HIEP HQI DOANH NGHIEP DU''''QC VIET NAM 7a; li@ t@ lt N~NG CAO CHAT LUONG HO SO BAO CO TH~'''' TU''''ONG DUONG SINH HOC TRONG • D~NG KY THU~C TAI VIET NAM • • TP H~ Chi Minh, Ng~y 14 thing 09 nm 2023 J NOI DUN[.]
H I E P HQI DOANH N G H I E P DU'QC VIET NAM 7a; li@ t@ lt N~NG CAO CHAT LUONG HO SO BAO C O TH~' TU'ONG DUONG SINH HOC TRONG • D~NG KY THU~C TAI VIET NAM • • TP.H~ Chi Minh, Ng~y 14 thing 09 nm 2023 NOI DUNG CHU'ONG TRINH • , ' , T~p hu~n N~ng cao ch~t long h~ so b o c~o th~ turong duong sinh hoc Ding k luru h~nh thu~c ti Vi~t Nam ' Ng~y 14/09/2023 tai TP.H6 Chi Minh : 0 - 8:30 8:30-08:35 Ngu~i the hi~n N@i dung chuong trinh Th~i gian Ban t~ chc D6n ti~p dai bi~u Tuyen b6 l Ban t~ chc do, gi~i thi~u dai bi~u TS Trinh Van L~u, Chi 8:35-8:40 Pht bi~u khai mac H@i nghi tjch Hip h@i - N6i dung co b~n c~a TT 07/2022/TT- TS Chuong Ngoc Nai, BYT ng~y 5/9/2022 quy dinh thu~c ph~i Ph6 th TDSH v~ c~c y~u c~u d~i v6i h~ so Ki~m nghi~m thu~c TP Vi&n tru~ng Vien : 8:40-10:15 b~o cio s~ d~ng li~u nghi~n c u TDSH H~ gIa ky luu h~nh thu~c tai VN Chi Minh, th~m Chuyen djnh so h~ DKT c~a BYT 10:15-10:30 Gi~i lao TS - Mot s6 vu~ng m~c thuong gip Chuong Ngoc Ni, Ph6 Vien tru~ng Vien chu~n bi H~ so b~o c~o th~ tuong duong Ki~m nghi~m thu~c TP 10:30-12:00 sinh hoc D~ng k thu~c v~ gi~i d~p ' H6 Chi Minh, Chuyen ki~n c~a hoc vi~n g1a th~m dinh h~ SO DKT c~a BYT 12:00- 3: Nghi ~n trua TS Nguy~n Tr~n Linh, • Ging - Mi quan h~ gi~a d~ h~a tan v~ th~ tuong 13:30- 15:00 A vIen , Dai hoc Duoc HN, Uy vien h~i duong sinh hoc dng tu van cap ding ky luu h~nh thu~c, BYT 15:00- : Gi~i lao TS Nguy~n Tr~n Linh, - M i quan h~ gi~a d@ h~a tan v~ th~ tuong • Giang duong sinh hoc (ti~p) J A ven , Dai hoc Duoc HN, Uy vien hpi : - 6: Th~o lu~n, gi~i dip y ki~n ca hoc vi~n d~ng tu van cip dang luu h~nh thudc, BYT k ■ill ■■■E ■■■K ■ I ■ ■ NOI DUNG CO B~N C~A TT 07/2022/TT-BYT • NG~Y 5/9/2022 QUY DINH THUC PH~I TH~ TUONG DUONG SINH HQC ■ V~ CC Y~U C~U DI VI HO SO BAO CAO S LIEU NGHI~N C~'U TDSH TRONG D~NG KY LU'U HANH THUC TAI VIET NAM ■ TS Chuong Ngoc N~i, r Ph6 Vien truong Vi~n Ki~m nghi~m thudc TP H Chi Minh r Chuyen gia th~m dinh h~ so d~ng k thu~c c~a Bo Y t~ -N~I D U N G CO' B~N CA TH~NG TU ' $0 07/2022/T-BYT NG4Y / / 2 CUA B Q Y T E "Quy dinh thu~c ph~i th~' tu'ong duong sinh hoc v~ c~c y~u cu d6 vi h~ so b~o c~0 s6 li~u nghi~n cu tuong dung sinh hoc luu h~nh thu~c tai Vi~t Nam" TS Chuong Ngoc N i Vien Ki~m Nghiem Thu6c TP.H Chi Minh TP Hb Chi Minh Ng~y 2 THONG TU O7/2022/TT-BYT Thay s a th~ ~i Thong 26/4/2010 "Hu~ng d~n b~o dung/turong urong sinh c o tu 08/2010/TT-BYT liu s~ hoc ng~y nghi~n cru sinh kh~ d~ng ky thu~c d~ gp ph~n n~ng cao ch~t long, an to~n v~ hi~u qu~ ca thu~c d~ng ky luu h~nh tr~n thi truong" Hi~u luyc ti ng~y 01/11/2022 THONG TU O7/2022/TT-BYT Thong tu gom c~ 05 chuong, • Chuong di~u I Nh~ng quy dinh chung (Di~u 1-2) • Chuong I I Thu~c