Stephen Hahn, FDA commissioner (AP Images)

PDU­FA VII: FDA, in­dus­try pre­view their reau­tho­riza­tion wish lists

At its first pub­lic meet­ing in the runup to the reau­tho­riza­tion of the Pre­scrip­tion Drug User Fee Actthe FDA, in­dus­try and oth­er stake­hold­ers on Thurs­day shed light on their goals for what will be the agency’s sev­enth PDU­FA pro­gram.

The meet­ing, held ful­ly vir­tu­al­ly for the first time due to the COVID-19 pan­dem­ic, is the start­ing point for the ne­go­ti­a­tions with in­dus­try and dis­cus­sions with stake­hold­ers that will shape FDA’s new drug re­view pro­gram from FY2023-FY2027.

Go­ing from VI to VII

FDA com­mis­sion­er Stephen Hahn opened the meet­ing by tout­ing the suc­cess­es of the cur­rent PDU­FA pro­gram. “Since FY2016, near­ly five years af­ter our pre­vi­ous meet­ing, CDER and CBER have ap­proved over 150 new mol­e­c­u­lar en­ti­ties, new drug ap­pli­ca­tions and bi­o­log­ics li­cense ap­pli­ca­tions,” Hahn said, near­ly half of which have been for or­phan in­di­ca­tions.

Hahn added that in the most re­cent fis­cal year, FDA “reached a new high for pri­or­i­ty ap­pli­ca­tions filed — 72 — and to­tal ap­pli­ca­tions filed — 166 — and again are on track to meet or ex­ceed most of our re­view per­for­mance goals.”

Out­side of the re­view goals, Hahn said FDA has pub­lished more than 30 draft or re­vised guid­ances, held more than 20 pub­lic meet­ings and work­shops and pub­lished nine pub­lic re­ports as part of its PDU­FA VI com­mit­ments.

An­drew Kish

An­drew Kish, di­rec­tor, Of­fice of Pro­gram and Strate­gic Analy­sis at the Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) gave an overview of the pre­vi­ous PDU­FA pro­grams and not­ed the mod­ern­ized user fee struc­ture in the lat­est agree­ment.

“PDU­VA VI mod­ern­ized the user fee struc­ture to im­prove pro­gram fund­ing pre­dictabil­i­ty, sta­bil­i­ty and ad­min­is­tra­tive ef­fi­cien­cy. The new struc­ture elim­i­nat­ed the sup­ple­ment fees, re­placed es­tab­lish­ment and prod­uct fees with the pro­gram fee, which shift­ed a greater pro­por­tion of the tar­get rev­enue to the new, more pre­dictable, sta­ble, an­nu­al pro­gram fee,” Kish said.

Kish al­so point­ed out that user fees have ac­count­ed for an in­creas­ing por­tion of fund­ing for FDA’s new drug re­view pro­gram. “User fee rev­enue has out­paced bud­get au­thor­i­ty avail­able for the pro­gram. As a point of com­par­i­son, PDU­FA user fee rev­enue fund­ed 7% of the pro­gram in 1993 and as of 2019 it funds 71% of the pro­gram,” he said.

For PDU­FA VII, Kish laid out FDA’s four over­ar­ch­ing pri­or­i­ties for the pro­gram: pro­mote sus­tain­able in­no­va­tion in drug de­vel­op­ment; en­hance reg­u­la­to­ry pre­dictabil­i­ty and post­mar­ket safe­ty; ad­vance the reg­u­la­to­ry in­fra­struc­ture for dig­i­tal tech­nolo­gies and new sources of da­ta; and en­hance op­er­a­tional ca­pa­bil­i­ties, ef­fi­cien­cy and agili­ty.

In­dus­try wish list

Rep­re­sen­ta­tives from both the Phar­ma­ceu­ti­cal Re­search and Man­u­fac­tur­ers of Amer­i­ca (PhRMA) and the Biotech­nol­o­gy In­no­va­tion Or­ga­ni­za­tion (BIO) pre­sent­ed their re­spec­tive in­dus­tries’ goals for the next user fee agree­ment that will be hashed out in meet­ings with FDA over the com­ing months.

Both Lucy Vereshchag­i­na, vice pres­i­dent of sci­ence and reg­u­la­to­ry ad­vo­ca­cy at PhRMA, and Carti­er Es­ham, ex­ec­u­tive vice pres­i­dent, emerg­ing com­pa­nies at BIO, stressed that PDU­FA VII should glean from lessons learned dur­ing the COVID-19 pan­dem­ic.

