CMIC: Japan’s first and largest CRO con­tin­ues 30-year evo­lu­tion to help glob­al spon­sors nav­i­gate the com­plex lo­cal mar­ket

Japan’s clin­i­cal tri­al land­scape has vast­ly ex­pand­ed over the last 30 years and CMIC has been at the fore­front of the coun­try’s evo­lu­tion in drug de­vel­op­ment. In the 80s, as for­eign com­pa­nies faced dif­fi­cul­ties en­ter­ing the Japan­ese mar­ket, CEO and founder Kazuo Naka­mu­ra saw op­por­tu­ni­ties to con­vert his con­sul­tan­cy busi­ness in­to Japan’s first CRO in 1992. As cus­tomer needs ex­pand­ed, CMIC al­so adapt­ed, lat­er adding CD­MO, SMO and CSO arms to the group. Now, with over 7,500 em­ploy­ees and op­er­a­tions around the globe, CMIC has firm­ly es­tab­lished it­self as the go-to play­er for in­ter­na­tion­al com­pa­nies seek­ing to bet­ter un­der­stand the reg­u­la­to­ry and com­mer­cial nu­ances of the Japan­ese and APAC mar­kets.

As CMIC looks to con­tin­ue its growth, it is lever­ag­ing its Per­son­al Health Val­ue Cre­ator (PHVC) busi­ness mod­el to pro­mote pa­tient-cen­tric drug de­vel­op­ment with its ther­a­peu­tic ex­per­tise and pa­tient sup­port so­lu­tions. CMIC al­so aims to con­tin­ue in­no­vat­ing with new tech­nol­o­gy plat­forms that sup­port dig­i­tal­iza­tion of the health­care mar­ket. The com­pa­ny’s ap­proach to drug de­vel­op­ment is based on the Japan­ese-orig­i­nat­ed con­cept IKI­GAI, help­ing pa­tients “live life to the fullest.” CMIC hopes to part­ner with in­ter­na­tion­al com­pa­nies de­ter­mined to achieve that ob­jec­tive for pa­tients.

Kazuo Naka­mu­ra, CEO and founder, and Keiko Oishi, pres­i­dent and COO, share their in­sights in­to CMIC Group’s unique sto­ry, while out­lin­ing their vi­sion for the fu­ture.

In­ter­view­er:

• Ar­salan Arif, Pub­lish­er & Founder, End­points News

In­ter­vie­wees:

• Kazuo Naka­mu­ra, Ph.D. – Founder & CEO, CMIC Group
• Keiko Oishi, Pres­i­dent & COO, CMIC Group

End­points: Kazuo, as the founder of the firm, can you tell us a lit­tle about the phar­ma­ceu­ti­cal ser­vice mar­ket in Japan 30 years ago and what drove you to cre­ate Japan’s first CRO? 

Kazuo Naka­mu­ra: In the 80s, Japan­ese phar­ma­ceu­ti­cal com­pa­nies were in the top ech­e­lon of glob­al drug de­vel­op­ment with top 10 sales fig­ures world­wide. To­wards the end of the 80s, biotech com­pa­nies were launch­ing prod­ucts like ery­thro­poi­etin – which is when CROs start­ed to play a cru­cial role in biotech drug de­vel­op­ment and ap­provals. In the 90s, biotech com­pa­nies like Genen­tech emerged with re­searchers who were re­cent col­lege grad­u­ates – and who pre­ferred to cre­ate new ther­a­pies rather than han­dle down­stream process­es like tri­als and ap­provals.

See­ing the suc­cess of Genen­tech and in­vest­ment groups like Gold­man Sachs sup­port­ing such ac­tiv­i­ties, I felt a press­ing need to make this hap­pen in Japan. As a for­mer re­search sci­en­tist I thought of run­ning my own biotech, but it re­quired big cap­i­tal in­vest­ments. The CRO idea emerged be­cause it matched with my glob­al mar­ket and reg­u­la­to­ry ex­pe­ri­ence. While Japan’s reg­u­la­to­ry bod­ies didn’t ban the idea of CROs, it was a brand-new busi­ness mod­el with­out prece­dent and it took us five years of ne­go­ti­a­tion and com­mu­ni­ca­tion to start the CRO busi­ness.

