title: Stability of ipilimumab in its original vial after opening allows its use for at least 4 weeks and facilitates pooling of residues.
abstract: OBJECTIVE
  Well-documented stability data of monoclonal antibodies are generally missing. That is why we studied the physicochemical and biological stability of undiluted ipilimumab (IPI) in glass vial (5 mg/ml) over 28 d after opening, stored at 4 °C and 25 °C.
  
  
  METHODS
  A stressed study (60 °C) was performed to validate our analytical methods as 'stability indicating'. The different methods used were turbidimetry, dynamic light scattering (DLS), second-derivative ultraviolet and chromatographic methods as size-exclusion chromatography (SEC) and cation-exchange (CEX). Biological characterisation was performed by an in vitro functional binding inhibition bioassay.
  
  
  RESULTS
  We demonstrated that ipilimumab in opened vials stored at 4 °C and 25 °C remained stable for at least 28 d. No physical, chemical or structural instability was found. No aggregation was observed by turbidimetry, SEC and DLS. Hydrodynamic diameters remained unchanged, as chromatographic profiles in CEX and thermal aggregation curves. Functionally, the ability of IPI to antagonise CTLA-4/B7.2 binding remained stable over 1 month at 4 °C.
  
  
  CONCLUSIONS
  These results indicate that unused residues of IPI in their original vials can be safely kept up to 28 d, following good manufacturing procedures, allowing re-use for another patient or in case of cold-chain rupture.
authors.affiliation: Department of Pharmacy, Henri Mondor University Hospitals, AP-HP, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. Electronic address: pascale.bardo@aphp.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Bardo-Brouard
authors.affiliation: Department of Pharmacy, Henri Mondor University Hospitals, AP-HP, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France.
authors.forename: Victoire
authors.initials: V
authors.lastname: Vieillard
authors.affiliation: CNRS UMR5286, INSERM U1052, Cancer Research Center of Lyon, Leon Berard Cancer Center, Lyon, France.
authors.forename: Tala
authors.initials: T
authors.lastname: Shekarian
authors.affiliation: CNRS UMR5286, INSERM U1052, Cancer Research Center of Lyon, Leon Berard Cancer Center, Lyon, France; Cancer Immunotherapy Program Drug Development Department (DITEP), INSERM U1015, Gustave Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
authors.affiliation: Department of Pharmacy, Henri Mondor University Hospitals, AP-HP, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Astier
authors.affiliation: Department of Pharmacy, Henri Mondor University Hospitals, AP-HP, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Paul
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051940:B7-2 Antigen / Q000378:metabolism; D001667:Binding, Competitive; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D004349:Drug Packaging; D004355:Drug Stability; D005898:Glass; D006825:Hybridomas / Q000378:metabolism; D000074324:Ipilimumab; D008027:Light; D009391:Nephelometry and Turbidimetry; D011485:Protein Binding; D011489:Protein Denaturation; D055550:Protein Stability; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D051940:B7-2 Antigen; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; D000074324:Ipilimumab
keywords: Immunotherapy; Ipilimumab; Monoclonal antibody; Stability