Comparative field study: impact of laboratory assay variability on the assessment of recombinant factor IX Fc fusion protein (rFIXFc) activity
Summary Due to variability in the one-stage clotting assay, the performance of new factor IX (FIX) products should be assessed in this assay. The objective of this field study was to evaluate the accuracy of measuring recombinant FIX Fc fusion protein (rFIXFc) activity in clinical haemostasis labora...
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| Veröffentlicht in: | Thrombosis and haemostasis 2014-11, Vol.111 (11), p.932-940 |
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| creator | Sommer, Jurg M. Buyue, Yang Bardan, Sara Peters, Robert T. Jiang, Haiyan Kamphaus, George D. Gray, Elaine Pierce, Glenn F. |
| description | Summary
Due to variability in the one-stage clotting assay, the performance of new factor IX (FIX) products should be assessed in this assay. The objective of this field study was to evaluate the accuracy of measuring recombinant FIX Fc fusion protein (rFIXFc) activity in clinical haemostasis laboratories using the one-stage clotting assay. Human haemophilic donor plasma was spiked with rFIXFc or BeneFIX
®
at 0.80, 0.20, or 0.05 IU/ml based on label potency. Laboratories tested blinded samples using their routine one-stage assay and in-house FIX plasma standard. The mean spike recoveries for BeneFIX (n=30 laboratories) were 121 %, 144 %, and 168 % of expected at nominal 0.80, 0.20, and 0.05 IU/ml concentrations, respectively. Corresponding rFIXFc spike recoveries were 88 %, 107 %, and 132 % of expected, respectively. All BeneFIX concentrations were consistently overestimated by most laboratories. rFIXFc activity was reagent-dependent; ellagic acid and silica gave higher values than kaolin, which underestimated rFIXFc. BeneFIX demonstrated significantly reduced chromogenic assay activity relative to one-stage assay results and nominal activity, while rFIXFc activity was close to nominal activity at three concentrations with better dilution linearity than the typical one-stage assay. In conclusion, laboratory- and reagent-specific assay variabilities were revealed, with progressively higher variability at lower FIX concentrations. Non-parallelism against the FIX plasma standard was observed in all one-stage assays with rFIXFc and BeneFIX, leading to significant overestimation of FIX activity at lower levels and generally high inter-laboratory variability. Compared to the accuracy currently achieved in clinical laboratories when measuring other rFIX products, most laboratories measured rFIXFc activity with acceptable accuracy and reliability using routine one-stage assay methods and commercially available plasma standards. |
| doi_str_mv | 10.1160/th13-11-0971 |
| format | Article |
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Due to variability in the one-stage clotting assay, the performance of new factor IX (FIX) products should be assessed in this assay. The objective of this field study was to evaluate the accuracy of measuring recombinant FIX Fc fusion protein (rFIXFc) activity in clinical haemostasis laboratories using the one-stage clotting assay. Human haemophilic donor plasma was spiked with rFIXFc or BeneFIX
®
at 0.80, 0.20, or 0.05 IU/ml based on label potency. Laboratories tested blinded samples using their routine one-stage assay and in-house FIX plasma standard. The mean spike recoveries for BeneFIX (n=30 laboratories) were 121 %, 144 %, and 168 % of expected at nominal 0.80, 0.20, and 0.05 IU/ml concentrations, respectively. Corresponding rFIXFc spike recoveries were 88 %, 107 %, and 132 % of expected, respectively. All BeneFIX concentrations were consistently overestimated by most laboratories. rFIXFc activity was reagent-dependent; ellagic acid and silica gave higher values than kaolin, which underestimated rFIXFc. BeneFIX demonstrated significantly reduced chromogenic assay activity relative to one-stage assay results and nominal activity, while rFIXFc activity was close to nominal activity at three concentrations with better dilution linearity than the typical