Japan was lack­ing the in­fra­struc­ture for out­sourc­ing at that time, so I start­ed work­ing as a con­sul­tant for US-based biotech Am­gen and helped them en­ter the Japan­ese mar­ket. It took a lot of time and ef­fort to build the CRO busi­ness here from scratch, but as bar­ri­ers pre­vent­ed for­eign CROs from en­ter­ing the Japan­ese mar­ket, we seized the chance to es­tab­lish the first CRO in Japan. In the fol­low­ing years, we built the Site Man­age­ment Or­ga­ni­za­tion (SMO) and Con­tract De­vel­op­ment and Man­u­fac­tur­ing Or­ga­ni­za­tion (CD­MO) busi­ness­es in the same way.

While fast glob­al ex­pan­sion mod­els go for M&A in an ear­li­er stage, I would say the re­al val­ue for Japan­ese CROs is through the Phar­ma­ceu­ti­cal Val­ue Chain (PVC) busi­ness mod­el I de­vised to make us the best CRO in our mar­ket. I al­so worked with founders from Quin­tiles, PPD and Parex­el who re­spect­ed that I start­ed the CRO busi­ness in Japan from scratch.

End­points: How has CMIC grown and its mis­sion ex­pand­ed over the last three decades, par­tic­u­lar­ly around shift­ing mar­ket dy­nam­ics? Can you share some im­por­tant mile­stones? 

Kazuo Naka­mu­ra: The biggest mile­stone was when we start­ed our busi­ness in Japan in a small “rab­bit hatch.” The founder of a lead­ing glob­al CRO in­vit­ed us to his grand vil­la and of­fered to ac­quire our busi­ness. I thought dili­gent­ly about his per­sis­tent of­fer, but I want­ed to pre­serve my orig­i­nal­i­ty in the busi­ness and chose not to sell the com­pa­ny. By not fo­cus­ing on glob­al ex­pan­sion and clin­i­cal tri­als, we had more vec­tors of ex­pan­sion for how the CRO busi­ness mod­el could be es­tab­lished in Asia. See­ing what we have achieved, I’m re­lieved about my choice.

Keiko Oishi: CMIC start­ed as the first CRO in Japan in 1992. We ex­pand­ed the busi­ness to in­clude the SMO, CD­MO and Con­tract Sales Or­ga­ni­za­tion (CSO) over the past 30 years, and es­tab­lished the Phar­ma­ceu­ti­cal Val­ue Cre­ator (PVC) busi­ness mod­el to sup­port phar­ma and biotech drug de­vel­op­ment through the en­tire val­ue chain. Our com­pa­ny has grown to meet the cus­tomers’ needs and to adapt to the chang­ing reg­u­la­tions.

We cur­rent­ly have over 7,500 em­ploy­ees and 26 sub­sidiaries – with of­fices and fa­cil­i­ties in 14 coun­tries in­clud­ing the US, Japan, Chi­na, South Ko­rea, Sin­ga­pore, and more. CMIC is list­ed on the Prime Mar­ket of Tokyo Stock Ex­change. As of Sep­tem­ber 30th, 2022, our an­nu­al sales grew 26.4% to 108.461 bil­lion JPY on a con­sol­i­dat­ed ba­sis.

End­points: What would you say are some key dif­fer­en­tia­tors or unique of­fer­ings that CMIC has ver­sus oth­er providers in Japan that clients val­ue the most?  

Keiko Oishi: CMIC Group is the on­ly end-to-end so­lu­tion provider in Japan with CRO, CD­MO, SMO, CSO ser­vices. CMIC’s CD­MO busi­ness start­ed in 2005 when full-out­sourc­ing of drug man­u­fac­tur­ing was ap­proved in Japan. It was a chal­leng­ing de­ci­sion to en­ter the CD­MO mar­ket know­ing it re­quires up-front in­vest­ment for in­fra­struc­ture and equip­ment, but we’ve since ex­pand­ed our CD­MO busi­ness with four man­u­fac­tur­ing sites in Japan, one in South Ko­rea and one in the US.

In Japan, we are the on­ly ser­vice com­pa­ny that pro­vides end-to-end so­lu­tions from non­clin­i­cal to clin­i­cal, from drug for­mu­la­tion to com­mer­cial man­u­fac­tur­ing, and from mar­ket ac­cess to post-mar­ket sup­port. We con­tin­ue to sup­port our clients’ needs across pa­tient-cen­tric so­lu­tions for drug de­vel­op­ment and pro­vide ther­a­peu­tic ex­per­tise in on­col­o­gy, CNS and or­phan drug stud­ies. We al­so con­duct de­cen­tral­ized clin­i­cal tri­als (DCT), link­ing re­al-world da­ta through the CMIC har­mo® and nanacara® plat­form and ad­dress lo­cal pa­tients’ needs through our Pa­tient Sup­port Pro­gram.

