인도네시아 의약품허가제도

Transcription

1 인도네시아 의약품허가제도

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3 1 인도네시아의약품허가제도

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5 약 어 ACTD: ASEAN Common Technical Dossier( 아세안공통기술문서 ) GCP: Good Clinical Practice( 임상시험관리기준 ) GDP: Good Distribution Practice( 유통관리기준 ) GMP: Good Manufacturing Practice( 의약품제조및품질관리기준 ) MOH: Ministry of Health( 보건부 ) NADFC: National Agency of Drug and Food Control ( 인도네시아식품의약품안전청 ) NIHRD: National Institute of Health Research & Development ( 국립보건연구개발원 ) Notice 1. 본허가안내서의정보는각국가의의약품규제기관홈페이지또는의약품규제관련지침및가이드라인에서인용되었습니다. 2. 본허가안내서의정보를참고할경우, 관련법령및가이드라인개정등의최신정보를확인하시기바랍니다.

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7 Chapter Ⅰ 의약품규제기관 6 1. 인도네시아보건부 6 2. 식품의약품안전청 9 Chapter Ⅱ Chapter Ⅲ 관련법령 13 의약품의분류 신약 제네릭의약품 생물의약품 희귀의약품 14 Chapter Ⅳ 의약품허가제도 임상시험계획승인신청 신약허가신청 제네릭의약품허가신청 희귀의약품 우선심사 품목허가갱신 30 Chapter Ⅴ 기타허가사항 의약품제조및품질관리기준 원료의약품등록 표시기재사항및첨부문서 의약품제조판매증명서 제조업허가 수입허가 수수료 41 Chapter Ⅵ 참고문헌 43

8 Ⅰ. 의약품규제기관 1. 인도네시아보건부 인도네시아보건부 (Ministry of Health, MOH) 는자국민을위해높은품질의필수 보건의료서비스제공을담당하는주요기관이다. 1.1 업무보건부의업무는다음과같다. Ÿ 국가보건정책수립 Ÿ 보건서비스기준을결정하는가이드라인수립 Ÿ 보건의료시스템국가계획마련 Ÿ 보건분야국제협정이행 Ÿ 보건분야지역허가기준결정 Ÿ 보건분야국가범위재난발생대응 Ÿ 보건분야국가정보시스템구축 Ÿ 보건서비스분야자격요건결정 Ÿ 공중보건의료보험정책수립 Ÿ 보건관계자대상교육및훈련프로그램을위한가이드라인및기준실행 Ÿ 보건기술및연구윤리기준심사, 개발, 실행 Ÿ 보건시설승인기준설정 Ÿ 역학조사, 전염병및이상증상발생예방 근절 Ÿ 기본적인보건서비스용필수의약품및치료제공 6

9 1.2 조직 (2015 년 11 월기준 ) [ 그림 1] 인도네시아보건부조직도 보건부의조직은다음과같다. 1), 2) Ÿ 사무총괄국 Ÿ 영양 모성보건의료국 Ÿ 보건정책국 1) 보건부규정제 1144/Menkes/PerVIII/2010 호 2) 7 인도네시아의약품허가제도

10 Ÿ 질병관리 환경보건국 Ÿ 의약품치료 의료기기국 Ÿ 국립보건연구개발원 (National Institute of Health Research & Development, NIHRD) Ÿ 국립보건인력개발원 Ÿ 조사총괄국 1.3 홈페이지 8

11 2. 식품의약품안전청 식품의약품안전청 (National Agency of Drug and Food Control, NADFC) 은독성물질, 마약류, 향정신성의약품등에대한특별조항을포함하여의약품규제관련법, 규정, 기준및운영지침수립 실행을목적으로 2001년보건부 (MOH) 산하독립기관으로설립되었다. 식품의약품청은인도네시아의약품분야규제를담당하는대통령직속주요기관이다. 3) 2.1 업무식품의약품안전청은의약품제조및품질관리기준 (Good Manufacturing Practices, GMP) 에따른제약산업의허가 증명, 제품시판전평가, 제품검체추출및실험실시험, 생산및유통시설실사, 제품광고및홍보사전 사후심사, 의약품 식품정책실행, 공중보건관련커뮤니케이션및교육을담당한다. 또한식품의약품안전청은치료제, 마약류, 향정신성 중독성물질, 전통의약품, 화장품, 건강보조제, 식품및기타유사제품을규제하며, 시판중인제품실사및시험권한을가지며, 약물감시활동도담당하고있다. 그러나식품의약품안전청은의료보건시스템의지방분권화로인하여지방및시 ( 市 ) 행정에대한직접적인권한은가지고있지않다. 일반적으로인도네시아의의약품분야규제담당기관은다음과같다. Ÿ 식품의약품안전청 (NADFC): 국가차원의안전성, 유효성, 품질담당 Ÿ 지방식품의약품안전청 (Drug & Food Agencies): 시 ( 市 ) 차원에서약국허가및모니터링담당 3) 대통령령제 166/2000 호 9 인도네시아의약품허가제도

12 2.2 조직 [ 그림 2] 식품의약품안전청조직도 (2017 년 7 월기준 ) 10

13 식품의약품안전청은다음과같이 3 개부서, 국립연구소, 3 개센터, 사무국으로 구성되어있다. 4) (1) 치료제, 마약류, 향정신성 중독성물질관리부 Ÿ 의약품또는생물의약품의유효성 안전성 품질에대한시판전평가 Ÿ 치료의약품, 마약류, 향정신성 중독성물질에대한시판후관리 Ÿ 의약품제조및품질관리기준, 생산 유통에대한실사 (2) 전통의약품, 화장품, 건강보조제관리부 Ÿ 전통의약품, 화장품, 식품보조제의시판전평가및품목허가 Ÿ 전통의약품, 화장품, 건강보조제의시판후관리및표시기재사항, 홍보등 Ÿ 의약품제조및품질관리기준, 생산 유통에대한실사 (3) 식품안전및유해물질관리부 Ÿ 식품의안전성시판전 후평가 Ÿ 식품의생산 유통실사 Ÿ 유해물질및유해식품관리 (4) 국립식품의약품연구소 Ÿ 치료의약품, 마약류, 향정신성 중독성물질, 의료기기, 전통의약품, 화장품, 건강보조제, 식품, 유해물질에대한시험, 시험절차개발및품질평가수행 (5) 식품의약품조사센터 Ÿ 치료의약품, 마약류, 향정신성 중독성물질, 의료기기, 전통의약품, 화장품, 건강보조제, 식품및기타유사제품관련위법행위조사 (6) 식품의약품연구센터 Ÿ 독성, 식품안전성, 치료의약품에대한연구활동 4) 11 인도네시아의약품허가제도

14 (7) 식품의약품정보센터 Ÿ 식품의약품및독성물질에대한정보제공및식품의약품청정보기술활동조정 (8) 사무국 Ÿ 전략계획조정 Ÿ 조직, 인력개발, 재정관리, 법률자문 입법, 홍보, 국제협력, 소비자불만등국민과의소통관리 Ÿ 식품의약품청내센터및기술이행전 ( 全 ) 부서내업무조정 2.3 홈페이지 12

15 Ⅱ. 관련법령 인도네시아의공중보건및의약품관련법과규정은다음과같다. Ÿ 법제 419/1949호 ( 처방의약품 ) Ÿ 법제 35/2009호 ( 마약류 ) Ÿ 법제 5/1997호 ( 향정신성의약품 ) Ÿ 법제 36/2009호 ( 보건법 ) Ÿ 식품의약품안전청장규정제 3호 : 식품의약품안전청장규정제 HK 호 ( 의약품품목허가기준및절차 ) 개정안 ( ) 보다상세한내용은인도네시아보건부 (MOH) 또는식품의약품안전청 (NADFC) 홈페이지를참고한다. 5) 5) 보건부 (MOH): 식품의약품안전청 (NADFC): ( 인도네시아어 ) 13 인도네시아의약품허가제도

16 Ⅲ. 의약품의분류 6),7),8) 1. 신약 신약은인도네시아에서허가받지않은새로운유효성분, 새로추가된성분, 제형및투여경로, 새로운효능또는새로운조성을가진의약품이다. 신약은인도네시아내판매 유통허가를목적으로인도네시아및해외연구기관또는제약사에서개발및생산중인새로운분자의의약품또는성분을포함한다. 2. 제네릭의약품 제네릭의약품은특허만료또는 2 년내특허만료예정인품목허가된의약품과동일한 유효성분을가진의약품으로, 상표명또는제네릭명으로시판될수있다. 3. 생물의약품 생물의약품은백신, 항체, 항원, 호르몬, 효소, 혈액제제, 기타발효산물 ( 재조합 DNA 기술유래제품및단일클론항체포함 ) 로질병의예방, 치료및건강회복, 개선을위해사용되는제품이다. 4. 희귀의약품 희귀의약품은희귀질병치료를목적으로, 수요가낮아경제적으로국내생산이어려운 의약품이해당된다. 6) 식품의약품안전청장규정제 16 호 : 신규개발의약품관리및평가 ( ) 7) 식품의약품안전청장규정제 3 호 : 식품의약품청장규정제 HK 호 ( 의약품품목허가기준및절차 ) 개정안 ( ) 8) 식품의약품안전청장규정제 HK 호 : 의약품품목허가기준및절차 ( ) 14

