Tham Dinh Media Fill

Thm nh m phng quy trnh sn
xut (media fill)

on Ch Thin
1|
Workshop on WHO prequalification requirements for reproductive health medicines,

Jakarta, October 2009
Ti sao phi thc hin media fill?

nh gi dy chuyn sn xut thuc v trng.
Tm ra nhng li trong qu trnh sn xut thuc v trng.
a ra c bin php khc phc.
Ci tin sn xut.
Media fill test l hnh ng ngn nga.
kim tra v trng trn tng l ri sao phi lm thm
nh media fill test?
2|

Thc hin media fill nh th no?

Quy trnh sn xut thuc tim v trng:
Bao b th cp
Nguyn liu
Chai l, nt cao su
Pha ch
Ra chai
V thuc, ng np
Soi cn
Hp tit trng
ng bao b th cp
3|

Thnh phm

Quy trnh m phng (media fill):
Tryptic soy broth
Chai l, nt cao su
Pha ch
Ra chai
V thuc, ng np
Soi cn
Hp tit trng
Kim tra dinh dng
(theo di v trng)
Kt qu
4|


1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
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Mi trng dinh dng dng cho th nghim media fill.

Th nghim kh nng dinh dng (Growth promotion test).
Phng php pha ch.
V sinh sau khi pha ch, v thuc.
Kim sot trong qu trnh thm nh media fill.
Loi chai l, kch thc l, th tch v mi trng, c l.
Tn sut thc hin.
Phng php .
Kim tra qu trnh - c kt qu.
Tiu chun chp nhn.
nh gi nhng trng hp xu c th xy ra.
nh gi kt qu thm nh media fill.
iu tra nguyn nhn tht bi v a ra bin php khc phc.
Nhng kh khn trong vic thc hin thm nh media fill.
Nhng ni dung cn chun b cho vic thc hin thm nh media fill.
1. Mi trng dinh dng dng cho th

nghim media fill
Mi trng dinh dng chung: Tryptic soy broth
Mi trng dinh dng phi c m bo v khun v
y dinh dng.
6|

2. Th nghim kh nng dinh dng

(Growth promotion test)
Tn chng vi sinh vt
iu kin
Kt qu
Bacillus subtilis ACTT 6633
30 35 0C / 3 ngy
Dng tnh
trng c)
Pseudomonas
9027
aeruginosa
ACTT
Staphylococcus aureus ACTT 6538

Candida albicans ACTT 10231
20 25 0C / 5 ngy
Aspergillus niger ATCC 16404
7|

(mi
3. Phng php pha ch

30 g Tryptic soy broth + Nc v 1000 mL 1000 mL mi
trng dinh dng.
V d: Pha ch nh trong sn xut: 500 L mi trng dinh
dng.
Cn 15 kg Tryptic soy broth.

Chun b khong 100 L nc ct c gia nhit 80 -850C
Cho lng TSB trn vo tank pha ch cha 100 L nc .
Khuy cho tan lng TSB trn ( khong 10 -15 pht).
B sung nc ct va 500 L.
Kim tra pH 7.2 0.2 (iu chnh pH nu cn)
Kim tra cm quan, trong.
8|

4. V sinh sau khi pha ch, v thuc

Vic v sinh thit b, dng c, phng c sau khi thm nh
media fill l vic cc k quan trng.
Phi thc hin ngay.
Phng php v sinh: nc nng, cn 700.
9|

5. Kim sot trong qu trnh thm nh

media fill
Kim sot trc, trong v sau qu trnh pha ch bao gm:
V sinh phng c, trang thit b, dng c, nguyn vt liu (TSB, nc ct, chai l), (
nhn sch)
Kim sot mi trng (RH%, t0C, chnh p, tiu phn, vi sinh).
Nhn vin tham gia thm nh.
Kim tra kn sau v chai, sau khi hp tit trng.
10 |

5. Kim sot trong qu trnh thm nh media

fill (tt)
Tiu chun tiu phn:
Trng thi ngh
Cp sch
ISO
14644
WHO
11 |
Trng thi ng
S tiu phn ti a cho php / m3

