Guidance for Industry: Nucleic Acid Testing (NAT) to Reduce the Possible Risk of Parvovirus B19 Transmission by Plasma-Derived Products
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For questions on the content of this guidance, contact OCOD at the phone numbers listed above.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research
Guidance for Industry
Nucleic Acid Testing (NAT) to Reduce the Possible Risk of Parvovirus B19 Transmission by Plasma-Derived Products
We, FDA, are issuing this guidance to provide you, manufacturers of plasma-derived products, with recommendations for performing nucleic acid testing (NAT) for human parvovirus B19 as an in-process test for Source Plasma and recovered plasma used in the further manufacturing of plasma-derived products. Such testing will identify and help to prevent the use of plasma units containing high levels of parvovirus B19. This guidance also recommends how to report to FDA implementation of parvovirus B19 NAT.
We recognize that in the current business practice for parvovirus B19 NAT in-process testing, several weeks can elapse between collection of the units of Source Plasma or recovered plasma and identification of B19 NAT-positive pools or units. We encourage manufacturers of plasma-derived products to employ practices that will reduce the time between product collection and in-process testing to allow for the meaningful notification of blood and plasma collection establishments of positive test results within the dating period of any blood components intended for use in transfusion.
This guidance finalizes the draft guidance of the same title, dated July 2008.
FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the FDA’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA’s guidances means that something is suggested or recommended, but not required.
We recommend that you implement the following procedures to detect the presence of parvovirus B19 DNA:
- For all plasma-derived products, you should perform parvovirus B19 NAT as an in-process test to ensure that the viral load of parvovirus B19 DNA in the manufacturing pools does not exceed 104 IU/mL.
- Use parvovirus B19 NAT on minipool samples to screen plasma units intended for further manufacturing into plasma-derived products. Primers and probes selected for parvovirus B19 NAT should detect all known genotypes of the virus (Ref. 19).
- When identified, you should not use individual plasma units, intended for further manufacturing into plasma-derived products, when such units are found to have a titer of parvovirus B19 DNA that might result in plasma manufacturing pools exceeding a parvovirus B19 DNA titer of 104 IU/mL.
You should assess validation data demonstrating the accuracy, sensitivity, specificity, reproducibility, and other performance characteristics of the parvovirus B19 NAT assay used for the detection of parvovirus B19 DNA in the Source Plasma and recovered plasma, and for demonstrating that the viral load of parvovirus B19 DNA in the manufacturing pool does not exceed 104 IU/mL.
If the above recommendations are implemented, you must inform FDA, as required under 21 CFR 601.12(a). You may submit these changes as a “Supplement-Changes Being Effected” supplement (CBE supplement), under 21 CFR 601.12(c)(5).
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