Similarity assessment by multivariate statistics method based on the distance between biosimilar and originator
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ABSTRACT:
SUBMITTER: Xu J
PROVIDER: S-EPMC10992075 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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Project description:BackgroundSB12 is being developed as a proposed biosimilar to eculizumab reference product (RP), a humanized monoclonal antibody (IgG2/4 kappa immunoglobulin) that binds to the human C5 complement protein. Binding to this protein inhibits complement-mediated intravascular hemolysis by blocking its cleavage into C5a and C5b. Eculizumab RP is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, generalized myasthenia gravis who are anti-acetylcholine receptor antibody-positive, and neuromyelitis optica spectrum disorder in adult patients who are anti-aquaporin-4 antibody-positive.ObjectiveThe objective of this study was to demonstrate structural, physicochemical, and biological similarity between eculizumab RP and SB12 using various state-of-the-art analytical methods.MethodsComprehensive analytical characterization was conducted with side-by-side comparison of SB12 with European Union (EU) and United States (US) eculizumab RPs using various analytical methods (more than 40 state-of-the-art assays). Comparisons included purity, product-related impurity, charge heterogeneity, primary structure, post-translational modification, higher-order structure, quantity, Fab-related biological activities (potency and binding activity), and Fc-related biological activities.ResultsBased on the analytical similarity assessment, the structural, physicochemical, and biological characterization results demonstrated that SB12 is highly similar to the EU and US eculizumab RP. In the structural aspects, it was confirmed that there is no difference between post-translational modification profiles and higher-order structures of SB12 compared with the eculizumab RP. Product-related impurities in the form of aggregates and charge variants were also confirmed to be similar. Mechanism of action (MoA)-related biological activities showed that SB12 is highly similar to the EU and US eculizumab RP with respect to overall critical and non-critical quality attributes analyzed. Moreover, similarity of comparative binding tendency of SB12 and eculizumab RP to Fc gamma receptors and C1q was confirmed through additional characterization methods. Based on these results, SB12 is expected to have highly similar safety and efficacy compared with eculizumab RP.ConclusionIn summary, the overall analytical characterization and similarity assessment results show that SB12 is highly similar to the EU and US eculizumab RP in terms of structural, physicochemical, biophysical, and biological attributes.
| S-EPMC10287819 | biostudies-literature
Project description:BackgroundSeveral tools have been developed to explore and search Gene Ontology (GO) databases allowing efficient GO enrichment analysis and GO tree visualization. Nevertheless, identification of highly specific GO-terms in complex data sets is relatively complicated and the display of GO term assignments and GO enrichment analysis by simple tables or pie charts is not optimal. Valuable information such as the hierarchical position of a single GO term within the GO tree (topological ordering), or enrichment within a complex set of biological experiments is not displayed. Pie charts based on GO tree levels are, themselves, one-dimensional graphs, which cannot properly or efficiently represent the hierarchical specificity for the biological system being studied.ResultsHere we present a new method, which we name PCA2GO, capable of GO analysis using complex multidimensional experimental settings. We employed principal component analysis (PCA) and developed a new score, which takes into account the relative frequency of certain GO terms and their specificity (hierarchical position) within the GO graph. We evaluated the correlation between our representation score R and a standard measure of enrichment, namely p-values to convey the versatility of our approach to other methods and point out differences between our method and commonly used enrichment analyses. Although p values and the R score formally measure different quantities they should be correlated, because relative frequencies of GO terms occurrences within a dataset are an indirect measure of protein numbers related to this term. Therefore they are also related to enrichment. We showed that our score enables us to identify more specific GO-terms i.e. those positioned further down the GO-graph than other common tools used for this purpose. PCA2GO allows visualization and detection of multidimensional dependencies both within the acyclic graph (GO tree) and the experimental settings. Our method is intended for the analysis of several experimental sets, not for one set, like standard enrichment tools. To demonstrate the usefulness of our approach we performed a PCA2GO analysis of a fractionated cardiomyocyte protein dataset, which was identified by enhanced liquid chromatography-mass spectrometry (GeLC-MS). The analysis enabled us to detect distinct groups of proteins, which accurately reflect properties of biochemical cell fractions.ConclusionsWe conclude that PCA2GO is an alternative efficient GO analysis tool with unique features for detection and visualization of multidimensional dependencies within the dataset under study. PCA2GO reveals strongly correlated GO terms within the experimental setting (in this case different fractions) by PCA group formation and improves detection of more specific GO terms within experiment dependent GO term groups than standard p value calculations.