USP
0.5 m
5.0 m
Th tch
ly mu
0.5 m
5.0 m
100
3,520
20
3,520
20
1000 L
100
3,520
29
352,000
2,900
1000 L
10 000
352,000
2,900
3,520,000
29,000
28 L
100 000
3,520,000
29,000
Khng quy nh
Khng quy nh
28 L


fill (tt)
Tiu chun vi sinh:
12 |
Cp sch
Th tch (cfu/m3)
t a (cfu/4h)
a tip xc (cfu/25cm2)
Gng tay (cfu/gng)
<1
<1
<1
<1
10
100
50
25
NA
200
100
50
NA


fill (tt)
K hoch ly mu:
i tng ly mu
Khng kh
Thi im ly mu
Trong qu trnh
Nc pha ch
Nc v sinh trang thit
b, phng
Nhn vin
Trc khi pha ch

Theo SOP hin hnh
B mt tip xc
Cui qu trnh
Bao b cp 1
Cc n v ng gi
c ly mu thc
hin test dinh dng
Trc khi ng thuc

Sau khi hp tit trng
13 |
Cui qu trnh
V tr ly mu
Phng pha ch, LAF pha
ch.
Phng ng thuc, Laf
ng thuc.
Phng pha ch
Theo SOP hin hnh
Lng mu
Theo quy nh trong quy
trnh ly mu (vi sinh,
tiu phn)
Theo SOP hin hnh
Theo SOP hin hnh
Trang phc (tay o,

Theo SOP hin hnh
ngc, bng).
Gng tay (lng bn tay, 5
ngn tay)
Tng, sn, thit b tham Theo SOP hin hnh
gia qu trnh thm nh
Theo SOP hin hnh
Cc v tr phn b trong
Theo SOP hin hnh
l, cc m khc nhau.

6. Loi chai l, kch thc l, th tch v

mi trng, c l.
Chai l thy tinh trng trong.
Th tch v mi trng dinh dng mi chai: khong 75%
th tch chai.
C l:
The number of containers used for media fills should be sufficient to enable a
valid evaluation. For small batches, the number of containers for media fills
should at least equal the size of the product batch. (mc 6.2 trang 9, Recommendation
on the validation of aseptic processes - PIC/S 007-6, 01/2011)
Thi gian thc hin media fill.

14 |

7. Tn sut thc hin.

A start-up simulation test consists of three consecutive
satisfactory simulation tests per shift and should be
carried out before routine manufacturing can start.
An on-going simulation testconsists of one satisfactory
simulation test per shift ... at least twice per year... ((mc
5.5.3 -5.5.6 trang 8, Recommendation on the validation of
aseptic processes - PIC/S 007-6, 01/2011)
15 |

8 . Phng php
nh du v tr cc khay.
V s tng ng vi bung tit trng.
Kim tra tt c cc n v c ng gi v c hp
trc khi a vo , tt c cc l h hng cn phi c
ghi nhn r trong tng cng on.
Cc l c o ngc u nhit 20 25 0C
trong 7 ngy, v c theo ng chiu nhit 30
350C trong 7 ngy k tip.
16 |

9. Kim tra qu trnh - c kt qu

Trch nhim c kt qu.
Nhng l ng gi b nhim vi sinh cn phi c ghi nhn
xem xt nguyn nhn thuc cng on no hay v tr
no trong bung tit trng.
Theo di hng ngy?
17 |

10. Tiu chun chp nhn

Khng c c n v no b nhim sau khi .
Nu c mt (1) n v nhim: Tin hnh iu tra nguyn
nhn bao gm c vic thc hin li qu trnh thm nh.
Nu c hai (2) n v nhim: Tin hnh iu tra nguyn
nhn v thm nh li.
18 |

11. nh gi nhng trng hp xu c th

xy ra
S phn b nhit khng ng u trong bung hp tit
trng.
Thi gian tit trng khng ph hp.
Chnh p t ngt dn n v l hay tro thuc ra ngoi
trong qu trnh hp tit trng.
L ng np khng kn.
19 |

12. nh gi kt qu thm nh media fill

L 5000 v
No
Khng nhim
Nhim 1 v
Xem slide sau
iu tra
Test Dinh dng

Yes
No
H s MFT
Lab error
Nguyn nhn khc
Th li
Bin php khc phc
Yes
MFT t
Lp li 1 MFT
20 |
Yes
No

