MT S KIN THC C BN V KH TRNG BNG BC X c trng ca k thut kh trng bng bc x Kh trng

Cc sn phm, d c sn xut trong cc iu kin v sinh nghim ngt vn cn b nhim cc vi sinh vt (VSV), tuy vi mt s lng ban u rt t. Cc sn phm nh vy c coi l sn phm cha v trng v mc ch ca qu trnh kh trng l loi b hoc bt hot cc VSV ny, lm cho cc sn phm cha v trng tr thnh sn phm v trng, m bo an ton cho ngi s dng.

Cc phng php kh trng

C 3 phng php c s dng kh trng qui m cng nghip:

- Nhit nng m p lc (steam)

- Kh Ethylene Oxide (EtO)

- Bc x ion ho: bc x gamma, electron beam v tia X

Mi phng php kh trng k trn c nhng u v nhc im, thch hp vi tng loi sn phm c th: nhit nng m c hiu lc kh trng tt, nhng ch thch hp kh trng dung dch, d lm h hng dng c bng plastic, lm chn gy bt hot cc dc phm, ch phm sinh hc v khi kh trng phi tho b bao gi. EtO c hiu lc kh trng cao, thm qua c bao gi nhng khng thm nhp vo bn trong cc sn pham cu trc c hoc nhiu lp. Ngoi ra EtO l kh c lun lu ng trong sn phm.

Kh trng bng bc x

Kh trng bc x l mt qu trnh vt l nhm bt hot cc vi sinh vt (VSV) trong sn phm nh cc hiu ng ion ha ca cc tia bc x. Qu trnh ny c thc hin bi cc thit b c thit k chuyn dng pht ra cc loi bc x ion ho: tia gamma ca Co-60 hoc Cs-137, chm in t ca my gia tc in t v tia X ca my chiu tia X.

So vi cc cng ngh kh trng bng nhit v ho hc, kh trng bc x c coi l mt cng ngh sch, hiu qu v an ton hn v kh trng bc x khc phc c nhiu nhc im ca cc phng php khc nh m xuyn ca tia bc x su cho php x l c khi sn phm ln, khng phi tho bao gi v c th dng nhiu loi vt liu khc nhau; tng tc ca bc x ln vt phm sinh nhit rt yu nn khng lm chn, lm hng sn phm. Ngoi

ra bc x khng li cc cht c tn d v cng ngh x l bng bc x kh n gin, d vn hnh v an ton.

Bng 1: So snh mt s phng php tit trng dng c y t

Ch tiu so snh Tia Gamma EtO Chm tia in t Thit k sn phm Khng hn ch Khng c cc hc kn Khng hn ch Vt liu Hu ht cc loi

vt liu

Hu ht cc loi vt liu

Mt s t khng thch hp

Bao gi sn phm Khng hn ch Bao gi kh qua c hoc ng gi ln 2

Khng hn ch

Cc thng s quy trnh x l

Thi gian - Nng EtO - Chn khng - p sut - Nhit - m - Thi gian

Thi gian

tin cy ca quy trnh x l

Rt tt

Tt Rt tt

Php th vi sinh vt sau kh trng

Khng cn Cn Khng cn

Thi gian lu gi trc khi dng sn phm

Khng cn t nht 14 ngy Khng cn

X l sau kh trng

Khng cn Thng kh c tn d Khng cn

Hiu qu kinh t C hiu qu kinh t khi lng hng x l nhiu hay t

C hiu qu kinh t khi lng hng x l

nhiu hay t

Ch co hiu qu kinh t khi lng hng

x l nhiu Yu cu i vi sn phm kh trng bng bc x

Kh trng c ngha quan trng trong vic nng cao cht lng v sinh v an ton sn phm. Tuy nhin, kh trng ch l mt khu (thng l khu cui cng) trong ton b dy chuyn sn xut. Qu trnh kh trng bng bc x khng th thay th cc yu cu v cht lng vt liu, cht lng bao gi cch ly vi khun cng nh cc yu cu v sinh mi trng trong sn phm c

sn xut, ng gi v lu tr. Ngha l sn phm trc khi kh trng bc x phi l sn phm c sn xut t tiu chun GMP - Thc hnh sn xut tt.