| S-EPMC2910024 | biostudies-literature
Project description:BackgroundRegulatory approval for a biosimilar product is provided on the basis of its comparability to an originator product. A thorough physicochemical and functional comparability exercise is a key element in demonstrating biosimilarity. Here we report the characterization of a proposed biosimilar rituximab (GP2013) and originator rituximab.ObjectiveTo compare GP2013 with originator rituximab using an extensive array of routine analytical and extended characterization methods.MethodsPrimary and higher order protein structures were analyzed using a variety of methods that included high-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS), peptide mapping with UV and MS detection, circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, hydrogen deuterium exchange (HDX) MS, 1D (1)H nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography and differential scanning calorimetry (DSC). Charge and amino acid modifications were assessed using cation exchange chromatography (CEX) and peptide mapping using reversed-phase (RP) HPLC. Boronate affinity chromatography was used to determine the relative amount of glycation. Glycans were identified and quantified after 2-aminobenzamide (2-AB) labeling and separation using normal phase HPLC with fluorescence and MS detection, respectively. Glycan site occupancy was determined using reducing capillary electrophoresis with sodium dodecyl sulfate (CE-SDS). Size heterogeneity was determined using reducing and non-reducing CE-SDS, size exclusion chromatography (SEC) and asymmetric flow field flow fractionation (AF4). Biological characterization included a series of bioassays (in vitro target binding, antibody-dependent cell-mediated cytotoxicity [ADCC], complement-dependent cytotoxicity [CDC] and apoptosis) and surface plasmon resonance (SPR) Fc receptor binding assays.ResultsIntact mass analysis of GP2013 and the heavy and light chains using RP HPLC-ESI-MS revealed the expected molecular mass of rituximab. The amino acid sequence was shown to be identical between GP2013 and the originator rituximab. Further sequence confirmation using RP-HPLC-UV/MS peptide mapping showed non-distinguishable chromatograms for Lys-C digested GP2013 and originator rituximab. The higher order structure of GP2013 was shown to be indistinguishable from originator rituximab using a large panel of redundant and orthogonal methods. GP2013 and originator rituximab were comparable with regard to charge variants, specific amino acid modifications and the glycan pattern. GP2013 was also shown to have similar purity, aggregate and particle levels when compared with the originator. Functionally, and by using a comprehensive set of bioassays and binding assays covering a broad range of rituximab's functional activities, GP2013 could not be distinguished from originator rituximab.ConclusionGP2013 was shown to be physicochemically highly similar to originator rituximab at the level of primary and higher order structure, post-translational modifications and size variants. An extensive functional characterization package indicated that GP2013 has the same biological properties as originator rituximab.
| S-EPMC3775154 | biostudies-literature
Project description:BackgroundWe compared the pharmacokinetic exposure, efficacy, safety and immunogenicity of biosimilar insulin aspart premix SAR341402 Mix 70/30 (SARAsp-Mix) with its originator NovoMix® 30 insulin aspart mix (NN-Mix) in adults with type 2 diabetes.MethodsThis was a randomized, open-label, parallel-group, substudy of the phase 3 GEMELLI M trial performed in three Indian centres. Totally 13 Indian participants previously treated with premix insulin received a single subcutaneous 0.3 U/kg dose of each treatment and underwent pharmacokinetic sampling for 16 h after dosing. Participants were then treated for 26 weeks as per the main GEMELLI M trial with efficacy, safety and immunogenicity compared between groups.ResultsThe extent of exposure (area under the plasma concentration-time curve and maximum insulin aspart concentration) to SAR341402 insulin aspart in SARAsp-Mix and to insulin aspart in NN-Mix was similar following single doses of the allocated treatment. After 26 weeks, the mean ± SD [median] change in HbA1c from baseline was similar in both treatment groups (SARAsp-Mix -0.38% ± 1.54 [-1.00%]; NN-Mix -0.18% ± 1.97 [-0.80%]). Other efficacy endpoints, insulin dosages, anti-insulin aspart antibody response, hypoglycemia and adverse events were similar between groups.ConclusionsOur results support the findings from previous studies, that SARAsp-Mix has a similar pharmacokinetic profile to NN-Mix and provides effective glycemic control with similar safety and immunogenicity profile in Indian adults with type 2 diabetes.