Kazuo Naka­mu­ra: Our CD­MO busi­ness has had a par­tic­u­lar­ly ad­van­ta­geous jour­ney. In the past, for­eign coun­tries’ CD­MOs tried to pro­duce drug-ac­tive in­gre­di­ents and prod­ucts at low costs lead­ing to alarm­ing qual­i­ty is­sues. This led to many phar­ma com­pa­nies from around the world seek­ing al­ter­na­tives and com­ing to CMIC for man­u­fac­tur­ing. We feel blessed to have built this qual­i­ty, trust­ed and world-class busi­ness in Japan.

End­points: As the largest CRO in Japan, how much in­volve­ment do you have in new drug de­vel­op­ment in the coun­try?

Keiko Oishi: To­day, CMIC Group is in­volved in close to 80% of new drug de­vel­op­ment and fil­ings in Japan. We are al­so in­volved in near­ly 70% of new on­col­o­gy drug de­vel­op­ment. CMIC is the lead­ing IC­CC (In-Coun­try Clin­i­cal Care­tak­er) with the largest num­ber of stud­ies among CROs in Japan. We are al­so in the top three of largest CD­MOs and top two of largest CSOs in Japan.

End­points: What type of spon­sors does CMIC usu­al­ly work with and are there any ther­a­peu­tic ar­eas or stages of drug de­vel­op­ment that the firm has par­tic­u­lar strengths/suc­cess in? 

Keiko Oishi: Half of our clients are lo­cal Japan­ese com­pa­nies vary­ing from small-to-large sized firms. We al­so work with a broad range of glob­al clients, from multi­na­tion­als to small and medi­um-sized en­ter­pris­es and biotech com­pa­nies. CMIC can act as an IC­CC for for­eign spon­sors, con­duct­ing pro­ce­dures for reg­u­la­to­ry au­thor­i­ties, med­ical in­sti­tu­tions, etc., on the spon­sor’s be­half. As the Japan­ese CRO with the most IC­CC study ex­pe­ri­ence, we un­der­stand the reg­u­la­tions, can best nav­i­gate dis­cus­sions with Japan’s reg­u­la­tor (PM­DA), and lever­age our net­work to in­ter­act with the KOLs. In re­la­tion to ther­a­peu­tic ar­eas, 24% of our mon­i­tor­ing ex­pe­ri­ence is in on­col­o­gy, fol­lowed by CNS. As men­tioned ear­li­er, we are in­volved in near­ly 70% of new on­col­o­gy drug de­vel­op­ment in Japan.

We are al­so fo­cus­ing ef­forts on dig­i­tal­iza­tion and con­struct­ing in­fra­struc­ture for the im­ple­men­ta­tion of DCTs in Japan. CMIC has three sep­a­rate plat­forms con­tribut­ing to the firms ef­forts in dig­i­tal­iza­tion: har­mo®, an elec­tron­ic pre­scrip­tion record ser­vice col­lect­ing pre­scrip­tion da­ta of study par­tic­i­pants in re­al time; Knock on the Door (KOD), a pa­tient sup­port plat­form for rare dis­eases al­low­ing greater in­sight in­to a pa­tient’s health sta­tus; and OKEIOS, a blockchain tech­nol­o­gy paired with per­son­al da­ta store (PDS) plat­forms to en­sure the au­then­tic­i­ty, con­fi­den­tial­i­ty and trace­abil­i­ty of per­son­al health in­for­ma­tion.

Kazuo Naka­mu­ra: In the ear­ly days, as our mis­sion was not wide­ly ac­cept­ed in Japan, we on­ly had a few Japan­ese clients. We re­ceived the most in­ter­est from US com­pa­nies look­ing to en­ter Japan and were en­thu­si­as­tic about our of­fer­ings. We nat­u­ral­ly start­ed with over­seas clients, while Japan­ese clients fol­lowed short­ly af­ter. Our busi­ness DNA is to keep doors open to in­ter­na­tion­al com­pa­nies and sup­port their Japan mar­ket ac­cess jour­ney.

End­points: What are spon­sors of­ten sur­prised to learn about when bring­ing drugs to mar­ket in Japan? 

