,,ii ,cal5d> ,no4 #dad #aad? ,,congress #b;d ,session ,s4 #agfg ,,9 ,,! ,,s5ate ,,( ,,! ,,unit$ ,,/ates ,july #ae1 #bjae,mr4 ,isakson 7= himself1 ,mr4 ,casey1 ,mr4 ,rob]ts1 ,mr4 ,toomey1 ,mr4 ,kirk1 ,mr4 ,donnelly1 & ,mr4 ,cassidy7 introduc$ ! foll[+ bill2 :i* 0 read twice & ref]r$ to ! ,committee on ,heal?1 ,education1 ,labor1 & ,p5sions ,april #e1 #bjaf,report$ by ,mr4 ,alex&]1 ) an amendment,strike out all aft] ! enact+ clause & ins]t ! "p pr9t$ 9 italic ,a ,,bill ,to am5d ! ,f$]al ,food1 ,drug1 & ,cosmetic ,act ) respect to comb9ation products1 & = o!r purposes4 #a4 ,%ort title ,?is ,act may be cit$ z ! ,comb9ation ,product ,regulatory ,fairness ,act ( #bjae4 #b4 ,device def9ition ,section #bja7;h7 ( ! ,f$]al ,food1 ,drug1 & ,cosmetic ,act 7#ba ,u4,s4,c4 #cba7;h77 is am5d$-- 7#a7 by r$esignat+ subp>agraphs 7#a71 7#b71 & 7#c7 z clauses 7,a71 7,b71 & 7,c71 respectively2 7#b7 by /rik+ 7h7 & ins]t+ 7h77#a72 & 7#c7 by add+ at ! end ! foll[+3 7#b7 7,a7 ,be=e det]m9+ t an article does n meet ! def9ition ( a device "u ?is p>agraph1 ! ,secret>y %all provide to ! sponsor ( ! article compet5t & reliable sci5tific rationale t-- 7i7 cites any sci5tific evid5ce reli$ ^u to support ! rationale2 & 7ii7 supports su* det]m9ation4 7,b7 ,if ! ,secret>y makes a det]m9ation describ$ 9 clause 7,a7-- 7i7 ! sponsor ( ! article may propose a noncl9ical or cl9ical /udy1 limit$ to n m data ?an necess>y to e/abli% ! significance1 if any1 ( ! *emical action 9 a*iev+ ! prim>y int5d$ purpose ( ! article2 & 7ii7 ! ,secret>y & ! sponsor ( ! article %all collaborate 9 good fai? to rea* agreem5t1 )9 a reasonable "t n to exce$ #ij days1 on ! design ( su* /udy4 7,c7 ,! data result+ f a /udy conduct$ "u clause 7,b7 %all in=m ! classification ( ! article4 4 #c4 ,comb9ation products ,section #ejc7;g7 ( ! ,f$]al ,food1 ,drug1 & ,cosmetic ,act 7#ba ,u4,s4,c4 #cec7;g77 is am5d$-- 7#a7 by r$esignat+ p>agraphs 7#b7 ?r\gh 7#e7 z p>agraphs 7#f7 ?r\gh 7#i71 respectively2 7#b7 by /rik+ 7g77#a7 & all t foll[s ?r\gh ! end ( p>agraph 7#a7 & ins]t+ ! foll[+3 7g7 7#a7 7,a7 ,! ,secret>y %all1 9 accordance ) ?is subsection1 assign an ag5cy c5t] to regulate products t con/itute a comb9ation ( a drug1 device1 or biological product 7ref]r$ to 9 ?is subsection z ! lead c5t]74 7,b7 ,! ,secret>y %all conduct ! prem>ket review ( any comb9ation product1 :5ev] possible1 "u a s+le application us+ exi/+ prem>ket review au?orities4 7,c7 ,! ,secret>y %all det]m9e ! prim>y mode ( action ( ! comb9ation product4 ,if ! ,secret>y det]m9es t ! prim>y mode ( action is t (-- 7i7 a drug 7o!r ?an a biological product71 ! ag5cy c5t] *>g$ ) prem>ket review ( drugs %all h prim>y jurisdiction2 7ii7 a device1 ! ag5cy c5t] *>g$ ) prem>ket review ( devices %all h prim>y jurisdiction2 or 7iii7 a biological product1 ! ag5cy c5t] *>g$ ) prem>ket review ( biological products %all h prim>y jurisdiction4 7,d7 ,9 det]m9+ ! prim>y mode ( action ( a comb9ation product1 ! ,secret>y %all n det]m9e t ! prim>y mode ( action is t ( a drug or biological product solely because ! comb9ation product has any *emical action )9 or on ! human body4 7,e7 ,if ! ,secret>y disagrees ) ! conclusions ( ! sponsor on ! prim>y mode ( action ( ! comb9ation product1 ! ,secret>y %all provide a compet5t & reliable sci5tific rationale to ! product sponsor t cites any sci5tific evid5ce reli$ ^u to support ! decision4 7,f7 ,= purposes ( ?is p>agraph-- 7i7 ! t]m prim>y mode ( action means ! s+le mode ( action ( a comb9ation product t provides ! mo/ important !rapeutic action ( ! comb9ation product2 & 7ii7 ! t]m mo/ important !rapeutic action means ! mode ( action expect$ to make ! greate/ contribution to ! ov]all int5d$ !rapeutic effects ( ! comb9ation product4 7#b7 7,a7 ,! sponsor ( a comb9ation product may submit a comb9ation product review plan 7ref]r$ to 9 ?is subsection z a ,,cprp7 = ! comb9ation product1 & may reque/ a meet+ prior to submission ( ! ,,cprp1 to e/abli% cl>ity & c]ta9ty = ! sponsor reg>d+ ! /&>ds & requirem5ts applicable to-- 7i7 ! review ( safety & effectiv5ess1 or sub/antial equival5ce1 ( ! comb9ation product2 7ii7 a po/m>ket modification ( ! comb9ation product2 or 7iii7 good manufactur+ practices = ! comb9ation product4 7,b7 ,n lat] ?an #fj days aft] ! sponsor ( a comb9ation product submits a propos$ ,,cprp1 includ+ a revision to a previ\sly propos$ or approv$ ,,cprp1 ! ,secret>y %all review ! ,,cprp &-- 7i7 if ! ,secret>y det]m9es t ! ,,cprp is appropriate to ensure adequate review ( ! safety & effectiv5ess1 or sub/antial equival5ce1 ( ! comb9ation product-- 7,i7 approve ! ,,cprp2 & 7,,ii7 issue to ! sponsor a response indicat+ su* approval2 or 7ii7 if ! ,secret>y f9ds t ! ,,cprp does n meet ! /&>d specifi$ 9 clause 7i7-- 7,i7 decl9e to approve ! ,,cprp2 & 7,,ii7 issue to ! sponsor a response indicat+ t ! ,secret>y has decl9$ su* approval & specify+ any defici5cies 9 ! propos$ ,,cprp4 7,c7 7i7 ,9 ! case ( a ,,cprp t ! ,secret>y decl9es to approve "u subp>agraph 7,b77ii71 unless ! sponsor submitt+ su* ,,cprp det]m9es a meet+ is n necess>y1 ! ,secret>y %all1 n lat] ?an #cj days aft] submitt+ a response "u su* subp>agraph1 meet ) su* sponsor to discuss ! ,,cprp4 7ii7 ,a meet+ "u clause 7i7 %all-- 7,i7 include any necess>y exp]ts f ! relevant ag5cy c5t]s2 & 7,,ii7 coord9ate ! advice ( su* exp]ts4 7,d7 ,! sponsor or applicant %all provide in=mation necess>y = discussion & agreem5t on ! level ( evid5ce necess>y to ensure adequate review ( ! safety & effectiv5ess1 or sub/antial equival5ce1 ( ! comb9ation product4 7,e7 ,n lat] ?an #cj days aft] ! date on :i* a meet+ is held "u subp>agraph 7,a77i71 ! m9utes ( su* meet+ %all be prep>$ by ! sponsor & made available to ! ,secret>y4 7,f7 ,any agreem5t t is rea*$ betwe5 ! ,secret>y & a sponsor or applicant ?r\gh a meet+ held "u subp>agraph 7,a77i7 %all be r$uc$ to writ+ by ! sponsor or applicant1 &1 once approv$ by ! ,secret>y1 made "p ( ! adm9i/rative record by ! ,secret>y )9 #fj days ( su* meet+4 7,g7 ,an agreem5t describ$ 9 subp>agraph 7,f7 %all n be *ang$ aft] approval ( ! agreem5t1 except-- 7i7 ) ! writt5 agreem5t ( ! sponsor or applicant2 or 7ii7 pursuant to a decision1 made 9 accordance ) subp>agraph 7,h7 by ! director ( ! review+ division ( ! lead c5t]1 9 consultation ) consult+ c5t]s & ! ,(fice1 t a sub/antial sci5tific issue ess5tial to det]m9+ ! safety or effectiv5ess1 or sub/antial equival5ce1 ( ! comb9ation product has be5 id5tifi$4 7,h7 ,) respect to a decision "u subp>agraph 7,g77ii71 ! ,secret>y %all provide notice1 )9 #b bus9ess days ( su* decision1 to ! sponsor ( ! comb9ation product & an opportunity = a meet+ to take place n lat] ?an #ad cal5d> days aft] issu+ su* notice1 at :i*-- 7i7 ! director ( ! review+ division ( ! lead c5t]1 /aff f ! consult+ ag5cy c5t]s1 repres5tatives ( ! ,(fice1 & ! sponsor w be pres5t2 & 7ii7 ! director ( ! review+ division ( ! lead c5t] w docum5t ! sci5tific issue involv$4 7#c7 ,= purposes ( conduct+ ! prem>ket review ( a comb9ation product t conta9s an approv$ con/itu5t product describ$ 9 p>agraph 7#d71 ! ,secret>y may require only t ! sponsor ( su* comb9ation product submit to ! ,secret>y data or in=mation t-- 7,a7 ! ,secret>y det]m9es is necess>y to assess ! specific safety & effectiv5ess que/ions & increm5tal risks pos$ by ! comb9ation product1 us+ a risk-bas$ approa* & tak+ into acc\nt any prior f9d+ ( safety & efficacy or sub/antial equival5ce = ! approv$ con/itu5t product2 & 7,b7 is n duplicative ( data or in=mation includ$ 9 an application or o!r mat]ial submitt$ to ! ,secret>y 9 connection ) ! approv$ con/itu5t product4 7#d7 ,= purposes ( p>agraph 7#c71 an approv$ con/itu5t product is-- 7,a7 a drug con/itu5t "p ( a comb9ation product be+ review$ 9 a s+le application "u section #eae or #eaj7k71 provid$ su* drug con/itu5t "p 0 previ\sly approv$ "u section #eje & su* application complies ) subp>agraph 7,a7 ( p>agraph 7#e7 & is subject to subp>agraphs 7,d7 & 7,e7 ( su* p>agraph2 7,b7 a device con/itu5t "p approv$ "u section #eae t is ref]5c$ by ! sponsor & :i* is available = use by ! ,secret>y "u section #ebj7;h77#d72 or 7,c7 any con/itu5t "p t 0 previ\sly approv$1 cle>$1 or lic5s$ "u section #eje1 #eaj7k71 or #eae ( ?is ,act or section #cea ( ! ,public ,heal? ,s]vice ,act1 = :i* ! sponsor has a "r ( ref]5ce or :i* is o!rwise available = consid]ation by ! ,secret>y "u ?is ,act or ! ,public ,heal? ,s]vice ,act4 7#e7 7,a7 ,if an application is submitt$ "u section #eae or #eaj7k7 = a comb9ation product conta9+ z a con/itu5t "p an approv$ drug-- 7i7 ! application %all include ! c]tification or /atem5t requir$ pursuant section #eje7;b77#b72 & 7ii7 ! applicant %all provide notice z requir$ pursuant to section #eje7;b77#c74 7,b7 ,= purposes ( ?is p>agraph1 ! t]m approv$ drug means a drug-- 7i7 t 0 previ\sly approv$ "u section #eje2 7ii7 = :i* full reports ( inve/igations t h be5 made to %[ :e!r su* drug is safe = use & :e!r su* drug is effective 9 use-- 7,i7 are reli$ ^u by ! applicant submitt+ ! application describ$ 9 subp>agraph 7,a72 & 7,,ii7 7 n conduct$ by or = su* applicant2 & 7iii7 ) respect to :i*1 ! applicant submitt+ ! application describ$ 9 subp>agraph 7,a7 has n obta9$ a "r ( ref]5ce or use f ! p]son by or = :om ! inve/igations 7 conduct$4 7,c7 ,! foll[+ provisions %all apply ) respect an application describ$ 9 subp>agraph 7,a73 7i7 ,subp>agraphs 7,a71 7,b71 7,c71 & 7,d7 ( section #eje7;c77#c74 7ii7 ,clauses 7ii71 7iii71 & 7iv7 ( section #eje7;c77#c77;,e74 7iii7 ,p>agraphs 7b7 & 7c7 ( section #eje;,a4 7iv7 ,section #eje;,e7a74 7v7 ,section #ebg7;a74 7,d7 ,not)/&+ section #ebj7;h77#d77;,a77i71 in=mation conta9$ 9 an application = prem>ket approval fil$ ) ! ,secret>y pursuant to section #eae7;c7 may n be us$ to approve any application submitt$ "u section #eae or #eaj7k7 = a comb9ation product conta9+ z a con/itu5t "p a drug previ\sly approv$ "u section #eje unless-- 7i7 ! application includes ! c]tification or /atem5t ref]5c$ 9 subp>agraph 7,a72 7ii7 ! applicant provides notice z describ$ 9 subp>agraph 7,a72 & 7iii7 ! ,secret>y's approval ( su* application is subject to ! provisions specifi$ 9 subp>agraph 7,c74 7,e7 ,an application = a comb9ation product describ$ 9 subp>agraph 7,a7 or 7,d7 %all be consid]$ an application submitt$ "u ,section #eje7;b77#b7 solely = purposes ( section #bga7;e77#b77;,a7 ( ! ,pat5t ,act4 2 7#c7 9 p>agraph 7#h7 7z r$esignat$ by p>agraph 7#a77-- 7,a7 9 subp>agraph 7,c7-- 7i7 by am5d+ clause 7i7 to read z foll[s3 7i7 ,9 c>ry+ out ?is subsection1 ! ,(fice %all ensure timely & effective prem>ket reviews involv+ m ?an "o ag5cy c5t] by-- 7,i7 ov]see+ ! timel9ess & alignm5t ( reviews2 & 7,,ii7 coord9at+ reviews4 2 7ii7 9 clause 7ii71 by ins]t+ & alignm5t aft] ! timel9ess ea* place x appe>s2 & 7iii7 by add+ at ! end ! foll[+ new clauses3 7iii7 ,! ,(fice %all ensure t ! lead c5t] be ! prim>y po9t ( contact = ! sponsor ( ! product4 ,! ,(fice %all also coord9ate communications to & f any consult+ ag5cy c5t] involv$ 9 su* prem>ket review4 ,ag5cy communications & commitm5ts1 to ! ext5t consi/5t ) o!r provisions ( law & ! requirem5ts ( all affect$ ag5cy c5t]s1 f ! lead c5t] %all be b9d+ on all o!r c5t]s involv$ 9 ! review4 7iv7 ,! ,(fice %all1 ) respect to ! prem>ket review ( a comb9ation product-- 7,i7 ensure t any meet+ betwe5 ! ,food & ,drug ,adm9i/ration & ! sponsor ( ! product is att5d$ by ea* ag5cy c5t] involv$ 9 ! review1 z appropriate2 7,,ii7 require t ea* consult+ ag5cy c5t] has complet$ its prem>ket review & provid$ ! results ( su* review to ! lead c5t] )9 timeframes t all[ ! lead c5t] to meet ! review goals e/abli%$ pursuant to ! mo/ rec5t au?orization or reau?orization ( p>ts #b1 #c1 #g1 & #h1 z applicable1 ( sub*apt] ,c ( title ,,vii2 & 7,,iii7 ensure t ea* consult+ ag5cy c5t] complies ) ! guidance describ$ 9 clause 7vi7 & o!r relevant regulations1 guidances1 & policies4 7v7 ,n lat] ?an #aj days aft] ! receipt by an ag5cy c5t] ( an application "u section #eje1 #eaj7k71 or #ebj ( ?is ,act1 or "u section #cea ( ! ,public ,heal? ,s]vice ,act1 = a comb9ation product or an application = inve/igational use ( a comb9ation product "u section #eje7;i7 or #ebj7;g71 ! ag5cy c5t] %all in=m ! ,(fice ( su* receipt4 7vi7 ,n lat] ?an #b ye>s aft] ! date ( enactm5t ( ! ,comb9ation ,product ,regulatory ,fairness ,act ( #bjae1 ! ,secret>y %all issue f9al guidance t describes ! responsibilities ( ea* ag5cy c5t] reg>d+ its review ( comb9ation products1 includ+ ea* c5t]'s role 9 evaluat+ evid5ce developm5t & review "u a risk-bas$ approa*1 dispute resolution1 label+1 