Trans­paren­cy: FDA to re­lease more in­fo on pre­mar­ket re­views

The FDA on Wednes­day sought com­ments on a new ef­fort to pro­vide more clar­i­ty on the agency’s phar­ma­ceu­ti­cal ap­pli­ca­tion re­view and de­ci­sion-mak­ing process.

FDA high­light­ed two ef­forts for which it’s seek­ing fur­ther com­ment: A fledg­ling pi­lot pro­gram launched in Jan­u­ary 2018 that sought to pro­vide more trans­paren­cy on spon­sors’ clin­i­cal study re­ports (CSRs) but on­ly re­sult­ed in the re­lease of one CSR, and a new in­te­grat­ed re­view tem­plate, cur­rent­ly be­ing im­ple­ment­ed, that can bet­ter con­vey the FDA’s analy­sis and de­ci­sion-mak­ing in drug ap­provals.

Be­cause of the is­sues as­so­ci­at­ed with the CSR pi­lot (the FDA notes that Janssen was the on­ly spon­sor that agreed to par­tic­i­pate), the agency is con­sid­er­ing whether to fo­cus its ef­forts to bet­ter com­mu­ni­cate the ba­sis for drug ap­provals on the de­vel­op­ment of these new in­te­grat­ed re­view doc­u­ments, rather than on the re­lease of CSRs.

To il­lus­trate the new in­te­grat­ed re­view tem­plate, which has three main com­po­nents — an ex­ec­u­tive sum­ma­ry (in­clud­ing FDA’s ben­e­fit-risk de­ter­mi­na­tion), an in­ter­dis­ci­pli­nary as­sess­ment, and ap­pen­dices (con­tain­ing as­sess­ments and analy­ses that are sup­port­ive to key facts/da­ta) — FDA rewrote the orig­i­nal re­view for Mer­ck’s Pifel­tro (do­ravirine) and Del­stri­go (do­ravirine, lamivu­dine, and teno­fovir diso­prox­il fu­marate) to pro­vide an ex­am­ple.

“This new re­view tem­plate would re­place the cur­rent doc­u­men­ta­tion where each dis­ci­pline pro­vides a sep­a­rate ap­pli­ca­tion re­view doc­u­ment. The up­dat­ed tem­plate would be a col­lab­o­ra­tive doc­u­ment with in­put from clin­i­cal, clin­i­cal phar­ma­col­o­gy, bio­sta­tis­tics, tox­i­col­o­gy re­view­ers, and oth­er dis­ci­plines based up­on the is­sues raised by the ap­pli­ca­tion. FDA be­lieves this pro­gram will al­so meet the goal of ef­fec­tive­ly com­mu­ni­cat­ing the ba­sis for new drug ap­provals,” the agency said.

The new re­view process and tem­plate were de­vel­oped un­der the New Drugs Reg­u­la­to­ry Pro­gram Mod­ern­iza­tion, which is part of an ef­fort to en­hance the new drugs reg­u­la­to­ry pro­gram through 2020. Oth­er ini­tia­tives re­lat­ed to this mod­ern­iza­tion deal with speed­ing IND re­views, new post-mar­ket safe­ty man­age­ment process­es, new staffing process­es and re­struc­tur­ing the clin­i­cal of­fices and di­vi­sions with­in FDA’s Of­fice of New Drugs.

“The pro­posed changes in­crease the num­ber of of­fices that over­see our re­view di­vi­sions from six to eight – and in­creas­es the num­ber of clin­i­cal re­view di­vi­sions from our cur­rent 18 di­vi­sions to 26 plus sev­en di­vi­sions of phar­ma­col­o­gy/tox­i­col­o­gy,” the FDA said.

And as far as trans­paren­cy at the agency goes, when for­mer FDA Com­mis­sion­er Scott Got­tlieb an­nounced the CSR pi­lot, he al­so men­tioned the pos­si­bil­i­ty of re­leas­ing cer­tain redact­ed com­plete re­sponse let­ters (CRLs) to help in­form the pub­lic about how a drug was re­ject­ed by the agency. But the FDA has not fur­ther dis­cussed the re­lease of CRLs.

In terms of what the FDA wants to hear from stake­hold­ers on the new in­te­grat­ed re­view and tem­plate, the agency asks:

  1. How does the new for­mat of the in­te­grat­ed re­view in­form your knowl­edge of FDA’s ba­sis for mak­ing de­ci­sions?
  2. How does the us­abil­i­ty and ac­ces­si­bil­i­ty of in­for­ma­tion in the new in­te­grat­ed re­view com­pare to the orig­i­nal re­view post­ed on FDA’s web­site?
  3. How could the in­for­ma­tion pro­vid­ed in the new in­te­grat­ed re­view for­mat be used, if at all?
  4. What do you be­lieve would be the po­ten­tial ad­van­tages and dis­ad­van­tages of post­ing re­view doc­u­ments in this for­mat?
  5. Based on the in­te­grat­ed re­view, were the is­sues that con­cerned the re­view team clear and un­der­stand­able? If so, what helped achieve this? If not, what can be im­proved?
  6. Is there im­por­tant in­for­ma­tion in the in­te­grat­ed re­view that is dif­fi­cult to lo­cate or should be added?

First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

So­cial im­age: Jacque­lyn Mar­tin. AP Im­ages


Zachary Brennan

managing editor, RAPS

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