Phng php xc nh liu kh trng

Liu x D10

Mi loi VSV c mt mc khng bm sinh i vi bc x v c c trng bng khng x chun c n v o l liu D10. Liu D10 c nh ngha l liu c kh nng lm gim 90% s lng qun th VSV ban u nhim trong sn phm.

Liu x kh trng (Dkt)

S bt hot cc VSV trong qu trnh kh trng bc x din ra theo qui lut hm s m v dc ca ng cong sng st l gi tr ca i lng D10 :

NNLogDD 010kt 10

ktDD

010NN

LogNLogN

DD0

10

N: S VSV sng st sau khi x l

N0: s VSV ban u nhim trong sn phm

D l liu kh trng

D10 l liu x nh gi mn cm bm sinh ca loi VSV

m bo v trng (Sterile Assurance Level - SAL)

Theo m hnh ton hc trn, xc sut sng st ca cc VSV sau qu trnh kh trng c th l rt nh nhng khng bao gi l s khng v s bt hot cc VSV trong chiu x kh trng ph thuc vo s lng VSV nhim ban u (N0), vo mc khng x ca cc loi VSV (Liu D10), vo nhng yu t mi trng din ra trong qu trnh chiu x.

V th, s v trng ca sn phm khng phi l mt gi tr tuyt i m ch l xc sut ca mt m bo v trng c qui nh trc nhm p ng nhu cu v mc tiu s dng ca sn phm. Khi nim v trng tuyt i c thay th bng khi nim m bo v trng.

bo m v trng c hiu nh l xc sut VSV cn sng st trong mt n v sn phm kh trng (i vi dng c y t) hoc l xc sut s n v sn phm cn VSV sng st trong tng s cc n v sn phm kh trng (i vi dc phm, m phm).

bo m v trng xc nh theo biu thc:

10

kt0 D

DLogNSALLog

nDDLogN

1010SAL 10kt

LogNDDn

10

kt

bo m v trng ph thuc vo bn cht ca sn phm v phn ng tng hp sinh hc gia sn phm vi c th con ngi khi s dng. m bo v trng c qui nh bi Nh sn xut sn phm hoc cc C quan Y t c thm quyn.

V d:

- i vi sn phm khi s dng thng phi trc tip tip xc vi vt thng hay h thng tun hon, h thng min dch ca c th th m bo v trng ca cc sn phm ny phi t SAL = 10-6, ngha l trong 1 triu sn phm (SP) kh trng ch cho php 1 SP c th cha v trng.

- i vi cc sn phm ch tip xc ngoi da, hoc ng tiu ho th m bo v trng SAL c yu cu phi t l 10-3, ngha l ch cho php 1/1000 SP c th cn cha v trng.

- Mt s sn phm ch yu cu bt hot cc VSV gy bnh v gim tng lng VSV hiu kh ti mc nht nh l t tiu chun v sinh, th m bo v trng SAL ch yu cu t 10-2 n 10-3. SAL trong trng hp ny thng p dng trong thanh trng bo qun thc phm, nguyn liu dc phm v cc dc liu.

Nh vy, v l thuyt, xc nh liu x kh trng cn phi c 3 d liu:

1) S lng trung bnh cc VSV nhim trong l sn phm (N0)

2) khng x bm sinh cc loi VSV nhim trong sn phm (D10)

3) Yu cu v m bo v trng i vi loi sn phm SAL

C s thc hnh nh liu x kh trng bc x

Thc hnh nh liu x kh trng c thc hin theo chun ISO 11137-Phn 2: Kh trng sn phm y t Kh trng bc x Xc nh liu x kh trng (ISO 11137-2, Sterilization of health care products-Radiation Sterilization Part 2: Establishing the sterilzation dose). Gn y theo ngh ca Hoa k, ISO b xung thm chun th 3 xc nh liu kh trng: ISO 11137-03, Phng php kh trng liu 25 kGy (ISO 11137-03, Dose substantiation of 25 kGy method)

Ni dung ca 2 phn ISO 11137 ny thc cht l hng dn 3 phng php nh liu kh trng cho sn phm y t (dng c y t v dc phm):

Phng php 1: liu kh trng c xc nh trn c s s lng VSV nhim trong sn phm cn chiu x kh trng.

Phng php 2: liu kh trng c xc nh trn c s khng x bm sinh ca nhng loi VSV hin din trong sn phm cn chiu x kh trng.