product usability assessm5ts1 & human factors te/+4 ,! ,(fice %all1 aft] solicit+ public comm5t1 review & update ! guidance at lea/ biannually & specify 9 su* updat$ guidance ! reasons = updates4 2 7,b7 9 subp>agraph 7,e7-- 7i7 by /rik+ clause 7i7 & ins]t+ ! foll[+ new clause3 7i7 ,dur+ ! review process1 any dispute reg>d+ ! sub/ance1 timel9ess1 review process1 requirem5ts1 or alignm5t ( ! prem>ket review may be pres5t$ to ! ,(fice = resolution & ! ,(fice %all conv5e ! relevant p>ties & resolve conflicts n lat] ?an #ij days aft] ! date on :i* ! ,(fice receives writt5 notice ( su* conflicts4 2 & 7ii7 9 clause 7ii71 by /rik+ ,dur+ ! review process1 any dispute reg>d+ ! sub/ance ( ! prem>ket review & ins]t+ ,any rema9+ dispute2 7,c7 9 subp>agraph 7,f71 9 ! fir/ s5t5ce-- 7i7 by ins]t+ or :i* involves det]m9+ ! safety or efficacy ( a compon5t ( a comb9ation product aft] assignm5t ( comb9ation products to ag5cy c5t]s2 & 7ii7 by ins]t+ & ) ! guidance describ$ 9 subp>agraph 7,c77vi74 be=e ! p]iod at ! end2 & 7,d7 9 subp>agraph 7,g7-- 7i7 9 clause 7ii71 by /rik+ & at ! end2 7ii7 9 clause 7iii71 by /rik+ ! p]iod at ! end & ins]t+ a semicolon2 & 7iii7 by add+ at ! end ! foll[+ new clauses3 7iv7 id5tify+ ! p]c5tage ( comb9ation products = :i* a dispute resolution1 ) respect to prem>ket review1 0 reque/$ by ! comb9ation product's sponsor2 & 7v7 id5tify+ ! p]c5tage ( meet+s betwe5 ! ,food & ,drug ,adm9i/ration & ! sponsor ( a comb9ation product at :i* all ( ! c5t]s p>ticipat+ 9 ! review ( ! comb9ation product 7 9 att5dance1 9 accordance ) subp>agraph 7,c77iv77,i74 2 7#d7 9 p>agraph 7#i7 7z r$esignat$ by p>agraph 7#a771 by add+ at ! end ! foll[+3 7,d7 ,! t]ms prem>ket review & reviews include all activities ( ! ,food & ,drug ,adm9i/ration conduct$ prior to approval or cle>ance ( an application or notification submitt$ "u section #eje1 #eaj7k71 #eae1 or #ebj ( ?is ,act or "u section #cea ( ! ,public ,heal? ,s]vice ,act1 includ+ ) respect to inve/igational use ( ! product4 2 & 7#e7 by add+ at ! end ! foll[+3 7#aj7 ,rule ( con/ruction ,no?+ 9 ?is subsection %all be con/ru$ z prohibit+ a sponsor1 at ! sponsor's discretion1 f submitt+ sep>ate applications = ! con/itu5t p>ts ( a comb9ation product1 unless ! ,secret>y det]m9es t a s+le application is necess>y to ensure ! safety & effectiv5ess1 or sub/antial equival5ce1 z applicable1 ( ! comb9ation product4 4 #a4 ,%ort title ,?is ,act may be cit$ z ! ,comb9ation ,product ,regulatory ,fairness ,act ( #bjaf4 #b4 ,comb9ation products 7a7 ,9 g5]al ,section #ejc7;g7 ( ! ,f$]al ,food1 ,drug1 & ,cosmetic ,act 7#ba ,u4,s4,c4 #cec7;g77 is am5d$-- 7#a7 by /rik+ p>agraph 7#c72 7#b7 by r$esignat+ p>agraph 7#b7 z p>agraph 7#g72 7#c7 by r$esignat+ p>agraphs 7#d7 & 7#e7 z p>agraphs 7#h7 & 7#i71 respectively2 & 7#d7 by /rik+ 7g77#a7 & all t foll[s ?r\gh ! end ( p>agraph 7#a7 & ins]t+ ! foll[+3 7g7 7#a7 7,a7 ,! ,secret>y %all1 9 accordance ) ?is subsection1 assign a prim>y ag5cy c5t] to regulate products t con/itute a comb9ation ( a drug1 device1 or biological product4 7,b7 ,! ,secret>y %all conduct ! prem>ket review ( any comb9ation product "u a s+le application1 :5ev] appropriate4 7,c7 ,= purposes ( ?is subsection1 ! t]m prim>y mode ( action means ! s+le mode ( action ( a comb9ation product expect$ to make ! greate/ contribution to ! ov]all int5d$ !rapeutic effects ( ! comb9ation product4 7,d7 ,! ,secret>y %all det]m9e ! prim>y mode ( action ( ! comb9ation product4 ,if ! ,secret>y det]m9es t ! prim>y mode ( action is t (-- 7i7 a drug 7o!r ?an a biological product71 ! ag5cy c5t] *>g$ ) prem>ket review ( drugs %all h prim>y jurisdiction2 7ii7 a device1 ! ag5cy c5t] *>g$ ) prem>ket review ( devices %all h prim>y jurisdiction2 or 7iii7 a biological product1 ! ag5cy c5t] *>g$ ) prem>ket review ( biological products %all h prim>y jurisdiction4 7,e7 ,9 det]m9+ ! prim>y mode ( action ( a comb9ation product1 ! ,secret>y %all n det]m9e t ! prim>y mode ( action is t ( a drug or biological product solely because ! comb9ation product has any *emical action )9 or on ! human body4 7,f7 ,if a sponsor ( a comb9ation product disagrees ) ! det]m9ation "u subp>agraph 7,d7-- 7i7 su* sponsor may reque/1 & ! ,secret>y %all provide1 a sub/antive rationale to su* sponsor t ref]5ces sci5tific evid5ce provid$ by ! sponsor & any o!r sci5tific evid5ce reli$ ^u by ! ,secret>y to support su* det]m9ation2 & 7ii7 7,i7 ! sponsor ( ! comb9ation product may propose "o or m /udies 7:i* may be noncl9ical1 cl9ical1 or bo?7 to e/abli% ! relevance1 if any1 ( ! *emical action 9 a*iev+ ! prim>y mode ( action ( su* product2 7,,ii7 if ! sponsor proposes any su* /udies1 ! ,secret>y & ! sponsor ( su* product %all collaborate & seek to rea* agreem5t1 )9 a reasonable "t ( su* proposal1 n to exce$ #ij cal5d> days1 on ! design ( su* /udies2 & 7,,iii7 if an agreem5t is rea*$ "u subclause 7,,ii7 & ! sponsor conducts "o or m ( su* /udies1 ! ,secret>y %all consid] ! data result+ f any su* /udy :5 reevaluat+ ! det]m9ation ( ! prim>y mode ( action ( su* product1 & unless & until su* reevaluation has occurr$ & ! ,secret>y issues a new det]m9ation1 ! det]m9ation ( ! ,secret>y "u subp>agraph 7,d7 %all rema9 9 effect4 7#b7 7,a7 7i7 ,to e/abli% cl>ity & c]ta9ty = ! sponsor1 ! sponsor ( a comb9ation product may submit a propos$ comb9ation product review plan ) respect to su* comb9ation product1 at any po9t foll[+ ! ,secret>y's det]m9ation ( ! prim>y mode ( action pursuant to p>agraph 7#a74 7ii7 ,su* propos$ comb9ation product review plan may-- 7,i7 address ! /&>ds & requirem5ts = m>ket approval or cle>ance ( ! comb9ation product2 7,,ii7 address o!r issues relevant to su* comb9ation product1 su* z requirem5ts relat$ to po/m>ket modification ( su* comb9ation product & good manufactur+ practices applicable to su* comb9ation product2 & 7,,iii7 id5tify elem5ts "u subclauses 7,i7 & 7,,ii7 t may be m appropriate = discussion & agreem5t ) ! ,secret>y at a lat] date giv5 t sci5tific or o!r in=mation is n available1 or agreem5t is o!rwise n feasible reg>d+ su* elem5ts1 at ! "t su* plan is submitt$4 7,b7 ,aft] ! sponsor ( a comb9ation product submits a propos$ comb9ation product review plan "u subp>agraph 7,a71 ! ,secret>y %all review su* plan &1 9 a writt5 response to su* sponsor-- 7i7 accept su* plan 9 its entirety1 :i* may include elem5ts to be ! subject ( discussion & agreem5t betwe5 ! sponsor & ! ,secret>y at a lat] date1 z describ$ 9 subp>agraph 7,a77ii77,,iii72 7ii7 accept ! plan 9 "p1 :i* may include elem5ts t h n be5 accept$ at ! "t ( ! response & are to be ! subject ( discussion & agreem5t betwe5 ! sponsor & ! ,secret>y at a lat] date1 z describ$ 9 subp>agraph 7,a77ii77,,iii71 & elem5ts t ! ,secret>y decl9es to accept2 or 7iii7 d5y su* plan 9 its entirety4 7,c7 ,:5 review+ a propos$ comb9ation product review plan "u subp>agraph 7,b71 ! ,secret>y %all accept su* plan1 or elem5ts ( su* plan1 if ! ,secret>y det]m9es t ! data to be collect$ is appropriate-- 7i7 = m>ket approval or cle>ance ( ! comb9ation product2 or 7ii7 to o!rwise meet relevant /&>ds "u ?is ,act1 z applicable4 7,d7 7i7 ,if ! ,secret>y decl9es to accept a propos$ comb9ation product review plan "u subp>agraph 7,b77iii71 or elem5ts ( su* a plan "u subp>agraph 7,b77ii71 ! ,secret>y %all1 9 ! writt5 response to su* sponsor-- 7,i7 include a description ( ! defici5cies ( su* plan or su* elem5ts1 z applicable2 & 7,,ii7 cl>ify :at elem5ts may be suitable = discussion at a lat] date4 7ii7 ,if ! ,secret>y decl9es to accept a propos$ comb9ation product review plan "u subp>agraph 7,b77iii71 or elem5ts ( su* a plan "u subp>agraph 7,b77ii71 ! sponsor ( su* plan may reque/ a meet+ ) ! ,secret>y4 ,^u ! reque/ ( ! sponsor1 ! ,secret>y1 includ+ any necess>y exp]ts f ! relevant ag5cy c5t]s1 %all meet ) ! sponsor to discuss a propos$ comb9ation product review plan or elem5ts ( a comb9ation product review plan t ! ,secret>y has decl9$ to accept1 = ! purpose ( discuss+ ! in=mation & requirem5ts necess>y to make ! plan or elem5ts ( su* plan acceptable4 ,m9utes ( su* meet+ %all be made "p ( ! adm9i/rative record4 7iii7 ,if ! ,secret>y decl9es to accept a propos$ comb9ation product review plan "u subp>agraph 7,b77iii71 or elem5ts ( su* a plan "u subp>agraph 7,b77ii71 a sponsor may resubmit a propos$ comb9ation product review plan = consid]ation by ! ,secret>y "u subp>agraph 7,a74 7,e7 ,a comb9ation