Pop­u­la­tion phar­ma­co­ki­net­ics: Drug­mak­ers seek clar­i­ty and ad­di­tions to re­vised FDA guid­ance

About a dozen drug­mak­ers and in­dus­try groups re­cent­ly of­fered their opin­ions on a re­vised FDA draft guid­ance re­lat­ed to pop­u­la­tion phar­ma­co­ki­net­ics (PK) analy­ses sub­mit­ted as part of new drug ap­pli­ca­tions and bi­o­log­ic li­cense ap­pli­ca­tions.

The com­ments large­ly seek spe­cif­ic tweaks to the 23-page re­vised draft, which was re­leased in Ju­ly, al­though some of the com­ments al­so seek fur­ther clar­i­ty and new ad­di­tions to the guid­ance.

In­dus­try group PhRMA, for in­stance, rec­om­mends that the FDA add more spe­cif­ic ex­am­ples or lit­er­a­ture ref­er­ences through­out “to pro­vide de­tail to the high-lev­el rec­om­men­da­tions and to sup­port the tech­ni­cal state­ments.” The FDA al­so should pro­vide spe­cif­ic ex­am­ples of where pop­u­la­tion PK da­ta may al­le­vi­ate the need for a post­mar­ket­ing re­quire­ment or post­mar­ket­ing com­mit­ment, PhRMA says.

Bay­er, mean­while, takes is­sue with the FDA’s in­clu­sion of an ex­ec­u­tive sum­ma­ry in the pop­u­la­tion PK re­port that should fo­cus on the key find­ings af­fect­ing ap­proval or la­bel de­ci­sion or any oth­er rec­om­men­da­tion based on the pop­u­la­tion PK analy­sis.

“Al­though Bay­er agrees that an ex­ec­u­tive sum­ma­ry could be ben­e­fi­cial, the pop­u­la­tion PK re­port is not the cor­rect place. Clin­i­cal in­ter­pre­ta­tion and la­bel de­ci­sion re­quire, in gen­er­al, an as­sess­ment of the all of the da­ta e.g. the re­sult of ex­po­sure re­sponse analy­sis and clin­i­cal safe­ty and ef­fi­ca­cy re­sults of the piv­otal study needs to be avail­able. Very of­ten pop­u­la­tion PK mod­els are de­vel­oped at dif­fer­ent stages of drug de­vel­op­ment and re­port­ed ear­li­er,” Bay­er adds.

The com­pa­ny al­so rais­es the con­cern that the struc­ture of the re­port will not be aligned with the Eu­ro­pean Med­i­cines Agency and Japan’s PM­DA guide­line, as well as the gen­er­al struc­ture of clin­i­cal re­ports.

In ad­di­tion, Astel­las seeks fur­ther specifics from the FDA, not­ing that the draft in­cludes “sub­jec­tive and non-quan­ti­ta­tive terms,” such as “ad­e­quate,” “suf­fi­cient,” “rel­e­vant” and “nar­row.”

“While we ap­pre­ci­ate that the Agency means for the guid­ance to be flex­i­bly in­ter­pret­ed, more quan­ti­ta­tive terms or sug­gest­ed ranges would be ap­pre­ci­at­ed,” Astel­las says.

Pfiz­er pro­pos­es adding a new sec­tion to the draft, ti­tled: “A. Scope of Da­ta for In­clu­sion in Pop­u­la­tion PK Analy­sis” to dis­cuss the use of da­ta from healthy vol­un­teer tri­als “to sup­port the struc­tur­al mod­el and aid com­par­i­son be­tween dif­fer­ent pop­u­la­tions be­fore the cur­rent sec­tion A on study sub­jects and co­vari­ates.”

And Re­gen­eron, among oth­er com­ments, rec­om­mends re­struc­tur­ing the rec­om­men­da­tions for the as­sess­ment of the ef­fects of co­vari­ates “such that all dis­cus­sions are pooled in­to a ded­i­cat­ed sec­tion spe­cif­ic to this top­ic. Such a sec­tion will pro­vide Spon­sors with a clear and con­cise re­source to guide the writ­ing of this com­po­nent of the pop­u­la­tion PK re­port in prepa­ra­tion for ap­ply­ing for mar­ket­ing au­tho­riza­tion.”


RAPS: 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.

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