FDA guides on Covid-19 considerations in cell and gene therapy – Endpoints News

Man­u­fac­tur­ers of cell and gene ther­a­pies have a new guid­ance from the FDA that pro­vides pan­dem­ic-re­lat­ed man­u­fac­tur­ing con­sid­er­a­tions.

The guid­ance specif­i­cal­ly ad­dress­es both li­censed and in­ves­ti­ga­tion­al cell and gene ther­a­py (CGT) man­u­fac­ture, and “is in­tend­ed to sup­ple­ment the rec­om­men­da­tions to drug and bi­o­log­i­cal prod­uct man­u­fac­tur­ers pro­vid­ed in FDA’s ‘Good Man­u­fac­tur­ing Prac­tice Con­sid­er­a­tions for Re­spond­ing to COVID-19 In­fec­tion in Em­ploy­ees in Drug and Bi­o­log­i­cal Prod­ucts Man­u­fac­tur­ing; Guid­ance for In­dus­try’ is­sued in June 2020,” ac­cord­ing to the guid­ance.

In­dus­try-spe­cif­ic is­sues ad­dressed in the guid­ance in­clude cells and tis­sues re­cov­ered from donors and the par­tic­u­lar meth­ods by which a CGT prod­uct will be man­u­fac­tured, such as cell ex­pan­sion, vi­ral re­duc­tion steps, and for­mu­la­tion. The guid­ance ap­plies to CGT prod­ucts reg­u­lat­ed as drugs and bi­o­log­ic prod­ucts alike, but not to de­vices or hu­man cells, tis­sues, and cel­lu­lar- or tis­sue-based prod­ucts (HCT/Ps) reg­u­lat­ed un­der sec­tion 361 of the PHS Act.

There has been no known con­t­a­m­i­na­tion of HCT/Ps with SARS-CoV-2, the virus that caus­es COVID-19, not­ed the agency. Fur­ther, res­pi­ra­to­ry virus­es are not gen­er­al­ly con­sid­ered to be trans­mit­ted through use of HCT/Ps. “How­ev­er, as not­ed in FDA’s June 2020 GMP Guid­ance, (Ref. 1), SARS-CoV-2 is a nov­el coro­n­avirus and, to en­sure com­pli­ance with cur­rent good man­u­fac­tur­ing prac­tice (CGMP) re­quire­ments, CGT man­u­fac­tur­ers are ex­pect­ed to eval­u­ate whether it pos­es new risks in the con­text of their spe­cif­ic prod­ucts, fa­cil­i­ties, process­es, and man­u­fac­tur­ing con­trols.”

A key con­sid­er­a­tion for risk as­sess­ment is the po­ten­tial for ac­ci­den­tal ex­pan­sion of SARS-CoV-2 virus dur­ing cell cul­ture of au­tol­o­gous or al­lo­gene­ic cells, if they were in­fect­ed with the virus. This, wrote FDA, could re­sult in “a fi­nal prod­uct with am­pli­fied SAR-CoV-2 vi­ral load.” Al­lo­gene­ic prod­ucts, es­pe­cial­ly those com­ing from cell banks, may car­ry high­er risk than au­tol­o­gous prod­ucts, for ex­am­ple.

FDA ad­vis­es con­tin­u­a­tion of rou­tine screen­ing mea­sures for donor as­sess­ment. The con­sid­er­a­tions FDA puts for­ward are based on “lim­it­ed in­for­ma­tion,” but in­clude whether an al­lo­gene­ic or au­tol­o­gous donor has, in the 28 days pre­ced­ing cell or tis­sue re­cov­ery, been in close con­tact with a Covid-19-in­fect­ed in­di­vid­ual, or been di­ag­nosed with or had a pos­i­tive test for Covid-19.

FDA con­tin­ues to rec­om­mend against screen­ing asymp­to­matic donors for SAR-CoV-2. How­ev­er, an au­tho­rized, cleared, or ap­proved test may be used as part of a risk mit­i­ga­tion strat­e­gy in CGT prod­uct man­u­fac­ture. “At this time, FDA rec­om­mends that es­tab­lish­ments not screen for or de­fer HCT/P donors who have been vac­ci­nat­ed against COVID-19 with non-repli­cat­ing, in­ac­ti­vat­ed, or RNA-based COVID-19 vac­cines,” added the agency in the guid­ance.

In terms of cel­lu­lar and tis­sue source ma­te­r­i­al, FDA should con­sid­er what is known about coro­n­avirus­es in gen­er­al and SARS-CoV-2 in par­tic­u­lar, in­clud­ing its propen­si­ty to prop­a­gate in par­tic­u­lar tis­sues. This is an evolv­ing area, and man­u­fac­tur­ers should cite the sci­en­tif­ic lit­er­a­ture and pro­vide jus­ti­fi­ca­tion for risk as­sess­ment and mit­i­ga­tion.

Man­u­fac­tur­ing con­sid­er­a­tions in­clude re­duc­ing con­t­a­m­i­na­tion risk through good em­ploy­ee san­i­ta­tion and health prac­tices. The guid­ance points out that SARS-CoV-2 “has been shown to be ca­pa­ble of in­fect­ing and repli­cat­ing in cells com­mon­ly used for vec­tor pro­duc­tion (e.g., HEK293 and Vero cells),” a fact that man­u­fac­tur­ers should weigh in risk as­sess­ment and in for­mu­lat­ing mit­i­ga­tion strate­gies.

No par­tic­u­lar ma­te­r­i­al test­ing rec­om­men­da­tions are in the guid­ance, but FDA does rec­om­mend ful­ly meet­ing CGMP re­quire­ments in­clud­ing ap­proval of all eval­u­a­tions by the man­u­fac­tur­er’s qual­i­ty unit and doc­u­men­ta­tion in the qual­i­ty man­age­ment sys­tem.

FDA has made the guid­ance im­me­di­ate­ly ef­fec­tive dur­ing the pub­lic health emer­gency of the Covid-19 pan­dem­ic, but the agency is still ac­cept­ing pub­lic com­ments on the guid­ance at any point.

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