product review plan accept$ "u subp>agraph 7,b77i71 or ! elem5ts ( a comb9ation product review plan t are accept$ "u subp>agraph 7,b77ii71 %all rema9 9 effect1 except-- 7i7 ) ! writt5 agreem5t ( ! ,secret>y & ! sponsor or applicant2 or 7ii7 pursuant to a decision1 made 9 accordance ) subp>agraph 7,f7 by ! director ( ! review+ division ( ! prim>y ag5cy c5t]1 or a p]son m s5ior ?an su* director1 9 consultation ) consult+ c5t]s & ! ,(fice1 t an important1 mat]ially relevant sci5tific issue ess5tial to det]m9+ ! safety or effectiv5ess1 or sub/antial equival5ce1 z applicable1 ( ! comb9ation product has be5 id5tifi$ s9ce a comb9ation product review plan or elem5ts ( a comb9ation product review plan 7 accept$1 z applicable4 7,f7 ,if ! ,secret>y makes a decision "u subp>agraph 7,e77ii71 ! ,secret>y %all provide notice1 )9 a reasonable "t aft] su* decision1 to ! sponsor ( ! comb9ation product subject to su* decision & provide an opportunity = a meet+ ) ! ,secret>y1 to take place )9 a reasonable "t aft] issu+ su* notice1 at :i*-- 7i7 ! director ( ! review+ division ( ! prim>y ag5cy c5t]1 or a p]son m s5ior ?an su* director1 /aff f ! consult+ c5t]s1 repres5tatives ( ! ,(fice1 & ! sponsor %all be repres5t$2 & 7ii7 ! director ( ! review+ division ( ! prim>y ag5cy c5t]1 or a p]son m s5ior ?an ! director1 %all describe ! important1 mat]ially relevant issue involv$ to su* sponsor4 7#c7 ,= purposes ( conduct+ ! prem>ket review ( a comb9ation product t conta9s an approv$ con/itu5t "p describ$ 9 p>agraph 7#d71 ! ,secret>y may require t ! sponsor ( su* comb9ation product submit to ! ,secret>y only data or in=mation t ! ,secret>y det]m9es is necess>y to assess ! safety & effectiv5ess ( ! comb9ation product1 includ+ any increm5tal risks & b5efits pos$ by su* comb9ation product1 us+ a risk-bas$ approa* & tak+ into acc\nt any prior f9d+ ( safety & effectiv5ess or sub/antial equival5ce = ! approv$ con/itu5t "p reli$ ^u by ! applicant 9 accordance ) p>agraph 7#e74 7#d7 ,= purposes ( p>agraph 7#c71 an approv$ con/itu5t "p is-- 7,a7 a drug con/itu5t "p ( a comb9ation product be+ review$ 9 a s+le application or reque/ "u section #eae1 #eaj7k71 or #eac7;f77#b7 7submitt$ 9 accordance ) p>agraph 7#e771 t is an approv$ drug1 provid$ su* application or reque/ complies ) p>agraph 7#e72 7,b7 a device con/itu5t "p approv$ "u section #eae t is ref]5c$ by ! sponsor & t is available = use by ! ,secret>y "u section #ebj7;h77#d72 or 7,c7 any con/itu5t "p t 0 previ\sly approv$1 cle>$1 or classifi$ "u section #eje1 #eaj7k71 #eac7;f77#b71 or #eae ( ?is ,act = :i* ! sponsor has a "r ( ref]5ce or any con/itu5t "p t is a nonprescription drug1 z def9$ 9 section #gfj7;a77#b74 7#e7 7,a7 ,if an application is submitt$ "u section #eae1 #eaj7k71 or a reque/ is submitt$ "u section #eac7;f77#b71 consi/5t ) any det]m9ation made "u p>agraph 7#a77;,d71 = a comb9ation product conta9+ z a con/itu5t "p an approv$ drug-- 7i7 ! application or reque/ %all include ! c]tification or /atem5t describ$ 9 section #eje7;b77#b72 & 7ii7 ! applicant or reque/] %all provide notice z describ$ 9 section #eje7;b77#c74 7,b7 ,= purposes ( ?is p>agraph & p>agraph 7#d71 ! t]m approv$ drug means an active +r$i5t-- 7i7 t 0 9 an application previ\sly approv$ "u section #eje7;c72 7ii7 :]e su* application is reli$ ^u by ! applicant submitt+ ! application or reque/ describ$ 9 subp>agraph 7,a72 7iii7 = :i* full reports ( inve/igations t h be5 made to %[ :e!r su* drug is safe = use & :e!r su* drug is effective 9 use 7 n conduct$ by or = ! applicant submitt+ ! application or reque/ describ$ 9 subp>agraph 7,a72 & 7iv7 = :i* ! applicant submitt+ ! application or reque/ describ$ 9 subp>agraph 7,a7 has n obta9$ a "r ( ref]5ce or use f ! p]son by or = :om ! inve/igations describ$ 9 clause 7iii7 7 conduct$4 7,c7 ,! foll[+ provisions %all apply ) respect to an application or reque/ describ$ 9 subp>agraph 7,a7 to ! same ext5t & 9 ! same mann] z if su* application or reque/ 7 an application describ$ 9 section #eje7;b77#b7 t ref]5c$ ! approv$ drug3 7i7 ,subp>agraphs 7,a71 7,b71 7,c71 & 7,d7 ( section #eje7;c77#c74 7ii7 ,clauses 7ii71 7iii71 & 7iv7 ( section #eje7;c77#c77;,e74 7iii7 ,subsections 7b7 & 7c7 ( section #eje;,a4 7iv7 ,section #eje;,e7a74 7v7 ,section #ebg7;a74 7,d7 ,not)/&+ any o!r provision ( ?is subsection1 an application or reque/ = classification = a comb9ation product describ$ 9 subp>agraph 7,a7 %all be consid]$ an application submitt$ "u section #eje7;b77#b7 = purposes ( section #bga7;e77#b77;,a7 ( title #ce1 ,unit$ ,/ates ,code4 7#f7 ,no?