A bad dose hits Chi­nese vac­cine player

BioSpectrum (Asia) - - FRONT PAGE - Narayan Kulka­rni narayan.kulka­rni@mmac­tiv.com

The Chi­nese gov­ern­ment has de­tained all the vac­cines in­volved, avoided giv­ing pa­tients a prob­lem vac­cine, and stopped the Changchun Chang­sheng Biotech­nol­ogy Co., Ltd’s vac­cine pro­duc­tion when it con­ducted a flight in­spec­tion of the pro­duc­tion site of the com­pany and it was found that the com­pany had record fraud dur­ing the pro­duc­tion of the batch of ra­bies vac­cine.

Re­act­ing

to the se­ri­ous­ness of this is­sue and to timely dis­cover and elim­i­nate po­ten­tial risks in the pro­duc­tion of vac­cines, the CFDA has con­ducted com­pre­hen­sive and

thor­ough risk in­ves­ti­ga­tion in less than six weeks. The re­sults of the in­ves­ti­ga­tion showed that the ex­ist­ing vac­cine va­ri­eties

in the pro­duc­tion en­ter­prises are nor­mal, and no prob­lems af­fect­ing the qual­ity and

safety of the vac­cine have been found.

On July 5, based on the clues, the China State Food and Drug Ad­min­is­tra­tion (CFDA), China’s drug reg­u­la­tor and the Jilin Provin­cial Bu­reau, con­ducted a flight in­spec­tion of Changchun Chang­sheng Biotech­nol­ogy Co., Ltd, en­gaged in re­search, de­vel­op­ment, pro­duc­tion and sale of hu­man vac­cine prod­ucts. The com­pany’s main prod­ucts in­clude live at­ten­u­ated freeze-dried vari­cella vac­cine, freeze-dried hu­man ra­bies vac­cine (Vero cells), freeze-dried live at­ten­u­ated hep­ati­tis A vac­cine, in­fluenza ly­sis vac­cine, DTP vac­cine, ad­sorp­tion of cell-free diph­the­ria com­bined vac­cine and ACYW Group 135 meningo­coc­cal polysac­cha­ride vac­cine. The com­pany dis­trib­utes its prod­ucts in the do­mes­tic mar­ket as well as over­seas mar­kets.

Again on July 15, both the agen­cies formed an in­ves­ti­ga­tion team to con­duct com­pre­hen­sive in­ves­ti­ga­tions and is­sued the “No­tice on July 22 on Changchun Chang­sheng Biotech­nol­ogy Co., Ltd.’s il­le­gal pro­duc­tion of freeze-dried hu­man ra­bies vac­cine.”

It has been found that the com­pany fab­ri­cates pro­duc­tion records and prod­uct in­spec­tion records, and ar­bi­trar­ily changes process pa­ram­e­ters and equip­ment. The above acts are a se­ri­ous vi­o­la­tion of the rel­e­vant pro­vi­sions of the Drug Ad­min­is­tra­tion Law of the Peo­ple’s Repub­lic of China and the Reg­u­la­tions on the Qual­ity Man­age­ment of Phar­ma­ceu­ti­cal Pro­duc­tion. The drug reg­u­la­tor has or­dered en­ter­prises to stop pro­duc­tion, re­cover the GMP cer­tifi­cate for drugs, and re­call un­used ra­bies vac­cines. The CFDA and the Jilin Provin­cial Bu­reau have filed in­ves­ti­ga­tions on en­ter­prises, and the sus­pected crimes have been trans­ferred to the pub­lic se­cu­rity

or­gans for crim­i­nal re­spon­si­bil­ity.

The per­son in charge of the in­ves­ti­ga­tions said that it was the se­cond time in a year that the qual­ity of the com­pany’s prod­uct was found to be not of good qual­ity. In Oc­to­ber last year, the orig­i­nal food and drug su­per­vi­sion bu­reau found in the sam­pling test that the batch of Baibai bro­ken vac­cine pro­duced by the com­pany was un­qual­i­fied, and the prod­uct is still in pro­duc­tion. The for­mer Na­tional Health and Safety Com­mis­sion and the orig­i­nal food medicine are re­lated to the re­plant­ing work. The Gen­eral Ad­min­is­tra­tion of Su­per­vi­sion has de­ployed in Fe­bru­ary this year.