C hai phng php trn u da trn cc hiu ng bt hot VSV trong qun th t nhin theo trn m tnh ton xc sut xc nh liu kh trng.

Phng php 3: Ch nh liu kh trng l 25 kGy nu sn phm p ng 2 yu cu:

- Nhng l hng sn xut tng m ring l hoc sn xut thng xuyn nhng s lng sn phm khng ln.

- nhim khun ban u khng vt qu 1000 VSV/n v sn phm v phi qua mt ln chiu x kim tra mi chnh thc c x l hng lot liu 25 kGy.

Trch nhim nh liu kh trng

- Nh sn xut, nh cung cp hng ho ra th trng l ngi chu trch nhim xc nh liu x kh trng cho chnh sn phm ca mnh.

- C s chiu x chu trch nhim vn hnh my chiu m bo hng ho nhn c liu x m khch hng yu cu. Liu lng bc x ny c c s chiu x lu li trong liu k thng qui, c th kim tra c bng cc my o chuyn dng.

- Do cng ngh kh trng bc x mi trin khai c vi nm Vit Nam, cho nn Trung tm Nghin cu v Trin khai Cng ngh Bc x thng h tr cc c s sn xut tnh ton liu kh trng trong thi gian u, ng thi hng dn k thut cc c s sn xut dn dn t xc nh liu kh trng cho sn phm ca mnh.

Tiu chun kim sot v nh gi qu trnh kh trng bng bc x

Hiu qu ca qu trnh kh trng khng th nh gi bng mt vi xt nghim v trng hay mt vi php th tnh cht vt liu mt s mu sn phm ring l trong hng triu n v sn phm kh trng. Hiu lc v Cht lng ca qu trnh kh trng bc x c coi l c hiu lc khi ton b cc yu t m bo cht lng ca cng ngh t thit k, lp t thit b, qui trnh x l kim sot sn phm chiu x n phng php lp v lu gi h s k thut c nh gi l t tiu chun ISO 11137. Mt trong nhng h qu c hiu lc

ca qu trnh kh trng bc x l sn phm khng phi kim nh sau khi chiu x kh trng.

Tiu chun Quc t ISO 11137 Sterilization of Healthcare Products- Requirements for Validation and Routine Control - Radiation Sterilization,1994-1995.

Hu ht cc nc trn th gii ly b chun ISO ny lm chun Quc gia.

B chun ISO 11137, hin c ban hnh thnh 4 phn:

- ISO11137-1, Sterilization of health care products - Radiation sterilization - Part 1, Requirements for the development, validation, and routine control

- ISO 11137-2, Sterilization of health care products Radiation Establishing the sterilization Dose

- ISO 11137-3, Sterilization of health care products Radiation Dose substantiation of 25 kGy

- ISO 11137- 4, Sterilization of health care products Radiation Dosimetry, dose mapping, and routine monitoring

Ngoi ra ISO cng ban hnh mt s tiu chun b xung nhm p ng cc yu cu kim nh v yu cu kh trung bc x i vi mt s loi sn phm, phng thc sn xut sn phm y dc:

- ISO/TS 15843: Sterilization of health care products Radiation sterilization- Product families and sampling plans for verfication dose experiments and sterilization dose audits, and frequency of sterilization audits

- ISO/TR 13409: Sterilization of health care products Radiation sterilization Substantiation of 25 kGy as a sterilization dose for small or infrequent batchs

Phng php Vi sinh trong nh lieu kh trng bc x, th v trng sn phm cng c ISO ban hnh trong b chun ISO 11737:

ISO 11737-1:1995 Sterilization of medical devices -- Microbiological methods -- Part 1: Estimation of population of microorganisms on products

ISO 11737-2:1998 Sterilization of medical devices -- Microbiological methods -- Part 2: Tests of sterility performed in the validation of a sterilization process

ISO 11737-3:2004 Sterilization of medical devices -- Microbiological methods -- Part 3: Guidance on evaluation and interpretation of bioburden data

Hin nay, Vit Nam ban hnh tiu chun chiu x kh trng cc vt phm y t: TCVN 7393:2004 ISO 111337:1995 Tit trng cc sn phm chm sc sc khe Yu cu xc nhn v kim sot thng quy Tit trng bng bc x (Sterilizatiob of health care products Requirements for validation and routine control Radiation sterilization).