title: Heterogeneity of commercial recombinant human growth hormone (r-hGH) preparations containing a thioether variant.
abstract: The objective of the present study was to assess (I) the potential presence of a recently discovered thioether variant in commercially available recombinant human growth hormone (r-hGH) preparations, and (II) the impact of the thioether modification on the in-vivo bioactivity and the receptor binding kinetics. Samples were tested employing European (EP) and US Pharmacopeia (USP) Somatropin monograph and mass spectrometry methods. None of the international standards contained this variant. All products conformed to EP specifications but six out of eight lots contained the variant. An artificially enriched thioether sample exhibited a significantly reduced in vivo biopotency and altered receptor-binding properties compared with a control. The absence of the variant in the pituitary hGH standard, and the possibility to generate it artificially suggests that it is not naturally occurring and that it may arise from an uncontrolled manufacturing process. Controlled studies may be required to assess its clinical efficacy and safety. EP and USP methods may need to be adapted to reliably detect the presence of the variant.
authors.affiliation: Medical Liaison Office, Merck Serono S.p.A., Roma, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Lispi
authors.forename: Antonio
authors.initials: A
authors.lastname: Datola
authors.forename: Horst
authors.initials: H
authors.lastname: Bierau
authors.forename: Domenico
authors.initials: D
authors.lastname: Ceccarelli
authors.forename: Carmelina
authors.initials: C
authors.lastname: Crisci
authors.forename: Katia
authors.initials: K
authors.lastname: Minari
authors.forename: Daniele
authors.initials: D
authors.lastname: Mendola
authors.forename: Aniello
authors.initials: A
authors.lastname: Regine
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ciampolillo
authors.forename: Mara
authors.initials: M
authors.lastname: Rossi
authors.forename: Carlo Emanuele
authors.initials: CE
authors.lastname: Giartosio
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Pezzotti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Musto
authors.forename: Carl
authors.initials: C
authors.lastname: Jone
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiarelli
mesh_terms: D000577:Amides / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D001681:Biological Assay; D004340:Drug Contamination; D013006:Growth Hormone / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D010449:Peptide Mapping; D051381:Rats; D011986:Receptors, Somatotropin / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013440:Sulfides / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000577:Amides; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D013440:Sulfides; D013006:Growth Hormone