Ac­cord­ing to the rel­e­vant reg­u­la­tions on vac­cine man­age­ment, the vac­cines for sale and mar­ket­ing of all en­ter­prises must be sub­mit­ted to the China Food and Drug Con­trol Re­search In­sti­tute for ap­proval. The safety of all batches of vac­cines should be tested dur­ing the batch is­suance process, and the ef­fec­tive­ness of a cer­tain pro­por­tion of batches of vac­cines should be tested. The com­pany has been legally tested for the sale and use of vac­cines, and no qual­ity prob­lems have been found. In or­der to fur­ther con­firm the ef­fec­tive­ness of the vac­cines al­ready in the mar­ket, a lab­o­ra­tory eval­u­a­tion of sam­ples has been ini­ti­ated.

Re­act­ing to the de­vel­op­ments, on the af­ter­noon of July 23, the na­tion’s drug reg­u­la­tor held an en­larged meet­ing to con­vey the spirit of the im­por­tant in­struc­tions of Xi Jin­ping, Pres­i­dent of China on the Jilin Changchun Longevity Vac­cine Case and to study and im­ple­ment the mea­sures. Li Li, sec­re­tary of the party group and deputy di­rec­tor, presided over the meet­ing. Xu Jinghe, a mem­ber of the party group and deputy di­rec­tor, at­tended the meet­ing. The di­rec­tor Jiao Hong at­tended the meet­ing and the per­son in charge of the rel­e­vant de­part­ment of the bu­reau was also present.

Ac­cord­ing to the re­ports, the meet­ing pointed out that the im­por­tant in­struc­tions of Xi Jin­ping, Pres­i­dent of China and at­taches great im­por­tance to the health of the peo­ple, and fur­ther in­ves­ti­gates and han­dles cases, in­ves­ti­gates po­ten­tial risks, im­proves the vac­cine man­age­ment sys­tem, and re­sponds to so­ci­ety. Con­cerns, pointed out the di­rec­tion, and pro­vided com­pli­ance. The CFDA should con­sci­en­tiously im­ple­ment the spirit of the im­por­tant in­struc­tions of the in­cum­bent Gen­eral Sec­re­tary Ping Ping and the in­struc­tions of Premier Li Ke­qiang, firmly es­tab­lish the “four aware­nesses”, im­prove the

po­lit­i­cal po­si­tion, en­hance po­lit­i­cal acu­men, and have a high sense of re­spon­si­bil­ity and mis­sion, in ac­cor­dance with the “four aware­nesses”. The most strin­gent re­quire­ments are to fully pro­tect the over­all safety of the peo­ple in drug use and so­cial se­cu­rity and sta­bil­ity.

The meet­ing de­cided that first, on the ba­sis of the pre­lim­i­nary work, fur­ther in­crease the num­ber of per­son­nel, en­rich the strength of the in­ves­ti­ga­tion and han­dling work lead­ing group, and fully co­op­er­ate with the in­ves­ti­ga­tion team of the State Coun­cil.

The se­cond is to con­duct a thor­ough in­ves­ti­ga­tion of the en­tire process of pro­duc­tion and sales of all Changchun Chang­sheng vac­cines, to find out the truth as soon as pos­si­ble, and to lock up ev­i­dence clues. The third is to per­sis­tently at­tack with heavy punches, se­verely pun­ish those who are not pun­ished, and use them to be ef­fec­tive. The fourth is to solve the hot is­sues of con­cern to the peo­ple and do a good job in solv­ing prob­lems. The fifth is to make a com­pre­hen­sive in­ves­ti­ga­tion of the na­tional vac­cine pro­duc­tion en­ter­prises, and strictly in­ves­ti­gate the risks. The sixth is to sys­tem­at­i­cally an­a­lyze the vac­cine life cy­cle su­per­vi­sion sys­tem, an­a­lyze the crux of the prob­lem one by one, and study and im­prove the vac­cine man­age­ment sys­tem in China.

The State Coun­cil in­ves­ti­ga­tion team in­ves­ti­gated that the com­pany’s pro­duc­tion of un­qual­i­fied

Baibai bro­ken vac­cine in­volves the same batch of 201605014-01 and 201605014-02 the batch num­ber of prod­ucts to­talled 499,800.