17 Ⅳ. 의약품허가제도 1. 임상시험계획승인신청 1.1 개요인도네시아에서실시하는모든임상시험은반드시헬싱키선언에따라임상시험대상자의권리및안전을고려해야한다. 9) 인도네시아에서임상시험을하고자하는시험의뢰자는반드시윤리위원회및식품의약품청의허가를받아야한다. 인도네시아에는 3가지종류의임상시험계획승인신청이있다. 1) 시판전임상시험 : 인체대상시험 2) 시판후임상시험 : 중재및비중재시험 ( 관찰시험 ) 의시판후임상 4상시험 3) 교육목적의임상시험 임상시험을실시하는기관또는시험의뢰자는인도네시아임상시험관리기준 (Good Clinical Practice, GCP) 가이드라인에따라과학위원회및윤리위원회의승인을받아야한다. 임상시험의필수서류는수행시험의타당성및수집자료의완전성 (integrity) 을확인하기위한절차로서규제당국의조사및실사를받아야한다. 임상시험을위한모든신청서및제출자료는반드시영어나인도네시아어 10) 로작성되어야한다. 9) 헬싱키선언 (Declaration of Helsinki): 사람시험대상자대상의학연구윤리원칙 ( 개정 ) 10) 인도네시아어는 Bahasa Indonesia 라고도불린다. 15 인도네시아의약품허가제도

18 1.2 절차 [ 그림 3] 임상시험신청절차 16

19 1.2.1 윤리위원회심사인도네시아에서제안된임상시험을시작하기위해서는반드시국립보건연구윤리위원회 (Komite Nasional Etik Penelitian Kesehatan) 또는공인된기관의윤리위원회들 ( 생의학연구윤리위원회, 인도네시아대학등 ) 중한곳에서승인을받아야한다. 윤리위원회의승인후임상시험계획승인신청서를식품의약품안전청에제출할수있으며, 윤리위원회의승인서를신청서에반드시첨부해야한다. 11) 심사절차는다음과같다. (1) 윤리위원회선정시험의뢰자는윤리심사를위해임상시험계획승인신청자료를제출하기전에반드시윤리위원회를선정해야한다. (2) 윤리위원회승인을위한제출자료다음의자료를반드시제출해야한다 ( 사본 10부 ): Ÿ 표지 ( 인도네시아어 ) Ÿ 윤리심사신청서 ( 인도네시아어 ) Ÿ 임상시험계획서 ( 영어 ) Ÿ 시험대상자에대한서면정보 ( 인도네시아어 / 영어 ) Ÿ 사전동의서 Ÿ 임상시험자자료집 (Investigator s Brochure, IB)/ 첨부문서 ( 필요시 ) Ÿ 시험자의현재이력서 (3) 수수료인도네시아의윤리위원회심사절차수수료는 5,000,000 루피아 12) 이다. 임상시험자나시험의뢰자가수수료를지불하지않을경우, 윤리위원회또는해당기관은과학 / 윤리심사신청을반려할수있다. 11) 인도네시아보건부장관규정제 66 호 : 임상시험등록실행 12) 인도네시아의화폐는루피아 (Rupiah) 로, RP 또는 IDR 로표기한다 17 인도네시아의약품허가제도

20 (4) 심사임상시험계획승인신청자료접수후, 윤리위원회는윤리요건에따라심사를수행한다. 윤리위원회는심사중추가정보또는명확한설명이요구될경우시험의뢰자에게연락하여요청할수있다. 윤리위원회는신청된임상시험계획서가요건을충족할경우, 승인서를시험의뢰자에게송부한다. 그러나미준수사항이나결점이있을경우윤리위원회는반려사유와함께반려서를송부한다. 시험계획서는윤리위원회에제출하기전에반드시기관또는회사내부에있는과학위원회의심사 승인을받아야한다. 과학위원회및윤리위원회의승인없이실시되는임상시험은윤리위원회또는인도네시아의약품청에의해연기또는종료될수있다 식품의약품안전청심사절차 시험의뢰자는윤리위원회의승인서수령후, 식품의약품안전청에임상시험계획 승인신청서및윤리위원회심사회의참석자명단을제출할수있다. 1) 심사및승인식품의약품안전청은시판전 후임상시험에대한과학위원회또는윤리위원회의승인과관련하여국립임상시험자문위원회 (National Advisory Board on Clinical Trial) 에과학적자문을요청할수있다. 2) 임상시험종료임상시험은윤리위원회및식품의약품안전청에서면통지를보냄으로써종료된다. 임상시험완료또는종료후임상시험보고서, 시험기관에서의임상시험용의약품수불기록 (accountability), 필수서류, 실사증명서를반드시작성해야한다. 18

21 3) 준수사항인도네시아에서실시하는모든임상시험은반드시국제의약품규제조화위원회 (International Council for Harmonisation, ICH) 임상시험관리기준(Good Clinical Practice, GCP) 에대한가이드라인 과 인도네시아임상시험관리기준가이드라인 에명시된요건을준수해야한다. 13), 14), 15) 4) 임상시험등록소인도네시아의모든임상연구와임상시험은보건부규정 16) 에따라 2014년 11월 12일부터반드시국립등록소 (National Registry) 에등록해야한다. 임상시험계획서는윤리위원회및식품의약품안전청의승인을받은후에등록될수있다. 5) 임상시험용의약품인도네시아에서국내제조또는수입되는모든임상시험용의약품은반드시 ICH나세계보건기구 (WHO) 에서제정하는임상시험관리기준 (GCP) 가이드라인과같이국제적으로통용되는가이드라인을준수해야한다. 또한, 모든임상시험용의약품은반드시의약품제조및품질관리기준 (GMP) 에따라제조, 공급, 보관, 유통되어야한다. 모든제조절차는반드시승인된계획서에명시된기준, 규격, 밸리데이션된방법에따라진행되어야한다. 13) ICH 가이드라인 E6(R1): 임상시험관리기준에대한가이드라인 ( ) 14) ICH 가이드라인 E8: 임상시험을위한일반적고려사항 ( ) 15) 임상시험관리기준에대한인도네시아가이드라인 ( ) 16) 인도네시아보건부규정제 66호 (2013) 19 인도네시아의약품허가제도

22 1.3 제출자료임상시험계획승인을위해서다음의자료를식품의약품안전청에제출해야한다. Ÿ 표지 Ÿ 신청서 ( 인도네시아어 ) Ÿ 임상시험계획서 ( 영어 ) Ÿ 사전동의서 (Informed consent form, ICF)( 인도네시아어 ) Ÿ 임상시험자자료집 Ÿ 각임상시험기관에대한국립윤리위원회의허가서 Ÿ 임상시험자이력서 ( 시험책임자및국립조정자 ) Ÿ 분석증명서 (Certificate of Analysis, CoA) Ÿ 의약품제조및품질관리기준 (GMP) 증명서 Ÿ 윤리위원회심사회의참석자명단상기자료는임상시험용의약품의수입허가신청시에도요구된다. 1.4 심사기간식품의약품안전청은 10일 ( 근무일기준 ) 내에시판전 후임상시험에대한승인서를발행하거나, 보완또는수정이필요할경우시험의뢰자에게 10일 ( 근무일기준 ) 내에통보한다. 임상시험계획승인은일반적으로약 1~2개월 ( 근무일기준 30~60일 ) 정도소요된다. 17) 17) 임상시험관리기준에대한인도네시아가이드라인 ( ) 20

23 2. 신약허가신청 인도네시아의의약품품목허가신청은품목허가신청및품목허가변경신청등총 7개로분류된다. 신약품목허가신청의분류는다음과같다. Ÿ 분류 1: 신약, 동등생물의약품 (Similar Biotherapeutic Product, SBP) 을포함한생물의약품 Ÿ 분류 2: 제네릭의약품 Ÿ 분류 3: 기타 그외품목허가분류는다음과같다. Ÿ 분류 4: 주요변경 Ÿ 분류 5: 허가가필요한일부변경 Ÿ 분류 6: 신고가필요한일부변경 Ÿ 분류 7: 갱신 2.1 절차 1) 신약개발허가승인 ( 인도네시아어로 OPB라칭함 ) 본절차는제출된시험계획서및서류의정확성및제안된임상시험 ( 임상 1상 ~3상 ) 또는비임상시험의적절성을확인하기위해수행된다. 보통서류제출일로부터 100일 ( 근무일기준 ) 소요된다. 2) 사전품목허가심사본심사는제출서류가필요한양식에맞게작성되었는지확인하기위해진행한다. 식품의약품안전청의심사자는이과정에서기언급한품목허가분류에따른심사경로를결정한다. 해당절차는일반적으로품목허가신청일경우 1~12개월, 변경신청일경우 40~80일소요된다. 21 인도네시아의약품허가제도

24 3) 품목허가신청자료심사 품목허가신청자료 ( 신약, 새로운생물의약품, 제네릭의약품 ) 에대한심사는아래표 1 과 같이 4 가지경로를통해진행된다. 경로유형경로 I 경로 II 경로 III 경로 IV - 허가가필요한일부변경 - 수출용의약품품목허가신청 의약품종류 - 구명용의약품 - 희귀의약품 - 국가프로그램대상의약품 - 인도네시아내의약품개발및모든임상시험용의약품 - 경로 II 에해당하는상기의약품에대한주요변경 ( 새로운적응증 / 약용량 ) - 규제조화심사시스템구축 실행을위한국가에서시판되는의약품 - 경로 III 에해당하는상기의약품에대한주요변경 ( 새로운적응증 / 약용량 ) - 경로 II, III 에해당하지않는신약, 생물의약품, 주요변경 ( 새로운적응증 / 약용량 ) [ 표 1] 품목허가심사경로 심사기간 ( 근무일기준 ) 40 일 100 일 150 일 300 일 Ÿ 어떤규제당국에서도허가를받지않은의약품의품목허가심사의경우 300일 ( 근무일기준 ) 소요된다 ( 경로 IV). Ÿ 인도네시아와상호인정협정을맺은규제당국중한곳에서기허가받은의약품의경우, 약식서류심사는 150일 ( 근무일기준 ) 소요된다 ( 경로 III). Ÿ 안전성 유효성확인을위한비임상 임상자료를요구하지않는제네릭의약품 ( 국가프로그램대상필수의약품 ) 과모든인도네시아국내제조의약품의심사는 100일 ( 근무일기준 ) 소요된다 ( 경로 III). 18) 18) 식품의약품안전청장규정제 3 호 (2013) 22