Keiko Oishi: Spon­sors are al­ways sur­prised to learn of reg­u­la­to­ry nu­ances, par­tic­u­lar­ly the study doc­u­men­ta­tion re­quired in Japan. Deal­ing with clin­i­cal sites and sign­ing con­tracts to ini­ti­ate clin­i­cal tri­als is al­so dis­tinct from oth­er coun­tries like the US. In ad­di­tion, in­ves­ti­ga­tors and site staff are high­ly en­gaged with a strict work eth­ic, and this leads to a unique lev­el of qual­i­ty and com­pli­ance in re­gards to clin­i­cal tri­al con­duct.

Kazuo Naka­mu­ra: There has al­ways been a gen­er­al cul­ture ad­just­ment for spon­sors com­ing to Japan, par­tic­u­lar­ly with spon­sors com­ing from more laid-back work­ing en­vi­ron­ments. It has been im­por­tant to deeply un­der­stand a spon­sor’s cul­ture and pro­fes­sion­al ap­proach to build trans­par­ent and trust­wor­thy part­ner­ships. The stan­dard Japan­ese ap­proach ap­pears to be some­what rigid – strict­ly fol­low­ing reg­u­la­tions and prece­dence with lit­tle room for any de­vi­a­tion. In­ter­na­tion­al spon­sors are of­ten more con­fi­dent to push the en­ve­lope with new en­deav­ors and chal­lenges, but this can be hard­er than ex­pect­ed to achieve in Japan. At CMIC we have adapt­ed our pro­fes­sion­al ap­proach to con­sid­er all op­tions and “pos­si­bil­i­ties,” while out­lin­ing var­i­ous risks to clients through an open com­mu­ni­ca­tion chan­nel. Our flex­i­bil­i­ty and adapt­abil­i­ty has re­sult­ed in for­eign spon­sors choos­ing to work with CMIC on Japan­ese tri­als. Reg­u­la­to­ry re­quire­ments are al­so a learn­ing curve for clients giv­en that most spon­sors pri­or­i­tize FDA re­quire­ments as a de­fault and may not pay close at­ten­tion to reg­u­la­to­ry up­dates from oth­er au­thor­i­ties. Japan has its in­de­pen­dent au­thor­i­ty (PM­DA), which is close­ly watch­ing its in­ter­na­tion­al peers, par­tic­u­lar­ly the FDA. The PM­DA reg­u­lar­ly re­views and re­vis­es its reg­u­la­to­ry re­quire­ments, which we al­ways care­ful­ly ex­plain to our in­ter­na­tion­al clients. De­spite mar­ket en­try hur­dles, Japan is a re­li­able mar­ket for com­mer­cial­iza­tion fol­low­ing ap­provals.

End­points: What are the most per­sis­tent chal­lenges when it comes to con­duct­ing clin­i­cal tri­als in Asia-Pa­cif­ic? How is CMIC help­ing spon­sors over­come those chal­lenges? 

Kazuo Naka­mu­ra: While chal­lenges are quite com­mon across the APAC re­gion, there are some nu­ances with each coun­try’s ap­proach to drug de­vel­op­ment and com­mer­cial­iza­tion. As CMIC launched its CRO in Ko­rea (1996) and Chi­na (2002), there have been some learn­ings around shift­ing mar­ket pri­or­i­ties and reg­u­la­to­ry align­ments – specif­i­cal­ly around com­pa­nies choos­ing to align with ei­ther the Japan­ese or US reg­u­la­tor de­pend­ing on which mar­kets were prefer­able for com­mer­cial­iza­tion. CMIC re­al­izes the im­por­tance of deeply un­der­stand­ing the com­pa­ny’s ob­jec­tives to help nav­i­gate and align nu­anced reg­u­la­to­ry re­quire­ments with R&D and com­mer­cial­iza­tion goals. As such, many Ko­re­an and Chi­nese com­pa­nies are reaf­firm­ing their re­la­tion­ship with CMIC. Aside from reg­u­la­to­ry is­sues, some­thing that may sur­prise spon­sors is that Japan has be­come a rel­a­tive­ly cost-ef­fec­tive place to con­duct tri­als vs oth­er APAC coun­tries (e.g. Ko­rea and Chi­na), but still main­tains high lev­els of speed and qual­i­ty com­pared to peers around the world.

End­points: What’s unique about CMIC Group’s ap­proach to pre­ven­tion and treat­ment? 