one-stage assay. In conclusion, laboratory- and reagent-specific assay variabilities were revealed, with progressively higher variability at lower FIX concentrations. Non-parallelism against the FIX plasma standard was observed in all one-stage assays with rFIXFc and BeneFIX, leading to significant overestimation of FIX activity at lower levels and generally high inter-laboratory variability. Compared to the accuracy currently achieved in clinical laboratories when measuring other rFIX products, most laboratories measured rFIXFc activity with acceptable accuracy and reliability using routine one-stage assay methods and commercially available plasma standards.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1160/th13-11-0971</identifier><identifier>PMID: 25144892</identifier><identifier>CODEN: THHADQ</identifier><language>eng</language><publisher>Stuttgart: Schattauer GmbH</publisher><subject>Biological and medical sciences ; Blood Coagulation Tests ; Blood Coagulation, Fibrinolysis and Cellular Haemostasis ; Blood coagulation. Blood cells ; Calibration ; Chromogenic Compounds ; Drug Monitoring ; Factor IX ; Fundamental and applied biological sciences. Psychology ; Hematologic and hematopoietic diseases ; Hemophilia B - blood ; Humans ; Immunoglobulin Fc Fragments - blood ; Indicators and Reagents ; Laboratories ; Laboratory Proficiency Testing ; Medical sciences ; Molecular and cellular biology ; Platelet diseases and coagulopathies ; Recombinant Fusion Proteins - blood ; Reference Standards ; Reproducibility of Results ; Single-Blind Method</subject><ispartof>Thrombosis and haemostasis, 2014-11, Vol.111 (11), p.932-940</ispartof><rights>2015 INIST-CNRS</rights><rights>Thieme Medical Publishers</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c559t-35e766c1ce9751cfef160672202f4f46c4b84ec2f738903251ba67ce662b42023</citedby><cites>FETCH-LOGICAL-c559t-35e766c1ce9751cfef160672202f4f46c4b84ec2f738903251ba67ce662b42023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1160/th13-11-0971.pdf$$EPDF$$P50$$Gthieme$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1160/th13-11-0971$$EHTML$$P50$$Gthieme$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3005,27903,27904,54537,54538</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28962216$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25144892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sommer, Jurg M.</creatorcontrib><creatorcontrib>Buyue, Yang</creatorcontrib><creatorcontrib>Bardan, Sara</creatorcontrib><creatorcontrib>Peters, Robert T.</creatorcontrib><creatorcontrib>Jiang, Haiyan</creatorcontrib><creatorcontrib>Kamphaus, George D.</creatorcontrib><creatorcontrib>Gray, Elaine</creatorcontrib><creatorcontrib>Pierce, Glenn F.</creatorcontrib><title>Comparative field study: impact of laboratory assay variability on the assessment of recombinant factor IX Fc fusion protein (rFIXFc) activity</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Summary
Due to variability in the one-stage clotting assay, the performance of new factor IX (FIX) products should be assessed in this assay. The objective of this field study was to evaluate the accuracy of measuring recombinant FIX Fc fusion protein (rFIXFc) activity in clinical haemostasis laboratories using the one-stage clotting assay. Human haemophilic donor plasma was spiked with rFIXFc or BeneFIX
®
at 0.80, 0.20, or 0.05 IU/ml based on label potency. Laboratories tested blinded samples using their routine one-stage assay and in-house FIX plasma standard. The mean spike recoveries for BeneFIX (n=30 laboratories) were 121 %, 144 %, and 168 % of expected at nominal 0.80, 0.20, and 0.05 IU/ml concentrations, respectively. Corresponding rFIXFc spike recoveries were 88 %, 107 %, and 132 % of expected, respectively. All BeneFIX concentrations were consistently overestimated by most laboratories. rFIXFc activity was reagent-dependent; ellagic acid and silica gave higher values than kaolin, which underestimated rFIXFc. BeneFIX demonstrated significantly reduced chromogenic assay activity relative to one-stage assay results and nominal activity, while