25 4) 행정절차국립의약품심사위원회는안전성 유효성심사후권고사항을서면으로작성하여식품의약품안전청에송부한다. 구비서류에대한심사보고서는각부서장, I부 (Deputy I) 의장또는식품의약품안전청장의승인을위해송부된다. 해외수입의약품의품목허가인경우식품의약품안전청에서허가서를승인하며, 인도네시아국내제조의약품인경우 I부에서품목허가를승인한다. 허가서 는최초품목허가번호발행전에발급하며, 유효기간은최대 2년이다. 2.3 규제상담신청자는품목허가절차중대면회의를요청할수있다. 대면회의신청절차는다음과같다. 1) I부장또는품목허가담당부장과의회의신청자는반드시회의목적, 참석자, 회의일, 연락담당자를명시한공문을작성해야한다 ( 회의 1개월전 ). 2) 부 ( 副 ) 담당자와의대면회의 신청자는반드시최소 1 주전관련비서관에게연락해야한다. 3) 과장과의대면회의신청자는신청자명, 회의제안일시, 논의사항, 요청희망대상식품의약품안전청담당자명을기입하여이메일 (penilaianobat@pom.go.id) 로공문을송부해야한다 ( 회의 1주전 ). 식품의약품안전청은신청자에게회의일시를통보한다. 23 인도네시아의약품허가제도

26 2.4 제출자료식품의약품안전청에제출하는품목허가신청서류는전체서류, 약식서류, 제네릭의약품허가서류중하나의형식으로가능하다. 각서류유형별제출자료는아래표와같다. 19), 20) 제출자료 전체서류 (Full Dossier) 약식서류 (Abbreviated Dossier) 제네릭의약품허가서류 (Generics Dossier) 신청서 ICH 또는 ACTD* 양식 ICH 또는 ACTD ICH 또는 ACTD ACTD 행정자료 공통기술문서개요및요약 비임상및임상개요및요약 품질 품질 비임상시험보고서 - 해당없음 임상시험보고서 생물학적동등성 (BE) 시험 / 생물학적동등성시험면제 허가서해당없음 해당없음 의약품제조및품질관리기준 (GMP) 증명서 승인된 PI/SmPC/PIL* * ICH: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use( 국제의약품규제조화위원회 ) ACTD: ASEAN Common Technical Dossier( 아세안공통기술문서 ) PI: Package Insert( 첨부서류 ) SmPC: Summary of Product Characteristics( 제품특성요약 ) PIL: Patient Information Leaflet( 환자용의약품설명서 ) [ 표 2] 서류유형에따른제출자료 19) 약식서류는규제조화심사시스템을적용한국가 (EU, 미국, 호주, 일본 ) 에서의약품이기허가된경우제출 20) 식품의약품안전청장규정제 3 호 : 식품의약품안전청장규정제 HK 호 ( 의약품품목허가기준및절차 ) 개정안 ( ) 24

27 1) 언어 모든자료 ( 신청서및근거서류 ) 는인도네시아어또는영어로작성 2) 서류유형 Ÿ 전체서류전체서류제출시, 신청사항을뒷받침하는화학적 생물학적자료, 의약품및제네릭의약품개발자료, 독성 약리자료, 임상시험자료제출 Ÿ 약식서류신청자는약식서류제출시반드시다른의약품규제당국에서허가받은근거를제출해야한다. 21) 제출자료는다음과같다. - 의약품품목허가상태를증명하는의약품규제당국발행의허가서또는동등서류 - 의약품규제당국에서발행한의약품제조업자에대한의약품제조및품질관리기준 (GMP) 증명서 - 의약품규제당국에서승인한첨부문서, 제품특성요약, 환자용의약품설명서 3) 허용양식 Ÿ 새로운화학물질 (new chemical entity, NCE) 및생물의약품은 ICH 공통기술문서 (Common Technical Document, CTD) 또는아세안공통기술문서 (ACTD) 양식으로작성 Ÿ 변경신청및제네릭의약품허가신청등기타신청서류는아세안공통기술문서 (ACTD) 양식으로작성 21) 인도네시아식품의약품안전청에서인정하는참조국 (Reference countries) 은호주 ( 연방의료제품청, TGA), 유럽연합 ( 유럽의약품청, EMA), 미국 ( 식품의약품청, FDA), 캐나다 ( 캐나다연방보건부, Health Canada), 뉴질랜드 ( 보건부 ) 등이다. 또한식품의약품안전청은다른국가와해외임상자료, 의약품제조및품질관리기준및해외규제기관의실사인정에대한상호인정협약및양자무역협정을체결하였다. 한국식품의약품안전처도 2012 년 7 월 12 일인도네시아와양해각서를맺었다. 25 인도네시아의약품허가제도

28 2.5 심사기간 인도네시아에서전체서류 ( 새로운화학물질및생물의약품에대한신규허가 ) 에대한 최대검토 심사기간은 720 일 ( 근무일기준 ) 소요된다. 단위 : 근무일기준 심사경로 품목허가사전심사 품목허가심사 I 1~12 개월 40 일 II 1~12 개월 100 일 III 1~12 개월 150 일 IV 1~12 개월 300 일 변경분류 4,5,6 1~12 개월 40~100 일 유보기간 120 일 ( 최대 ) 120 일 ( 최대 ) 120 일 ( 최대 ) 120 일 ( 최대 ) 120 일 ( 최대 ) 행정처리기간 ( 허가 ) 최대심사기간 1~2 개월 460 일 1~2 개월 520 일 1~2 개월 570 일 1~2 개월 720 일 1~2 개월 460~520 일 갱신분류 7 해당없음 40 일해당없음 1~2 개월 80 일 [ 표 3] 신약허가신청심사기간 심사자가신청자에게추가자료또는명확한설명을요청할경우유보기간 (stop-the-clock) 이발생한다. 심사절차는신청자가추가자료나명확한설명을제출할때까지유보되며, 그기간은 120일을초과해서는안된다. 식품의약품안전청은요청한자료제출이지연될경우해당품목허가를반려한다. 그러나신청자는해당서류를새로운품목허가신청으로다시제출할수있다. 26

29 3. 제네릭의약품허가신청 3.1 절차본가이드라인 IV. 의약품허가제도 의 2. 신약허가신청 에명시된바와같이제네릭의약품은분류 2에해당하며, 의약품의안전성 유효성을증명하는비임상 임상자료를요구하지않는제네릭허가신청서류로심사한다. 22) 3.2 심사기간본가이드라인 IV. 의약품허가제도 의 2.5 심사기간 에명시된바와같이제네릭의약품허가신청서류에대한심사는 100일소요된다 ( 식품의약품안전청심사절차경로 II). [ 그림 4] 제네릭의약품심사절차 22) 식품의약품안전청장규정제 3 호 : 식품의약품안전청장규정제 HK 호 ( 의약품품목허가기준및절차 ) 개정안 ( ) 27 인도네시아의약품허가제도

30 3.3 제출서류 23) 본가이드라인 IV. 의약품허가제도 의 2.4 제출자료 에명시된바와같이제네릭의약품품목허가신청서류는아세안공통기술문서 (ACTD) 양식을따라야한다. 제네릭의약품의품목허가는첨부문서가식품의약품안전청양식 (STINEL 24) ) 을바탕으로작성되었을경우비임상 임상자료를요구하지않는다. 그러나제네릭의약품신청서류가식품의약품안전청양식을준수하지않을경우, 신청자는식품의약품안전청에서인정하는다른국가에서사용한첨부문서를참고자료로제출해야한다. 제네릭의약품품목허가시중요한서류는행정자료및품질자료이다. 신청자는약력학 / 약동학자료가제네릭의약품의생물학적동등성을증명할경우, 생물학적동등성시험자료대신비교용출시험자료를대신제출할수있다 ( 생물학적동등성시험의면제 ). 의약품의투여경로가기존의제네릭의약품과동일하지않을경우, 생체이용률시험이요구되며, 해당시험은다른국가 ( 예. 아세안국가 ) 에있는추천연구소에위임할수있다 생물학적동등성식품의약품안전청은신청자가제출한제네릭의약품 ( 카피약 / 유사약품 ) 이인도네시아대조약과동일한생물학적동등성을가지고있다고증명할수있을경우에만해당의약품의판매 유통을허가한다. 25) 신청자는생물학적동등성시험을실시하기위해서반드시인도네시아에서이미시판중인대조약을사용해야한다. 만일식품의약품안전청에서해당대조약의시판을허가하지않았거나수입문제로인하여해당대조약을이용할수없는경우, 신청자는시판대조약또는유럽, 미국, 캐나다, 호주등국가의시장선도의약품사용에대한요청서를의약품평가부에제출할수있다. 23) 식품의약품안전청장규정제 HK 호 ( 생물학적동등성시험을실시하는의약품 ) 24) STINEL: 전자정보기준 25) 식품의약품안전청장규정제 17 호 : 바이오시밀러제품심사에대한관리지침 (2015) 28

