Transcript 2009 SoGAT talk

National Standards for
Blood Viruses in Taiwan
Yi-Chen Yang, Yu-Hsuan Chen, Show-Lan Chiu, Hwei-Fang Cheng
Drug Biology Division, Bureau of Food and Drug Analysis
Department of Health, Taiwan, ROC
SoGAT XXI
May 2009
Current Status of NAT Regulations
• To improve the safety of plasma products
– NAT requirements in Taiwan (2002)
• The plasma pool or mini-pool should be HBV NAT (-),
HCV NAT (-), and HIV NAT (-)
• For S/D treated blood products, one additional VI/R
step should be performed, or the plasma pool should
be HAV NAT (-)
• B19 NAT on plasma pool or mini-pool is suggested
~ the cut-off limit of B19 DNA should be < 105 IU/mL
2
Regulatory Framework of Medical Device
Class I
low risk
Class II
higher risk
Class III
highest risk
• Most exempt from the
Medical Device GMP/QSD
• Sterile products shall still
comply with Medical
Device GMP/QSD
Medical Device
GMP/QSD
Medical Device
GMP/QSD
Registration and Market
approval
Registration and
Market approval
Registration and
Market approval*
* Special Requirements for Class III IVD
~ Submit sample to BFDA for licensing tests
The current focus of BFDA’s work in biological standards is for
IVDs that are either used in blood screening or plasma pool
testing for further fractionation process.
3
HBV DNA National Standard
and Working Reagent
• High titer HBV DNA (+) plasma
– Screening for other blood viruses
– Quantitative analysis and genotyping
• Diluted with pooled human plasma*
– *Screening for all major blood viruses
• Calibrate the titers of candidates against the IS (97/746) by a
collaborative study
– 11 Labs from 7 countries
• Official Medicine Control Laboratories (OMCL) & CDC (Taiwan)
• Hospital laboratory & Reference laboratory
• Blood Service
• Manufacturers of in vitro diagnostics
• Stability study
 4℃ , -20 ℃ , -80 ℃
Product
Item
Conc. (IU/mL)
Genotype
Lot number
HBV DNA National Standard
106
genotype B
BFDA lot 92-08
HBV DNA Working Reagent
103
genotype B
BFDA lot 92-08W
4
HBV DNA standard
HBV DNA standard
HBV DNA working reagent
 Exclude the data out of the range of mean ± 2 SD
5
HCV RNA National Standard
and Working Reagent
• High titer HCV RNA (+) plasma
– Screening for other blood viruses
– Quantitative analysis and genotyping
• Diluted with pooled human cryosupernatant*
– *Screening for all major blood viruses
• Calibrate the titers of candidates against the IS (96/790) by a
collaborative study
– 8 Labs from 6 countries
• Official Medicine Control Laboratories (OMCL) & CDC (Taiwan)
• Hospital laboratory & Reference laboratory
• Blood Service
• Manufacturers of in vitro diagnostics
• Stability study
 4 ℃ , -20 ℃ , -80 ℃
Product
Item
Conc. (IU/mL)
Genotype
Lot number
HCV RNA National Standard
5.2 × 104
genotype 1b
BFDA lot 93-09
HCV RNA Working Reagent
890
genotype 1b
BFDA lot 93-09W
6
 Exclude the data out of the range of mean ± 2 SD
7
B19 DNA National Standard
and Working Reagent
• High titer B19 DNA (+) plasma
– Screening for other blood viruses
– Quantitative analysis and genotyping
• Diluted with pooled human cryosupernatant*
– *Screening for all major blood viruses
• Calibrate the titers of candidates against the IS (99/800) by a
collaborative study
– 10 Labs from 7 countries
• Official Medicine Control Laboratories (OMCL)
• NAT testing laboratory
• Manufacturers of plasma products
• Manufacturers of in vitro diagnostics
• Stability study
 25℃, 4 ℃ , -20 ℃ , -80 ℃
Product
Item
Conc. (IU/mL)
Genotype
Lot number
B19 DNA National Standard
1.9 × 106
genotype 1
BFDA lot 94-08
B19 DNA Working Reagent
2.0 × 104
genotype 1
BFDA lot 94-08W
8
 All data were within the range (mean ± 2 SD), showed that
all laboratories are in good agreement with the results.
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National Standards and Working Reagents for NAT Assays
No.
Item
1
1st National Standard for HBV DNA*
Lot
92-08
Note
2
1st Working Reagent for HBV DNA*
92-08W
103 IU/mL
3
1stNational Standard for HCV RNA*
93-09
5.2×104 IU/mL
4
1st Working Reagent for HCV RNA*
93-09W
890 IU/mL
5
1st National Standard for Parvovirus B19 DNA
94-08
1.9×106 IU/mL
6
1st Working Reagent for Parvovirus B19 DNA
94-08W
2×104 IU/mL
106 IU/mL
• Candidate Standard for HIV-1 RNA being formulated
National Standards and Reference Panels for Serological Assays
No.
