FDA rolls out ex­pec­ta­tions for a loom­ing reg­u­la­to­ry shift for in­sulin and oth­er bi­o­log­ics

Cer­tain bi­o­log­ics will be re­moved from the FDA’s Or­ange Book on 23 March 2020 and in­clud­ed in the Pur­ple Book, and all sub­se­quent fol­low-on ap­pli­cants will not be able to re­ly up­on these new drug ap­pli­ca­tions for ap­proval but will have to win ap­proval as biosim­i­lars un­der new pro­posed rules on biosim­i­lar de­vel­op­ment.

The agency on Tues­day re­leased two new draft Q&A guid­ance doc­u­ments on biosim­i­lar de­vel­op­ment and the “deemed to be a li­cense” pro­vi­sion of the Bi­o­log­ics Price Com­pe­ti­tion and In­no­va­tion Act of 2009 (BP­CIA), as well as two fi­nal guid­ance doc­u­ments on the same top­ics and one pro­posed rule amend­ing the de­f­i­n­i­tion of a bi­o­log­i­cal prod­uct.

The ef­forts are part of the FDA’s decade-long work to be­gin — start­ing in March 2020 — tran­si­tion­ing the ap­proved mar­ket­ing ap­pli­ca­tions for a sub­set of bi­o­log­i­cal prod­ucts, such as in­sulin and hu­man growth hor­mone — which were pre­vi­ous­ly ap­proved as drugs un­der sec­tion 505 of the FD&C Act — to be deemed to be bi­o­log­ics li­cens­es.

The fi­nal guid­ance al­so de­scribes the FDA’s plans for sup­ple­ments to ap­proved NDAs that re­main pend­ing on 23 March 2020. “We in­tend to ad­min­is­tra­tive­ly con­vert these pend­ing NDA sup­ple­ments to pend­ing BLA sup­ple­ments un­der the PHS Act,” the agency said. In­dus­try pre­vi­ous­ly took is­sue with the FDA’s in­ten­tions on the mat­ter.

Got­tlieb Com­ments

While high­light­ing the need to bring down the price of in­sulin, FDA Com­mis­sion­er Scott Got­tlieb ex­plained at the CMS/FDA Sum­mit in Wash­ing­ton DC on Tues­day that the goal of the guid­ances and new poli­cies is two-fold: to min­i­mize spon­sors’ abil­i­ty to game the ex­clu­siv­i­ty pro­vi­sions and fore­stall biosim­i­lar en­try, and to make sure that when drugs tran­si­tion in­to bi­o­log­ics, they do not re­ceive ad­di­tion­al ex­clu­siv­i­ties that they are not en­ti­tled to.

In ad­di­tion to the guid­ance doc­u­ments and pro­posed rule, Got­tlieb ex­plained that the FDA is is­su­ing no­tice of how it will — up­on re­quest — re­view study pro­to­cols sub­mit­ted by biosim­i­lar ap­pli­cants to as­sess whether their pro­to­cols con­tain com­pa­ra­ble safe­ty pro­tec­tions to those in the risk eval­u­a­tion and mit­i­ga­tion strat­e­gy (REMS) for the prod­uct they’re try­ing to ref­er­ence — as ex­plained in the re­vised draft Q&A on biosim­i­lar de­vel­op­ment and the BP­CI Act.

“If re­quest­ed, the FDA will is­sue a let­ter to the ref­er­ence prod­uct hold­er in­form­ing them that com­pa­ra­ble pro­tec­tions ex­ist, and that the FDA won’t con­sid­er it to be a vi­o­la­tion of the brand­ed drug com­pa­ny’s REMS to pro­vide the biosim­i­lar spon­sor with a suf­fi­cient quan­ti­ty of the ref­er­ence prod­uct to per­form test­ing nec­es­sary to sup­port its biosim­i­lar ap­pli­ca­tion,” Got­tlieb said.

Rule and Guid­ance

New ques­tions in the re­vised draft Q&A al­so in­clude more in­for­ma­tion on the na­ture and type of in­for­ma­tion that a spon­sor should pro­vide to sup­port a post-ap­proval man­u­fac­tur­ing change for a li­censed biosim­i­lar prod­uct.

Oth­er new ques­tions, which the agency re­spond­ed no to, in­clude: “May a spon­sor seek ap­proval, in a 351(k) ap­pli­ca­tion or a sup­ple­ment to an ap­proved 351(k) ap­pli­ca­tion, of a route of ad­min­is­tra­tion, a dosage form, or a strength that is not the same as that of the ref­er­ence prod­uct?” and “May a spon­sor seek ap­proval, in a 351(k) ap­pli­ca­tion or a sup­ple­ment to an ap­proved 351(k) ap­pli­ca­tion, for a con­di­tion of use that has not pre­vi­ous­ly been ap­proved for the ref­er­ence prod­uct?”

The oth­er Q&A doc­u­ment fea­tures nu­mer­ous ques­tions and an­swers on biosim­i­lar­i­ty or in­ter­change­abil­i­ty, pro­vi­sions re­lat­ed to the re­quire­ment to sub­mit a BLA for a bi­o­log­i­cal prod­uct, and ex­clu­siv­i­ty.

The fi­nal and draft guid­ances on the “deemed to be a li­cense” pro­vi­sion spell out the tran­si­tion pe­ri­od for the bi­o­log­ics to which the pro­vi­sion ap­plies, how to iden­ti­fy prod­ucts sub­ject to the tran­si­tion, statu­to­ry or reg­u­la­to­ry re­quire­ments for BLAs, and tran­si­tion­ing bi­o­log­ics from the Or­ange to the Pur­ple Book.

The pro­posed rule, mean­while, would amend FDA’s reg­u­la­tion that de­fines “bi­o­log­i­cal prod­uct” to make a tech­ni­cal re­vi­sion and to con­form to the statu­to­ry de­f­i­n­i­tion en­act­ed in the BP­CIA.

Im­age: Scott Got­tlieb SHUT­TER­STOCK

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.


Zachary Brennan

managing editor, RAPS

John Hood [file photo]

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