12. nh gi kt qu thm nh media fill (tt)

L 5000 v
Khng nhim
Nhim 1 v
iu tra
Xem slide trc

Yes
Bit nguyn nhn
No
Bin php khc phc
Lp li 1 MFT
21 |

Lp li 3 MFT
13. iu tra nguyn nhn tht bi v a ra

bin php khc phc
Tt c cc nguyn nhn dn n tht bi thm nh phi
c iu tra:
nh danh vi sinh vt trong cc n v b nhim.
Mi trng sn xut.
V sinh, thao tc, hun luyn nhn vin.
Qu trnh sn xut v nhng can thip din ra trong qu trnh thm nh.
Mi trng dinh dng s dng.
Cc thm nh lin quan n t hp tit trng (IQ, OQ, PQ).
Loi nguyn vt liu s dng.
Xem xt iu kin bo qun: dng c sn xut, bao b.
22 |


bin php khc phc (tt)
ngh v thc hin hnh ng khc phc i vi cc
nguyn nhn c xc nh.
nh gi hiu nng t hp tit trng:
C chc chn rng iu kin 1210C/ 30 pht th sn phm v trng?
Nhng dng c ha cht dng cho nh gi hiu nng t hp: ch th nhit m, ch
th sinh hc (Geobacillus stearothermophilus ATCC 7953 ).
S phn b nhit kh c ti v khng ti.
23 |


S phn b nhit kh c ti v khng ti.
Theo l thuyt, iu kin tit trng nhit m l 1210C trong 15 pht.
Gi tr F0 ca qu trnh tit trng nhit m c biu din tng ng thi gian
1210C ca 1 qu trnh tit trng sn phm c ch th vi sinh i chiu c gi tr Z l
thuyt l 10.
Gi tr F0 (l thuyt) = D121*log10t/D
Vi t: thi gian tip xc
D121: Gi tr D chun 1210C (theo BP 2013 l 1.5 pht).
D: Gi tr D ca vi sinh trong iu kin tip xc.
24 |


Tnh ton F0 (thc t) = t 10 (T Tb) / Z
Trong : t : khong cch thi gian ghi nhn nhit
T : Nhit thc t ca chu trnh nhit.
Tb : 1210C nhit chun.
Z : n v nhit logarit thay i kh nng tit trng (100C)
F0 (thc t) F0 (l thuyt)
25 |

V d tnh F0
Chng vi sinh ch th: Geobacillus stearothermophilus
ATCC 7953 trn CoA c thng tin nh sau:
D(1210C): 2.5 pht; Steam kill: 26.1 pht; Z: 13.70C..
F0(l thuyt) 1.5*log1030/2.5 = 18 pht

F0(thc t) = 26.56 pht.
Chu trnh hp 1210C / 30 pht ny t.
26 |

V d tnh F0
Thi gian, pht
27 |
V tr ghi nhn nhit

T1
10(T 121.1) /10
T2
120
0.78
10
119
0.62
15
121
0.98
20
123
1.55
25
120
0.78
30
119
0.62
10(T 121.1) / 10
5.31
F0 = 5 10(T 121.1) / 10
26.56

10(T 121.1)/10
14. Nhng kh khn trong vic thc hin thm

nh media fill.
Do iu kin sn xut.
Do iu kin nh xng, phng Lab.
Do nhn vin cha c kinh nghim media fill test.
Do kinh ph.
Nhng nguyn nhn khc?
28 |

15. Nhng ni dung cn chun b cho vic thc

hin thm nh media fill
Ti liu:
H s l thm nh media fill.
cng thm nh media fill.
Bo co thm nh media fill.
Cc mu form kim sot iu kin mi trng (RH%, t0C, chnh p, m bi, vi
sinh).
Hun luyn nhn vin.
Cc ti liu lin quan khc (SOP vn hnh, kim nghim,)
29 |


