{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:33:42Z","timestamp":1777905222850,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merck KGaA, Darmstadt, Germany","award":["10.13039\/100009945"],"award-info":[{"award-number":["10.13039\/100009945"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Various preparations of follicle-stimulating hormone (FSH) are commercially available; however, they differ in glycoforms composition and purity owing to their respective sources. Additional chemical\/physical changes can also be introduced during manufacturing and can impact their biological activity (biopotency), which is routinely assessed using an in vivo bioassay (Steelman\u2013Pohley). This study aimed to determine whether an in vitro bioassay could assess biopotency by distinguishing between r-hFSH chemical\/physical variants with similar ability to the in vivo bioassay. The specific activity (units of biological activity per mg of product) of variants of r-hFSH generated through enrichment (acidic\/basic), stress (oxidative\/acidic pH) and enzymatic treatment (desialylation and desialylation\/degalactosylation) was compared using the in vivo and in vitro bioassays. The in vitro bioassay reliably detected potential chemical\/physical modifications in r-hFSH variants that may impact biopotency. Overall, the methods demonstrated a comparable ability to detect changes in specific activities due to chemical\/physical differences in r-hFSH variants. These data indicate that the in vitro bioassay is suitable to replace the in vivo bioassay.<\/jats:p>","DOI":"10.3390\/ijms24098040","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T10:51:52Z","timestamp":1682679112000},"page":"8040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Biological Assay to Determine Gonadotropin Potency: From In Vivo to In Vitro Sustainable Method"],"prefix":"10.3390","volume":"24","author":[{"given":"Francesco","family":"Nevelli","sequence":"first","affiliation":[{"name":"Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Istituto di Ricerche Biomediche \u201cAntoine Marxer\u201d RBM S.p.A., Colleretto Giacosa, Via Ribes, 1, 10010 Samone, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Palmese","sequence":"additional","affiliation":[{"name":"Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Merck Serono S.p.A., Piazza del Pigneto, 9, 00176 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Gleixner","sequence":"additional","affiliation":[{"name":"Ares Trading S.A., Rue de l\u2019Ouriette 151, 1170 Aubonne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio","family":"Peroglio","sequence":"additional","affiliation":[{"name":"GHO Ivrea QC & Scientific Excellence\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Istituto di Ricerche Biomediche \u201cAntoine Marxer\u201d RBM S.p.A., Colleretto Giacosa, Via Ribes, 1, 10010 Samone, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cosimo-Walter","family":"D\u2019Acunto","sequence":"additional","affiliation":[{"name":"Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Istituto di Ricerche Biomediche \u201cAntoine Marxer\u201d RBM S.p.A., Colleretto Giacosa, Via Ribes, 1, 10010 Samone, Italy"},{"name":"Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Merck Serono S.p.A., Piazza del Pigneto, 9, 00176 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurora","family":"Dadone","sequence":"additional","affiliation":[{"name":"Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Istituto di Ricerche Biomediche \u201cAntoine Marxer\u201d RBM S.p.A., Colleretto Giacosa, Via Ribes, 1, 10010 Samone, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"D\u2019Hooghe","sequence":"additional","affiliation":[{"name":"Global Medical Affairs Fertility, Merck Healthcare KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany"},{"name":"Department of Development and Regeneration, Laboratory of Endometrium, Endometriosis & Reproductive Medicine, KU Leuven, Oude Markt 13, 3000 Leuven, Belgium"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University Medical School, 333 Cedar St., New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9920-3208","authenticated-orcid":false,"given":"Monica","family":"Lispi","sequence":"additional","affiliation":[{"name":"Global Medical Affairs Fertility, Merck Healthcare KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany"},{"name":"PhD School of Clinical and Experimental Medicine, Unit of Endocrinology, University of Modena and Reggio Emilia, Viale A. Allegri 9, 42121 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3389\/fendo.2019.00305","article-title":"Molecular Mechanisms of Action of FSH","volume":"10","author":"Casarini","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"636038","DOI":"10.3389\/fendo.2021.636038","article-title":"New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect","volume":"12","author":"Dias","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bergandi, L., Canosa, S., Carosso, A.R., Paschero, C., Gennarelli, G., Silvagno, F., Benedetto, C., and Revelli, A. (2020). 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