Got­tlieb, Marks de­tail plans to ad­vance de­vel­op­ment of cell and gene ther­a­pies

FDA Com­mis­sion­er Scott Got­tlieb and Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search (CBER) Di­rec­tor Pe­ter Marks on Tues­day de­tailed plans for the agency to keep pace with an ex­pect­ed in­flux of ap­pli­ca­tions for cell and gene ther­a­pies over the com­ing years.

“The FDA is wit­ness­ing a surge of cell and gene ther­a­py prod­ucts en­ter­ing ear­ly de­vel­op­ment, ev­i­denced by a large up­swing in the num­ber of in­ves­ti­ga­tion­al new drug (IND) ap­pli­ca­tions,” Got­tlieb and Marks say.

Scott Got­tlieb

By 2020, Got­tlieb and Marks say they ex­pect to be re­ceiv­ing up­wards of 200 INDs for cell and gene ther­a­pies each year, adding to the 800 ac­tive INDs for such prod­ucts al­ready filed with the agency. By 2025, they pre­dict the agency will be ap­prov­ing be­tween 10 and 20 cell and gene ther­a­py prod­ucts an­nu­al­ly.

The two FDA lead­ers draw a com­par­i­son be­tween the cur­rent land­scape for cell and gene ther­a­pies to the pro­lif­er­a­tion of an­ti­body drugs in the late 1990s once plat­forms for cre­at­ing an­ti­bod­ies that wouldn’t be re­ject­ed by a pa­tient’s im­mune sys­tem were wide­ly avail­able.

“In this case, it was the ad­vent of safe and ef­fec­tive vec­tors for the de­liv­ery of gene ther­a­py prod­ucts, such as the adop­tion of ade­no-as­so­ci­at­ed virus (AAV) vec­tors,” Got­tlieb and Marks say.

Pe­ter Marks

To pro­mote the con­tin­ued de­vel­op­ment of new cell and gene ther­a­pies, Got­tlieb and Marks say that the FDA will take a num­ber of steps, in­clud­ing adding as many as 50 ad­di­tion­al re­view­ers to its staff, lever­ag­ing ex­pe­dit­ed path­ways, is­su­ing new guid­ance and tak­ing en­force­ment ac­tion against clin­ics that fail to com­ply with FDA reg­u­la­tions.

Ac­cord­ing to Got­tlieb and Marks, ac­cel­er­at­ed ap­proval is par­tic­u­lar­ly rel­e­vant for gene ther­a­pies as the agency can man­date post­mar­ket stud­ies to mea­sure the dura­bil­i­ty of the treat­ment and long-term safe­ty is­sues that would be dif­fi­cult to ad­dress in the pre­mar­ket set­ting.

As for new guid­ance, Got­tlieb and Marks say the agency will de­vel­op a se­ries of clin­i­cal guid­ance doc­u­ments for dif­fer­ent ar­eas of prod­uct de­vel­op­ment, such as gene ther­a­pies for in­her­it­ed blood dis­or­ders and neu­rode­gen­er­a­tive dis­eases.

In some cas­es, Got­tlieb and Marks say that a more tra­di­tion­al ap­proach to drug de­vel­op­ment may be war­rant­ed for cer­tain gene ther­a­pies, such as those in­tend­ed to ad­dress the symp­toms of a neu­rode­gen­er­a­tive dis­ease or tar­get an “ex­pres­sion of a pro­tein or en­zyme be­lieved to play a role in the ad­vance of the dis­ease.”

In an­oth­er planned guid­ance, Got­tlieb and Marks say the agency will tack­le the man­u­fac­tur­ing com­plex­i­ties of cell-based gene ther­a­pies, such as chimeric anti­gen re­cep­tor (CAR) T-cell ther­a­pies, in a fu­ture guid­ance.

“The guid­ance that we in­tend to is­sue will pro­mote a bet­ter un­der­stand­ing of the crit­i­cal qual­i­ty at­trib­ut­es and oth­er fac­tors re­lat­ed to prod­uct man­u­fac­tur­ing,” they write, adding that one of their goals will be to min­i­mize the need for bridg­ing stud­ies for mi­nor man­u­fac­tur­ing changes for cell ther­a­pies.

The two al­so say that the FDA will is­sue a guid­ance lat­er this year out­lin­ing how re­searchers can “pool their clin­i­cal da­ta af­ter fol­low­ing a com­mon man­u­fac­tur­ing pro­to­col, and there­by de­vel­op a more ro­bust da­ta set for pur­pos­es of gain­ing a [Bi­o­log­ics Li­cense Ap­pli­ca­tion] BLA.”

First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email for more in­for­ma­tion.

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A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at with any issues.

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