hin thm nh media fill (tt)
Nguyn vt liu:
Chai thy tinh trng trong, np, nt cao su, nc pha ch, cn 70 0.
Mi trng Tryptic soy broth
Cc chng vi sinh vt th nghim: Bacillus subtilis ACTT 6633, Pseudomonas
aeruginosa ACTT 9027, Staphylococcus aureus ACTT 6538, Candida albicans ACTT
10231, Aspergillus niger ATCC 164044.
My ly mu tiu phn (m bi).
My ly mu vi sinh khng kh (nu khng c th t a thch).
a contact plate ly mu vi sinh b mt.
Ch th nhit m.
30 |


hin thm nh media fill (tt)
Nh xng:
V sinh nh xng, trang thit b.
Ni l media fill nhit 20 - 25.C/ 7 ngy v 30 - 35.C/ 7 ngy cui.
Bin php x l mi trng dinh dng sau media fill.
31 |

Ti liu tham kho

WHO GMP guidelines Technical Report series n. 937
EU cGMP Audit Checklist ; ISO 14644-1 Cleanrooms and
associated controlled environments
FDA Guidance for Industry: sterile drug products produced
by aseptic processing cGMP
PIC/S Recommendations PI 007-5
USP <797> media fill testing / <71> growth promotion
test
32 |

Cm n qu anh ch lng nghe!
33 |


Tham Dinh Media Fill

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Thm nh m phng quy trnh sn

xut (media fill)

Workshop on WHO prequalification requirements for reproductive health medicines,

Ti sao phi thc hin media fill?

Workshop on WHO prequalification requirements for reproductive health medicines,

Thc hin media fill nh th no?

Workshop on WHO prequalification requirements for reproductive health medicines,

Thc hin media fill nh th no?

Kim tra dinh dng

Workshop on WHO prequalification requirements for reproductive health medicines,

Thc hin media fill nh th no?

Mi trng dinh dng dng cho th nghim media fill.

1. Mi trng dinh dng dng cho th

Workshop on WHO prequalification requirements for reproductive health medicines,

2. Th nghim kh nng dinh dng

Bacillus subtilis ACTT 6633

Staphylococcus aureus ACTT 6538

Aspergillus niger ATCC 16404

Workshop on WHO prequalification requirements for reproductive health medicines,

3. Phng php pha ch

Cn 15 kg Tryptic soy broth.

Workshop on WHO prequalification requirements for reproductive health medicines,

4. V sinh sau khi pha ch, v thuc

Workshop on WHO prequalification requirements for reproductive health medicines,

5. Kim sot trong qu trnh thm nh

Workshop on WHO prequalification requirements for reproductive health medicines,

5. Kim sot trong qu trnh thm nh media

S tiu phn ti a cho php / m3

Workshop on WHO prequalification requirements for reproductive health medicines,

5. Kim sot trong qu trnh thm nh media

Gng tay (cfu/gng)

Workshop on WHO prequalification requirements for reproductive health medicines,

5. Kim sot trong qu trnh thm nh media

Trc khi pha ch

Trc khi ng thuc

Trang phc (tay o,

Workshop on WHO prequalification requirements for reproductive health medicines,

6. Loi chai l, kch thc l, th tch v

Thi gian thc hin media fill.

Workshop on WHO prequalification requirements for reproductive health medicines,

7. Tn sut thc hin.

Workshop on WHO prequalification requirements for reproductive health medicines,

Workshop on WHO prequalification requirements for reproductive health medicines,

9. Kim tra qu trnh - c kt qu

Workshop on WHO prequalification requirements for reproductive health medicines,

10. Tiu chun chp nhn

Workshop on WHO prequalification requirements for reproductive health medicines,

11. nh gi nhng trng hp xu c th

Workshop on WHO prequalification requirements for reproductive health medicines,

12. nh gi kt qu thm nh media fill

Xem slide sau

Test Dinh dng

Nguyn nhn khc

Bin php khc phc

Workshop on WHO prequalification requirements for reproductive health medicines,

12. nh gi kt qu thm nh media fill (tt)

Xem slide trc

Bit nguyn nhn

Workshop on WHO prequalification requirements for reproductive health medicines,

13. iu tra nguyn nhn tht bi v a ra

Workshop on WHO prequalification requirements for reproductive health medicines,

13. iu tra nguyn nhn tht bi v a ra

S phn b nhit kh c ti v khng ti.

Workshop on WHO prequalification requirements for reproductive health medicines,