generic ch~a duoc ch~t, dang b~o c~ b~o c~0 • Chuong th~ turong s ch~ phi li~u nghi~n cu tuong duong sinh hoc (Di~u 3-5) I I I Quy dinh v~ thu~c d6i ch~ng v~ y~u cu d~i v~i durong sinh hoc (Di~u 6-7) • Chuong IV H~ so b~o c~0 s~ li~u n g h i ~ n cu turong duong sinh hoc (Di~u - ) • Chuong V Di~u khon thi h~nh (Di~u - ) THONG TU 07/2022/TT-BYT Thong tu g~m c~ 07 phu luc • Phu luc I Danh muc duroc ch~t cha thuc generic phi b~0 c~o s~ li~u nghi~n cu TDSH d~ng ky luu h~nh thu~c • Phu luc II Di~u kien d~ duoc ~p dung d i v~i thu~c khong y~u c~u th TDSH in vivo • Phu luc I I I C~c y~u cu cu th~ bo c~o s~ li~u nghi~n cu TDSH theo d~c tinh gi~i ph~ng duroc cht • Phu luc b o IV Yu cu chung di vi v~ du~ng dung thuc c~0 s~ liu nghi~n cru th' tuong duong h~a tan • Phu luc V Quy dinh v~ c l~ s~n xuat quy m~ th~ nghi~m • Phu luc VI C~c d~n kjy thu~t tham chi~u • Phu luc V I I Cc bi~u m~u TH~NG TU O7/2022/TT-BYT QUY D I N H C H U N G Di~u Pham vi di~u chinh Di~u Gi ~ i thich t~ ng~ THU~T NG~ Thu~c generic (generic product): ham luong, duroc s~ dang dung b~o thay th~ l~ thu~c c~ c~ng dugc ch~t, vi ch~ thu~c thu~c ph~t phat minh minh v~ v~/ho~c thurong thu~c d~i ch(ng Thu~c d~i ch~ng (comparator product/ thu~c m~ thu~c generic s~ duoc dung di~u tr[ Thong thurong, thu6c 6i reference product): d~ thay th~ l~ n~ ch~ng l~ c~c thuc ph~t minh ho~c c~c thuc d~ duoc chp qi~y d~ng k luu h~nh v~i d y ~ d~ li~u v~ hi~u qu~, an to~n v~ ch~t luong d~ duoc thi~t l~p Thu~c pht m i n h (innovator pharmaceutical duroc c~p ph~p luu h~nh ~u ti~n, tr~n co d~ li~u v~ ch~t luong, an to~n v~ hi~u qu~ s product): d~ c~ l~ thu~c dy d c~c THU~T NG~ Tong duong thuc c~ng ph~n) b~o cha ho~c c~ng ch~ (Pharmaceutical mt loai duoc ch~t equivalence): (6i vi thu~c Chi don chc th~nh ch~a mt s~ loai dupc ch~t (d6i v~i thu~c da th~nh ph~n), duroc ch~t c~c thu~c gibng h@t v~ c~ c~ng ham lupng tinh theo mol d~ng th~i b~o ch~, co ch~ gii phong cc duc thu~c ny c~ c~ng dang ch~t nhu nhau, c~ c~ng du~ng dung v~ c~ ti~u chu~n ch~t long tuong durong Th~ phm b~o ch~ (Pharmaceutical c~ng ch~a mot loai ho~c c~ng cha ph~n) alternatives): Chi c c thubc dupc ch~t (di vi thuc don th~nh ph~n) m@t s~ loai dugc ch~t (d~i vi thu~c da th~nh nhung kh~c v~ dang ho~ hoc (mu~i/ estel ether ph~c ch~t/ d~n ch~t) ho~c dang ly (dong ca duoc ch~t h o c kh~c v~ phan/ h~n hop dong ph~n) ham lurong duoc ch~t ho~c kh~c v~ dang b~o ch~ THU~T NG~ Tuong duwong s i n h hoc (In vivo Bioequivalence Study): L~ nghi~n cu l~m sang tr~n ngur~i tinh nguy~n duoc thi~t k~ nh~m so s~nh sinh kh~ dung ca thu~c generic vi thu~c d6i ch~ng hu~ng d~n muc ti~u ch~ng minh kh~ n~ng thay th~ thu~c d6i ch~ng ca thu~c generic Tuong duong dissolution): L~ nghi~n cu so snh bi~u d~ tan gi~ra c~c thu~c cc d hoa tan (Equivalence moi trurong tan kh~c Tuong duong goi l~ n g h i n cu tuong duong in d tan vitro P H ~ P TH~ DO HO~ TAN VA THAY DI (VARIATION) SAU KHI THU' TUONG DU'ONG S I N H HOC 127 THAY DOI C~ L I ~ N QUAN TI N G H I ~ N C~'U TU'ONG DU'ONG S I N H HOC Thay d6i nh~ cung c~p/TCCL duroc ch~t • Thay d6i c~ng th~c (Ma!