+ 9 ?is subsection %all be con/ru$ z prohibit+ a sponsor f submitt+ sep>ate applications = ! con/itu5t p>ts ( a comb9ation product1 unless ! ,secret>y det]m9es t a s+le application is necess>y4 2 7#e7 9 p>agraph 7#h7 7z r$esignat$ by p>agraph 7#c77-- 7,a7 9 subp>agraph 7,c7-- 7i7 by am5d+ clause 7i7 to read z foll[s3 7i7 ,9 c>ry+ out ?is subsection1 ! ,(fice %all help to ensure timely & effective prem>ket review t involves m ?an "o ag5cy c5t] by coord9at+ su* reviews1 ov]see+ ! timel9ess ( su* reviews1 & ov]see+ ! alignm5t ( fe$back reg>d+ su* reviews4 2 7ii7 9 clause 7ii71 by ins]t+ & alignm5t aft] ! timel9ess ea* place x appe>s2 & 7iii7 by add+ at ! end ! foll[+ new clauses3 7iii7 ,! ,(fice %all ensure t1 ) respect to a comb9ation product1 a designat$ p]son or p]sons 9 ! prim>y ag5cy c5t] be ! prim>y po9t or po9ts ( contact = ! sponsor ( su* comb9ation product4 ,! ,(fice %all also coord9ate communications to & f any consult+ c5t] involv$ 9 su* prem>ket review1 if reque/$ by su* prim>y ag5cy c5t] or any su* consult+ c5t]4 ,ag5cy communications & commitm5ts1 to ! ext5t consi/5t ) o!r provisions ( law & ! requirem5ts ( all affect$ ag5cy c5t]s1 f ! prim>y ag5cy c5t] %all be consid]$ z communication f ! ,food & ,drug ,adm9i/ration on behalf ( all ag5cy c5t]s involv$ 9 ! review4 7iv7 ,! ,(fice %all1 ) respect to ! prem>ket review ( a comb9ation product-- 7,i7 ensure t any meet+ betwe5 ! ,food & ,drug ,adm9i/ration & ! sponsor ( su* product is att5d$ by ea* ag5cy c5t] involv$ 9 ! review1 z appropriate2 7,,ii7 ensure t ea* consult+ ag5cy c5t] has complet$ its prem>ket review & provid$ ! results ( su* review to ! prim>y ag5cy c5t] 9 a timely mann]2 & 7,,iii7 ensure t ea* consult+ c5t] foll[s ! guidance describ$ 9 clause 7vi7 & advises1 z appropriate1 on o!r relevant regulations1 guidances1 & policies4 7v7 ,9 seek+ ag5cy action ) respect to a comb9ation product1 ! sponsor ( su* product-- 7,i7 %all id5tify ! product z a comb9ation product2 & 7,,ii7 may reque/ 9 writ+ ! p>ticipation ( repres5tatives ( ! ,(fice 9 meet+s relat$ to su* comb9ation product1 or to h ! ,(fice o!rwise engage on su* regulatory matt]s conc]n+ ! comb9ation product4 7vi7 ,n lat] ?an #d ye>s aft] ! date ( enactm5t ( ! ,comb9ation ,product ,regulatory ,fairness ,act ( #bjaf1 & aft] a public comm5t p]iod ( n less ?an #fj cal5d> days1 ! ,secret>y %all issue a f9al guidance t describes-- 7,i7 ! responsibilities ( ea* ag5cy c5t] reg>d+ its review ( comb9ation products1 includ+ ea* c5t]'s role 9 evaluat+ evid5ce developm5t & review "u a risk-bas$ approa*1 dispute resolution1 label+1 product usability assessm5ts1 & human factors te/+2 7,,ii7 ! /ructur$ process = manag+ pre-submission int]actions ) sponsors develop+ comb9ation products2 7,,iii7 ! be/ practices = ensur+ t ! fe$back 9 su* pre-submission int]actions repres5ts ! ,ag5cy's be/ advice bas$ on ! in=mation provid$ dur+ su* pre-submission int]actions2 7,,iv7 ! be/ practices reg>d+ submissions by sponsors1 & review by ! ,secret>y1 ( comb9ation product review plans "u p>agraph 7#b71 includ+ ! appropriate tim+ = discussion & agreem5t ( su* plans1 & ! v>i\s elem5ts ( su* plans1 bas$ on sci5tific & te*nical und]/&+ dur+ product developm5t2 7,v7 ! ,secret>y's processes = ensur+ input f exp]ts f ea* relevant ag5cy c5t] 9 su* pre-submission int]actions ) sponsors develop+ comb9ation products & 9 fulfill+ ! requirem5ts ( ?is subsection2 7,,vi7 ! timel9es associat$ ) respond+ to1 & hold+ meet+s reg>d+1 comb9ation product review plans "u p>agraph 7#b72 & 7,,vii7 disputes appropriate = pres5tation to ! ,(fice z describ$ 9 subp>agraph 7,e77i74 4 7,b7 9 subp>agraph 7,e7-- 7i7 by /rik+ clause 7i7 & ins]t+ ! foll[+ new clause3 7i7 ,dur+ ! review process1 disputes betwe5 diff]5t ag5cy c5t]s reg>d+ ! sub/ance1 timel9ess1 review process1 