Se­rial testers: In­dia’s flawed generic drug tri­als busi­ness

Kuwait Times - - INTERNATIONAL -

Va­sudeva Prakash left his job as a me­chanic in Hy­der­abad three years ago for what he calls a more lu­cra­tive ca­reer: tak­ing part in clin­i­cal tri­als on generic drugs. For two years, Prakash par­tic­i­pated in tri­als of drugs be­ing tested to treat HIV/AIDS and other dis­eases for con­tract re­search or­ga­ni­za­tions (CROs) hired by global phar­ma­ceu­ti­cal com­pa­nies. The drugs tested at In­dian CROs have been key in get­ting sev­eral hun­dred medicines ap­proved for sale around the world.

Yet, Prakash did not fol­low in­ter­na­tional guide­lines for test­ing - and the CROs that hired him didn’t re­quire him to. He says that to earn more money he would par­tic­i­pate in back-to-back tri­als on dif­fer­ent drugs with gaps of only a few weeks or even a few days, in­stead of wait­ing the 90 days that the World Health Or­ga­ni­za­tion rec­om­mends.

Half of more than a dozen vol­un­teers in­ter­viewed by Reuters across four cities Chen­nai, Hy­der­abad, Ben­galuru, and New Delhi - also said they waited much less than 90 days be­tween tri­als. In the past three-to-four years, they said they spent sev­eral months at a time in dif­fer­ent cities so that they could par­tic­i­pate in as many stud­ies as pos­si­ble.

Prakash pro­vided doc­u­men­ta­tion prov­ing he un­der­went tri­als with short gaps at Apo­tex Re­search Pvt Ltd, owned by Cana­dian drug­maker Apo­tex Inc; Lo­tus Labs, owned by US gener­ics gi­ant Ac­tavis; Ethics Bio Lab, owned since last year by US drug­maker Par Phar­ma­ceu­ti­cal Inc; and In­dia’s Sem­ler Re­search Cen­ter Pvt Ltd, among oth­ers. Ethics Bio and Apo­tex did not re­spond to re­quests for com­ment. Lo­tus Labs and Sem­ler said they had sys­tems in place to check for cross-par­tic­i­pa­tion by trial vol­un­teers.

The guide­lines of the WHO, which de­cides on ap­provals for drugs sold in sev­eral coun­tries de­pen­dent on United Na­tions pro­grams for ba­sic medicines, are not le­gally-bind­ing for the CROs. While In­dia has guide­lines on clin­i­cal tri­als, they don’t spec­ify the length of time par­tic­i­pants should take be­tween tri­als.

Still, the se­rial test­ing of some vol­un­teers is rais­ing new ques­tions about the level of over­sight of In­dia’s generic drug tri­als in­dus­try, af­ter some CROs came un­der re­cent in­ter­na­tional reg­u­la­tory scru­tiny. Last year, the Euro­pean Medicines Agency banned about 700 medicines across Europe af­ter an in­ves­ti­ga­tion re­vealed data tam­per­ing in some tri­als of generic drugs in In­dia.

In­ter­na­tional med­i­cal ex­perts said that un­der­go­ing back-to-back tri­als en­dan­gers the health of pa­tients par­tic­i­pat­ing. It can also com­pro­mise clin­i­cal data gath­ered through th­ese tri­als, on the ba­sis of which drug­mak­ers seek ap­proval to sell generic medicines around the world. “The time gap be­tween par­tic­i­pa­tion in two dif­fer­ent tri­als should be 90 days min­i­mum,” said Stephanie Croft, a lead in­spec­tor at the WHO. “When is in­com­plete or in­cor­rect it could pose a se­ri­ous risk to pa­tients.”

Gya­nen­dra Nath Singh, head of In­dia’s na­tional drug watch­dog, the Cen­tral Drugs Stan­dard Con­trol Or­ga­ni­za­tion (CDSCO), said that it has been try­ing to in­spect more CROs in the past two years. The watch­dog is also con­sid­er­ing the in­tro­duc­tion of a trackand-trace sys­tem through which pa­tients can be tracked across CROs, he told Reuters. “We are em­pha­siz­ing on good reg­u­la­tory prac­tices some re­ports have shown that the CROs have de­vi­ated from (the) sys­tem,” said Singh. In­dia’s Health Min­istry did not re­spond to re­quests for com­ment.

Sev­eral large in­ter­na­tional drug­mak­ers, in­clud­ing Teva Phar­ma­ceu­ti­cal In­dus­tries Ltd and My­lan NV, rely on CROs in In­dia to carry out tests on cheaper ver­sions of branded drugs. The aim of th­ese so-called “bioe­quiv­a­lence” stud­ies is to gauge whether non-branded drugs are equally safe and ef­fec­tive. The faster the tri­als are un­der­taken, the faster the drugs can come to mar­ket.