31 4. 희귀의약품 규정에명시되어있지않음 5. 우선심사 5.1 우선심사대상의약품인도네시아는국내유통의약품에대한우선심사나신속심사를실시하지않는다. 현재의약품 생물의약품품목허가는 브라운북 (Brown Book) 이라고불리는인도네시아규정 26) 을바탕으로하며, 본문서에는품목허가심사기간 ( 근무일기준100일, 150일, 300일 ) 이명시되어있다. 근무일기준 100일심사대상의약품은다음과같다. Ÿ 구명용신약및새로운생물의약품 Ÿ 희귀의약품 Ÿ 공중보건프로그램용신약및새로운생물의약품 Ÿ 개발부터임상시험까지의모든과정이인도네시아에서진행되는신약및새로운생물의약품 Ÿ 필수제네릭의약품에해당하는제네릭의약품 (Copy drugs) 인도네시아정부가자국의수출활동을지원 장려하고있기때문에식품의약품안전청은수출허가를우선순위로정하여, 수출용의약품의심사기간은 40일소요된다. 26) 식품의약품안전청장규정제 HK 호 : 의약품품목허가에대한기준및절차 ( ) 29 인도네시아의약품허가제도

32 6. 품목허가갱신 27) 식품의약품안전청은품목허가를 5년마다갱신하도록하고있으며, 갱신은품목허가만료최소 4개월전에해야한다. 28), 29) 또한의약품제조및품질관리기준 (GMP) 증명서의유효기간은 5년이다. 갱신신청서류는 ICH-공통기술문서 (CTD) 또는아세안공통기술문서 (ACTD) 양식으로작성되어야한다. 현재식품의약품안전청에서는품목허가갱신시스템을온라인시스템으로전환하고있기때문에모든제약회사는반드시 의약품 e-품목허가신청 (AeRO) 30) 또는영문 AeRO 사이트 31) 담당자를지정해야한다. 신청자는갱신신청서류제출일주일전수요일 ( 또는식품의약품안전청의통지일 ) 에식품의약품안전청으로이메일을보내야한다. 식품의약품안전청은매주금요일에이메일또는웹사이트를통해갱신일정을안내하며, 신청자는해당일에추가서류를식품의약품안전청에제출해야한다. 32) 27) 식품의약품안전청장규정제 HK 호 : 의약품품목허가에대한기준및절차 ( ) 28) 인도네시아보건부규정제 1010/MENKES/PER/XI/2008호 29) 인도네시아보건부규정제 1120/MENKES/PER/XII/2008호 30) 의약품 e-품목허가신청 ( 인도네시아어 ): 31) 의약품 e-품목허가신청 ( 영어 ): 32) 보통매주월 화 ( 제네릭의약품및유사의약품의갱신신청 ), 수 목 ( 새로운화학물질및생물의약품갱신신청 ) 30

33 Ⅴ. 기타허가사항 1. 의약품제조및품질관리기준 의약품제조및품질관리기준 (GMP) 의기본원칙은부지, 장비, 직원, 교육, 생산, 시험, 문서기록, 불만사항, 품질관리절차, 제품회수, 자체실사를포함한다. 인도네시아의 GMP 기준에따라제조공정및설비를정립하고사용자표준운영지침서등을명확히확립해야한다. 의약품을해외로수출하고자하는인도네시아제조업자는반드시해외규제기관의실사를받아 GMP 증명서를받아야한다. 또한만일해외제조업자가인도네시아식품의약품안전청의실사를받았을경우, 인도네시아제조업자는해당제조업자의의약품을수입할수있다. 33) 1.1 GMP 증명서 GMP 증명서를받기위해서는다음의자료를식품의약품안전청에제출해야한다. Ÿ 제조업자명및소재지 Ÿ 제조할의약품의종류 34) Ÿ 통제구역을포함한생산시설 Ÿ 공기조화시스템 Ÿ 품질시스템 Ÿ 조직도 Ÿ 문서기록 Ÿ 폐기 / 위생시스템 33) 식품의약품안전청장법령제 HK /2011 호 : GMP 증명서절차 ( ) 34) GMP 증명서별한종류의의약품 ( 예. 일반정무항생제, 코팅정무항생제, 무항생좌약등 ) 31 인도네시아의약품허가제도

34 신청자는모든제조공장및제조소의품질보증 (QA) 및품질관리 (QC), 생산부서내에자격을갖춘숙련된직원 약사 과학자 운영자가있음을명시해야한다. 또한자격을갖춘약사는보건부및식품의약품안전청에등록되어있어야한다. 모든시설현장및문서기록시스템도세부적으로식품의약품안전청의실사를받는다. GMP 준수사항을기준으로실사결과가만족스러울경우식품의약품안전청에서 GMP 증명서를발행한다. 현재식품의약품안전청은최초신청에대한실사뿐만아니라등록된제조소에대해서도무작위로정기실사를수행한다. 만일제조업자가등록된제조소또는제조시설을변경할경우 치료제및가정상비약생산관리과 (Directorate of Production Control of Therapeutic Product and Household Supplies) 에서도실사를실시한다. GMP 증명서의유효기간은 5년이며, 매 5년마다갱신해야한다. GMP 증명서의갱신은유효기간만료 6개월전에해야한다. 식품의약품안전청에서 GMP 실사가필요하다고간주하는경우갱신절차중실사를수행한다. 1.2 GMP 실사해외및인도네시아제조업자는제조업허가를받기위해반드시시설에대한실사를받아야한다. 식품의약품안전청은미국 (FDA), 유럽 (EMA), 캐나다 (Health Canada) 또는호주 (TGA) 등참조국의규제기관에서시설에대한실사를실시한경우라도, 필요하다고판단되는경우해당시설에대한실사를수행한다. 식품의약품안전청은미리공지하거나공지하지않고불시에시설에대한정기실사를수행하며, 문서기록, 제조과정, 제조부지, 장비, 절차, 품질관리시험, 품질보증시스템, 배치문서기록, 완제의약품보관등에대하여평가한다. 1.3 해외제조업자에대한 GMP 적합성평가의약품을인도네시아로수출하기원하는해외제조업자는반드시 GMP 증명서를제출하고, 인도네시아식품의약품안전청의실사를받아야한다. 아세안 10개회원국의경제부장관들은 2009년 4월아세안분야별상호인정협정 (ASEAN Sectoral Mutual Recognition Arrangement) 에동참하였고, 이에따라아세안회원국간 GMP 증명서는상호인정된다. 32

35 해당상호인정협정의내용은다음과같다. Ÿ 단일아세안회원국에서 GMP 요건을준수하는제조시설에대한증명서는추가시험없이다른아세안회원국에서도인정 Ÿ 규제당국간의정보교환 ( 적합성평가를위한절차 ) Ÿ 규제조화장려 35) 2. 원료의약품등록 식품의약품안전청은의약품의화학 제조 품질관리 (CMC) 정보평가및제조소에대한 GMP 실사계획 실행을위해제약사또는신청자가원료의약품등록 (Drug Master File, DMF) 을품목허가신청서류의일부로제출해야한다. 또한신청자는의약품의품질을증명하기위해새로운화학물질, 신약, 제네릭의약품및유사의약품에대한원료의약품등록을제출해야한다. 제출한원료의약품등록은반드시필요한정보 36) 를포함해야하며인도네시아어또는영어로명확하게작성되어야한다. 현재인도네시아에는원료의약품등록에대한구체적인작성기준이없다. 그러나식품의약품안전청은미국식품의약품청 (FDA), 캐나다연방보건부 (Health Canada), 호주연방의료제품청 (TGA), 유럽의약품청 (EMA) 과같은해외주요기관에서인정하는양식으로작성된원료의약품등록의제출을허용한다. 35) 식품의약품안전청장규정제 HK 호 : GMP 신청 (2012) 36) 화학 제조 품질관리 (CMC), 의약품안전성 유효성, 의약품구성성분, 품질관리정책, 의약품생산활동및품질관리, 유효성분제조소및시설관련정보등 33 인도네시아의약품허가제도

36 3. 표시기재사항및첨부문서 3.1 개요표시기재사항은의약품포장의라벨, 브로셔, 카톤 (carton) 에표시될만큼중요하다고간주되는의약품의전체정보, 유효성, 안전성, 용량및기타정보를의미한다. 일반의약품 (OTC) 에대한표시기재사항은반드시인도네시아어 ( 의무사항 ) 또는영어 ( 선택사항 ) 로작성되어야한다. 윤리사항에대한내용은영어로작성해야하며, 인도네시아어는선택사항이다. 수입의약품인경우 처방전필요 (Harus dengan Resep dokter) 라는문구를반드시영어및인도네시아어로표시해야한다. 표시기재사항에인도네시아및영어외다른언어의사용은허용되지않으며, 이러한경우영문또는인도네시아어번역이요구된다. 3.2 일반정보 1) 일반요건포장에포함될최소한의필수정보는의약품정보, 제형, 구성성분, 적응증, 용량, 경고 금기, 보관조건, 품목허가상태이다. 외부포장면적이적은경우라도제품명, 등록번호및로고는반드시표기되어야한다. 2) 특별요건 Ÿ 제네릭명제네릭명의글자크기는브랜드명의 80% 정도로하되, 동일한글꼴 색 스타일 ( 기울임, 굵기 ) 을사용해야한다. 예 : 브랜드명 (10 포인트 ) 제네릭명 (8 포인트 ) 34

