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
National Standards for Blood Viruses in Taiwan
SoGAT XXI May 2009
2
• 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
Current Status of NAT Regulations
3
Class Ilow risk
Class IIhigher 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*
Regulatory Framework of Medical Device
* 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.
4
• 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 ℃ ℃ ℃
HBV DNA National Standard and Working Reagent
ProductItem HBV DNA National Standard HBV DNA Working Reagent
Conc. (IU/mL) 106 103
Genotype genotype B genotype B
Lot number BFDA lot 92-08 BFDA lot 92-08W
5
Exclude the data out of the range of mean ± 2 SD
HBV DNA standard HBV DNA standard
HBV DNA working reagent
6
HCV RNA National Standard and Working Reagent
ProductItem HCV RNA National Standard HCV RNA Working Reagent
Conc. (IU/mL) 5.2 × 104 890
Genotype genotype 1b genotype 1b
Lot number BFDA lot 93-09 BFDA lot 93-09W
• 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 ℃ ℃ ℃
7
Exclude the data out of the range of mean ± 2 SD
8
B19 DNA National Standard and Working Reagent
ProductItem B19 DNA National Standard B19 DNA Working Reagent
Conc. (IU/mL) 1.9 × 106 2.0 × 104
Genotype genotype 1 genotype 1
Lot number BFDA lot 94-08 BFDA lot 94-08W
• 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 ℃ ℃ ℃ ℃
9
All data were within the range (mean ± 2 SD), showed that all laboratories are in good agreement with the results.
10
National Standards and Reference Panels for Serological AssaysNational Standards and Reference Panels for Serological Assays
No. Item Lot Note
1 1st National Standard for HBsAg (subtype ad)* 89-06 106 IU/mL
2 Anti-HCV Reference Panel 92-01
3 HBsAg Sensitivity Panel 94-12
4 Anti-HIV-1 Reference Panel 96-11
National Standards and Working Reagents National Standards and Working Reagents for for NATNAT Assays Assays
No. Item Lot Note
1 1st National Standard for HBV DNA* 92-08 106 IU/mL
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
• Candidate Standard for HIV-1 RNA being formulated
11
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
12
• 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.)
Current Status of National Standards Used in Taiwan
13
Quantitative Data from Users (I)
HBV STD (Lot 92-08)
Lab-Sample code
Log IU/mL
106 IU/mL TCD-BAbm1 5.699
TCD-BAbm2 5.580
TCD-BAbm3 5.505
TCD-BRoT1 6.041
TCD-BRoT2 6.215
BFD-BRoT1 6.371
HBV WR (Lot 92-08W)
Lab-Sample code
Log IU/mL
103 IU/mL TCD-BWAbm1 3.146
TCD-BWRoT1 3.326
Med-BWRoT1 3.049
Med-BWRoT2 3.021
Med-BWRoT3 3.196
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 resultMean ± 2SD: 6 ± 0.38 Log IU/mL
• Collaborative study resultMean ± 2SD: 3 ± 0.44 Log IU/mL
14
Quantitative Data from Users (II)
HCV STD (Lot 93-09)
Lab-Sample code
Log IU/mL
5.2 ×104 U/mL TCD-CAbm1 4.199
TCD-CAbm2 3.700
TCD-CAbm3 4.155
TCD-CRoT1 4.869
TCD-CRoT2 4.913
TCD-CRoT3 5.045
HCV WR (Lot 93-09W)
Lab-Sample code
Log IU/mL
890 IU/mL TCD-CWAbm1 2.389
TCD-CWRoT1 3.243
Reg-CWRoT1 2.807
Reg-CWRoT2 2.455
Med-CWRoT1 2.799
Med-CWRoT2 2.736
Med-CWRoT3 2.732
Com-CWRoT1 2.600
Com-CWRoT2 2.630
• Collaborative study resultMean ± 2SD: 4.719 ± 0.192 Log IU/mL
• Collaborative study resultMean ± 2SD: 2.949 ± 0.486 Log IU/mL
15
• 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
Summary
Thank you for your attention
AcknowledgementsThanks to all participants
of the collaborative study groups
Thanks to all data-feedback users
Top Related