In some ma­jor mar­kets, such as the United States, be­ing the first to launch generic guar­an­tees mar­ket ex­clu­siv­ity for a pe­riod of time, which can reap mil­lions more in sales. In­ter­na­tional and lo­cal reg­u­la­tors have strug­gled to keep its over­sight in line with the growth of an in­dus­try that ex­panded rapidly in the 2000s, as drug­mak­ers shipped clin­i­cal trial work to In­dia to save money. The mar­ket is es­ti­mated to have crossed $1 bil­lion in 2016, ac­cord­ing to con­sul­tants Frost and Sul­li­van.

Over the past two years, in­ter­na­tional reg­u­la­tors have sus­pended or banned medicines tested by four ma­jor In­dian CROs af­ter find­ing ma­nip­u­la­tion of clin­i­cal trial data and other vi­o­la­tions. Is­sues found at In­dian CROs are “a big prob­lem that is gain­ing more and more at­ten­tion from all sorts of agen­cies,” said An­ders Fuglsang, a con­sul­tant and for­mer reg­u­la­tor long in­volved in au­dits and in­spec­tions of CROs around the world on be­half of in­ter­na­tional reg­u­la­tory agen­cies and com­pa­nies.

Last year, the Euro­pean Union banned about 700 medicines that had been ap­proved based on clin­i­cal trial data pro­vided by GVK Bio­sciences, then In­dia’s largest CRO. Euro­pean reg­u­la­tors said they found GVK had ma­nip­u­lated data con­cern­ing the heart read­ings of pa­tients tak­ing part in the study. GVK de­nied any vi­o­la­tion, but sev­eral large drug­mak­ers that had won drug ap­provals based on GVK’s data were asked to re-ap­ply for ap­proval with fresh ev­i­dence.

Such re-test­ing is a headache for drug­mak­ers, as it is ex­pen­sive, and de­lays lead to a loss in sales, said Nilesh Gupta, man­ag­ing di­rec­tor of In­dia’s Lupin Ltd, which was one of the com­pa­nies to be af­fected by a US ban on tri­als by Sem­ler ear­lier this year. GVK, part of the In­dian con­glom­er­ate GVK Group, has since lim­ited its busi­ness in­ter­ests in the generic drugs test­ing busi­ness, said Shankar Chel­luri, a spokesman for the com­pany. Over­all, sen­ti­ment to­wards the generic drug tri­als busi­ness is weak, Chel­luri said.

Another CRO, Quest Life Sciences, was found last year to have ma­nip­u­lated clin­i­cal data on cer­tain tri­als, ac­cord­ing to in­spec­tion re­ports from the WHO and the UK’s medicines author­ity. The Span­ish and Ger­man reg­u­la­tors had also found prob­lems with Quest’s tri­als, and the WHO said it found Quest had fal­si­fied data on drugs in­clud­ing the an­tibi­otic doxy­cy­cline hy­clate and HIV/AIDS drugs lamivu­dine, zi­dovu­dine and nevi­rap­ine.

Quest man­ag­ing di­rec­tor TS Jais­hankar said his CRO, which has con­ducted dozens of generic drug tri­als for com­pa­nies in­clud­ing In­dia’s top drug­maker Sun Phar­ma­ceu­ti­cal In­dus­tries , has since in­vested heav­ily in im­prov­ing its sys­tems and been cleared by all in­ter­na­tional reg­u­la­tors. In a re­sponse to Reuters, a spokes­woman for the Euro­pean Medicines Agency said they were “closely mon­i­tor­ing” the in­volve­ment of Quest in the drug ap­proval ap­pli­ca­tions they re­ceive.

In­dia, like other coun­tries, has ethics com­mit­tees - groups of in­de­pen­dent ex­perts - meant to ap­prove the de­sign and con­duct of clin­i­cal tri­als. Their stamp of ap­proval is re­quired by for­eign reg­u­la­tors con­sid­er­ing al­low­ing a generic drug to be sold. How­ever, th­ese com­mit­tees de­pend on the CROs for re­im­burse­ment in ex­change for re­view­ing tri­als. Three mem­bers of dif­fer­ent com­mit­tees Reuters spoke to said na­tional guide­lines did not clearly de­fine their roles and re­spon­si­bil­i­ties.

Newspapers in English

Newspapers from Kuwait

© PressReader. All rights reserved.