Evaluation of the Virus-elimination Efficacy of Nanofiltration (Viresolve NFP) for the Parvovirus B19 and Hepatitis A Virus

Deok Ja Oh; Yoo La Lee; Jae Won Kang; So Yong Kwon; Nam Sun Cho; In Seop Kim

doi:10.3343/kjlm.2010.30.1.45

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Oh, Lee, Kang, Kwon, Cho, and Kim: Evaluation of the Virus-elimination Efficacy of Nanofiltration (Viresolve NFP) for the Parvovirus B19 and Hepatitis A Virus

Original Article

Korean J Leg Med 2010;30(1):45-50.

Published online: 14 January 2010

DOI: https://doi.org/10.3343/kjlm.2010.30.1.45

Evaluation of the Virus-elimination Efficacy of Nanofiltration (Viresolve NFP) for the Parvovirus B19 and Hepatitis A Virus

Deok Ja Oh, M.D.¹, Yoo La Lee¹, Jae Won Kang¹, So Yong Kwon, M.D.¹, Nam Sun Cho, M.D.², In Seop Kim, Ph.D.³

¹Blood Transfusion Research Institute, Korean Red Cross, Central Blood Test Center, Korean Red Cross, Seoul, Korea

²Department of Biological Sciences, Daejeon, Korea

³Department of Hannam University, Daejeon, Korea

Corresponding author: Deok Ja Oh, M.D. Blood Transfusion Research Institute, Korean Red Cross, 764 Sanggye 6-dong, Nowon-gu, Seoul 139-831, Korea Tel: +82-2-3210-0331, Fax: +82-2-3210-0360 E-mail: dj57_2000@redcross.or.kr

Revised 30 September 20095 January 2010 Accepted 15 January 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

The safety of plasma derivatives has been reinforced since 1980s by variable pathogen inactivation or elimination techniques. Nucleic acid amplification test (NAT) for the source plasma has also been implemented worldwide. Recently nanofiltration has been used in some country for ensuring safety of plasma derivatives to eliminate non-enveloped viruses such as parvovirus B19 (B19V) and hepatitis A virus (HAV). We evaluated the efficacy of nanofiltration for the elimination of B19V and HAV.

Methods:

To verify the efficacy of nanofiltration, we adopted a 20 nm Viresolve NFP (Millipore, USA) in the scaling down (1:1,370) model of the antithrombin III production. As virus stock solutions, we used B19V reactive plasma and porcine parvovirus (PPV) and HAV obtained from cell culture. And 50% tissue culture infectious dose was consumed as infectious dose. The methods used to evaluate the virus-elimination efficacy were reverse-transcriptase polymerase chain reaction for B19V and the cytopathic effect calculation after filtration for PPV and HAV.

Results:

B19V was not detected by RT-PCR in the filtered antithrombin III solutions with initial viral load of 6.42×10⁵ IU/mL and 1.42×10⁵ IU/mL before filtration. The virus-elimination efficacy of nanofiltration for PPV and HAV were ≥10^3.32 and ≥10^3.31, respectively.

Conclusions:

Nanofiltration would be an effective method for the elimination of B19V and HAV. It may be used as a substitute for NAT screening of these viruses in source plasma to ensure safety of plasma derivatives in Korea.

Keywords: Plasma derivatives, Nanofiltration, Human parvovirus B19, Hepatitis A virus

REFERENCES

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Fig. 1.

Manufacturing scheme of antithrombin III.

Table 1.

Parameters of nanofiltration in practical and scale-down schemes

Parameter	Practical scheme	Scale-down scheme	Scale-down ratio
Prefilter type	4 inch cartridge	47 mm prefilter	-
Nanofiltration	10 inch cartridge (4,800 cm²)	25 mm disk (3.5 cm²)	≈1,370
Elute volume	25 L	18.2 mL	≈1,370
Pressure	2.0±0.5 bar	2.0±0.5 bar	-
pH	7.0±0.1	7.0±0.1	-

Table 2.

Virus-elimination efficacy of nanofiltration for human parvovirus B19

Sample description		Virus titer (IU/mL)	Volume (mL)	Total virus (IU)
1st	Stock solution	1.36×10⁹	0.0066	8.98×10⁶
	Spiked starting material (load sample)	3.21×10⁴	20	6.42×10⁵
	Filtrate	ND (<3.3)	18.2	<60
2nd	Stock solution	2.31×10⁸	0.0066	1.52×10⁶
	Spiked starting material (load sample)	7.08×10³	20	1.42×10⁵
	Filtrate	ND (<3.3)	18.2	<60

Abbreviations: ND, not detected.

Table 3.

Virus-elimination efficacy of nanofiltration for porcine parvovirus

	Sample description	Virus titer (Log₁₀ TCID₅₀/mL)	Volume (mL)	Total virus (Log₁₀ TCID₅₀)
1st	Stock solution	6.39	0.125	5.48
	Spiked starting material (load sample)	3.96	20	5.26
	Filtrate	ND (≤0.58)∗	18.2	≤1.84
2nd	Stock solution	6.18	0.125	5.27
	Spiked starting material (load sample)	3.75	20	5.05
	Filtrate	ND (≤0.58)∗	18.2	≤1.84

^∗ Theoretical minimum detectable levels were calculated where porcine parvovirus infectivity was not detected.

Abbreviations: TCID₅₀, 50% tissue culture infectious dose; ND, not detected.

Table 4.

Virus-elimination efficacy of nanofiltration for hepatitis A virus

Sample description		Virus titer (Log₁₀ TCID₅₀/mL)	Volume (mL)	Total virus (Log₁₀ TCID₅₀)
1st	Stock solution	6.39	0.125	5.48
	Spiked starting material (load sample)	3.85	20	5.15
	Filtrate	ND (≤0.58)∗	18.2	≤1.84
2nd	Stock solution	6.49	0.125	5.58
	Spiked starting material (load sample)	3.75	20	5.14
	Filtrate	ND (≤0.58)∗	18.2	≤1.84

^∗ Theoretical minimum detectable levels were calculated where hepatitis A virus infectivity was not detected.

Abbreviations: TCID₅₀, 50% tissue culture infectious dose; ND, not detected.

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