requirem5ts1 or alignm5t ( ! prem>ket review ) respect to a comb9ation product1 includ+ conflict+ fe$back1 responses1 & decisions f su* ag5cy c5t]s1 may be pres5t$ to ! ,(fice by ! sponsor ( su* comb9ation product = resolution & ! ,(fice %all conv5e ! relevant p>ties & seek to resolve su* conflicts4 2 & 7ii7 9 clause 7ii71 by /rik+ ,dur+ ! review process1 any dispute reg>d+ ! sub/ance ( ! prem>ket review & ins]t+ ,any dispute rema9+ aft] ! process "u clause 7i7 is complet$2 7,c7 9 subp>agraph 7,f71 9 ! fir/ s5t5ce-- 7i7 by ins]t+ or t involves det]m9+ ! safety or efficacy1 reasonable assurance ( safety & efficacy1 or sub/antial equival5ce ( a compon5t ( a comb9ation product aft] assignm5t ( comb9ation products to ag5cy c5t]s2 & 7ii7 by ins]t+ & ) ! guidance describ$ 9 subp>agraph 7,c77vi7 be=e ! p]iod at ! end2 & 7,d7 9 subp>agraph 7,g7-- 7i7 9 clause 7ii71 by /rik+ & at ! end2 7ii7 9 clause 7iii71 by /rik+ ! p]iod at ! end & ins]t+ a semicolon2 & 7iii7 by add+ at ! end ! foll[+ new clauses3 7iv7 id5tify+ ! p]c5tage ( comb9ation products = :i* a dispute resolution1 ) respect to prem>ket review1 0 reque/$ by ! comb9ation product's sponsor2 7v7 /at+ ! av]age1 m$ian1 & range ( response times to comb9ation product review plans "u p>agraph 7#b72 7vi7 id5tify+ ! p]c5tage ( meet+s betwe5 ! ,food & ,drug ,adm9i/ration & ! sponsor ( a comb9ation product at :i* all ( ! ag5cy c5t]s p>ticipat+ 9 ! review ( ! comb9ation product 7 9 att5dance1 9 accordance ) subp>agraph 7,c77iv77,i72 & 7vii7 = ! report submitt$ 9 #bjag1 & 9 a report at lea/ once e #e ye>s !reaft]1 reg>d+ any recomm5dations to /reaml9e prem>ket review ( comb9ation products4 2 & 7#f7 9 p>agraph 7#i7 7z r$esignat$ by p>agraph 7#c77-- 7,a7 9 subp>agraph 7,c7-- 7i7 9 clause 7ii71 by /rik+ &2 7ii7 9 clause 7iii71 by /rik+ ! p]iod & ins]t+ 1 &2 & 7iii7 by add+ at ! end ! foll[+3 7iv7 de novo classification "u section #eac7;a77#a74 2 & 7,b7 by add+ at ! end ! foll[+3 7,d7 ,! t]ms prem>ket review & reviews include all activities ( ! ,food & ,drug ,adm9i/ration conduct$ prior to approval or cle>ance ( an application1 notification1 or reque/ = classification submitt$ "u section #eje1 #eaj7k71 #eac7;f77#b71 #eae1 or #ebj ( ?is ,act or "u section #cea ( ! ,public ,heal? ,s]vice ,act1 includ+ ) respect to inve/igational use ( ! product4 4 7b7 ,in=mation = approval ( comb9ation products ,section #ebj7;h77#d7 ( ! ,f$]al ,food1 ,drug1 & ,cosmetic ,act 7#ba ,u4,s4,c4 #cfj;j7 is am5d$-- 7#a7 9 subp>agraph 7,a71 by /rik+ ,any in=mation & ins]t+ 8,subject to subp>agraph 7,c71 any in=mation02 & 7#b7 by add+ at ! end ! foll[+ new subp>agraph3 7,c7 ,no in=mation conta9$ 9 an application = prem>ket approval fil$ ) ! ,secret>y pursuant to section #eae7;c7 may be us$ to approve or cle> any application submitt$ "u section #eae or #eaj7k7 or to classify a product "u section #eac7;f77#b7 = a comb9ation product conta9+ z a con/itu5t "p an 8approv$ drug0 z def9$ 9 section #ejc7;g77#e77;,b7 unless-- 7i7 ! application includes ! c]tification or /atem5t ref]5c$ 9 section #ejc7;g77#e77;,a72 7ii7 ! applicant provides notice z describ$ 9 ,section #ejc7;g77#e77;,a72 & 7iii7 ! ,secret>y's approval ( su* application is subject to ! provisions 9 section #ejc7;g77#e77;,c74 4 7c7 ,v>iations ,f ,,cgmp ,/reaml9$ ,approa* ,n lat] ?an #ah mon?s aft] ! date ( enactm5t ( ?is ,act1 ! ,secret>y %all id5tify types ( comb9ation products t ! ,secret>y proposes may adopt good manufactur+ practices t v>y f ! requirem5ts set =? 9 section #d4d ( title #ba1 ,code ( ,f$]al ,regulations 7or any successor regulations74 ,! ,secret>y %all id5tify su* types1 & id5tify v>iations f su* requirem5ts1 9 a propos$ li/ publi%$ 9 ! ,f$]al ,regi/]4 ,aft] a public comm5t p]iod reg>d+ ! appropriate good manufactur+ practices = su* types1 ! ,secret>y %all publi% a f9al li/ 9 ! ,f$]al ,regi/]1 not)/&+ section #eec ( title #e1 ,unit$ ,/ates ,code4 ,! ,secret>y %all evaluate su* types & su* appropriate v>iations us+ a risk-bas$ approa*4 ,! ,secret>y %all p]iodically review su* types on su* f9al li/1 includ+ :e!r additional types ( comb9ation products are appropriate = su* f9al li/4 ,april #e1 #bjaf,report$ ) an am5dm5t