Human plasma is utilized in the production of life-saving pharmaceuticals, including fibrinogen, a key player in clot formation, tissue repair, and hemostasis. Fibrinogen deficiency results in impaired blood clotting and potentially severe hemorrhagic events. Fibrinogen concentrate or cryoprecipitate are the preferred options for fibrinogen replacement therapy. Both increase plasma fibrinogen levels, but utilization of fibrinogen concentrate is advantageous. It offers enhanced pathogen safety through manufacturing procedures that remove or inactivate viruses or prions potentially present in human plasma. We developed a novel manufacturing process that yields a fibrinogen concentrate (BT524) and coagulation factor VIII (Haemoctin® SDH) in one workflow. This process contains several virus inactivation steps, including an innovative UV-C irradiation and a cation exchange chromatography (CEX) step for prion removal. While successfully inactivating potential viral contamination, UV-C irradiation showed no influence on fibrinogen structure and composition, and no formation of neoantigenic structures could be identified. Fibrinogen concentrate (BT524) contained almost exclusively fibrinogen with activity close to 100
SB16 has been developed and recently approved as a biosimilar to denosumab reference product, which inhibits osteoclast formation by targeting receptor activator of nuclear factor kappa-B ligand. This study presents a comprehensive analytical characterization of SB16 denosumab biosimilar to demonstrate high similarity to the reference product (Prolia and Xgeva). Analytical similarity was assessed using side-by-side comparisons and similarity range approaches with state-of-the-art methods. Critical quality attributes evaluated included primary structure, post-translational modifications, higher order structure, purity, glycosylation, charge heterogeneity, and biological activities. Similarity ranges were established using extensive reference product lot testing (up to 68 EU Prolia, 35 US Prolia, 29 EU Xgeva, and 17 US Xgeva lots). Peptide mapping confirmed 100
Intravenous (IV) and subcutaneous (SC) belimumab are approved in the USA, Europe, and Japan for patients aged ≥ 5 years with active systemic lupus erythematosus. In China, IV belimumab is approved for patients aged ≥ 5 years. This analysis updates the global pediatric population pharmacokinetic model by integrating data from IV and SC Chinese pediatric studies and evaluates the suitability of a 200-mg SC dosing regimen for pediatric systemic lupus erythematosus in China. This analysis utilized the previously established two-compartment model while re-evaluating the impact of potential covariates. Allometric scaling was incorporated to account for variations in body size, and other covariates were systematically assessed through stepwise selection and their relevance to pharmacokinetic parameters. To support extrapolation of the established efficacy from the IV belimumab pediatric study to SC belimumab in pediatric patients, simulations were conducted to compare pharmacokinetic exposures between the proposed SC and approved IV regimens in Chinese pediatric patients. Furthermore, to provide additional evidence for supporting dose selection in this population, clinical response was predicted using a pre-established exposure-response model. The estimated pharmacokinetic parameters for a representative Chinese pediatric patient were: clearance, 158 mL/day; steady-state volume of distribution, 3930 mL; SC bioavailability, 77.9
Trientine dihydrochloride (TETA-2HCl) is an oral copper chelator used for Wilson disease. Because available formulations differ in marketed strength and may have formulation-specific pharmacokinetic properties, this study compared a 250 mg test capsule and a 300 mg reference capsule administered under fasting conditions. This randomized, open-label, balanced, two-treatment, two-period, two-sequence crossover study enrolled 36 healthy adults. Plasma samples collected over 48 h after single-dose administration were analyzed for parent trientine and N1-acetyltriethylenetetramine using validated liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The primary comparative pharmacokinetic evaluation was based on parent trientine Cmax and AUC0–t at the administered strengths. Dose-normalized and metabolite analyses were supportive. Thirty-five participants were included in the pharmacokinetic and statistical analyses. Parent trientine was absorbed more rapidly after the test formulation, with median Tmax values of 1.25 versus 2.25 h. At the administered strengths, test/reference geometric least-squares mean ratios (90
Transdermal administration of estrogen has established its positioning among hormone replacement therapies in menopause. In Divigel® (estradiol hemihydrate gel 0.1
