Doug Throckmorton speaks via video conference to the Senate Finance Committee, June 2, 2020 (Andrew Caballero-Reynolds, AP Images)

FDA de­fends its over­sight of for­eign drugs amid Sen­ate, GAO crit­i­cism

Dur­ing a Sen­ate Com­mit­tee on Fi­nance hear­ing Tues­day, of­fi­cials from the FDA re­spond­ed to crit­i­cism from sen­a­tors and a new re­port from the Gov­ern­ment Ac­count­abil­i­ty Of­fice (GAO) on its over­sight of for­eign drug man­u­fac­tur­ers.

The hear­ing fol­lows FDA’s move to halt most for­eign in­spec­tions in March as a re­sult of the coro­n­avirus dis­ease (COVID-19) pan­dem­ic.

Much of the crit­i­cism cen­tered on the agency’s prac­tice of giv­ing for­eign fa­cil­i­ties ad­vanced no­tice of in­spec­tions while most do­mes­tic sur­veil­lance in­spec­tions are unan­nounced, as well as US re­liance on for­eign drug man­u­fac­tur­ing.

Open­ing the hear­ing, Chair­man Chuck Grass­ley (R-IA) point­ed out that most man­u­fac­tur­ing sites for fin­ished drugs and ac­tive phar­ma­ceu­ti­cal in­gre­di­ents (API) are lo­cat­ed out­side the US. Oth­er sen­a­tors raised con­cerns about the se­cu­ri­ty of the US phar­ma­ceu­ti­cal sup­ply chain, in­clud­ing Sens. John Cornyn (R-TX) and Mark Warn­er (D-VA).

Doug Throck­mor­ton, deputy di­rec­tor for reg­u­la­to­ry pro­grams at FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search, told sen­a­tors that FDA is look­ing for ways to lever­age ad­vanced man­u­fac­tur­ing to both im­prove drug qual­i­ty and pro­mote the on­shoring of drug man­u­fac­tur­ing.

“CDER’s vi­sion is to spur the in­dus­try to mod­ern­ize so that qual­i­ty can be con­sis­tent­ly and re­li­ably built in­to each tablet and vial they pro­duce,” he said.

How­ev­er, Throck­mor­ton al­so ac­knowl­edged that FDA lacks some of the in­for­ma­tion to have a thor­ough un­der­stand­ing of the ear­li­er stages of the phar­ma­ceu­ti­cal sup­ply chain, such as the sources of chem­i­cals used to pro­duce API and the API them­selves.

“We know sub­stan­tial­ly less about the sources of those prod­ucts than we do about API and … we know less about API and its man­u­fac­tur­ing and dis­tri­b­u­tion than we do about fin­ished dosage forms,” Throck­mor­ton said.

Ju­dith McMeekin

In re­sponse to crit­i­cisms over FDA’s prac­tice of no­ti­fy­ing for­eign fa­cil­i­ties in ad­vance of in­spec­tions, Ju­dith McMeekin, as­so­ciate com­mis­sion­er for reg­u­la­to­ry af­fairs at FDA’s Of­fice of Reg­u­la­to­ry Af­fairs (ORA) said that pre­an­nounc­ing in­spec­tions helps to avoid po­ten­tial re­fusals and con­serve FDA re­sources.

McMeekin al­so point­ed out that both for­eign and do­mes­tic man­u­fac­tur­ers are held to the same stan­dards and that FDA must deal with ju­ris­dic­tion­al dif­fer­ences in con­duct­ing for­eign in­spec­tions. Be­cause FDA does not have the same au­thor­i­ties that it does in the US when op­er­at­ing in oth­er coun­tries, the pre­an­nounce­ment process gives the agency a chance to doc­u­ment a firm’s agree­ment to al­low an in­spec­tion, McMeekin said. When a for­eign firm re­fus­es an in­spec­tion, FDA may take oth­er ac­tions to ad­dress the safe­ty of the US drug sup­ply, such as plac­ing the firm on Im­port Alert.

“The FDA does not draw up­on the same en­force­ment mech­a­nisms or have a com­pa­ra­ble lev­el of in­fra­struc­ture,” McMeekin said, not­ing that in the US the agency can seek a war­rant if a firm re­fus­es in­spec­tion.

McMeekin al­so lat­er clar­i­fied that FDA does con­duct some unan­nounced in­spec­tions in oth­er coun­tries, but they are typ­i­cal­ly for-cause in­spec­tions. She said she does not know how many unan­nounced in­spec­tions the agency con­duct­ed in In­dia and Chi­na in 2019.

Mary Deni­gan-Macauley

How­ev­er, GAO’s Mary Deni­gan-Macauley told sen­a­tors that GAO feels “that unan­nounced in­spec­tions are very im­por­tant … but they are very few and it does raise ques­tions about the equiv­a­len­cy to what we do here in the Unit­ed States.” In 2018, GAO found that on­ly a small per­cent­age of in­spec­tions car­ried out by FDA’s Chi­na and In­dia of­fice in­ves­ti­ga­tors were unan­nounced or con­duct­ed on short no­tice, while most of FDA’s for­eign in­spec­tions were car­ried out by US-based in­ves­ti­ga­tors and were typ­i­cal­ly pre­an­nounced 12 weeks in ad­vance.

When asked by Sen. Mag­gie Has­san (D-NH) about FDA’s de­ci­sion to halt for­eign in­spec­tions amid the COVID-19 pan­dem­ic, Deni­gan-Macauley said that, “The fact that [for­eign in­spec­tions have] stopped – I un­der­stand the need for be­ing able to pro­tect their own peo­ple – but it is con­cern­ing and I would want to en­sure that the oth­er steps that they have in place are rig­or­ous.”

Has­san re­spond­ed by say­ing she be­lieves “FDA’s de­ci­sion to cur­tail in­spec­tions is in­ap­pro­pri­ate.”


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