lev­els of prog­es­terone cross-con­t­a­m­i­na­tion.”

The site al­so failed to demon­strate that it was prop­er­ly clean­ing its fa­cil­i­ty, ac­cord­ing to FDA.

“Dur­ing your API repack­ag­ing and re­la­bel­ing op­er­a­tions, in­clud­ing high­ly po­tent drugs such as testos­terone, estra­di­ol, be­tametha­sone, ta­mox­ifen and opi­oids, your firm failed to con­duct ad­e­quate clean­ing val­i­da­tion stud­ies to demon­strate that your clean­ing pro­ce­dures for your non-ded­i­cat­ed “cab­ins” (pro­duc­tion rooms) are ad­e­quate to pre­vent po­ten­tial cross-con­t­a­m­i­na­tion,” the let­ter says.

The let­ter al­so stat­ed that an em­ploy­ee de­stroyed a log on when clean­ing at cer­tain parts of the site oc­curred, and the firm was un­able to pro­vide a copy to in­ves­ti­ga­tors.

“In­ves­ti­ga­tors al­so ob­served that the clean­ing log for Cab­in (b)(4) was (b)(4) dur­ing repack­ag­ing of li­do­caine HCl, even though the clean­ing ac­tiv­i­ties had not been ini­ti­at­ed. You lat­er stat­ed that an em­ploy­ee de­stroyed the clean­ing log and were un­able to pro­vide a copy to our in­ves­ti­ga­tors,” the let­ter says.

The FDA al­so found the com­pa­ny’s re­sponse in­ad­e­quate be­cause of a fail­ure to demon­strate that clean­ing pro­ce­dures were able to pre­vent cross-con­t­a­m­i­na­tion of repack­aged API.

An­oth­er ma­jor ob­ser­va­tion iden­ti­fied is the plant failed to ad­e­quate­ly in­ves­ti­gate and doc­u­ment out-of-spec­i­fi­ca­tion re­sults and cor­rect these ac­tions.

For ex­am­ple, the let­ter states that the com­pa­ny did not ini­ti­ate an in­ves­ti­ga­tion in­to OOS biobur­den counts from its wa­ter sys­tem, which is used as a drug com­po­nent and no in­ves­ti­ga­tion was launched in­to wa­ter test re­sults.

Ad­di­tion­al­ly, the com­pa­ny’s qual­i­ty unit failed to per­form sev­er­al crit­i­cal func­tions to en­sure that repacked APIs meet CGMP re­quire­ments. For ex­am­ple, in­ves­ti­ga­tors ob­served com­put­ers con­nect­ed to cGMP-re­lat­ed lab­o­ra­to­ry equip­ment al­lowed changes to or dele­tion of da­ta gen­er­at­ed to sup­port the re­lease of drugs with­out re­stric­tion.

Fur­ther­more, dur­ing the in­spec­tion, the com­pa­ny ac­knowl­edged that its qual­i­ty unit did not qual­i­fy for the con­tract lab­o­ra­to­ries it used to sup­port prod­uct re­leas­es due to re­source is­sues.

The FDA rec­om­mend­ed that these pro­ce­dures be fixed as soon as pos­si­ble, and the com­pa­ny had 15 days from June 14 to re­spond to the let­ter. Fail­ure to ad­dress any of these de­vi­a­tions may cause the FDA to with­hold the is­suance of ex­port cer­tifi­cates or ap­proval of any new ap­pli­ca­tions or sup­ple­ments list­ing Fa­gron as a drug man­u­fac­tur­er un­til any de­vi­a­tions are com­plete­ly ad­dressed and con­firm com­pli­ance. A re-in­spec­tion may al­so be on the cards.

End­points News reached out to Fa­gron for com­ment but has not yet re­ceived a re­sponse to the in­quiry.

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