The in­ves­ti­ga­tion found that com­pany pro­duced a to­tal of 252,600 batches of 201605014-01 Baibai Break­ing Vac­cine, all of which were sold to Shan­dong Prov­ince, 247,359 pieces have been used, and 5,241 losses and stor­ages have been used. Batch num­ber 201605014-02 Baibai bro­ken vac­cine has a to­tal of 247,200, of which 223,800 are sold to Shan­dong, and more than 10,000 are sealed; 23,400 are sold to An­hui, and 3,277 are lost and sealed.

On Au­gust 7, CFDA is­sued a cir­cu­lar stat­ing that the Na­tional Health Com­mit­tee and the State Food and Drug Ad­min­is­tra­tion have for­mu­lated Vac­ci­na­tion pro­gramme in all lo­cal­i­ties, where ra­bies vac­cines from Changchun Chang­sheng Com­pany were ad­min­is­tered.

The chil­dren who were in­oc­u­lated with the batch num­ber 201605014-01 un­qual­i­fied DTP (diph­the­ria-tetanus-per­tus­sis) vac­cine pro­duced by the com­pany have been re­planted ac­cord­ing to the re­plant­ing work no­tice on Fe­bru­ary 6 this year. As of now, 76.2 per cent of the to­tal num­ber of chil­dren to be re­ha­bil­i­tated has been com­pleted. The fol­lowup doses that have not been re­planted need to be

de­ter­mined ac­cord­ing to the ac­tual vac­ci­na­tion sit­u­a­tion of the af­fected chil­dren.

The Na­tional Health Com­mis­sion and the CFDA have made ar­range­ments for the re­plant­ing of chil­dren who have been in­oc­u­lated with Changchun Chang­sheng Com­pany’s batch num­ber 20160501402.

In or­der to com­pre­hen­sively eval­u­ate the risk of vac­ci­na­tion of Chang­bai Chang­sheng Co., Ltd., the China Food and Drug Ad­min­is­tra­tion In­sti­tute used the rapid vac­cine test method for all batches of DTP vac­cine dur­ing the va­lid­ity pe­riod of the com­pany for

anti­gen de­tec­tion. No ab­nor­mal­i­ties were found.

At present, an in-depth in­ves­ti­ga­tion into the sus­pected vi­o­la­tions of law by com­pany for the pro­duc­tion of un­qual­i­fied DTP vac­cine is un­der­way. The vi­o­la­tions of laws and reg­u­la­tions and per­son­nel shall be se­verely pun­ished ac­cord­ing to the law, and the lo­cal gov­ern­ments and com­pe­tent au­thor­i­ties with su­per­vi­sory re­spon­si­bil­i­ties shall be held ac­count­able for their dere­lic­tion of duty, de­fault, over­sight and in­ac­tion.

Ac­cord­ing to the in­ves­ti­ga­tion team, since

April 2014, Changchun Chang­sheng Com­pany has se­ri­ously vi­o­lated the rel­e­vant reg­u­la­tions on the qual­ity man­age­ment reg­u­la­tions for phar­ma­ceu­ti­cal pro­duc­tion and the na­tional drug stan­dards in the process of pro­duc­ing ra­bies vac­cine. Some batches are mixed with ex­pired stock so­lu­tion, and the date and batch num­ber are not truth­fully filled. Some batches are marked back­wards with the date of man­u­fac­ture. Cur­rently, the re­call is in progress. The vac­cines in­volved in the case were sold abroad, and the no­ti­fi­ca­tion and re­call work was ini­ti­ated.

In or­der to as­sess the safety and ef­fec­tive­ness risks of the vac­cines that have been mar­keted, the State Coun­cil in­ves­ti­ga­tion team has es­tab­lished an ex­pert group con­sist­ing of ex­perts in vi­rol­ogy, vac­ci­nol­ogy, epi­demi­ol­ogy, clin­i­cal medicine, vac­ci­na­tion, health emer­gency, and qual­ity con­trol. In-depth in­ves­ti­ga­tion and anal­y­sis were con­ducted. Ex­perts com­pre­hen­sively eval­u­ated and rec­om­mended that the vac­ci­na­tion unit has not com­pleted the vac­ci­na­tion pro­gramme, and the vac­ci­na­tion unit will con­tinue to con­tin­u­ally ad­min­is­ter other qual­i­fied vac­cines.