-10, M a V- 1 , MIV-PA15, MiV-PA16) • Thay d6i quy trinh s~n xu~t (MaV-9, MIV-PA20) Thay di kich thuc v~lho~c hinh dang vi~n n~n, vin nang, vi~n dan ho~c vi~n d~t ~m da0 (MIiV-PA26) • Cong b~ thu~c c~ ch~ng minh tuong duong sinh hoc (MiV-PA37) • Tham kh~0: SUPAC, EMA 128 Immediate Release Products (Conventional Release Products) Drug Product: BA/BE Postapproval Dissolution Proflle BE Study Generic Drug Class Class 1: HS/HP HS/HP/RD Class 2, , Dissolution Higher Strength Lower Strength BE Study Dlssolutlon Study 129 Dressman J B., Kr~mer J (2005), Pharmaceutical dissolution testing, Taylor & Francis Yes 0es the change apply to ls the change caused by changed composltlon of No LJ] ingredients? No Yes ls the drug solubility defined as high or low? high sobity f i dose/solublty ratio Dissolution < 250 mt Dissolution Does the drug exhibit high or low panesbility? est accordording !o No high permeablty if absorption pp/cation > 90 % test according to 0pplication Yes Y es Case A- high solubility/ Does the change apply to low permeability high permeability n i Dissolution ests t (n = 12) in 900 mL 0.1N Issolution profiling accord CI with agitation speed (BCS Class 2) the compenal or f not avalable In the estabi shed media wih sampling at 15, 30,45, 60, and 120 or of 100 rpm (basket) unbl plateau s s reachod or 50 rpm (paddle) (opporatus! spood accord Note: non-rapidly dissoing forms {release 85% th.in 15 minutes fo r test and ro'rone • (l t o t not rocommondod) Figure guidance Ctedon; f , value Dissolution profiling accord to Case B Postapproval changes of IR forms supported by in vitro dissolution data according to SUPAC-IR Modified Release Dosage Forms I Drug Product: BA/BE ] I + + Preapproval Postapproval t i New Drug ] Dlssolutlon Profile, f, Generic Drug BE Study [ BA Study each strength Food effect study Higher Multiple dose study + ] BE Study at higher strength Strength J Food effect study Lower strength ] Tablots Formulation y proportional Beaded capsule Dissolution profile Dlssolutlon Profile f, In one medium f, In medla Dressman J B., Kr~mer J (2005), Pharmaceutical dissolution testing, Taylor & Francis controlled release form Level change: 131 delayed release form Level change: Perform dissolution tests for changed drug product Perform dissolution tests for changed drug product and the blobatch or marketed batch according to and the blobatch or marketed batch according to application release requirements application release requirements Level change (oxcapt narrow therapeutic range drugs in Level change (except narrow therapeutic range drugs): case of change in rolease controlling excipiont:): Perform dissolution tests for changed drug