Measuring factor IX activity of nonacog beta pegol with commercially available one-stage clotting and chromogenic assay kits : A two-center study
(2016) In Journal of Thrombosis and Haemostasis 14(7). p.1428-1435- Abstract
Essentials: Validated assays are required to precisely measure factor IX (FIX) activity in FIX products. N9-GP and two other FIX products were assessed in various coagulation assay systems at two sites. Large variations in FIX activity measurements were observed for N9-GP using some assays. One-stage and chromogenic assays accurately measuring FIX activity for N9-GP were identified. Summary: Background: Measurement of factor IX activity (FIX:C) with activated partial thromboplastin time-based one-stage clotting assays is associated with a large degree of interlaboratory variation in samples containing glycoPEGylated recombinant FIX (rFIX), i.e. nonacog beta pegol (N9-GP). Validation and qualification of specific assays and conditions... (More)
Essentials: Validated assays are required to precisely measure factor IX (FIX) activity in FIX products. N9-GP and two other FIX products were assessed in various coagulation assay systems at two sites. Large variations in FIX activity measurements were observed for N9-GP using some assays. One-stage and chromogenic assays accurately measuring FIX activity for N9-GP were identified. Summary: Background: Measurement of factor IX activity (FIX:C) with activated partial thromboplastin time-based one-stage clotting assays is associated with a large degree of interlaboratory variation in samples containing glycoPEGylated recombinant FIX (rFIX), i.e. nonacog beta pegol (N9-GP). Validation and qualification of specific assays and conditions are necessary for the accurate assessment of FIX:C in samples containing N9-GP. Objectives: To assess the accuracy of various one-stage clotting and chromogenic assays for measuring FIX:C in samples containing N9-GP as compared with samples containing rFIX or plasma-derived FIX (pdFIX) across two laboratory sites. Methods: FIX:C, in severe hemophilia B plasma spiked with a range of concentrations (from very low, i.e. 0.03 IU mL-1, to high, i.e. 0.90 IU mL-1) of N9-GP, rFIX (BeneFIX), and pdFIX (Mononine), was determined at two laboratory sites with 10 commercially available one-stage clotting assays and two chromogenic FIX:C assays. Assays were performed with a plasma calibrator and different analyzers. Results: A high degree of variation in FIX:C measurement was observed for one-stage clotting assays for N9-GP as compared with rFIX or pdFIX. Acceptable N9-GP recovery was observed in the low-concentration to high-concentration samples tested with one-stage clotting assays using SynthAFax or DG Synth, or with chromogenic FIX:C assays. Similar patterns of FIX:C measurement were observed at both laboratory sites, with minor differences probably being attributable to the use of different analyzers. Conclusions: These results suggest that, of the reagents tested, FIX:C in N9-GP-containing plasma samples can be most accurately measured with one-stage clotting assays using SynthAFax or DG Synth, or with chromogenic FIX:C assays.
(Less)
- author
- Bowyer, A. E. ; Hillarp, A. LU ; Ezban, M. ; Persson, P. LU and Kitchen, S.
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Blood coagulation test, Factor IX, Hemophilia B, Nonacog beta pegol, Poly(ethylene glycol)
- in
- Journal of Thrombosis and Haemostasis
- volume
- 14
- issue
- 7
- pages
- 1428 - 1435
- publisher
- Elsevier
- external identifiers
-
- pmid:27107268
- wos:000380022700015
- scopus:84990198558
- ISSN
- 1538-7933
- DOI
- 10.1111/jth.13348
- language
- English
- LU publication?
- yes
- id
- 01fe584c-bca0-41c6-b9ea-a5dd9e59239f
- date added to LUP
- 2016-07-21 12:09:05
- date last changed
- 2025-01-12 09:10:45
@article{01fe584c-bca0-41c6-b9ea-a5dd9e59239f,
abstract = {{<p>Essentials: Validated assays are required to precisely measure factor IX (FIX) activity in FIX products. N9-GP and two other FIX products were assessed in various coagulation assay systems at two sites. Large variations in FIX activity measurements were observed for N9-GP using some assays. One-stage and chromogenic assays accurately measuring FIX activity for N9-GP were identified. Summary: Background: Measurement of factor IX activity (FIX:C) with activated partial thromboplastin time-based one-stage clotting assays is associated with a large degree of interlaboratory variation in samples containing glycoPEGylated recombinant FIX (rFIX), i.e. nonacog beta pegol (N9-GP). Validation and qualification of specific assays and conditions are necessary for the accurate assessment of FIX:C in samples containing N9-GP. Objectives: To assess the accuracy of various one-stage clotting and chromogenic assays for measuring FIX:C in samples containing N9-GP as compared with samples containing rFIX or plasma-derived FIX (pdFIX) across two laboratory sites. Methods: FIX:C, in severe hemophilia B plasma spiked with a range of concentrations (from very low, i.e. 0.03 IU mL<sup>-1</sup>, to high, i.e. 0.90 IU mL<sup>-1</sup>) of N9-GP, rFIX (BeneFIX), and pdFIX (Mononine), was determined at two laboratory sites with 10 commercially available one-stage clotting assays and two chromogenic FIX:C assays. Assays were performed with a plasma calibrator and different analyzers. Results: A high degree of variation in FIX:C measurement was observed for one-stage clotting assays for N9-GP as compared with rFIX or pdFIX. Acceptable N9-GP recovery was observed in the low-concentration to high-concentration samples tested with one-stage clotting assays using SynthAFax or DG Synth, or with chromogenic FIX:C assays. Similar patterns of FIX:C measurement were observed at both laboratory sites, with minor differences probably being attributable to the use of different analyzers. Conclusions: These results suggest that, of the reagents tested, FIX:C in N9-GP-containing plasma samples can be most accurately measured with one-stage clotting assays using SynthAFax or DG Synth, or with chromogenic FIX:C assays.</p>}},
author = {{Bowyer, A. E. and Hillarp, A. and Ezban, M. and Persson, P. and Kitchen, S.}},
issn = {{1538-7933}},
keywords = {{Blood coagulation test; Factor IX; Hemophilia B; Nonacog beta pegol; Poly(ethylene glycol)}},
language = {{eng}},
number = {{7}},
pages = {{1428--1435}},
publisher = {{Elsevier}},
series = {{Journal of Thrombosis and Haemostasis}},
title = {{Measuring factor IX activity of nonacog beta pegol with commercially available one-stage clotting and chromogenic assay kits : A two-center study}},
url = {{http://dx.doi.org/10.1111/jth.13348}},
doi = {{10.1111/jth.13348}},
volume = {{14}},
year = {{2016}},
}