FDC Ban – a well-in­tended but over­done de­vel­op­ment

BioSpectrum (India) - - BIO CONTENT -

Pushpa Vi­jayragha­van,

Director, Sathguru Man­age­ment Con­sul­tants

Shree Divyya,

Se­nior Con­sul­tant, Sathguru Man­age­ment Con­sul­tants

On July 26, the sub-com­mit­tee of Drugs Tech­ni­cal Ad­vi­sory Board (DTAB), the high­est drug ad­vi­sory body on tech­ni­cal mat­ters in the coun­try formed by the Health Min­istry, has rec­om­mended pro­hi­bi­tion of 343 fixed drug com­bi­na­tions (FDCs) af­ter re­view­ing 349 and called for reg­u­la­tion and re­stric­tion of re­main­ing six. The 12 mem­ber DTAB, which was re­con­sti­tuted in May 2018 with Director Gen­eral of Health Ser­vices (DGHS) Dr Promila Gupta as an ex-of­fi­cio chair­man and Drugs Con­troller Gen­eral of In­dia Dr S Eswara Reddy as an ex-of­fi­cio Mem­ber Sec­re­tary with 8 mem­bers (in­clud­ing Pankaj Pa­tel, Chair­man and Managing Director, Zy­dus Cadila Group) and 2 spe­cial in­vi­tees. The ex­pert sub-com­mit­tee in its re­ports sug­gested ban­ning 343 FDCs, three should be re­stricted for spe­cific in­di­ca­tions or dis­eases and other three FDCs should be re­stricted to spe­cific quan­ti­ties of in­gre­di­ents and for spe­cific in­di­ca­tions. It stated that for most FDCs, their use will lead to un­nec­es­sary overuse and pa­tients will be ex­posed to risk of mul­ti­ple in­gre­di­ents when one will suf­fice.

Although the re­port of the Drug Test­ing Ad­vi­sory Board (DTAB) sub-com­mit­tee con­sti­tuted to re­view 343 (plus 6) Fixed Dose Com­bi­na­tions (FDCs) is not yet in pub­lic do­main, it is akin to an ex­e­cu­tion sen­tence for sev­eral com­pa­nies and brands they have toiled to cre­ate. While the cof­fin is still not nailed, it has been an ar­du­ous and long drawn jour­ney so far for the 343 FDCs - On 10th March, 2016, based on the Kokate Com­mit­tee re­port, the health min­istry banned 344 FDC drugs. Given the sweep­ing busi­ness im­pli­ca­tions of this de­ci­sion, pharma com­pa­nies moved the Delhi High Court with 454 pe­ti­tions chal­leng­ing the de­ci­sion and claim­ing it was not done through a statu­tory body con­sul­ta­tion process. While this led to a with­drawal of the ban, the gov­ern­ment took this mat­ter to the Supreme Court which man­dated the DTAB to make fi­nal rec­om­men­da­tions. The pro­posed ban and the im­pend­ing judg­ment is bound to have far reach­ing im­pli­ca­tions for both, the Pharma in­dus­try and the In­dian pa­tients:

FDCs are not al­ways harm­ful and are clin­i­cally pre­ferred in sev­eral cases

There is no deny­ing that overuse or abuse of com­bi­na­tions could re­sult in un­in­tended harm to pa­tients. Specif­i­cally, FDCs with phar­ma­co­dy­namic mis­match be­tween the two com­po­nents, chem­i­cal non-com­pat­i­bil­ity and bizarre com­bi­na­tions of many in­gre­di­ents with or with­out ra­tio­nal­ity for their pres­ence and in the quan­tity com­bined are not ac­cept­able. How­ever, un­like the pop­u­lar in­fer­ence from de­vel­op­ments over the last cou­ple of years, FDCs are not al­ways harm­ful. In fact, FDCs are re­quired for the treat­ment of in­fec­tious dis­eases like HIV, hep­ati­tis-C, malaria and tu­ber­cu­lo­sis, where us­age of mul­ti­ple an­timi­cro­bial agents is nec­es­sary to com­bat the disease. The clin­i­cal im­por­tance of FDCs is ev­i­dent from the fact that even WHO’s list of Es­sen­tial medicines in­cludes about more than 30 FDCs as these drugs are use­ful for chronic con­di­tions, es­pe­cially when mul­ti­ple dis­or­ders co-ex­ist. Not just in in­fec­tious dis­eases, there is also sig­nif­i­cant clin­i­cal jus­ti­fi­ca­tion for use of FDCs in var­i­ous chronic con­di­tions. Glob­ally, they have gained pop­u­lar­ity as a means of en­sur­ing ease of use and ad­min­is­tra­tion as well. Given that no two FDCs are com­pa­ra­ble on clin­i­cal ra­tio­nale or harm to pa­tients, it is sur­pris­ing that a blan­ket de­ci­sion has been made with a sin­gle lens for the 343 FDCs cur­rently un­der con­sid­er­a­tion.