37 Ÿ 돼지유래성분 표기 돼지유래특정성분을함유한의약품, 전통의약품, 건강보조제는아래예시와같이 돼지유래성분 (Mengandung Babi) 이라는문구를라벨상에표기해야한다. Ÿ 의약품이제조과정중돼지유래특정성분과접촉할경우 제조과정에서돼지유래성분과접촉한제품입니다 (Pada proses pembuatannya bersinggungan dengan bahan bersumber babi) 라는문구를라벨상에아래예시와같이표기해야한다. Ÿ 알코올을함유한의약품, 전통의약품, 식품보조제는백분율 (%) 형식으로라벨상에 알코올함유량을표기해야한다. Ÿ 포장별표시기재사항에대한요건은아래표와같다. No 필요정보단위카톤 박스포장스트립 / 내부라벨 (Catch Cover) 블리스터 앰플 / 바이알 1 제품명 2 제형 (-) d) 3 포장크기 ( 단위 ) (-) 4 유효성분명 함량 5 신청자명 소재지 c) c) 6 제조업자명 소재지 c) e) 7 품목허가권자명 소재지 c) (-) 8 투여경로 (-) 9 등록번호 10 배치번호 11 제조일 (-) (-) (-) 12 유효기간 13 적응증 a) b) (-) (-) 14 용량 a) b) (-) (-) 35 인도네시아의약품허가제도

38 No 필요정보단위카톤 박스포장스트립 / 내부라벨 (Catch Cover) 블리스터 앰플 / 바이알 15 금기사항 b) b) (-) (-) 16 부작용 b) b) (-) (-) 17 약물상호작용 b) b) (-) (-) 18 경고 b) b) (-) (-) 19 특별경고 처방전필요 (Harus dengan resep dokter) 일반의약품 (OTC) 경고문 (-) (-) 경고박스 (-) (-) 돼지유래성분 접촉 (-) 알코올함량 (-) 20 보관조건 (-) (-) 21 특별표시 최고소매가 d) 의약품분류로고 37) (-) (-) 제네릭로고 ( 제네릭의약품만해당 ) d) Note: a) 일반의약품 (OTC) 및제한적일반의약품 (limited-otc) 정보에반드시포함될정보. 처방약에대한보다자세한내용은환자용의약품정보를참고 b) 환자용의약품정보포함할수있음 c) 신청자 제조업자 품목허가권자의이름표기 d) 10 ml 미만의앰플 바이알은해당없음 e) 국가명만표기 37) 인도네시아의의약품분류코드및로고는다음과같다. - O: 마약류 - G: 처방의약품 ( 빨간점 ) - W: 약국을통해서만이용할수있는제한적일반의약품 ( 파란점 ) - B: 어디서든이용할수잇는일반의약품 ( 녹색점 ) 36

39 3.3 첨부문서및리플릿인도네시아에서시판되는의약품은식품의약품안전청에서규정한요건을준수하는첨부문서및리플릿을사용해야한다. 신청자는첨부문서의내용갱신및유지관리에대한책임을져야한다. 또한참조국 ( 유럽, 호주, 미국, 영국등 ) 의제품특성요약 (summary of product characteristics, SmPC) 은인도네시아의의약품정보 첨부문서내용으로사용할수있다. 첨부문서및리플릿은다음과같은정보를포함해야하며, 영문및 / 또는인도네시아어로작성되어야한다. 1) 제품특성요약 (SmPC) Ÿ 제품명 Ÿ 제형 Ÿ 의약품에대한설명 Ÿ 구성성분 Ÿ 약력학 약동학자료 Ÿ 안전성자료 ( 필요시 ) Ÿ 적응증 Ÿ 용량 Ÿ 금기사항 Ÿ 경고 Ÿ 약물상호작용 Ÿ 임신 수유시주의사항 Ÿ 운전및기계작동능력에대한영향 ( 필요시 ) Ÿ 부작용 Ÿ 과다복용 ( 해당하는경우 ) Ÿ 첨가제 Ÿ 보관조건 ( 온도 습도 ) Ÿ 유효기간 Ÿ 포장크기 Ÿ 등록번호 Ÿ 신청자명및소재지 37 인도네시아의약품허가제도

40 Ÿ 제조업자명및소재지 Ÿ 품목허가권자명및소재지 ( 필요시 ) Ÿ 사용설명서 Ÿ 최초허가일및갱신일 ( 필요시 ) Ÿ 변경일 ( 필요시 ) Ÿ 의약품분류 Ÿ 특별경고등 - 처방필요 (Harus dengan resep dokter) - 일반의약품 (OTC) 에대한경고문 - 경고박스 - 돼지유래성분 접촉 - 알코올함량 2) 환자정보안내서 (Patient Information Leaflet, PIL)( 인도네시아어 ) Ÿ 제품명 Ÿ 제형 Ÿ 의약품에대한설명 Ÿ 구성성분 Ÿ 함량 Ÿ 적응증 Ÿ 용량 Ÿ 금기사항 Ÿ 경고 Ÿ 약물상호작용 Ÿ 임신 수유시주의사항 Ÿ 운전및기계작동능력에대한영향 ( 필요시 ) Ÿ 부작용 Ÿ 과다복용 ( 해당하는경우 ) Ÿ 보관조건 Ÿ 사용설명서 38

41 Ÿ 등록번호 Ÿ 신청자명및소재지 Ÿ 변경일 ( 필요시 ) Ÿ 특별경고등 - 처방필요 (Harus dengan resep dokter) - 일반의약품 (OTC) 에대한경고문 - 경고박스 - 돼지유래성분 접촉 - 알코올함량 4. 의약품제조판매증명서 인도네시아에서의약품을해외로수출하고자하는회사는식품의약품안전청에서발행한의약품제조판매증명서 (Certificate of a Pharmaceutical Product, CPP) 를필요로한다. 의약품제조판매증명서는인도네시아내의약품의유통 판매여부가명시되어있다. 해당의약품제조판매증명서는세계보건기구 (WHO) 의양식을기준으로영어로발행되며, 절차는 2달소요된다. 의약품제조판매증명서는수입국당제품한개씩에대해발행된다. 만일대상의약품이수출전용일경우, 해당사유를증명서에포함시켜야한다. 신청자는증명서당수수료 50,000루피아를지불해야한다. 발행된증명서의유효기간은 1년이다. 5. 제조업허가 인도네시아에서제조전체또는일부를담당하는모든제조업자는반드시인도네시아보건부및식품의약품안전청에서발급하는제조업허가를받아야한다. 인도네시아에서제조된의약품은제조업허가를받은해외기업이인도네시아또는해외에서제조한제품도포함한다. 제조업허가신청서는보건부에제출해야하고, 의약품제조및품질관리기준 (GMP) 증명신청서는식품의약품안전청에제출해야한다. 식품의약품안전청은설계, 장비, 품질관리구역, 보관구역등제조소 공장에대한실사를수행하고의약품제조및품질관리기준 (GMP) 실사및평가결과를기준으로권고서를발행한다. 식품의약품안전청의권고서는제조업허가발급승인을위해보건부에송부한다. 보건부는자격조건심사후신청자에게제조업허가를발급한다. 39 인도네시아의약품허가제도

42 6. 수입허가 38) 인도네시아는상품의수출무역장벽을없애거나낮추기위하여아세안회원국, 호주, 브라질, 유럽연합 (EU), 뉴질랜드, 멕시코, 미국등과국제협정및상호무역협정을맺고있다. 일반적으로인도네시아내유통 판매를위한의약품수입시식품의약품안전청의허가를받아야한다. 39) 이때해당의약품이외국에서이미유통 판매되고있음을증명하기위해의약품제조판매증명서 (CPP) 가요구되며, 자유판매증명서 (Free Sale Certificate, FSC) 로대체할수있다. 40), 41) 근시일내에할랄 (HALAL) 법에따른규정이실행될경우, 수입의약품은반드시해당규정을준수해야한다. 인도네시아에서제조시설을갖추고있으며, GMP 승인을받은제약회사는품목허가된의료제품을수입할수있다. 식품의약품안전청에서발행하는수입허가증의유효기간은 5년이다. 수입허가증은수입업자가허가만료후에도인도네시아에서의약품을제조하려면 5년간의허가유효기간동안기술이전을수행해야한다는의무사항을명시하고있다. 원료등수입된의약품은반드시식품의약품안전청에등록해야한다. 의약품수입업자는유통허가뿐만아니라식품의약품안전청의허가가필요하며, 수입허가증은수입건별로유효하다. 38) 식품의약품안전청장규정제 12 호 : 인도네시아식품 의약품수입관리 ( ) 39) 식품의약품안전청장규정제 3 호 : 식품의약품안전청장규정제 HK 호 ( 의약품품목허가기준및절차 ) 개정안 ( ) 40) 인도네시아보건부규정제 1010/MENKES/PER/XI/2008 호 41) 인도네시아보건부규정제 1120/MENKES/PER/XII/2008 호 40