rFIXFc activity was close to nominal activity at three concentrations with better dilution linearity than the typical one-stage assay. In conclusion, laboratory- and reagent-specific assay variabilities were revealed, with progressively higher variability at lower FIX concentrations. Non-parallelism against the FIX plasma standard was observed in all one-stage assays with rFIXFc and BeneFIX, leading to significant overestimation of FIX activity at lower levels and generally high inter-laboratory variability. Compared to the accuracy currently achieved in clinical laboratories when measuring other rFIX products, most laboratories measured rFIXFc activity with acceptable accuracy and reliability using routine one-stage assay methods and commercially available plasma standards.</description><subject>Biological and medical sciences</subject><subject>Blood Coagulation Tests</subject><subject>Blood Coagulation, Fibrinolysis and Cellular Haemostasis</subject><subject>Blood coagulation. Blood cells</subject><subject>Calibration</subject><subject>Chromogenic Compounds</subject><subject>Drug Monitoring</subject><subject>Factor IX</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hemophilia B - blood</subject><subject>Humans</subject><subject>Immunoglobulin Fc Fragments - blood</subject><subject>Indicators and Reagents</subject><subject>Laboratories</subject><subject>Laboratory Proficiency Testing</subject><subject>Medical sciences</subject><subject>Molecular and cellular biology</subject><subject>Platelet diseases and coagulopathies</subject><subject>Recombinant Fusion Proteins - blood</subject><subject>Reference Standards</subject><subject>Reproducibility of Results</subject><subject>Single-Blind Method</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>0U6</sourceid><sourceid>EIF</sourceid><recordid>eNptkU-LFDEQxYMo7uzqzbPkIrhoa5JOpzseBBkcHVjwojC3kM5UnCzdnSHJDPSX8DNb46yrgqf8qd97ldQj5BlnbzhX7G3Z8brivGK65Q_IQjSqrVSnNw_JgtWSVUrI5oJc5nzLGFdSN4_JhWi4lJ0WC_JjGce9TbaEI1AfYNjSXA7b-R0NeO8KjZ4Oto9IxDRTm7Od6dGmYPswhDLTONGyg1MBch5h-qVI4OLYh8ni0aNLTHS9oStH_SEHVOxTLBAm-jKt1puVu6bIhCPaPSGPvB0yPL1br8i31cevy8_VzZdP6-WHm8o1jS5V3UCrlOMOdNtw58HjJFQrBBNeeqmc7DsJTvi27jSr8bu9Va0DpUQvEaqvyPuz7_7Qj7B1-O5kB7NPYbRpNtEG829lCjvzPR6Nqlupa44Gr88GLsWcE_h7LWfmlIs55YI7c8oF8ed_97uHfweBwIs7wGZnB5_s5EL-w3VaCcEVcq_OXNkFGMHcxkOacFL_b_sT-aamwQ</recordid><startdate>20141101</startdate><enddate>20141101</enddate><creator>Sommer, Jurg M.</creator><creator>Buyue, Yang</creator><creator>Bardan, Sara</creator><creator>Peters, Robert T.</creator><creator>Jiang, Haiyan</creator><creator>Kamphaus, George D.</creator><creator>Gray, Elaine</creator><creator>Pierce, Glenn F.</creator><general>Schattauer GmbH</general><general>Schattauer</general><scope>0U6</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20141101</creationdate><title>Comparative field study: impact of laboratory assay variability on the assessment of recombinant factor IX Fc fusion protein (rFIXFc) activity</title><author>Sommer, Jurg M. ; Buyue, Yang ; Bardan, Sara ; Peters, Robert T. ; Jiang, Haiyan ; Kamphaus, George D. ; Gray, Elaine ; Pierce, Glenn F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c559t-35e766c1ce9751cfef160672202f4f46c4b84ec2f738903251ba67ce662b42023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Biological and medical sciences</topic><topic>Blood Coagulation Tests</topic><topic>Blood Coagulation, Fibrinolysis and Cellular Haemostasis</topic><topic>Blood coagulation. Blood cells</topic><topic>Calibration</topic><topic>Chromogenic Compounds</topic><topic>Drug Monitoring</topic><topic>Factor IX</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hemophilia B - blood</topic><topic>Humans</topic><topic>Immunoglobulin Fc Fragments - blood</topic><topic>Indicators and Reagents</topic><topic>Laboratories</topic><topic>Laboratory Proficiency Testing</topic><topic>Medical sciences</topic><topic>Molecular and cellular biology</topic><topic>Platelet diseases and coagulopathies</topic><topic>Recombinant Fusion Proteins - blood</topic><topic>Reference Standards</topic><topic>Reproducibility of Results</topic><topic>Single-Blind Method</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sommer, Jurg M.