{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T07:14:44Z","timestamp":1778915684385,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>In the late1990s, reacting to the outbreak of bovine spongiform encephalopathy (BSE) in the United Kingdom that caused a new variant of Creutzfeldt\u2010Jakob disease (vCJD) in humans, manufacturers withdrew bovine heparin from the market in the United States. There have been growing concerns about the adequate supply and safety of porcine heparin. Since the BSE epidemic has been declining markedly, the US Food and Drug Administration reevaluates the vCJD risk via use of bovine heparin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We developed a computational model to estimate the vCJD risk to patients receiving bovine heparin injections. The model incorporated information including BSE prevalence, infectivity levels in the intestines, manufacturing batch size, yield of heparin, reduction in infectivity by manufacturing process, and the dose\u2010response relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The model estimates a median risk of vCJD infection from a single intravenous dose (10 000 USP units) of heparin made from US\u2010sourced bovine intestines to be 6.9\u2009\u00d7\u200910<jats:sup>\u22129<\/jats:sup> (2.5\u201097.fifth percentile: 1.5\u2009\u00d7\u200910<jats:sup>\u22129<\/jats:sup>\u20104.3\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>), a risk of 1 in 145 million, and 4.6\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup> (2.5\u201097.fifth percentile: 1.1\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>\u20102.6\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>), a risk of 1 in 22 million for Canada\u2010sourced products. The model estimates a median risk of 1.4\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup> (2.5\u201097.fifth percentile: 2.9\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>\u20109.3\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>) and 9.6\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup> (2.5\u201097.fifth percentile: 2.1\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>\u20105.6\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>) for a typical treatment for venous thromboembolism (infusion of 2\u20104 doses daily per week) using US\u2010sourced and Canada\u2010sourced bovine heparin, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The model estimates the vCJD risk from use of heparin when appropriately manufactured from US or Canadian cattle is likely small. The model and conclusions should not be applied to other medicinal products manufactured using bovine\u2010derived materials.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.4982","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T13:29:26Z","timestamp":1583414966000},"page":"575-581","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Assessment of risk of variant creutzfeldt\u2010Jakob disease (vCJD) from use of bovine heparin"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7333-2784","authenticated-orcid":false,"given":"Yin","family":"Huang","sequence":"first","affiliation":[{"name":"FDA Center for Biologics Evaluation and Research Office of Biostatistics and Epidemiology  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Forshee","sequence":"additional","affiliation":[{"name":"FDA Center for Biologics Evaluation and Research Office of Biostatistics and Epidemiology  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Keire","sequence":"additional","affiliation":[{"name":"FDA Center for Drug Evaluation and Research Office of Pharmaceutical Quality  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sau","family":"Lee","sequence":"additional","affiliation":[{"name":"FDA Center for Drug Evaluation and Research Office of Pharmaceutical Quality  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Gregori","sequence":"additional","affiliation":[{"name":"FDA Center for Biologics Evaluation and Research Office of Blood Research and Review  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Asher","sequence":"additional","affiliation":[{"name":"FDA Center for Biologics Evaluation and Research Office of Blood Research and Review  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyrus","family":"Bett","sequence":"additional","affiliation":[{"name":"FDA Center for Biologics Evaluation and Research Office of Blood Research and Review  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Niland","sequence":"additional","affiliation":[{"name":"FDA Center for Biologics Evaluation and Research Office of Tissues and Advanced Therapies  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott A.","family":"Brubaker","sequence":"additional","affiliation":[{"name":"FDA Center for Biologics Evaluation and Research Office of Tissues and Advanced Therapies  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven A.","family":"Anderson","sequence":"additional","affiliation":[{"name":"FDA Center for Biologics Evaluation and Research Office of Biostatistics and Epidemiology  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Yang","sequence":"additional","affiliation":[{"name":"FDA Center for Biologics Evaluation and Research Office of Biostatistics and Epidemiology  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"FDA. 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