Phar­ma­co­ge­net­ics: FDA re­leas­es ta­ble of gene-drug in­ter­ac­tions

The FDA on Thurs­day pub­lished a ta­ble iden­ti­fy­ing more than 50 gene-drug in­ter­ac­tions that the agency says are sup­port­ed by sci­en­tif­ic ev­i­dence and an­nounced it is con­sid­er­ing new ap­proach­es to eval­u­at­ing phar­ma­co­ge­net­ic as­so­ci­a­tions.

“Con­sis­tent with our mis­sion to pro­tect and pro­mote pub­lic health, we be­lieve it is im­por­tant to take steps now to help en­sure that claims be­ing made for phar­ma­co­ge­net­ic tests of­fered to­day are ground­ed in sound sci­ence to avoid in­ap­pro­pri­ate man­age­ment of pa­tients’ med­ica­tions,” said Cen­ter for De­vices and Ra­di­o­log­i­cal Health Di­rec­tor Jeff Shuren and Cen­ter for Drug Eval­u­a­tion and Re­search Di­rec­tor Janet Wood­cock.

Back­ground

The re­lease of the ta­ble comes af­ter years of grap­pling over how the FDA should ap­proach phar­ma­co­ge­net­ic (PGx) test­ing and the broad­er field of lab­o­ra­to­ry de­vel­oped tests (LDTs). In 2018, the FDA is­sued a safe­ty com­mu­ni­ca­tion and state­ment ad­vis­ing that many ge­net­ic tests pur­port­ing to pre­dict a pa­tient’s re­sponse to med­ica­tions have not been re­viewed by the agency and may not be sup­port­ed by sci­en­tif­ic or clin­i­cal ev­i­dence.

At the same time, var­i­ous in­dus­try groups, in­clud­ing the Amer­i­can Clin­i­cal Lab­o­ra­to­ry As­so­ci­a­tion (ACLA) and the Coali­tion to Pre­serve Ac­cess to Phar­ma­coge­nomics In­for­ma­tion, have pushed back against the FDA’s ef­forts to crack down on phar­ma­co­ge­net­ics tests.

In a cit­i­zen pe­ti­tion filed last month on be­half of the Coali­tion to Pre­serve Ac­cess to Phar­ma­coge­nomics In­for­ma­tion, law firm Hy­man, Phelps & Mc­Na­ma­ra called on the FDA to re­vise its safe­ty com­mu­ni­ca­tion to state that test mak­ers “may com­mu­ni­cate in­for­ma­tion about gene-drug in­ter­ac­tions as part of ge­net­ic test re­ports to the ex­tent that such in­for­ma­tion is sup­port­ed by ad­e­quate ev­i­dence and is not con­traindi­cat­ed by in­for­ma­tion in drug la­bels.”

Phar­ma­co­ge­net­ics As­so­ci­a­tions Table

The FDA says the ta­ble is “in­tend­ed to pro­vide the agency’s view of the state of the cur­rent sci­ence in phar­ma­co­ge­net­ics” and in­cludes es­tab­lished gene-drug in­ter­ac­tions that ap­pear in la­bel­ing and some in­ter­ac­tions that, while not ap­pear­ing in la­bel­ing, are sup­port­ed by suf­fi­cient sci­en­tif­ic ev­i­dence.

The ta­ble al­so de­notes phar­ma­co­ge­net­ic as­so­ci­a­tions that may in­di­cate an im­pact on a drug’s safe­ty or a pa­tient’s re­sponse and gene-drug as­so­ci­a­tions for which an im­pact has not been es­tab­lished.

The FDA stress­es that the ta­ble is not com­plete and that it will con­tin­ue to re­view sci­en­tif­ic ev­i­dence, in­clud­ing guide­lines de­vel­oped by the Clin­i­cal Phar­ma­co­ge­net­ics Im­ple­men­ta­tion Con­sor­tium, to ex­pand the list. The agency has al­so opened a pub­lic dock­et to so­lic­it com­ments from stake­hold­ers on spe­cif­ic phar­ma­co­ge­net­ic as­so­ci­a­tions that should or should not be con­sid­ered for the ta­ble.

The ta­ble comes with a host of dis­claimers, in­clud­ing that, “Each pa­tient’s ge­net­ic make­up is on­ly one of many fac­tors that may im­pact drug con­cen­tra­tions and re­sponse,” and that the FDA does not nec­es­sar­i­ly en­dorse phar­ma­co­ge­net­ic tests for in­ter­ac­tions in­clud­ed on the list.

The FDA al­so says the ta­ble “is not in­tend­ed to af­fect cur­rent reg­u­la­to­ry re­quire­ments or poli­cies, in­clud­ing the FDA’s pol­i­cy re­gard­ing com­pan­ion di­ag­nos­tics. Nor is the ta­ble in­tend­ed to make an as­sess­ment on the safe and ef­fec­tive use of, or reg­u­la­to­ry re­quire­ments for, tests that de­tect vari­ants in the ref­er­enced genes, or to pro­vide com­pre­hen­sive in­for­ma­tion on the de­scribed gene-drug in­ter­ac­tions.”

De­spite those dis­claimers, the list could of­fer in­sight to phar­ma­co­ge­net­ic test mak­ers on what the agency con­sid­ers suf­fi­cient ev­i­dence to sup­port spe­cif­ic phar­ma­co­ge­net­ic as­so­ci­a­tions.


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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