FDA ex­plains plans for new phar­ma­ceu­ti­cal qual­i­ty as­sess­ment sys­tem

As part of its work to im­prove and mod­ern­ize the qual­i­ty as­sess­ment of drug ap­pli­ca­tions, the FDA is de­vel­op­ing a new, more stan­dard­ized sys­tem, to be known as the Knowl­edge-aid­ed As­sess­ment & Struc­tured Ap­pli­ca­tion (KASA), ac­cord­ing to an ar­ti­cle au­thored by of­fi­cials from the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search and pub­lished in the lat­est is­sue of the In­ter­na­tion­al Jour­nal of Phar­ma­ceu­tics.

The au­thors de­scribe KASA as a new sys­tem that cap­tures and man­ages in­for­ma­tion in a struc­tured for­mat about the in­her­ent risk and con­trol ap­proach­es for prod­uct de­sign, man­u­fac­tur­ing and fa­cil­i­ties.

The sys­tem is meant to help the FDA ad­dress chal­lenges re­lat­ed to its qual­i­ty as­sess­ments. The au­thors note that when a qual­i­ty as­ses­sor cur­rent­ly re­views a reg­u­la­to­ry ap­pli­ca­tion, “it is not pos­si­ble to eas­i­ly lo­cate his­tor­i­cal da­ta about sim­i­lar prod­ucts, process­es, or the fa­cil­i­ties. Such a prac­tice has sig­nif­i­cant­ly re­duced the ef­fi­cien­cy of the reg­u­la­to­ry as­sess­ment and in­creased the like­li­hood of in­con­sis­ten­cies. Fur­ther, in par­tic­u­lar­ly ur­gent cas­es, the FDA may not have read­i­ly avail­able up-to-date in­for­ma­tion to pro­vide time­ly, thor­ough, and com­plete re­spons­es, hin­der­ing the FDA’s reg­u­la­to­ry over­sight.”

But with KASA, cer­tain rules and al­go­rithms will be able to es­ti­mate the ini­tial in­her­ent prod­uct and man­u­fac­tur­ing risks.

“Af­ter the as­ses­sor en­ters in­for­ma­tion in the sys­tem based on the ap­pli­ca­tion, a fail­ure modes, ef­fects and crit­i­cal­i­ty analy­sis (FME­CA) ap­proach is em­ployed. This is used to ob­jec­tive­ly and quan­ti­ta­tive­ly as­sess and rank risks as­so­ci­at­ed with the fail­ure modes of drug prod­uct de­sign and man­u­fac­tur­ing. These are the risks that have the great­est chance of caus­ing prod­uct and man­u­fac­tur­ing fail­ure or un­ex­pect­ed harm to the pa­tient,” FDA of­fi­cials ex­plain.

KASA al­so will help with risk con­trols re­lat­ed to prod­uct de­sign and man­u­fac­tur­ing.

In ad­di­tion, the CDER of­fi­cials note that al­though KASA is be­ing pri­mar­i­ly de­vel­oped as an as­sess­ment tool, “it is ca­pa­ble of al­le­vi­at­ing prob­lems” as­so­ci­at­ed with the sub­mis­sion of drug ap­pli­ca­tions via the elec­tron­ic com­mon tech­ni­cal doc­u­ment (eCTD) for­mat.

In the fu­ture, the sub­mis­sion struc­ture rec­om­men­da­tions, such as those ini­ti­at­ed for stan­dard­iza­tion of Phar­ma­ceu­ti­cal Qual­i­ty/Chem­istry Man­u­fac­tur­ing and Con­trol (PQ/CMC) da­ta and ter­mi­nolo­gies could be made to in­ter­face with KASA’s struc­tured as­sess­ment ap­proach. “Un­der this par­a­digm, au­to­mat­ed tools would be used to pop­u­late the KASA tem­plate from the struc­tured sub­mis­sion with, for ex­am­ple, spec­i­fi­ca­tions and crit­i­cal process pa­ra­me­ter ranges,” the ar­ti­cle notes.

As far as the ma­jor ben­e­fits of this shift to a KASA sys­tem, the au­thors note that it “moves reg­u­la­to­ry ap­pli­ca­tion as­sess­ment from the cur­rent un­struc­tured text doc­u­ment to an is­sue-based reg­u­la­to­ry and tech­ni­cal as­sess­ment us­ing struc­tured da­ta and in­for­ma­tion with stan­dard for­mat­ting, a com­mon vo­cab­u­lary, and a uni­form out­put. In turn, this im­proves con­sis­ten­cy, trans­paren­cy, com­mu­ni­ca­tion, and ob­jec­tiv­i­ty of reg­u­la­to­ry ac­tions, as well as knowl­edge man­age­ment with­in the Agency.”

So, when is KASA com­ing?

The ar­ti­cle did not pro­vide a time­line, but the FDA said last Sep­tem­ber that a draft guid­ance would be re­leased for in­dus­try com­ment be­fore any­thing takes ef­fect.


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.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

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Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

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Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

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Stephen Hahn, AP

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