FDA, NIH look to stream­line over­sight of gene ther­a­pies

The FDA and NIH are propos­ing to fur­ther lim­it the role of the NIH and its Re­com­bi­nant DNA Ad­vi­so­ry Com­mit­tee (RAC) in the re­view of hu­man gene ther­a­pies.

The changes, an­nounced in the Fed­er­al Reg­is­ter on Thurs­day, are aimed at re­duc­ing over­laps in the two agen­cies’ over­sight of gene ther­a­pies which re­sult in du­plica­tive work for spon­sors as the field pro­gress­es fol­low­ing the ap­proval of the first three gene ther­a­pies last year.

Scott Got­tlieb

In an ac­com­pa­ny­ing per­spec­tive by FDA Com­mis­sion­er Scott Got­tlieb and NIH Di­rec­tor Fran­cis Collins in the New Eng­land Jour­nal of Med­i­cine, the two agency heads write that there is no longer a com­pelling need to sub­ject gene ther­a­pies to ad­di­tion­al over­sight com­pared to oth­er types of bio­med­ical prod­ucts.

“In the view of the se­nior lead­ers of the FDA and the NIH, there is no longer suf­fi­cient ev­i­dence to claim that the risks of gene ther­a­py are en­tire­ly unique and un­pre­dictable—or that the field still re­quires spe­cial over­sight that falls out­side our ex­ist­ing frame­work for en­sur­ing safe­ty,” they write.

Cur­rent­ly, spon­sors of clin­i­cal tri­als in­volv­ing gene ther­a­pies are re­quired to sub­mit ini­tial pro­to­cols, an­nu­al re­ports, amend­ments and se­ri­ous ad­verse event re­ports to both agen­cies.

Fran­cis Collins

His­tor­i­cal­ly, the RAC al­so played a role in re­view­ing gene ther­a­py pro­to­cols and safe­ty da­ta aris­ing from such stud­ies, though in 2016 the NIH lim­it­ed the com­mit­tee’s role to pro­to­cols “that raised ex­cep­tion­al is­sues or con­cerns” based on a rec­om­men­da­tion from the In­sti­tute of Med­i­cine. Ac­cord­ing to the NIH, the RAC has on­ly re­viewed three of the 275 gene ther­a­py pro­to­cols sub­mit­ted since that change took ef­fect.

How­ev­er, un­der the FDA and NIH’s pro­pos­al, the RAC’s role in re­view­ing gene ther­a­py pro­to­cols would be en­tire­ly elim­i­nat­ed and spon­sors would no longer be re­quired to sub­mit re­ports to NIH on such pro­to­cols.

Ad­di­tion­al­ly, the NIH says it will re­vise the roles of In­sti­tu­tion­al Biosafe­ty Com­mit­tees (IBCs), which are tasked with lo­cal over­sight of stud­ies in­volv­ing re­com­bi­nant or syn­thet­ic nu­cle­ic acid mol­e­cules, to en­sure their over­sight of hu­man gene ther­a­py pro­to­cols is con­sis­tent with oth­er re­search sub­ject to the NIH Guide­lines.

Ac­cord­ing to Got­tlieb and Collins, ad­vances in the gen­er­al frame­work for clin­i­cal tri­al and med­ical prod­uct over­sight and the cre­ation of Clin­i­cal­Tri­als.gov have re­duced the need for spe­cial over­sight for gene ther­a­pies.

The two al­so cite oth­er ef­forts, such as re­vi­sions to the Com­mon Rule and the FDA’s re­lease of draft guid­ance on man­u­fac­tur­ing is­sues, long-term fol­low up and clin­i­cal de­vel­op­ment path­ways for gene ther­a­pies, as re­duc­ing the need for spe­cial over­sight of gene ther­a­py pro­to­cols by the NIH.

“Even as our un­der­stand­ing of gene ther­a­py has ad­vanced, so has our gen­er­al frame­work for med­ical prod­uct safe­ty. The tools we use to ad­dress oth­er ar­eas of sci­ence are now well suit­ed to gene ther­a­py,” they write.

Go­ing for­ward, the NIH says the RAC will con­tin­ue to func­tion as an ad­vi­so­ry board to the NIH on emerg­ing fields such as gene edit­ing, syn­thet­ic bi­ol­o­gy and neu­rotech­nol­o­gy.


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 news@raps.org for more in­for­ma­tion. 

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