43 7. 수수료 신청자는수수료를인도네시아은행 (Bank of Negara Indonesia, BNI) 계좌번호 42) 로 직접입금하여지불할수있다. 인도네시아화폐인루피아 (RP) 로만식품의약품안전청에 지불가능하다. 1) 의약품및생물의약품품목허가수수료 * 2015 년 12 월기준 No 품목허가유형수수료 (RP) a 새로운유효성분또는새로운조합을가진신약또는새로운생물의약품 30,000,000 b 새로운적응증 용량, 제형, 투여경로, 함량을가진신약또는새로운생물의약품 20,000,000 c 상기 (a), (b) 에해당하는신약또는새로운생물의약품으로추가제형및함량이추가되었거나포장크기가변경된경우 7,500,000 d 상호명이있는새로운유사의약품 ( 임상자료필요없음 ) 7,500,000 e 임상시험 ( 생물학적동등성시험포함 ) 이필요한상호명이있는새로운유사의약품 12,500,000 f 새로운유사제네릭의약품 ( 임상자료필요없음 ) 2,000,000 g 임상시험 ( 생물학적동등성시험포함 ) 이필요한제네릭명을가진새로운유사의약품 7,000,000 2) 변경신청수수료 No 변경신청유형 수수료 (RP) a 품목허가의약품명또는제조업자명 ( 또는생산업자명 ) 변경 7,500,000 b 품질심사가필요한변경 ( 추가임상자료필요없음 ) 2,000,000 c 품질심사가필요한변경 ( 추가임상자료필요 ) 12,500,000 d 품질심사의필요유무와관계없는표기시재사항및포장재의디자인 크기변경 1,000,000 3) 심사수수료 No 심사유형 수수료 (RP) a 신약허가신청에대한심사 10,000,000 b 임상시험계획승인신청에대한심사 5,000,000 c 생물학적동등성시험신청에대한심사 2,500,000 d 의료제품광고에대한심사 ( 버전별 ) 100,000 e 전통의약품, 표준생약, 식물성의약품광고에대한심사 ( 버전별 ) 100,000 42) 은행계좌번호 : 인도네시아의약품허가제도

44 4) 사전품목허가및갱신 ( 재품목허가 ) 수수료 No 사전품목허가및재품목허가유형 수수료 (RP) a 사전품목허가 1,000,000 b 의약품및생물의약품에대한재품목허가또는갱신 (5년마다) 5,000,000 c 제네릭의약품및생물의약품에대한재품목허가또는갱신 (5년마다) 1,000,000 d 전통의약품, 표준생약, 식물성의약품의사전품목허가 50,000 5) GMP 실사및승인 No GMP 실사및승인유형 수수료 (RP) a 실사전서류심사 7,500,000 b 시설에대한 GMP 실사 ( 실사자당 / 일기준 ) 10,000,000 c 해외시설에대한 GMP 실사 ( 실사자당 / 일기준 : 교통 숙박비제외 ) 10,000,000 d 해외실사전서류심사 ( 국가별 ) 5,000,000 e GMP 승인에대한신규신청 ( 증명서당 / 신청서당 ) 20,000,000 f 기존 GMP 증명서내상호또는소재지변경 500,000 g 비 ( 非 ) 무균생산시설에대한변경 2,000,000 h 무균생산시설에대한변경 5,000,000 i GMP 증명서갱신 (5년마다) 5,000,000 42

45 Ⅵ. 참고문헌 홈페이지 1. 인도네시아보건부 (MOH): 2. 인도네시아식품의약품안전청 (NADFC): 법, 규정, 가이드라인 1. 식품의약품안전청장법령제 HK /2011 호 ( ) 2. ICH 가이드라인 E6(R1): 임상시험관리기준에대한가이드라인 ( ) 3. ICH 가이드라인 E8: 임상시험을위한일반적고려사항 ( ) 4. 임상시험관리기준에대한인도네시아가이드라인 ( ) 5. 대통령령제 166/2000 호 6. 식품의약품안전청장규정제 3 호 ( ) 7. 식품의약품안전청장규정제 12 호 ( ) 8. 식품의약품안전청장규정제 16 호 ( ) 9. 식품의약품안전청장규정제 17 호 (2015) 10. 식품의약품안전청장규정제 HK 호 (2011) 11. 식품의약품안전청장규정제 HK 호 ( ) 12. 식품의약품안전청장규정제 HK 호 (2012) 13. 보건부규정제 1144/Menkes/PerVIII/2010 호 14. 인도네시아보건부규정제 1010/MENKES/PER/XI/2008 호 15. 인도네시아보건부규정제 1120/MENKES/PER/XII/2008 호 16. 인도네시아보건부장관규정제 66 호 ( ) 43 인도네시아의약품허가제도

46

47 2 Drug Approval System of Indonesia APEC Harmonization Center

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49 Abbreviation ACTD: ASEAN Common Technical Dossier GCP: Good Clinical Practice GDP: Good Distribution Practice GMP: Good Manufacturing Practice MOH: Ministry of Health NADFC: National Agency of Drug and Food Control NIHRD: National Institute of Health Research & Development Notice 1. Due to the purpose of this document, most of the information was quoted directly from the website or related guidelines of each economy s drug regulatory agencies. 2. When referring to the content of this document, check the up-to-date information including related laws and regulations, and revision of guidelines.

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51 Chapter Ⅰ Drug Regulatory Agency Ministry of Health Republic of Indonesia National Agency of Drug and Food Control 53 Chapter Ⅱ Chapter Ⅲ Related Laws and Regulations 57 Classification of Pharmaceutical Products New drugs Generic drugs Biological products Orphan drugs 59 Chapter Ⅳ Drug Approval System Investigational new drug application New drug application Generic drug approval application Orphan drug Priority review Renewal of marketing authorization 75 Chapter Ⅴ Others Good Manufacturing Practice Drug Master File Labeling and package inserts Certificate of Pharmaceutical Product Manufacturing license Import license Fee 86 Chapter Ⅵ References 88

52 Ⅰ. Drug Regulatory Agency 1. Ministry of Health Republic of Indonesia The Ministry of Health (MOH) Republic of Indonesia is the main body with responsibility to provide the quality and essential public healthcare services to all Indonesians with equal access. 1.1 Tasks The MOH has the following tasks: Ÿ Establishment of national health policies Ÿ Establishment of guidelines to determine the health service standards Ÿ Preparation of national plans for healthcare system Ÿ Implementation of international agreements in health sector Ÿ Determination of local licensing standards in health sector Ÿ Outbreak response for disaster on a national scale in health sector Ÿ Establishment of national information system policies in health sector Ÿ Determination of qualification requirements in the health services business Ÿ Establishment of policies for public health care insurance system Ÿ Implementation of guidelines and standards for education and training programs for health personnel Ÿ Setting guidelines for screening, development, and implementation of health technologies and research ethics standards Ÿ Setting standards for accreditation of health facilities Ÿ Epidemiological surveillance; and prevention and eradication of outbreaks of infectious diseases and unusual conditions Ÿ Provision of essential drugs and medicines for basic health services 50

53 1.2 Organization (As of November, 2015) [Figure 1] Organization of Ministry of Health, Republic of Indonesia 51 Drug Approval System of Indonesia

54 The MOH consists of the following: 1), 2) Ÿ Secretariat General Ÿ Directorate General of Nutritional, Maternal & Health care Ÿ Directorate General of Health Efforts Ÿ Directorate General of Diseases Control & Environmental Health Ÿ Directorate General of Pharmaceutical Care & Medical Devices Ÿ National Institute of Health Research & Development (NIHRD) Ÿ National Institute of Health Human Resources Development & Empowerment Ÿ Inspectorate General 1.3 Website 1) Regulation of the Minister of Health No. 1144/Menkes/PerVIII/2010 2) 52

55 2. National Agency of Drug and Food Control Under the MOH, the National Agency of Drug and Food Control (NADFC) was established in 2001 as an independent agency to implement and establish a range of laws, regulations, standards, and operating instructions concerning pharmaceutical regulations, including special provisions for toxicological substances, narcotics, and psychotropic medicines. It is the main agency in charge of regulating a pharmaceutical sector under the President of Indonesia. 3) 2.1 Task The NADFC has the responsibilities such as licensing and certification of pharmaceutical industries based on Good Manufacturing Practices (GMP); pre-market evaluation of products; post-marketing vigilance including product sampling and laboratory testing, inspection of production and distribution facilities; pre-audit and post-audit of product advertisement and promotion; research on drug and food policies implementation; and public communication and education regarding public health. Moreover, the NADFC regulates therapeutic products, narcotics, psychotropic, addictive substances, traditional medicines, cosmetics, complementary products, food, and other similar products. The NADFC also has responsibilities concerning pharmacovigilance activities with an authorization to inspect and test products on the market. However, the agency has no direct authority over local and municipal administration due to the decentralization of the healthcare system. In general, the pharmaceutical sector in Indonesia is regulated by: Ÿ National Agency of Drug and Food Control at the national level for safety, efficacy, and quality Ÿ Drug & Food Agencies at the municipal level are responsible for licensing and monitoring pharmacies 3) Presidential Decree No. 166/ Drug Approval System of Indonesia

56 2.3 Organization (As of July, 2017) [Figure 2] Organization of National Agency of Drug and Food Control 54

57 The NADFC consists of three (3) Deputies, one (1) National Laboratory, three (3) Centers and one (1) Secretariat as described below: 4) (1) Deputy of Therapeutic Products and Narcotics, Psychotropic and Addictive Substance Control is responsible for: Ÿ Pre-market evaluation on efficacy, safety, and quality of drugs or biological products Ÿ Post-market control of therapeutic products, narcotics, psychotropic and addictive substances Ÿ GMP inspection of production and distribution units (2) Deputy of Traditional Medicines, Cosmetics and Complementary Product Control is responsible for: Ÿ Pre-market evaluation and registration of traditional medicines, cosmetics, and food supplements Ÿ Post-market control of traditional medicines, cosmetics, and complementary products, including labeling and promotion Ÿ GMP inspection of production and distribution units (3) Deputy of Food Safety and Hazardous Substance Control is responsible for: Ÿ Pre- and post-market evaluation of food safety Ÿ Inspection of food production and distribution Ÿ Control of hazardous products and substances (4) National Laboratory of Drug and Food Control is responsible for: Ÿ Testing; development of test procedure; and quality assessment of therapeutic products, narcotics, psychotropic and addictive substances, medical devices, traditional medicines, cosmetics, complementary products, foods, and hazardous substances 4) 55 Drug Approval System of Indonesia