Ac­cord­ing to the char­ac­ter­is­tics of ra­bies, those who have com­pleted the vac­ci­na­tion pro­gram do not need to re­plant. If the re­cip­i­ent has the will­ing­ness to re­plant, the in­oc­u­la­tion unit can re­plen­ish the seed free of charge af­ter no­ti­fy­ing the pre­ven­tion and con­trol knowl­edge, the pro­tec­tion of the vac­cine, and the pre­cau­tions af­ter in­oc­u­la­tion.

Ac­cord­ing to the World Health Or­ga­ni­za­tion’s re­port on ra­bies pub­lished in April 2018, the in­cu­ba­tion pe­riod for ra­bies is usu­ally 1-3 months, rarely more than 1 year.

Af­ter con­tin­u­ing its in­ves­ti­ga­tion in this case re­vealed many loop­holes such as the lack of su­per­vi­sion by the for­mer State Food and Drug Ad­min­is­tra­tion and the State Drug Ad­min­is­tra­tion, the lack of su­per­vi­sion and guid­ance, and the over­sight of the com­pany. On Au­gust 17, 2018, it was de­cided by the State Ad­min­is­tra­tion of Mar­ket Su­per­vi­sion to dis­miss six se­nior of­fi­cials in the ad­min­is­tra­tion. The dis­missed ones in­clude Ding Jian­hua, Di­rec­tor of the Drug and Cos­met­ics Su­per­vi­sion De­part­ment of the State Food and Drug Ad­min­is­tra­tion (the State Drug Ad­min­is­tra­tion) and Di­rec­tor of the Food and Drug In­spec­tion and In­spec­tion Cen­ter; Dong Run­sheng, deputy di­rec­tor of the Drug and Cos­met­ics Su­per­vi­sion De­part­ment of the for­mer State Food and Drug Ad­min­is­tra­tion (the State Drug Ad­min­is­tra­tion); Sun Jinglin, deputy di­rec­tor of the De­part­ment of Drug and Cos­metic Su­per­vi­sion of the for­mer State Food and Drug Ad­min­is­tra­tion (Na­tional Drug Ad­min­is­tra­tion) (Novem­ber 2014 to April 2017, deputy di­rec­tor of the Food and Drug In­spec­tion and In­spec­tion Cen­ter of the for­mer State Food and Drug Ad­min­is­tra­tion) Dis­missal; Ye Guo­qing, the di­rec­tor of the Spe­cial Drug Su­per­vi­sion Divi­sion of the Drug and Cos­met­ics Su­per­vi­sion De­part­ment of the for­mer State

Food and Drug Ad­min­is­tra­tion (the State Drug Ad­min­is­tra­tion); Guo Xi­uxia, an in­ves­ti­ga­tor of the Spe­cial Drug Su­per­vi­sion De­part­ment of the Drug and Cos­metic Su­per­vi­sion De­part­ment of the for­mer State Food and Drug Ad­min­is­tra­tion (Na­tional Drug Ad­min­is­tra­tion) and Wang Youchun, vice pres­i­dent of China Food and Drug Ad­min­is­tra­tion Re­search In­sti­tute.

Li Bo, the dean (Di­rec­tor) of the China Food and Drug Ad­min­is­tra­tion Re­search In­sti­tute (for­merly

the State Food and Drug Ad­min­is­tra­tion Gen­eral Ad­min­is­tra­tion of Med­i­cal De­vice Stan­dards Man­age­ment), was asked to make an in-depth ex­am­i­na­tion in the case.

The in­ves­ti­ga­tion team, on Au­gust 23 has sus­pected of se­ri­ous vi­o­la­tions of the law by Wang Lifeng, for­mer di­rec­tor of the Drug and Cos­met­ics Regis­tra­tion and Man­age­ment De­part­ment of the State Food and Drug Ad­min­is­tra­tion, and is cur­rently un­der­go­ing dis­ci­plinary re­view and sur­veil­lance in­ves­ti­ga­tions.

Ac­cord­ing to the mon­i­tor­ing by the Chi­nese Cen­ter for Dis­ease Con­trol and Pre­ven­tion, the in­ci­dence of ra­bies in China has grad­u­ally de­clined in re­cent years.

