Janet Woodcock, acting FDA commissioner (AP Images)

FDA is­sues new rec­om­men­da­tions to take on Covid-19 vari­ants

The FDA on Mon­day un­veiled rec­om­men­da­tions for vac­cine, drug and di­ag­nos­tic test de­vel­op­ers to ad­dress the im­pact of Covid-19 vari­ants on the ef­fi­ca­cy and per­for­mance of their prod­ucts.

The rec­om­men­da­tions are made across four new and up­dat­ed guid­ances tar­get­ing vac­cines, drugs and bi­o­log­ics, mon­o­clon­al an­ti­bod­ies and di­ag­nos­tic tests.

“The pur­pose of these guid­ances is to ad­dress the emer­gence and po­ten­tial fu­ture emer­gence of vari­ants of SARS-CoV-2, the virus that caus­es COVID-19. The rea­son for these guid­ances is any of these prod­ucts might be im­pact­ed by changes to the virus, par­tic­u­lar­ly their ef­fi­ca­cy or per­for­mance. There­fore, we need to iden­ti­fy ef­fi­cient ways to mod­i­fy the prod­ucts that are ei­ther in the pipeline or are [emer­gency use au­tho­riza­tion] EUA prod­ucts to ad­dress these vari­ants,” Act­ing FDA com­mis­sion­er Janet Wood­cock said dur­ing a press con­fer­ence.

Wood­cock al­so said that au­tho­rized or ap­proved prod­ucts for Covid-19 should be mon­i­tored to en­sure that if per­for­mance is al­tered, the agency and man­u­fac­tur­ers are aware right away.

Sev­er­al vari­ants of the SARS-CoV-2 virus, in­clud­ing those first iden­ti­fied in the Unit­ed King­dom (B.1.1.7), South Africa (B.1.351) and Brazil (B.1.1.28), have raised in­ter­na­tion­al con­cern as they ap­pear to be more trans­mis­si­ble and may di­min­ish the ef­fi­ca­cy of cer­tain treat­ments or vac­cines. FDA has al­so warned that some ge­net­ic vari­ants of the virus may con­found the re­sults of mol­e­c­u­lar tests, po­ten­tial­ly lead­ing to false neg­a­tives.

The re­lease of the new and up­dat­ed guid­ance comes weeks af­ter Wood­cock an­nounced that such guid­ance would be forth­com­ing. The EMA has al­so said that it will pro­vide its own guid­ance up adapt­ing vac­cines for Covid-19 vari­ants.

While the guid­ance was re­leased pub­licly on Mon­day, Wood­cock said that FDA “has al­ready been com­mu­ni­cat­ing with the in­di­vid­ual med­ical prod­uct spon­sors to pro­vide in­for­ma­tion and sci­en­tif­ic ad­vice as they eval­u­ate the im­pact of these vari­ants on their prod­ucts,” and that the agency is re­leas­ing the guid­ances as a mat­ter of trans­paren­cy and to gath­er feed­back.

Wood­cock al­so em­pha­sized that con­tain­ing the virus and new vari­ants will re­quire a glob­al ef­fort. “The virus, wher­ev­er it is repli­cat­ing, is mu­tat­ing, and so as long as there’s a large amount of in­fec­tion around the world, prob­a­bly ad­di­tion­al virus vari­ants will emerge. We need a glob­al ap­proach to this glob­al pan­dem­ic,” she said.


FDA has so far au­tho­rized vac­cines de­vel­oped by Pfiz­er-BioN­Tech and Mod­er­na for emer­gency use and is set to re­view John­son & John­son’s sin­gle-shot vac­cine at a Vac­cines and Re­lat­ed Bi­o­log­i­cal Prod­ucts Ad­vi­so­ry Com­mit­tee meet­ing lat­er this week.

“At this time, as you know, avail­able da­ta sug­gests the FDA-au­tho­rized vac­cines are ef­fec­tive in pro­tect­ing the Amer­i­can pub­lic against cir­cu­lat­ing strains of SARS-CoV-2; how­ev­er, if there’s an emer­gence of vari­ants in the Unit­ed States that are mod­er­ate­ly or ful­ly re­sis­tant to the an­ti­body re­sponse elicit­ed by the cur­rent gen­er­a­tion of COVID-19 vac­cines, it may be nec­es­sary to mod­i­fy vac­cines or the vac­ci­na­tion reg­i­men,” Wood­cock said.

In an up­date to its guid­ance on EUAs for Covid-19 vac­cines, FDA de­tails the non­clin­i­cal, clin­i­cal and chem­istry, man­u­fac­tur­ing and con­trols (CMC) da­ta need­ed to sup­port an amend­ment to an EUA.