| S-EPMC9519840 | biostudies-literature
Project description:PurposeABP 710 has been developed as a biosimilar to infliximab reference product (RP). The objective of this study was to assess analytical similarity (structural and functional) between ABP 710 and infliximab RP licensed by the United States Food and Drug Administration (infliximab [US]) and the European Union (infliximab [EU]), using sensitive, state-of-the-art analytical methods capable of detecting minor differences in product quality attributes.MethodsComprehensive analytical characterization utilizing orthogonal techniques was performed with 14 to 28 unique lots of ABP 710 or infliximab RP, depending on the assay. Comparisons were used to investigate the primary structure related to amino acid sequence; post-translational modifications (PTMs) including glycans; higher order structure; particles and aggregates; primary biological properties mediated by target and receptor binding; product-related substances and impurities; and general properties.ResultsABP 710 had the same amino acid sequence, primary structure, higher order structure, PTM profiles and biological activities as infliximab RP. The finished drug product had the same strength (protein content and concentration) as infliximab RP.ConclusionsBased on the comprehensive analytical similarity assessment, ABP 710 was found to be highly analytically similar to infliximab RP for all biological activities relevant for clinical efficacy and safety.
| S-EPMC7261735 | biostudies-literature
Project description:Biosimilars are products that are similar in terms of quality, safety, and efficacy to an already licensed reference/ innovator product and are expected to offer improved affordability. The most significant source of reduction in the cost of development of a biosimilar is the reduced clinical examination that it is expected to undergo as compared to the innovator product. However, this clinical relief is predicated on the assumption that there is analytical similarity between the biosimilar and the innovator product. As a result, establishing analytical similarity is arguably the most important step towards successful development of a biosimilar. Here, we present results from an analytical similarity exercise that was performed with five biosimilars of rituximab (Ristova®, Roche), a chimeric mouse/ human monoclonal antibody biotherapeutic, that are available on the Indian market. The results show that, while the biosimilars exhibited similarity with respect to protein structure and function, there were significant differences with respect to size heterogeneity, charge heterogeneity and glycosylation pattern.
| S-EPMC5800382 | biostudies-literature
Project description:A spectroscopic investigation of beeswax adulteration by paraffin and/or stearic acid was undertaken via Attenuated Total Reflectance Infra-Red spectroscopy (ATR-IR) combined with multivariate statistical analyses. Principal Component Analysis (PCA) was successfully applied for the first time as an exploratory tool for the differentiation among pure beeswax and adulterated beeswax by paraffin and stearic acid with detection limits (LOD) of ~5% and 1%, respectively. Partial Least Square (PLS) modelling was used to build chemometric models based on beeswax/paraffin and beeswax/stearic acid calibration mixtures and subsequently used to predict concentrations of paraffin and stearic acid on a set of unknown test samples. PLS predictions demonstrated that beeswax adulteration by paraffin is much more prominent (74%) than the one by stearic acid (26%) and that commercial beeswax products (candles, pearls, blocks, etc.) are more prone to adulteration (27%) than honeycomb-type samples (12.5%).