“There is a press­ing need for FDA, and in­dus­try, to iden­ti­fy ac­tions tak­en dur­ing the COVID-19 pan­dem­ic and eval­u­ate their ef­fec­tive­ness and ap­plic­a­bil­i­ty to in­no­v­a­tive drug de­vel­op­ment be­yond the pub­lic health emer­gency,” Vereshchag­i­na said.

The phar­ma­ceu­ti­cal in­dus­try group would al­so like to see “More pre­dictable and time­ly en­gage­ment and bet­ter com­mu­ni­ca­tion dur­ing drug de­vel­op­ment,” Vereshchag­i­na said, not­ing the group’s de­sire for more risk-based in­spec­tions and en­hanced tech­no­log­i­cal in­fra­struc­ture at the agency.

Vereshchag­i­na al­so said that, “PhRMA would sup­port the es­tab­lish­ment of a flex­i­ble and scal­able glob­al frame­work for dig­i­tal tech­nol­o­gy de­vel­op­ment,” build­ing on ex­pe­ri­ence with a shift to telemed­i­cine and dig­i­tal health tech­nolo­gies dur­ing the pan­dem­ic.

Ad­di­tion­al­ly, Vereshchag­i­na stressed that PhRMA would like to see greater sup­port for re­al world ev­i­dence (RWE) in FDA’s de­ci­sion-mak­ing. “PhRMA be­lieves that re­al world ev­i­dence, for ex­am­ple, can be used for demon­strat­ing ef­fec­tive­ness ei­ther on its own in some cir­cum­stances or in com­bi­na­tion with oth­er da­ta,” she said.

Carti­er Es­ham

Speak­ing for BIO, Es­ham said the group has three main ob­jec­tives, on top of its “ever­green po­si­tion” sup­port­ing the agency’s abil­i­ty to hire and re­tain “world-class per­son­nel.”

Those ob­jec­tives, Es­ham said, are to “con­tin­ue to op­ti­mize the cur­rent pro­gram and process­es; to en­sure sci­ence-based and ef­fec­tive postap­proval re­quire­ments and ac­tiv­i­ties; and third, to de­vel­op new ini­tia­tives that will best pre­pare us for the fu­ture.”

For PDU­FA VII, Es­ham said BIO would like to see more fund­ing go­ing to the Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search (CBER) to ac­com­mo­date the in­creased work­load around cell and gene ther­a­pies.

“With these prod­ucts comes in­creased de­mand on CBER re­sources, in­clud­ing ex­pert per­son­nel, ad­di­tion­al meet­ings and en­gage­ment with FDA,” Es­ham said.

BIO would al­so like fur­ther clar­i­fi­ca­tion on the ev­i­den­tiary stan­dards for FDA’s ex­pe­dit­ed path­ways such as the agency’s new re­gen­er­a­tive med­i­cine ad­vanced ther­a­py (RMAT) des­ig­na­tion, Es­ham said. FDA has grant­ed more than 50 RMAT des­ig­na­tions since the des­ig­na­tion’s cre­ation un­der the 21st Cen­tu­ry Cures Act, but has yet to ap­prove a sin­gle RMAT-des­ig­nat­ed prod­uct.

Es­ham al­so called for the es­tab­lish­ment of process­es and best prac­tices to im­prove the ef­fi­cien­cy and ef­fec­tive­ness of meet­ings be­tween spon­sors and FDA. “Best prac­tices can en­sure FDA-spon­sor in­ter­ac­tions are as ef­fi­cient as pos­si­ble and if prop­er­ly done, could serve to de­crease the amount of meet­ing re­quests,” she said. While FDA has gen­er­al­ly met most of its PDU­FA re­view per­for­mance goals over the last decade, it has fared less well with its meet­ing and com­mu­ni­ca­tions goals.

Ad­di­tion­al­ly, BIO would like to see FDA es­tab­lish new mech­a­nisms and time­lines for com­mu­ni­ca­tion with in­dus­try, such as pro­vid­ing an op­por­tu­ni­ty for spon­sors to ask clar­i­fy­ing ques­tions af­ter mile­stone meet­ings and set­ting struc­tured time­lines for com­mu­ni­ca­tion for la­bel­ing, post­mar­ket re­quire­ment (PMR) and post­mar­ket com­mit­ment (PMC) process­es and pe­di­atric study plans.

Es­ham added that it will be crit­i­cal­ly im­por­tant to “con­tin­ue to ad­vance mod­ern man­u­fac­tur­ing qual­i­ty and in­spec­tions method­ol­o­gy and process­es,” and called for risk-based ap­proach­es to preap­proval in­spec­tions.


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