product Perform dissolution tests for changod drug product and the blobatch or marketed batch according to and the biobatch or marketed batch according to application requirement Additionally, multipoint dissolution application requirement and multipoint dissolution tests in the acid stage (0.1N HCI for hours) followed by profiling in threg additional other media (e.g water, testing in buffer stage (USP buffer in the range of pH 4.5 - 0.1N HCI, USP buffer at pH 4.5, 6.8) Sampling intervals under application test conditions and two additional agitation should be adequate (e.g at , 2, hours and every two Speeds (basket: 50/ 100/ 150 rpm; paddle: 50/ 75/ 100 rpm) hours until either 80% drug re'ease or asymptote ls reached) should be performed Sampling Intervals in buffer stage shouk bo adequate (0.g at 15, 30, , 60 and 120 or until either 80% drug release or asymptote is reached) or In case of established IV/VC, dissolution tests for changed drug product and the blobatch or marketed batch according to IVIVC-method are sufficient In case of established IVIVC, dissolution tests for changed drug product and the biobatch or marketed batch according to IVIVC-method are sufficient drug product and the biobatch or marketed batch according In case of established /IVG, dissolution tests for changed to IVINC-method are sufficient drug product and the blobatch or marketed batch according to IVIVC-method are sufficient Test for similarity of dissolution profiles of pre- and postchanged product Similarity of dissolution profiles should be evaluated by statistical testing (e.g.1, test) Level change and level change of narrow therapeutic Level change and level change of narrow therapeutic range drugs ln case of change in release controlling range drugs in case of change in release controlling excipient: excipient: If IVIVC s i established BE in vivo study may be waived IfIVIVC is established BE in vivo study may be waived In general perform dissolution tests for changed drug In general perform dissolution tests for changed drug product product and the biobatch or marketed batch according to and the biobatch or marketed batch according to application application release test corditions Sampling intervals should release test conditions Sampling intervals in buffer stage be adequate (e.g at 1, 2, hours and every two hours untl shouldbo adequate (e.g at 15, 30, , 60 and 120 either 80% drug release or asymptote is reached) until either 80% drug release or asymptote ls reached) Figure Postapproval changes of MR forms supported by in vitro dissolution data according to SUPAC-MR guidance 13 SUPAC (US-FDA) • SUPAC-IR: Approval Immediate-Release Changes: Chemistry, Solid Oral Dosage Manufacturing And Forms: Controls, Scale-Up In Vitro And Post Dissolution Testing, And In Vivo Bioequivalence Documentation • SUPAC-MR: Approval Modified Changes: Release