58 (5) Center of Drug and Food Investigation is responsible for: Ÿ Investigation of illegal activities involving therapeutic products, narcotics, psychotropic and addictive substances, traditional medicines, cosmetics, complementary products, foods, and other similar products (6) Center of Drug and Food Research is responsible for: Ÿ Research activities on toxicology, food safety and therapeutic product (7) Center of Drug and Food Information is responsible for: Ÿ Providing information on drug and food as well as toxicological substances and coordinating information technology activities of the NAFDC (8) Secretariat is responsible for: Ÿ Coordination of strategic planning Ÿ Management of organization, human resources development, financial management, legal advice and legislation, public relation, international cooperation, and communication including consumer complaints Ÿ Coordination of works among the NADFC centers and all the technical implementation units 2.4 Website 56

59 Ⅱ. Related Laws and Regulations In Indonesia, there are several laws and regulations related to the public health and drugs which include the following: Ÿ Law No. 419/1949 (on Prescription Drugs) Ÿ Law No. 35/2009 (on Narcotics) Ÿ Law No. 5/1997 (on Psychotropics) Ÿ Law No. 36/2009 (Health Law) Ÿ Regulation of the Head of NADFC No. 3 : Amendment to Regulation of the Head of NADFC No. HK on Criteria and Procedure of Drug Registration (Mar-2013) For more detailed information, visit the MOH or NADFC website. 5) 5) MOH: NADFC: (in Bahasa Indonesia) 57 Drug Approval System of Indonesia

60 Ⅲ. Classification of Pharmaceutical Products 6),7),8) 1. New drugs A new drug is a drug with a new active ingredient(s), new additive substances, new form of the dosage, new administration route, new effectiveness, or new combinations that have not been approved in Indonesia. This includes a drug or ingredient(s) in the form of a new molecule which is being developed and produced by a research institution or pharmaceutical companies in Indonesia or abroad with an aim to get a marketing/distribution license in Indonesia. 2. Generic drugs A generic drug is a drug which contains the same active ingredients of a registered drug which is off patent or will be off patent within two (2) years. It may be marketed with a brand name or a generic name. 3. Biological products Biological products include vaccines, antibodies, antigens, hormones, enzymes, blood products, and other fermentation products (including monoclonal antibodies and products derived from recombinant DNA technology), which are used for disease prevention and treatment; and health recovery and improvement. 6) Regulation of the Head of NADFC No.16 : Management and Assessment of New Developed Drugs (Dec-2015) 7) Regulation of the Head of NADFC No. 3 : Amendment to Regulation of the Head of NADFC No. HK on Criteria and Procedure of Drug Registration (Mar-2013) 8) Regulation of the Head of NADFC No. HK on Criteria and Procedure of Drug Registration (Oct-2011) 58

61 4. Orphan drugs An orphan drug is a drug developed to treat rare diseases with difficulty to produce domestically due to low demand. 59 Drug Approval System of Indonesia

62 Ⅳ. Drug Approval System 1. Investigational new drug application 1.1 Overview All clinical trials conducted in Indonesia must consider the rights and safety aspects of clinical trial subjects in accordance with the Declaration of Helsinki. 9) The sponsor who wishes to conduct a clinical trial in Indonesia must obtain approval from both an ethics committee and the NADFC. In Indonesia, there are three (3) types of clinical trial submission: 1) Submission for pre-marketing trials: studies in human subjects 2) Post-marketing clinical trials: post-marketing studies (phase IV) for both intervention studies and non-intervention studies (observation studies) 3) Clinical trials for educational purposes Institutions or sponsors conducting clinical trials need to have an approval letter issued by scientific committee (SC) and ethics committee (EC) in accordance with the Indonesian Good Clinical Practice (GCP) guideline. Essential documents of clinical trials will be audited and inspected by the regulatory authority as part of the process to confirm the validity of the trials conducted and the integrity of data collected. All the application and supporting documents for submission of clinical trials must be written in English or Indonesian. 10) 9) Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects, as amended in October ) Indonesian language is also called as Bahasa Indonesia. 60

63 1.2 Procedure [Figure 3] Flowchart for Clinical Trial Application Process 61 Drug Approval System of Indonesia

64 1.2.1 Evaluation of ethics committees In order to initiate a clinical trial in Indonesia, a proposed clinical trial protocol must be approved by the National Committee of Health Research Ethics or one of the accredited institutional ethics committees (such as Biomedical Research Ethics Committee, University of Indonesia). Only after obtaining the approval from one of the ethics committees, the clinical trial application can be submitted to the NADFC for approval and the approval from ethics committee must be attached to the application. 11) The evaluation process is as follows: (1) Selecting an ethics committee: Before submitting proposed clinical trial protocols for ethical review, a sponsor must choose an ethics committee. (2) Required documents for ethics committees approval: Following required documents must be submitted (10 copies): Ÿ Covering letter (in Indonesian) Ÿ Ethical review application form (in Indonesian) Ÿ Clinical trial protocol (in English) Ÿ Written information for subjects/participants (in Indonesian/English) Ÿ Informed consent Ÿ Investigator s brochure (IB)/package insert (as applicable) Ÿ Investigator s current CV (3) Fees The fee for the ethics committee s review process in Indonesia is RP 5,000, ) When the investigator or sponsor cannot make the required payment, the ethics committee or its institution can reject the scientific/ ethical review. 11) Regulation of the Minister of Health of the Republic of Indonesia No. 66 : Implementation of Registry of Clinical Research (Oct-2013) 12) The currency of Indonesia is the Rupiah, usually marked as RP or IDR 62

65 (4) Review Upon the receipt of proposed clinical trial protocol, the ethics committee conducts a review based on ethical requirements. The ethics committee may contact the sponsor if additional information or clarification is required during the review assessment. If the clinical trial protocol satisfactorily complies with the requirements, the ethics committee sends a letter of approval concerning the clinical trial application to the sponsor. However, if there are any non-compliance issues or deficiencies, the ethics committee will send a refusal letter with reasons for refusal. The protocol must be reviewed and approved by the scientific committee in the institution/company before submitting to the ethics committee. The trial conducted without an approval of scientific committee/ethics committee can be either postponed or terminated by the ethics committee or the NADFC NADFC Review Process After receiving a letter of approval from ethics committee, the sponsor may submit a clinical trial application to the NADFC including the participant list of the ethics committee s review meeting. 1) Review and approval The NADFC may ask for scientific advice from the National Advisory Board on clinical trial regarding the approval of scientific or ethics committee for the pre- and post-marketing trials. 2) Termination of clinical trials Both ethics committee and the NADFC can terminate clinical trials by sending a written notification. After the completion or termination of the trial, a clinical study report, investigational products accountability at the laboratories, essential documents, and audit certificate must be prepared. 63 Drug Approval System of Indonesia

66 3) Compliance All clinical trials conducted in Indonesia must be in compliance with the requirements set out in the ICH GCP and Indonesian Guideline for Good Clinical Practice. 13), 14), 15) 4) Clinical trial registry Effective from 12th November 2014, all clinical research and studies in Indonesia must be registered into the National Registry according to the Regulation of the Minister of Health. 16) This registration can be done after a proposed clinical study has received approvals from the ethics committee and NADFC. 5) Investigational products All locally manufactured investigational products or imported investigational products in Indonesia must be in compliance with internationally recognized guidelines such as a GCP guideline established by ICH or WHO. Moreover, all investigational products must be manufactured, supplied, stored, and distributed in accordance with GMP. All the manufacturing processes must be carried out in accordance with validated methods, specifications, and criteria as included in the approved protocol. 13) ICH Guideline E6(R1): Guideline for Good Clinical Practice, May ) ICH Guideline E8: General Considerations for Clinical Trials, Jul ) Indonesian Guideline for Good Clinical Practice, Dec ) Regulation of the Minister of Health of the Republic of Indonesia No. 66 (2013) 64

67 1.3 Required dossiers Following documents are required to be submitted to the NADFC for clinical trial approval: Ÿ Covering letter Ÿ Application form (in Indonesian) Ÿ Clinical trial protocol (in English) Ÿ Informed consent form (ICF) (in Indonesian) Ÿ Investigator s Brochure (IB) Ÿ Approval from national ethic committee for each clinical site Ÿ CV of investigators (principal investigator and national coordinator) Ÿ Certificate of analysis (CoA) Ÿ GMP certificate Ÿ Participant list of ethics committee meetings Above documents are also required for import license application for investigational products. 1.4 Review period The NADFC issues a clinical trial approval letter for both pre- and post-marketing trials within 10 working days or will notify the sponsor within 10 working days if any supplementation or correction is required. In general, it takes approximately 1-2 months (30-60 working days) for the approval. 17) 17) Indonesian Guideline for Good Clinical Practice, Dec Drug Approval System of Indonesia