“As­sum­ing the pro­to­type vac­cine has been au­tho­rized un­der an EUA it is ex­pect­ed that the mod­i­fied COVID-19 vac­cine against a SARS-CoV-2 vari­ant made by the same man­u­fac­tur­er and process as the pro­to­type COVID-19 vac­cine would be au­tho­rized through an EUA amend­ment to the EUA for the pro­to­type COVID-19 vac­cine,” FDA writes in a new ap­pen­dix in the guid­ance. FDA notes that the guid­ance does not ad­dress how it will be de­ter­mined that an up­dat­ed vac­cine will be need­ed, which pro­tein se­quences should be ex­pressed or the fol­low-up of mod­i­fied vac­cines, nor does it ad­dress mul­ti­va­lent COVID-19 vac­cines.

Ther­a­peu­tics and mon­o­clon­al an­ti­bod­ies

For ther­a­peu­tics, FDA has up­dat­ed its ex­ist­ing guid­ance on de­vel­op­ing drugs and bi­o­log­ics for Covid-19 and is­sued a new guid­ance specif­i­cal­ly tai­lored to the de­vel­op­ment of mon­o­clon­al an­ti­bod­ies to ad­dress the emer­gence of vari­ants.

“We have up­dat­ed this guid­ance, since a lot has hap­pened over the last months to ad­dress the evolv­ing land­scape of COVID-19 drug de­vel­op­ment, in­clud­ing the emer­gence of vari­ants and the avail­abil­i­ty of au­tho­rized COVID-19 vac­cines,” Wood­cock said.

The guid­ance now in­cludes an ap­pen­dix on con­duct­ing drug re­sis­tance analy­sis, in­clud­ing rec­om­men­da­tions for drug de­vel­op­ers to con­tin­u­ous­ly mon­i­tor for emerg­ing SARS-CoV-2 vari­ants. “We will do this as well,” Wood­cock said, “We will con­tin­u­ous­ly mon­i­tor the sit­u­a­tion and up­date our plans as more in­for­ma­tion be­comes avail­able.”

In FDA’s new guid­ance on de­vel­op­ing mon­o­clon­al an­ti­bod­ies for Covid-19, FDA de­tails the ap­proach­es to gen­er­at­ing non­clin­i­cal, clin­i­cal and CMC da­ta to sup­port an EUA for an­ti­body prod­ucts that neu­tral­ize spe­cif­ic vari­ants of the virus.

“We know that some of the mon­o­clon­al an­ti­bod­ies that are cur­rent­ly au­tho­rized are less ac­tive against some of the SARS-CoV-2 vari­ants that have emerged and are preva­lent in some parts of the world,” Wood­cock said. “For­tu­nate­ly, there are a lot of mon­o­clon­als in the pipeline … we can fair­ly eas­i­ly un­der­stand their per­for­mance against dif­fer­ent vari­ants, so we have a lot of pri­or knowl­edge about this to work on.”

In the guid­ance, FDA “strong­ly rec­om­mends” that mon­o­clon­al an­ti­bod­ies be de­vel­oped with the ex­pec­ta­tion that they will be com­bined with one or more oth­er mon­o­clon­al an­ti­bod­ies that bind to dif­fer­ent epi­topes to min­i­mize the risk of los­ing ac­tiv­i­ty against new vari­ants. FDA al­so rec­om­mends that spon­sors mon­i­tor ge­nom­ic data­bas­es for emerg­ing vari­ants and eval­u­ate the neu­tral­iz­ing ac­tiv­i­ty of mon­o­clon­al an­ti­bod­ies against cir­cu­lat­ing vari­ants.


In a new guid­ance, FDA sets out its pol­i­cy for eval­u­at­ing the im­pact of vi­ral mu­ta­tions on Covid-19 tests.

“There’s a lot of tests out there and we need the man­u­fac­tur­ers to be vig­i­lant and make sure that their tests are not im­pact­ed ad­verse­ly by changes to the virus,” Wood­cock said.

The guid­ance pro­vides spe­cif­ic rec­om­men­da­tions for as­sess­ing the im­pact of vi­ral mu­ta­tions on mol­e­c­u­lar di­ag­nos­tics, anti­gen tests and serol­o­gy tests and ex­plains that FDA is con­sid­er­ing in­clud­ing a con­di­tion of au­tho­riza­tion for test de­vel­op­ers in EUAs that would re­quire them to eval­u­ate the im­pact of virus mu­ta­tions on test per­for­mance. The guid­ance al­so dis­cuss­es de­sign con­sid­er­a­tions for mak­ing tests more ro­bust against changes in the virus.

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