Chemistry, Solid, Oral Dosage Manufacturing, and Forms, Controls; Scale-Up In Vitro and Post Dissolution Testing and In Vivo Bioequivalence Documentation • SUPAC-SS: Nonsterile Semisolid Dosage Forms; Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation SO S~NH TU'ONG DU'ONG DQ HOA TAN (SUPAC) Thu~c IR: • Case A: Q = 85%/15 ph~t, 900 ml H C I 0, N, thi~t bi - 0 vVp hoc thi~t bi - 50 v/p • Case B: DT h~a tan nhi~u di~m theo TC ( , , 45, 60, ph~t ho~c d~n g~n nhu khong GP) • Case C: DT h~a tan nhi~u di ~ m nu~c, H C I 0, N, d~m pH 4,5, 6,5, 7,5 ( , 30, 45, 60, ph~t d~n 90% DC GP ho~c d~n g~n nhu hong GP) Thu~c MR: • Extended release: DT h~a tan nhi~u di~m the0 TC + mi trurong (d~n 80% DC GP ho~c d~n g~n nhu khOng GP) • Delayed release: DT h~a tan nhi~u di~m the TC kh~c SUPAC-IR (IV SITE CHANGES) + Level : Trong c~ng khu nh~ xurng • Level 2: Trong c c khu nh~ xurong canh Level 3: Sang dia di~m kh~c c~ch xa Level & : D Level 3: So s~nh h a tan theo TC d h~a tan theo Case B + HCI0,1 N/2 gi » D~m ~ t6c d¢ khu~y SUPAC-IR (V CHANGES IN BATCH SIZE (SCALE-UP/SCALE-DOWN)) Mc d@ thay d6i d~ So s~nh hoa tan ��vel : Uiay d,6i cfr 16 fo>i � 10J�n pil6�6ipbJ!tclj,_\/_6'i: 1) k�6n� c~ng trang thi~t bi sn xu~t v~ quy trinh v~n h~nh; 2) d~ ic~c l~ duoc s~n xu~t d~p ng d~y d cGMP; v~ 3) lc�ng cac SOP va ki�m soat, cung nhll' cung c6n.g thll'c (Iii! li~u d~ h~a tan theo JC) va@18 #o= Level 2: thay d~i c~ l~n pilot/biobatch, v~i: 1) cung trang thi~t bi s~n xu~t v~ quy trinh van h~nh; 2) c~c lo duoc s n l6 t~i > xu~t d~p (ng d~y cGMP; v~ Case B 3) c~ng c~c SOP v~ ki~m so~t, c~ng nhu c~ng cong th~c v~ QTSX 137 SU PAC-MR (V CHANGES IN BATCH SIZE (SCALE-UP/SCALE-DOWN)) M c thay So s~nh d@ d~i tan Level 1: thay d~i c~ l~ t~i < 10 l~n pilot/biobatch, v~i: 1) cing trang thi~t bj s~n xu~t v~ quy trinh v~n h~nh; 2) cGMP; c~c l~ duroc s~n v~ 3) xu~t d~p cing c~c SOP v~ nhu c~ng cong thc Level 2: thay di c v~ ~ng ki~m d~y d so~t, 2) c~c l~ li~u d~ (tr~ d~ h~a tan theo TC) cing QTSX l~ ti > 1~n pilot/biobatch, v~i: ) cing trang thi~t bi s~n xu~t v~ quy trinh v~n h~nh; Khong doc s~n xu~t d~p ~ng ER: m~i trur~ng DR:HCI 0.1 (acid stage), cGMP; v~ 3) cing c~c SOP v~ nhu c~ng cong th~c v~ QTSX ki~m N, d~y d soat, USP cng buffer media (pH 4.5-7.5) :a\that SUPAC-IR (VI MANUFACTURING - A Equipment) M~rc d¢ thay d~i So s~nh d¢ hoa tan Level : 1) thay ~i t r bi trang thi~t khong t dong hoc Khong (tr~r khong co'_ h6a san[_ !rang lhiet bj tv• di)ng va� CO' kh�1· fdO, Jiiju h~a d~ van chuy~n nguy~n li~u; 2) thay d~i sang trang bi thi~t m~i c~ cingnguyen t~c thi~t k~ v~ cung ho~c kh~c dung tich Level 2: van h~nh h~a di) tan c~ theo TC) i • ~.±i thay d~i sang trang thi~t bj m~i kh~c nguyen Case C t~c thi~t k~ v~ v~n h ~ n h %4 -' 93 • SUPAC-MR (VII MANUFACTURING EQUIPMENT CHANGES) M~c thay d~i So sanh d~ hoa tan Level : 1J !hay° dOi t(r !rang thiet 6i!'i9)19 11,1' di)ng [i