68 2. New drug application In Indonesia, drug registrations are categorized into drug registration and variations (7 categories in total). New drug registration can be categorized into: Ÿ Category 1: New drug and biological products, including Similar Biotherapeutic Product (SBP) Ÿ Category 2: Copy drug/generics Ÿ Category 3: Others The other registration categories are as follows: Ÿ Category 4: Major variation Ÿ Category 5: Minor variation with approval Ÿ Category 6: Minor variation with notification Ÿ Category 7: Renewal 2.1 Procedure 1) License approval for new drug development (OPB in Indonesian language) This process is to check and ensure that protocols and documents submitted are correct and acceptable for the proposed clinical trials (phase 1 to 3) or non-clinical trials. It normally takes 100 working days from the date of submission. 2) Pre-registration evaluation This review is to ensure that submitted documents are prepared in the required format. During this phase, evaluators at the NADFC will decide the evaluation path depending on aforementioned registration categories. The process normally takes 1 to 12 months for registration application and 40 to 80 days for variation application. 66

69 3) Evaluation of registration applications The evaluation process for registration of market authorization (for new drugs, new biological products, and generics/copy drugs) is processed through four (4) paths as shown in the Table 1: Path type Types of Products Review time Path I Path II Path III Path IV - Minor variation(s) which need approval - Application for export only - Life-saving drugs - Orphan drugs - Drugs for national programs - Drug development and all investigational drugs in Indonesia - Major variation(s) (i.e. new indication/posology) for the above products included in Path II - Drug which has been marketed in the economies which have implemented harmonized evaluation system or established evaluation system - Major variation (i.e. new indication/posology) for the above products included in Path III - New drugs, biological products, major variation(s) (new indication/ posology) which are not included in Path II and Path III 40 working days 100 working days 150 working days 300 working days [Table 1] Evaluation Path for Registration of Market Authorization Ÿ For products that have not been approved by any competent regulatory agency, the review of these full dossiers will take 300 working days (Path IV). Ÿ For products that have been already approved by one of the competent regulatory agencies with whom Indonesia has signed the mutual recognition agreement and other agreements, the review of these abbreviated dossiers will take 150 working days (Path III). Ÿ For generic products/copy drugs (essential drugs for government program) that do not require non-clinical and clinical data to establish safety and efficacy, and all the domestically manufactured drugs, the review of these dossiers will take 100 working days (Path II). 18) 18) Regulation of the Head of NAFDC No. 3 (2013) 67 Drug Approval System of Indonesia

70 4) Administration Process After the safety and efficacy evaluation, the National Committee on Drug Evaluation will prepare written recommendations and forward it to the NADFC. The evaluation reports of the completed dossiers will be sent for approval to the head of the sections, Deputy I or head of the NADFC. For the registration for market authorization of imported products from overseas economies, the NADFC will sign the approval certificate. For the registration of products domestically manufactured in Indonesia, the Deputy I will sign the approval of market authorization. An approval letter will be issued prior to the issuance of the original marketing authorization (MA) number. This is valid for a maximum of two (2) years. 2.3 Regulatory consultation system The applicant may request for a face-to-face meeting with the regulatory authority during the registration process. The procedures to request a face-to-face meeting with the authority are as follows: 1) Meeting with either head of Deputy I or Registration director: The applicant must write an official letter stating the purpose of meeting and meeting participants, contact points, as well as date of the meeting (one month before the meeting). 2) Meeting with a sub-directorate head: The applicant must contact to their respective secretaries at least a week before the meeting. 3) A face-to-face consultation with a head of section: The applicant shall send an official letter by (penilaianobat@pom.go.id) with the following: name of the applicant, proposed date/time of the meeting, agenda, and the name of NADFC evaluator to whom the meeting is being requested (one week before the meeting). Then, the NADFC will inform the applicant of the meeting date and time. 68

71 2.4 Required dossiers The registration submission to the NADFC can be in one of three (3) following dossier types: Full dossier, Abbreviated dossier, and Generics dossier. The required data for each type of dossier should be submitted as the table below: 19), 20) Required Documents Full Dossier Abbreviated Dossier Generics Dossier Application form ICH or ACTD format ICH or ACTD ICH or ACTD ACTD only Administrative information CTD Overviews & Summary Non-clinical and clinical overviews and summary Quality only Quality Non-Clinical Reports - NA Clinical Study Reports Bioequivalence studies/ Biowaivers Approval Letter NA NA GMP Certificates Approved PI/SmPC/PIL* * ICH: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ACTD: ASEAN Common Technical Dossier PI: Package Insert SmPC: Summary of Product Characteristics PIL: Patient Information Leaflet [Table 2] Required Documents for Each Dossier Type 19) Abbreviated Dossier submitted when the drug has been approved in economies (EU, USA, Australia, Japan) that implemented harmonized evaluation system 20) Regulation of the Head of NADFC No. 3 : Amendment to Regulation of the Head of NADFC No. HK on Criteria and Procedure of Drug Registration (Mar-2013) 69 Drug Approval System of Indonesia

72 1) Language All documents (application form and supporting dossier) are written either in Indonesian or English. 2) Dossier Types Ÿ Full Dossier: When submitting a full dossier, detailed information on chemical/biological and pharmaceutical/genetic development data, toxicological and pharmacological data and clinical documentation shall be submitted in support of the application. Ÿ Abbreviated Dossier: When submitting abbreviated dossier, the applicant must submit a proof of approval by another competent drug regulatory agency. 21) Required documents are as follows: - An official approval letter or equivalent document from a competent drug regulatory agency, certifying the registration status of the drug product - GMP certificate of the drug product manufacturer(s) issued by the relevant competent drug regulatory authority - Package insert (PI)/Summary of product characteristics (SmPC)/Patient information leaflet (PIL) approved by the drug regulatory agency 3) Acceptable format Ÿ Application for new chemical entity (NCE) and biologics: ICH Common Technical Document (CTD) format or ACTD format Ÿ All others submissions such as variations and generic application: ACTD format 21) Reference countries recognized by the NADFC include, but not limited to, Australia (Therapeutic Goods Administration, TGA), European Union (European Medicines Agency, EMA), United States (Food and Drug Administration, FDA), Canada (Health Canada), and New Zealand (Ministry of Health). The NADFC also signed mutual recognition agreements and bilateral trade agreements with other economies for acceptability of foreign clinical data, GMP standard and inspections done by other foreign agencies. The Ministry of Food and Drug Safety in Korea has also signed an MOU on 12-July

73 2.5 Review period In Indonesia, the maximum review and evaluation period for full dossier (new license submission for NCE and biologics) is approximately 720 working days. Evaluation Path Pre-registration review Registration review Stop-theclock Administrative process (Granting approval) Maximum review time I 1-12 months 40 working days 120 working days (Max.) 1-2 months 460 working days II 1-12 months 100 working days 120 working days (Max.) 1-2 months 520 working days III 1-12 months 150 working days 120 working days (Max.) 1-2 months 570 working days IV 1-12 months 300 working days 120 working days (Max.) 1-2 months 720 working days Variation Category 4, 5, months working days 120 working days (Max.) 1-2 months working days Renewal Category 7 NA 40 working days NA 1-2 months 80 working days [Table 3] NDA Review Period Stop-the-clock will take place if the reviewers request any additional data or any clarification from the applicant. The process will stop until the applicant submits the additional data or clarification, but not more than 120 working days. When there is delay in submission of data requested, the registration process will be rejected by the NADFC. However, the applicant has an option to resubmit the dossier through a new registration application process. 71 Drug Approval System of Indonesia

74 3. Generic drug approval application 3.1 Procedure As mentioned in 2. New drug application under IV. Drug Approval System of this guideline, generic drugs belong to Category 2 and are evaluated by generics dossier which do not require non-clinical and clinical data to prove pharmaceutical safety and efficacy. 22) 3.2 Review period As mentioned in 2.5 Review period under IV. Drug Approval System of this guideline, the review of generic drug application dossiers will take 100 working days (PATH II of evaluation process by the NADFC). [Figure 4] Generic Drug Evaluation Process 22) Regulation of the Head of NADFC No. 3 : Amendment to Regulation of the Head of NADFC No. HK on Criteria and Procedure of Drug Registration, Mar

75 3.3 Required dossiers 23) As mentioned in 2.4 Required dossiers under IV. Drug Approval System of this guideline, application dossiers for generic drug approval is required to follow ACTD format. The registration of generic product does not require preclinical and clinical data as long as the packing insert is based on the NADFC template (STINEL 24) ). However, if the dossiers are not following the NADFC template, the applicants should provide the package insert used in other recognized economies as reference. The important documents during registration of generic drugs are administrative data and quality data. If pharmacokinetic/pharmacodynamic data prove bioequivalence (BE) of the generic product, the applicant may submit comparative dissolution test data instead of BE test data (waiver of BE test). If the route of administration of the proposed product is not the same as that of the established generic drug, then bioavailability (BA) study is required and the test could be referred to recommended laboratory(ies) in others economies (e.g. ASEAN economies) Bioequivalence The NADFC will only grant the authorization to market and distribute generics if the applicant can demonstrate that proposed generic drugs (copy/me-too drug) has the same bioequivalence as Indonesian reference medicinal product. 25) To conduct bioequivalence studies, applicants must use the reference products that are already marketed in Indonesia. If the reference product has not been authorized by the NADFC to market or not available due to import issue, the applicant may file a request to the Director of Drug Evaluation to use marketed reference product or market leader product from another economy such as Europe, USA, Canada, Australia, etc. 23) Regulation of the Head of NADFC No. HK on drugs with bioequivalence test 24) STINEL: Electronic Information Standard 25) Regulation of the Head of NADFC No. 17 : Management Guideline for the Assessment of Biosimilar Products (2015) 73 Drug Approval System of Indonesia