Reg­u­la­tory gaps that led to the prob­lem con­tinue to re­main un­plugged

Although Ap­pendix VI of Sched­ule Y (Drugs & Cos­met­ics Rules 1945, In­dia) pro­vides de­tails about the re­quire­ments for man­u­fac­ture/im­port ap­proval and mar­ket­ing of var­i­ous types of FDCs which in gen­eral, seeks jus­ti­fi­ca­tion and ther­a­peu­tic ra­tio­nale for com­bi­na­tion of ac­tive sub­stances, level of re­quire­ment to gen­er­ate new data is un­clear. There is also no spe­cific path­way for ap­proval of OTC drugs. In the ab­sence of reg­u­la­tory clar­ity, some of the drugs cur­rently banned were ap­proved by State Li­cens­ing Author­ity with no ap­proval from the CD­SCO and the oth­ers have ap­proval from no reg­u­la­tor in In­dia. The prob­lem was trigged by a com­bi­na­tion of reg­u­la­tory am­bi­gu­ity as well as the ten­dency of some com­pa­nies to take ad­van­tage of reg­u­la­tory gaps to launch un­ap­proved com­bi­na­tions.

The reg­u­la­tory gaps are em­phat­i­cally ev­i­dent when com­pared to a more evolved global con­text such as the US where there are sep­a­rate reg­u­la­tory path­ways for var­i­ous drug cat­e­gories in­clud­ing New Drug Ap­pli­ca­tions for NCES, re­for­mu­lated or re­pur­posed drugs through the 505(b)(2) path­way and the OTC path­way with Prod­uct Mono­graph for OTCs. While the 505(b)(2) path­way al­lows ref­er­enc­ing of data from the pre­vi­ously ap­proved drugs, the OTC path­way al­lows drugs to be launched with­out any ad­di­tional ap­proval from USFDA if ac­tive in­gre­di­ents (and dosage) be­ing used are as stated in the OTC mono­graph. The miss­ing OTC reg­u­la­tory path­way par­tic­u­larly rep­re­sents a glar­ing gap in the cur­rent land­scape.

Em­phatic ex­am­ple of stretch­ing too far – glob­ally sold OTC prod­ucts are now banned in In­dia

While the ban against 343 drugs and is jus­ti­fi­able in part of the list, merit of en­forc­ing the axe in sev­eral cases is ques­tion­able. Most poignant ex­am­ples of this reg­u­la­tory action be­ing more ex­treme than needed are the long suite of OTC drugs that are banned. Sev­eral OTC com­bi­na­tions have been glob­ally driven by clin­i­cian or con­sumer pref­er­ence, ease of use and clin­i­cal/ non-clin­i­cal ben­e­fit. Even the WHO and FDA in­di­cate ‘Ease of use’ for pa­tients and pre­scribers as a po­ten­tial ad­van­tage of FDCs. It is alarm­ing to note that many of the OTC com­bi­na­tions drugs banned are pop­u­lar off the shelf prod­ucts across sev­eral highly reg­u­lated mar­kets such as UK, US et al. In these reg­u­lated mar­kets, sim­i­lar OTC for­mu­la­tions are sold and are found to be in com­pli­ance with for­mu­la­tions per­mis­si­ble per the OTC mono­graphs. As il­lus­trated be­low, Vicks Action 500 now banned in In­dia has the same com­bi­na­tion as Ther­aflu sold in USA, UK. The only ad­di­tion in­gre­di­ent in Vicks Action 500 is caf­feine with lev­els com­pa­ra­ble to a can of coke or one third cup of cof­fee.

A fi­nal mixed out­come – pa­tient ben­e­fit in some cases but ero­sion of con­sumer choice and mar­kets in oth­ers

The ban is es­ti­mated to shave off close to Rs 7000 crore of erst­while peak rev­enues from the Pharma In­dus­try. It is a sig­nif­i­cant blow to the in­dus­try that has found it­self in the midst of a per­fect storm – two quar­ters im­pacted by de­mo­niza­tion and GST in In­dia, the FDC axe, API sup­ply con­straints and per­va­sive pric­ing pres­sure across global mar­kets.

From a con­sumer per­spec­tive, it is en­cour­ag­ing to see proac­tive reg­u­la­tory action in the in­ter­est of pa­tient safety and ben­e­fit. How­ever, with blan­ket de­ci­sions un­der­lined by re­dun­dancy in action, pa­tients could be de­nied ac­cess to con­ve­nient choices that cit­i­zens in sev­eral other coun­tries con­tinue to have. If OTC drugs avail­able in sev­eral other coun­tries are banned in In­dia and no clear reg­u­la­tory path­way is cre­ated for OTC drugs in In­dia, both in­dus­try and con­sumers stand to lose. Most im­por­tantly, a reg­u­la­tory en­vi­ron­ment that is not in­dus­try friendly could threaten do­mes­tic self­suf­fi­ciency in the longer term, and the In­dian pa­tients should be most in­se­cure about this im­pli­ca­tion. To en­sure such ca­su­al­ties don’t re­peat in the fu­ture, it is also im­por­tant that we ur­gently bridge reg­u­la­tory gaps and points of am­bi­gu­ity – es­pe­cially with cre­ation of a glob­ally com­pa­ra­ble OTC path­way. The pa­tient should con­tinue to be at the heart of ev­ery reg­u­la­tory de­ci­sion – but with greater un­der­stand­ing of im­pli­ca­tions for to­day, to­mor­row and the longer term.

(Note: The opin­ions dis­cussed here are based on the as­sump­tion that the DTAB sub-com­mit­tee re­port has

rec­om­mended ban of all 343 drugs re­viewed.)

Shree Divyya, Se­nior Con­sul­tant, Sathguru Man­age­ment Con­sul­tants

Pushpa Vi­jayragha­van, Director, Sathguru Man­age­ment Con­sul­tants

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