In or­der to timely dis­cover and elim­i­nate po­ten­tial risks in the pro­duc­tion of vac­cines, the

State Food and Drug Ad­min­is­tra­tion has sent 45 in­spec­tion teams from July 23 to Au­gust 9, and has 45 vac­cine pro­duc­tion en­ter­prises in the coun­try (ex­clud­ing Changchun Chang­sheng Biotech­nol­ogy Co., Ltd.) to con­duct com­pre­hen­sive and thor­ough risk in­ves­ti­ga­tion. Ac­cord­ing to the drug pro­duc­tion qual­ity man­age­ment stan­dard (drug GMP) cri­te­ria, the re­sults of the in­ves­ti­ga­tion showed that the ex­ist­ing vac­cine va­ri­eties in the pro­duc­tion en­ter­prises are nor­mal, and no prob­lems af­fect­ing the qual­ity and safety of the vac­cine have been found.

Ac­cord­ing to CFDA re­lease on Septem­ber 7, af­ter in­ves­ti­ga­tion, among the 45 vac­cine man­u­fac­tur­ers, 38 vac­cine man­u­fac­tur­ers can or­ga­nize pro­duc­tion ac­cord­ing to the re­quire­ments of drug GMP, and es­tab­lish a rel­a­tively com­plete qual­ity man­age­ment sys­tem; staffing, fa­cil­i­ties and equip­ment meet pro­duc­tion re­quire­ments, and pro­duc­tion and de­sign ca­pac­ity match. The qual­ity of the vac­cine can be con­trolled in ac­cor­dance with the re­quire­ments of the Chi­nese Phar­ma­copoeia and the drug regis­tra­tion stan­dards. Seven vac­cine pro­duc­tion en­ter­prises have been sus­pended for more than three years due to the ex­pi­ra­tion of the li­cense, the fail­ure to ap­ply for re­place­ment, the poor man­age­ment of the com­pany, and the ren­o­va­tion of the work­shop. No prod­ucts are cir­cu­lat­ing in the mar­ket.

The State Food and Drug Ad­min­is­tra­tion said that it will res­o­lutely im­ple­ment the cen­tral gov­ern­ment’s de­ci­sion on the in­ves­ti­ga­tion and han­dling of the vac­cine case of Jilin Changchun Chang­sheng Com­pany, ef­fec­tively strengthen the su­per­vi­sion of vac­cine qual­ity, timely iden­tify and elim­i­nate po­ten­tial risks, and en­sure the safety of the peo­ple. It is nec­es­sary to im­ple­ment the daily su­per­vi­sion re­spon­si­bil­ity of the provin­cial drug reg­u­la­tory au­thor­i­ties for vac­cine man­u­fac­tur­ers, main­tain the high pres­sure on the su­per­vi­sion of vac­cine prod­ucts; im­ple­ment the main re­spon­si­bil­ity of en­ter­prises, fur­ther im­prove the qual­ity man­age­ment sys­tem, es­tab­lish a qual­ity and safety trace­abil­ity sys­tem, and im­ple­ment a prod­uct risk re­port­ing sys­tem; Guide­lines for the is­suance of vac­cines for batches of vac­cines, es­pe­cially for ra­bies vac­cines, ra­bies vac­cines, po­lio vac­cines, etc., which are more com­plex in pro­duc­tion pro­cesses and qual­ity con­trol, com­pre­hen­sively en­hance risk con­trol; in­crease the in­ten­sity of flight in­spec­tions and fol­low-up in­spec­tions, and timely strictly in­ves­ti­gate and deal with vi­o­la­tions of laws and reg­u­la­tions.

The Food and Drug Ad­min­is­tra­tion has de­ployed na­tional vac­cine pro­duc­tion en­ter­prises to con­duct self-in­spec­tion to en­sure that en­ter­prises or­ga­nize pro­duc­tion ac­cord­ing to the ap­proved tech­nol­ogy, strictly abide by GMP pro­duc­tion stan­dards, and all pro­duc­tion in­spec­tion process data should be true, com­plete, re­li­able and trace­able. The State Food and Drug Ad­min­is­tra­tion will or­ga­nize the flight in­spec­tion of all vac­cine pro­duc­tion en­ter­prises, and se­ri­ously in­ves­ti­gate and deal with vi­o­la­tions of laws and reg­u­la­tions.

Newspapers in English

Newspapers from India

© PressReader. All rights reserved.