Heterogeneity of commercial recombinant human growth hormone (r-hGH) preparations containing a thioether variant.
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.
Lispi
Monica
M
Medical Liaison Office, Merck Serono S.p.A., Roma, Italy.
Datola
Antonio
A
Bierau
Horst
H
Ceccarelli
Domenico
D
Crisci
Carmelina
C
Minari
Katia
K
Mendola
Daniele
D
Regine
Aniello
A
Ciampolillo
Cinzia
C
Rossi
Mara
M
Giartosio
Carlo Emanuele
CE
Pezzotti
Anna Rita
AR
Musto
Raffaella
R
Jone
Carl
C
Chiarelli
Francesco
F
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
D000577:Amides; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D013440:Sulfides; D013006:Growth Hormone