{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:34:45Z","timestamp":1765355685459},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,12,17]],"date-time":"2012-12-17T00:00:00Z","timestamp":1355702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The variant <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>reutzfeldt\u2010<jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>akob disease incidence peaked a decade ago and has since declined. Based on epidemiologic evidence, the causative agent, pathogenic prion, has not constituted a tangible contamination threat to large\u2010scale manufacturing of human plasma\u2010derived proteins. Nonetheless, manufacturers have studied the prion removal capabilities of various manufacturing steps to better understand product safety. Collectively analyzing the results could reveal experimental reproducibility and detect trends and mechanisms driving prion removal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design and Methods<\/jats:title><jats:p>Plasma Protein Therapeutics Association member companies collected more than 200 prion removal studies on plasma protein manufacturing steps, including precipitation, adsorption, chromatography, and filtration, as well as combined steps. The studies used a range of model spiking agents and bench\u2010scale process replicas. The results were grouped based on key manufacturing variables to identify factors impacting removal. The log reduction values of a group are presented for comparison.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall prion removal capacities evaluated by independent groups were in good agreement. The removal capacity evaluated using biochemical assays was consistent with prion infectivity removal measured by animal bioassays. Similar reduction values were observed for a given step using various spiking agents, except highly purified prion protein in some circumstances. Comparison between combined and single\u2010step studies revealed complementary or overlapping removal mechanisms. Steps with high removal capacities represent the conditions where the physiochemical differences between prions and therapeutic proteins are most significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results support the intrinsic ability of certain plasma protein manufacturing steps to remove prions in case of an unlikely contamination, providing a safeguard to products.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.12050","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T17:19:33Z","timestamp":1355851173000},"page":"1894-1905","source":"Crossref","is-referenced-by-count":30,"title":["Prion removal capacity of plasma protein manufacturing processes"],"prefix":"10.1111","volume":"53","author":[{"given":"Kang","family":"Cai","sequence":"first","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albrecht","family":"Gr\u00f6ner","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert O.","family":"Dichtelm\u00fcller","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Fabbrizzi","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eckhard","family":"Flechsig","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Gajardo","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilka","family":"von Hoegen","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan I.","family":"Jorquera","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Kempf","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas R.","family":"Kreil","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mila","family":"Moscardini","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"P\u00f6lsler","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan J.","family":"Roth","sequence":"additional","affiliation":[{"name":"Baxter BioScience  Vienna Austria"},{"name":"Biotest AG  Dreieich Germany"},{"name":"CSL Behring  Marburg Germany"},{"name":"CSL Behring  Berne Switzerland"},{"name":"Grifols  Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,12,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13363"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/38925"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07376.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02181.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02719-7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-83-11-2897"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023169"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)24035-9"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16812-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1998.38998408999.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0041-1132.2003.00586.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69897-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1999.39111169.x"},{"key":"e_1_2_8_15_1","volume-title":"Risk assessment of exposure to vCJD infectivity in blood and blood products for the Department of Health of United Kingdom","author":"Comer PJ","year":"2003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2011.03199.x"},{"key":"e_1_2_8_17_1","unstructured":"National CJD Research & Surveillance Unit.vCJD statistics by the National Creutzfeldt\u2010Jakob Disease Research & Surveillance Unit.2012. [cited 2012 Sep 10]. Available from: URL:http:\/\/www.cjd.ed.ac.uk\/"},{"key":"e_1_2_8_18_1","unstructured":"European Creutzfeldt Jakob Disease Surveillance Network.vCJD statistics by European Creutzfeldt Jakob Disease Surveillance Network.2012. [cited 2012 Sep 10]. Available from: URL:http:\/\/www.eurocjd.ed.ac.uk\/"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)15171-9"},{"key":"e_1_2_8_20_1","unstructured":"US Food and Drug Administration.Guidance for industry revised preventive measures to reduce the possible risk of transmission of Creutzfeldt\u2010Jakob disease (CJD) and variant Creutzfeldt\u2010Jakob disease (vCJD) by blood and blood products. May2010."},{"key":"e_1_2_8_21_1","unstructured":"Committee for Medicinal Products for Human.Use (CHMP) position statement on Creutzfeldt\u2010Jakob disease and plasma\u2010derived and urine\u2010derived medicinal products. June2011 EMA\/CHMP\/BWP\/303353\/2010."},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1423-0410.2000.7820086.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0042-9007.2004.00403.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-0934(99)00135-4"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.2001.41040449.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1423-0410.2003.00279.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1423-0410.2002.00211.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1423-0410.2003.00312.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(02)00282-0"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2003.08.004"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1006\/biol.2002.0327"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tracli.2007.04.008"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.2006.00829.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.2217\/17460794.1.5.659"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2008.01.004"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02067.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2010.08.003"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.2002.00216.x"},{"key":"e_1_2_8_39_1","unstructured":"Committee for Proprietary Medicinal Products.Guideline on the investigation of manufacturing processes for plasma\u2010derived medicinal products with regard to vCJD risk. October2004 EMEA\/CPMP\/BWP\/5136\/03."},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.18996-0"},{"key":"e_1_2_8_41_1","first-page":"119","volume-title":"Prion biology and diseases","author":"Prusiner SB","year":"1999"},{"key":"e_1_2_8_42_1","unstructured":"Committee for Proprietary Medicinal Products.Note for guidance on virus validation studies: the design contribution and interpretation of studies validating the inactivation and removal of viruses. February1996. (Revised) (CPMP\/BWP\/268\/95)."},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01207a034"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.1962.tb03274.x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68930-7"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.11.6675"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90168-X"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103629200"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.8.2310"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(99)77270-X"}],"container-title":["Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ftrf.12050","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.12050","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T00:27:44Z","timestamp":1696033664000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/trf.12050"}},"subtitle":["A data collection from <scp>PPTA<\/scp> member companies"],"short-title":[],"issued":{"date-parts":[[2012,12,17]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1111\/trf.12050"],"URL":"https:\/\/doi.org\/10.1111\/trf.12050","archive":["Portico"],"relation":{},"ISSN":["0041-1132","1537-2995"],"issn-type":[{"value":"0041-1132","type":"print"},{"value":"1537-2995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,17]]}}}