Kazuo Naka­mu­ra:  While sup­port­ing the op­er­a­tion of clin­i­cal tri­als is one ob­jec­tive, I think the true mis­sion of a CRO is al­so to sup­port the iden­ti­fi­ca­tion of new promis­ing drugs and be a strong part­ner for bio-ven­ture busi­ness­es. We want to sup­port con­tin­ued in­no­va­tion to bring more ef­fec­tive and af­ford­able so­lu­tions to pa­tients and em­pow­er them to op­ti­mize their health­care jour­neys. This led us to the con­cept of Per­son­al Health Val­ue. New per­son­al­ized med­i­cines along with dig­i­tal tech­nolo­gies such as wear­able de­vices may en­able us to bet­ter uti­lize per­son­al health records when de­vel­op­ing more per­son­al­ized med­i­cines. Right now, we are col­lab­o­rat­ing with mu­nic­i­pal­i­ties to uti­lize health­care da­ta to help re­al­ize this vi­sion as a “next-gen­er­a­tion CRO.”

End­points: How has CMIC ex­pand­ed its glob­al foot­print and pres­ence to build deep­er re­la­tion­ships with multi­na­tion­al spon­sors? 

Keiko Oishi: Since 1992, CMIC Group has grad­u­al­ly ex­pand­ed its glob­al pres­ence in Asia (Ko­rea, Chi­na, Sin­ga­pore and Tai­wan) and since 2013 our APAC foot­print has grown sig­nif­i­cant­ly to help meet client needs – e.g. ac­cel­er­ate pa­tient re­cruit­ment. In 2007, we ex­pand­ed in the US with a CD­MO op­er­a­tion and al­so launched a bio­analy­sis op­er­a­tion in 2015. Our Aus­tralia of­fice was es­tab­lished in 2018, where we cur­rent­ly run Phase I tri­als.

End­points: What can we ex­pect to see from CMIC Group in the next 10 years?

Keiko Oishi: With fur­ther in­no­va­tion of AI and tech­nolo­gies, I ex­pect more ef­fi­cien­cy in the fu­ture. I an­tic­i­pate that the way we run/man­age the clin­i­cal tri­als, the roles of our staff and how we op­er­ate will change. For ex­am­ple, AI may de­vel­op in the fu­ture to per­form what da­ta sci­en­tists are do­ing to­day, how­ev­er, project man­agers will still be re­quired. CMIC Group aims to be the top CRO in Asia by stay­ing ahead of the trend and set­ting up an ef­fi­cient op­er­a­tion im­ple­ment­ing these in­no­va­tions.

Kazuo Naka­mu­ra: In the fu­ture we hope to help in­no­vate drugs and med­ical de­vices that ad­dress com­pli­cat­ed dis­eases. We will con­tin­ue to sup­port spon­sors to achieve this, but the way we sup­port them might change, par­tic­u­lar­ly with the use of in­no­v­a­tive dig­i­tal plat­forms to mon­i­tor pa­tients and get a bet­ter un­der­stand­ing of their health sta­tus. We al­so hope to help lead the charge to stan­dard­ize op­ti­mal treat­ment prac­tices, by col­lect­ing pa­tient da­ta and rais­ing physi­cian and hos­pi­tal aware­ness on new treat­ments. Ad­di­tion­al­ly, at CMIC we up­lift the con­cept of “one fam­i­ly, one health,” and could al­so ex­plore new in­no­va­tions ex­tend­ing to fam­i­ly pets. Our ap­proach is not on­ly for the pur­pose of cur­ing dis­eases or longevi­ty, but to fo­cus on the ob­jec­tive of liv­ing life to the fullest – a Japan­ese con­cept known as “IKI­GAI.” We hope this con­cept and our com­pa­ny val­ues will en­cour­age more com­pa­nies to part­ner with us and hope­ful­ly we will be­come a big­ger and more in­ter­na­tion­al com­pa­ny.

End­points: Any last words for over­seas phar­ma/biotech/health­care com­pa­nies?

Kazuo Naka­mu­ra: We be­lieve that rather than fo­cus­ing on com­pe­ti­tion and a race to ap­proval, the in­dus­try should be more col­lab­o­ra­tive to bring the best drugs to pa­tients. We have ac­cess to a large amount of ac­cu­rate in­for­ma­tion about Japan’s health­care sys­tem, pa­tients and drugs, and we are open to shar­ing such in­for­ma­tion with com­pa­nies in­ter­est­ed in en­ter­ing the Japan­ese mar­ket. As mu­tu­al­ly agree­able dis­cus­sions are of high im­por­tance to us, we hope to en­gage with more com­pa­nies fo­cused on lever­ag­ing post-mar­ket­ing in­for­ma­tion to de­vel­op drugs that help pa­tients for longer pe­ri­ods of time. We hope to con­tin­ue do­ing all this as a Phar­ma­ceu­ti­cal Val­ue Cre­ator.