| S-EPMC10814946 | biostudies-literature
Project description:We propose a similarity measure based on the multivariate hypergeometric distribution for the pairwise comparison of images and data vectors. The formulation and performance of the proposed measure are compared with other similarity measures using synthetic data. A method of piecewise approximation is also implemented to facilitate application of the proposed measure to large samples. Example applications of the proposed similarity measure are presented using mass spectrometry imaging data and gene expression microarray data. Results from synthetic and biological data indicate that the proposed measure is capable of providing meaningful discrimination between samples, and that it can be a useful tool for identifying potentially related samples in large-scale biological data sets.
| S-EPMC4983430 | biostudies-literature
Project description:BackgroundTransitioning patients from an originator to a corresponding biosimilar has been extensively studied in both randomized controlled trials and observational studies. Although transitioning is considered well-tolerated, with no negative impacts on efficacy and/or safety, 2.6-25.8% of patients restart treatment with the originator (retransitioning). Retransitioning to the originator can be considered an indication of biosimilar treatment failure or dissatisfaction with biosimilar treatment. Increasing our knowledge of patients who retransition might help to reduce the number of patients retransitioning.ObjectiveOur objective was to estimate the cumulative incidence of patients who retransitioned from a tumor necrosis factor (TNF)-α inhibitor biosimilar to originator and to explore potential patient, disease, and treatment and implementation strategy factors associated with retransitioning.MethodWe conducted a systematic literature search in the PubMed, EMBASE, and Cochrane Central Register of controlled trials databases until March 2021. Studies on TNFα inhibitors, biosimilar transitioning, and retransitioning were included. Transitioning was defined as switching from an originator to a biosimilar, and retransitioning was defined as switching from an originator to a biosimilar and back to the originator. Characteristics of the studies were descriptively analyzed. Studies were weighted by the number of patients transitioning, and the primary outcome was the median cumulative incidence of retransitioning. For each of the factors related to patient, disease, and treatment and implementation strategy, studies were stratified according to the categories of that factor. The weighted medians and interquartile ranges (IQRs) of the cumulative incidence of retransitioning in these studies were calculated and compared to explore whether a potential association existed between these factors and the cumulative incidence of retransitioning.ResultsOf 994 screened publications, 37 were included. The weighted median cumulative incidence of retransitioning was 7.6% (IQR 6.8-17.2). Studies that included only patients with inflammatory bowel disease (6.6 vs. 15.1-17.7% for other indications), included only patients with stable disease (7.0 vs. 13.7% for including all patients), and did not offer retransitioning at the introduction of the biosimilar (7.0 vs. 11.1% for studies that offered retransitioning) reported less retransitioning. In addition, the incidence of retransitioning was lower when extra laboratory monitoring was part of the implementation strategy (1.6 vs. 6.1%) and when gainsharing (patients' healthcare directly benefits from financial savings from transitioning) (1.4 vs. 7.2% for studies without gainsharing) was applied.ConclusionsIn studies on transitioning patients from TNFα originator to biosimilar, 8% of patients retransitioned. Retransitioning appeared to be lower in studies that included only patients with stable disease and in studies that did not offer patients the option of retransitioning at the introduction of the biosimilar. In addition, retransitioning appeared to be lower in studies that implemented extra laboratory monitoring as part of the biosimilar implementation strategy. Clinicians should consider implementing these suggestions as they might reduce retransitioning rates and improve the introduction of biosimilars in clinical practice. PROSPERO registration ID: CRD42021226381.
| S-EPMC8847209 | biostudies-literature
Project description:Six preregistered studies show that the degree of similarity of two objects biases people's spatial memory of these objects. When objects are high in similarity, people remember having seen them closer together in space than when they are low in similarity. All six studies provide correlational evidence, showing that the more similar participants rated two stimuli, the smaller they remembered the distance between them. This was true for both conceptual and perceptual similarity (Study 3). Furthermore, Studies 2, 4A, and 4B provide evidence of causality by manipulating similarity experimentally. Replicating the correlational findings, highly similar stimuli were remembered as closer together than stimuli low in similarity. This pattern was found across different stimulus categories and similarity dimensions. Overall, these findings show that the similarity of stimuli influences perceivers' reconstruction of their spatial locations.
| S-EPMC10716182 | biostudies-literature