</creatorcontrib><creatorcontrib>Buyue, Yang</creatorcontrib><creatorcontrib>Bardan, Sara</creatorcontrib><creatorcontrib>Peters, Robert T.</creatorcontrib><creatorcontrib>Jiang, Haiyan</creatorcontrib><creatorcontrib>Kamphaus, George D.</creatorcontrib><creatorcontrib>Gray, Elaine</creatorcontrib><creatorcontrib>Pierce, Glenn F.</creatorcontrib><collection>Thieme Connect Journals Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sommer, Jurg M.</au><au>Buyue, Yang</au><au>Bardan, Sara</au><au>Peters, Robert T.</au><au>Jiang, Haiyan</au><au>Kamphaus, George D.</au><au>Gray, Elaine</au><au>Pierce, Glenn F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative field study: impact of laboratory assay variability on the assessment of recombinant factor IX Fc fusion protein (rFIXFc) activity</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2014-11-01</date><risdate>2014</risdate><volume>111</volume><issue>11</issue><spage>932</spage><epage>940</epage><pages>932-940</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><coden>THHADQ</coden><abstract>Summary
Due to variability in the one-stage clotting assay, the performance of new factor IX (FIX) products should be assessed in this assay. The objective of this field study was to evaluate the accuracy of measuring recombinant FIX Fc fusion protein (rFIXFc) activity in clinical haemostasis laboratories using the one-stage clotting assay. Human haemophilic donor plasma was spiked with rFIXFc or BeneFIX
®
at 0.80, 0.20, or 0.05 IU/ml based on label potency. Laboratories tested blinded samples using their routine one-stage assay and in-house FIX plasma standard. The mean spike recoveries for BeneFIX (n=30 laboratories) were 121 %, 144 %, and 168 % of expected at nominal 0.80, 0.20, and 0.05 IU/ml concentrations, respectively. Corresponding rFIXFc spike recoveries were 88 %, 107 %, and 132 % of expected, respectively. All BeneFIX concentrations were consistently overestimated by most laboratories. rFIXFc activity was reagent-dependent; ellagic acid and silica gave higher values than kaolin, which underestimated rFIXFc. BeneFIX demonstrated significantly reduced chromogenic assay activity relative to one-stage assay results and nominal activity, while rFIXFc activity was close to nominal activity at three concentrations with better dilution linearity than the typical one-stage assay. In conclusion, laboratory- and reagent-specific assay variabilities were revealed, with progressively higher variability at lower FIX concentrations. Non-parallelism against the FIX plasma standard was observed in all one-stage assays with rFIXFc and BeneFIX, leading to significant overestimation of FIX activity at lower levels and generally high inter-laboratory variability. Compared to the accuracy currently achieved in clinical laboratories when measuring other rFIX products, most laboratories measured rFIXFc activity with acceptable accuracy and reliability using routine one-stage assay methods and commercially available plasma standards.</abstract><cop>Stuttgart</cop><pub>Schattauer GmbH</pub><pmid>25144892</pmid><doi>10.1160/th13-11-0971</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Thieme Connect Journals |
| subjects | Biological and medical sciences Blood Coagulation Tests Blood Coagulation, Fibrinolysis and Cellular Haemostasis Blood coagulation. Blood cells Calibration Chromogenic Compounds Drug Monitoring Factor IX Fundamental and applied biological sciences. Psychology Hematologic and hematopoietic diseases Hemophilia B - blood Humans Immunoglobulin Fc Fragments - blood Indicators and Reagents Laboratories Laboratory Proficiency Testing Medical sciences Molecular and cellular biology Platelet diseases and coagulopathies Recombinant Fusion Proteins - blood Reference Standards Reproducibility of Results Single-Blind Method |
| title | Comparative field study: impact of laboratory assay variability on the assessment of recombinant factor IX Fc fusion protein (rFIXFc) activity |
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