Item
Lot
Note
106 IU/mL
1
1st National Standard for HBsAg (subtype ad)*
89-06
2
Anti-HCV Reference Panel
92-01
3
HBsAg Sensitivity Panel
94-12
4
Anti-HIV-1 Reference Panel
96-11
10
Anti-HIV-1 Reference Panel
• Anti-HIV-1 (+) plasma selection
– Screening for other blood viruses
– Characterized with anti-HIV diagnostic kits, HIV viral-load kit
• Panel members characterization by a collaborative study
– 12 Labs from 5 countries
• Official Medicine Control Laboratories (OMCL) & CDC (Taiwan)
• Hospital laboratory & Reference laboratory
• Blood Service
• Manufacturers of in vitro diagnostics
– Include 22 anti-HIV diagnostic kits & Lab. in-house WB assay
• Stability study
 25℃, 4 ℃ , -20 ℃ , -80 ℃
• The panel contains 6 characterized specimens
– Include strong-reactive, weak-reactive, and negative samples
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Current Status of National Standards
Used in Taiwan
• Class III IVD licensing test (BFDA)
• Post-market surveillance for high risk class III IVD (BFDA)
– HBsAg diagnostic kits (2008)
• Pick up 2 products fail to meet the sensitivity requirement
– Anti-HCV diagnostic kits (2009)
• kits receiving test in blood service & hospital lab. (IVD
manufactures)
• R&D and quality control for diagnostic kits (IVD/Biotech
manufactures)
• Sensitivity evaluation for purchasing diagnostic kits (Taiwan CDC)
• Research (BFDA & Hospital lab.)
12
Quantitative Data from Users (I)
HBV STD
(Lot 92-08)
106 IU/mL
Lab-Sample
code
Log
IU/mL
HBV WR
(Lot 92-08W)
Lab-Sample
code
Log
IU/mL
TCD-BAbm1
5.699
103 IU/mL
TCD-BWAbm1
3.146
TCD-BAbm2
5.580
TCD-BWRoT1
3.326
TCD-BAbm3
5.505
Med-BWRoT1
3.049
TCD-BRoT1
6.041
Med-BWRoT2
3.021
TCD-BRoT2
6.215
Med-BWRoT3
3.196
BFD-BRoT1
6.371
Med-BWRoT4
3.253
Med-BWRoT5
3.212
Med-BWRoT6
3.161
Med-BWRoT7
3.299
BFD-BWRoT1
3.146
BFD-BWRoT2
3.079
BFD-BWRoT3
3.255
BFD-BWRoT4
3.079
BFD-BWRoT5
3.176
• Collaborative study result
Mean ± 2SD: 6 ± 0.38 Log IU/mL
• Collaborative study result
Mean ± 2SD: 3 ± 0.44 Log IU/mL
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Quantitative Data from Users (II)
Lab-Sample
code
Log
IU/mL
TCD-CWAbm1
2.389
3.700
TCD-CWRoT1
3.243
TCD-CAbm3
4.155
Reg-CWRoT1
2.807
TCD-CRoT1
4.869
Reg-CWRoT2
2.455
TCD-CRoT2
4.913
Med-CWRoT1
2.799
TCD-CRoT3
5.045
Med-CWRoT2
2.736
Med-CWRoT3
2.732
Com-CWRoT1
2.600
Com-CWRoT2
2.630
HCV STD
(Lot 93-09)
Lab-Sample
code
Log
IU/mL
5.2 ×104 U/mL
TCD-CAbm1
4.199
TCD-CAbm2
• Collaborative study result
Mean ± 2SD: 4.719 ± 0.192 Log IU/mL
HCV WR
(Lot 93-09W)
890 IU/mL
• Collaborative study result
Mean ± 2SD: 2.949 ± 0.486 Log IU/mL
14
Summary
• We have established HBV, HCV, and B19 national
standards and working reagents for NAT assays.
– The standards were prepared by BFDA, and established
through the international collaborative studies.
• Candidate standard for HIV-1 RNA being formulated.
• These NAT standards are currently used for evaluation of
the molecular diagnostics market in Taiwan.
– Licensing test & post-market surveillance for high risk class
III IVD
– Kits receiving test in blood service & hospital lab
– R&D and quality control for diagnostic kits
– Sensitivity evaluation for purchasing diagnostic kits
15
Acknowledgements
Thanks to all participants
of the collaborative study groups
Thanks to all data-feedback users
Thank you for your attention