FDA re­vis­es 1999 draft guid­ance on pop­u­la­tion phar­ma­co­ki­net­ics

The FDA on Thurs­day re­leased re­vised draft guid­ance to help keep spon­sors in­formed on the da­ta and mod­el re­quire­ments for pop­u­la­tion phar­ma­co­ki­net­ics (PK) analy­ses sub­mit­ted as part of new drug ap­pli­ca­tions and bi­o­log­ic li­cense ap­pli­ca­tions.

Since the orig­i­nal pop­u­la­tion PK guid­ance was pub­lished in 1999, the FDA says the num­ber of ap­pli­ca­tions rel­e­vant for pop­u­la­tion PK analy­sis has in­creased and, “The so­phis­ti­ca­tion and re­li­a­bil­i­ty of pop­u­la­tion PK analy­sis meth­ods have im­proved.”

Specif­i­cal­ly, the re­vised, 23-page draft guid­ance in­cludes a de­scrip­tion of the types of sci­en­tif­ic and reg­u­la­to­ry ques­tions ap­pro­pri­ate for pop­u­la­tion PK analy­sis and out­lines the FDA’s rec­om­men­da­tions for da­ta analy­sis and mod­el­ing. Rec­om­men­da­tions on the for­mat and con­tent of pop­u­la­tion PK re­ports sub­mit­ted to the FDA as well as any la­bel­ing state­ments in­formed by the re­sults of these analy­ses are al­so in­clud­ed.

“Pop­u­la­tion PK analy­sis typ­i­cal­ly in­cludes da­ta di­rect­ly col­lect­ed from pa­tients, al­low­ing an as­sess­ment of mul­ti­ple in­trin­sic and ex­trin­sic fac­tors that are not oth­er­wise eval­u­at­ed in healthy vol­un­teers,” the draft says. “In ad­di­tion, the rel­a­tive­ly large num­bers of pa­tients in­clud­ed in pop­u­la­tion PK analy­sis may im­prove the pre­ci­sion of the es­ti­mat­ed ef­fect of the fac­tors that af­fect drug ex­po­sures and con­firm which fac­tors do not change drug ex­po­sures.”

The draft ad­dress­es the ap­pli­ca­tion of pop­u­la­tion PK analy­sis in drug de­vel­op­ment and to in­form drug use, with fur­ther dis­cus­sions on se­lect­ing dos­ing reg­i­mens to be test­ed in clin­i­cal tri­als, de­riv­ing ex­po­sure met­rics for con­duct­ing ex­po­sure-re­sponse analy­sis, pe­di­atric study de­signs and drug-drug in­ter­ac­tions, among oth­er sec­tions.

The sec­tion on da­ta analy­sis al­so pro­vides fur­ther help on the method­olog­i­cal as­pects of pop­u­la­tion PK analy­sis and in­cludes a dis­cus­sion of sim­u­la­tions based on pop­u­la­tion PK mod­els, which touch­es on fixed-ef­fect es­ti­mates and es­ti­mates of be­tween-sub­ject vari­abil­i­ty.

At the end of the draft, the FDA al­so in­cludes a ta­ble ex­plain­ing the ex­pect­ed con­tent in each sec­tion of the pop­u­la­tion PK study re­port.

Pop­u­la­tion Phar­ma­co­ki­net­ics: Draft Guid­ance for In­dus­try

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: FDA, AP Im­ages


Zachary Brennan

managing editor, RAPS

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