Systematic Verification of Bioanalytical Similarity Between a Biosimilar and a Reference Biotherapeutic: Committee Recommendations for the Development and Validation of a Single Ligand-Binding Assay to Support Pharmacokinetic Assessments
Marini J.C.,Janssen Research and Development LLC |
Anderson M.,BDS Immunoassay Services |
Cai X.-Y.,Merck & Company |
Chappell J.,CPR Pharma Services Pty Ltd |
And 7 more authors.
Botanical Review | Year: 2014
For biosimilar drug development, it is critical to demonstrate similar physiochemical characteristics, efficacy, and safety of the biosimilar product compared to the reference product. Therefore, pharmacokinetic (PK) and immunogenicity (antidrug antibody, ADA) assays that allow for the demonstration of biosimilarity are critical. Under the auspices of the American Association of Pharmaceutical Scientists (AAPS) Ligand-Binding Assay Bioanalytical Focus Group (LBABFG), a Biosimilars Action Program Committee (APC) was formed in 2011. The goals of this Biosimilars APC were to provide a forum for in-depth discussions on issues surrounding the development and validation of PK and immunogenicity assays in support of biosimilar drug development and to make recommendations thereof. The Biosimilars APC’s recommendations for the development and validation of ligand-binding assays (LBAs) to support the PK assessments for biosimilar drug development are presented here. Analytical recommendations for the development and validation of LBAs to support immunogenicity assessments will be the subject of a separate white paper. © 2014, American Association of Pharmaceutical Scientists.
Mayr C.M.,Australian Wine Research Institute |
Mayr C.M.,Cara Technology Ltd |
Geue J.P.,Australian Wine Research Institute |
Geue J.P.,CPR Pharma Services Pty Ltd. |
And 5 more authors.
Journal of Agricultural and Food Chemistry | Year: 2014
The key aroma compounds of premium Australian Shiraz wines from the warm Barossa Valley and cooler Margaret River regions were characterized. GC-Olfactometry was conducted to determine the most important volatile compounds, which were then quantitated. The wine from the Barossa Valley had higher concentrations of ethyl propanoate, dimethyl sulfide (DMS), and oak-derived compounds, whereas the Margaret River wine contained above threshold concentrations of the 'cheesy' compounds 2- and 3-methylbutanoic acid, as well as rotundone, the 'pepper'-smelling compound. The aromas were reconstituted by combining 44 aroma compounds, and sensory descriptive analysis was used to investigate the importance of the omission of several compounds, including DMS, rotundone, fatty acids, and β-damascenone, and the influence of nonvolatiles was also assessed. The study showed that the aroma of the Shiraz wines could be reconstituted in both cases, with the changes in the nonvolatile fraction having a large influence. © 2014 American Chemical Society.
Reuter S.E.,University of South Australia |
Evans A.M.,University of South Australia |
Shakib S.,IDT |
Lungershausen Y.,CPR Pharma Services Pty Ltd |
And 5 more authors.
Clinical Drug Investigation | Year: 2015
Background and Objective: Piperaquine–dihydroartemisinin combination therapy has established efficacy for the treatment of malaria; however, a more comprehensive understanding of the pharmacokinetic properties and factors contributing to inter- and intra-individual variability is critical to optimize clinical use. This study assessed the effects of food on the pharmacokinetics of combination piperaquine–dihydroartemisinin administration in healthy volunteers. Methods: This was an open-label, single-dose, parallel-group study. Participants were randomly allocated to receive oral piperaquine–dihydroartemisinin either after an overnight fast or immediately after a standardized, high-fat, high-calorie meal. Blood samples were collected for analysis of plasma piperaquine and dihydroartemisinin concentrations, which were utilized for calculation of pharmacokinetic parameters, using a standard model-independent approach. Results: Consumption of a high-fat, high-calorie meal resulted in substantial increases in the extent of exposure to piperaquine (ratio between area under the plasma concentration–time curve [AUC] values from 0 to 168 h in the fed and fasted states [AUC0–168 h FED/AUC0–168 h FASTED] = 299 %, 90 % confidence interval [CI] 239–374 %). This likely reflects an increase in the oral bioavailability of the drug, directly related to the fat content of the meal. Co-administration of food was also found to result in both delayed and enhanced absorption of dihydroartemisinin (ratio between AUC values from time zero to infinity in the fed and states [AUC∞ FED/AUC∞ FASTED] = 142 %, 90 % CI 113–178 %; ratio between mean transit time [MTT] values in the fed and fasted states [MTTFED/MTTFASTED] = 135 %, 90 % CI 114–160 %). Conclusion: Although food was found to significantly impact on the pharmacokinetics of piperaquine and dihydroartemisinin, given the low fat content of standard meals within endemic regions and the anorexic effects of malaria infection, these results are unlikely to impact on the clinical utility of these drugs. However, co-administration of food with these anti-malarials by populations consuming a typical Western diet should be avoided to reduce the risk of toxic side effects. It is therefore a general recommendation that piperaquine–dihydroartemisinin not be administered within ±3 h of food consumption. © 2015, Springer International Publishing Switzerland.
Keelan J.A.,University of Western Australia |
Mattes E.,University of Western Australia |
Tan H.,CPR Pharma Services Pty Ltd |
Dinan A.,CPR Pharma Services Pty Ltd |
And 4 more authors.
PLoS ONE | Year: 2012
The aim of this study was to measure umbilical blood androgen concentrations in a birth cohort using a highly specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and assesses the effects of sex, labor, and gestational age on fetal androgen levels at birth. We performed a prospective cohort study of androgen concentrations in mixed arterial and venous umbilical cord serum from 803 unselected singleton pregnancies from a general obstetric population in Western Australia. Total testosterone (TT), Δ4-androstenedione, and dehydroepiandrosterone were extracted from archived cord serum samples and measured using LC-MS/MS. SHBG was measured by ELISA; free testosterone (FT) and bioavailable testosterone (BioT) values were also calculated. Median values for all three androgens were generally lower than previously published values. Levels of TT, FT, BioT, and SHBG were significantly higher in male verses female neonates (P<0.0001), while dehydroepiandrosterone levels were higher in females (P<0.0001). Labor was associated with a significant (~15-26%) decrease in median cord blood TT and FT levels (both sexes combined), but a modest (~16-31%) increase in SHBG, Δ4-androstenedione, and dehydroepiandrosterone concentrations. TT and FT were significantly negatively correlated with gestational age at delivery, while SHBG, Δ4-androstenedione, and dehydroepiandrosterone were positively correlated. Antenatal glucocorticoid administration also had a significant effect in the multiple regression models. This is the first study to report umbilical cord androgen levels in a large unselected population of neonates using LC-MS/MS. Our findings suggest that previous studies have over-estimated cord androgen levels, and that fetal, maternal, and obstetric factors influence cord androgen levels differentially. Caution should be exercised when interpreting previously-published data that have not taken all of these factors into account. © 2012 Keelan et al.