scholarly journals Type and Extent of Information on (Potentially Critical) Quality Attributes Described in European Public Assessment Reports for Adalimumab Biosimilars

2021 ◽  
Vol 14 (3) ◽  
pp. 189
Author(s):  
Ali M. Alsamil ◽  
Thijs J. Giezen ◽  
Toine C. Egberts ◽  
Hubert G. Leufkens ◽  
Helga Gardarsdottir
Keyword(s):  
Quality Attributes ◽  
Regulatory Approval ◽  
Clinical Profile ◽  
Test Results ◽  
Critical Quality Attributes ◽  
Functional Attributes ◽  
European Public ◽  
Charge Variants ◽  
Assessment Reports

Regulatory approval of biosimilars predominantly relies on biosimilarity assessments of quality attributes (QAs), particularly the potentially critical QAs (pCQAs) that may affect the clinical profile. However, a limited understanding exists concerning how EU regulators reflect the biosimilarity assessments of (pC)QAs in European public assessment reports (EPARs) by different stakeholders. The type and extent of information on QAs and pCQAs in EPARs were evaluated for seven adalimumab biosimilars. Seventy-seven QAs, including 31 pCQAs, were classified and assessed for type (structural and functional attributes) and extent (biosimilarity interpretation and/or test results) of information in EPARs. Reporting on the QAs (35–75%) varied between EPARs, where the most emphasis was placed on pCQAs (65–87%). Functional attributes (54% QAs and 92% pCQAs) were reported more frequently than structural attributes (8% QAs and 22% pCQAs). About 50% (4 structural and 12 functional attributes) of pCQAs were consistently reported in all EPARs. Regulators often provided biosimilarity interpretation (QAs: 83% structural and 80% functional; pCQAs: 81% structural and 78% functional) but rarely include test results (QAs: 1% structural and 9% functional and pCQAs: 3% structural and 9% functional). Minor differences in structural attributes, commonly in glycoforms and charge variants, were often observed in adalimumab biosimilars but did not affect the functions and clinical profile. Despite the variability in reporting QAs in EPARs, the minor observed differences were largely quantitative and not essentially meaningful for the overall conclusion of biosimilarity of the seven adalimumab biosimilars.

Energieverbrauchssimulation von Werkzeugmaschinen*/Process-specific energetic simulation of machine tools

2016 ◽  
Vol 106 (01-02) ◽  
pp. 60-64
Author(s):  
S. Braun ◽  
P. Schraml ◽  
E. Abele
Keyword(s):  
Energy Consumption ◽  
Machine Tools ◽  
Value Added ◽  
Quality Attributes ◽  
Resource Efficiency ◽  
Prediction System ◽  
Critical Quality Attributes ◽  
Milling Operations ◽  
Nc Program ◽  
Modern Machine

Energie- und Ressourceneffizienz sind Qualitätsmerkmale, die auch für moderne Werkzeugmaschinen gelten. Der Energieverbrauch von Maschinen bis zu gesamten Fertigungsstandorten muss im Verhältnis zur erzielten Wertschöpfung deutlich gesenkt werden, um wettbewerbsfähig zu bleiben und unserer Verantwortung gegenüber der Umwelt zu entsprechen. Dieser Beitrag präsentiert anhand eines Fräsprozesses ein modellgestütztes Simulations- und Prognosesystem des Energieverbrauchs von kompletten Bearbeitungsoperationen auf einer Werkzeugmaschine als Basis energetischer Optimierungen.   Resource efficiency and energy consumption are critical quality attributes of modern machine tools. The energy consumption of machine tools, plants and facilities must be significantly reduced relative to the value added in order to stay competitive and fulfil our responsibility towards the environment. This article presents a model-based simulation and prediction system of the expected energy consumption of machine tools executing a given process NC-program as a basis for energetic optimization measures. It is exemplified by milling operations.

Determination of critical quality attributes for monoclonal antibodies using quality by design principles

Biologicals ◽  
2016 ◽  
Vol 44 (5) ◽  
pp. 291-305 ◽  
Author(s):  
Nadja Alt ◽  
Taylor Y. Zhang ◽  
Paul Motchnik ◽  
Ron Taticek ◽  
Valerie Quarmby ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Quality By Design ◽  
Design Principles ◽  
Quality Attributes ◽  
Critical Quality Attributes

scholarly journals New Opportunities in Glycan Engineering for Therapeutic Proteins

Antibodies ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 5
Author(s):  
Xiaotian Zhong ◽  
Aaron M. D’Antona ◽  
John J. Scarcelli ◽  
Jason C. Rouse
Keyword(s):  
Fusion Proteins ◽  
Therapeutic Proteins ◽  
Quality Attributes ◽  
Efficacy And Safety ◽  
Biological Functions ◽  
Next Generation ◽  
Lysosomal Degradation ◽  
Critical Quality Attributes ◽  
Recombinant Fusion Proteins ◽  
Antibody Diversification

Glycans as sugar polymers are important metabolic, structural, and physiological regulators for cellular and biological functions. They are often classified as critical quality attributes to antibodies and recombinant fusion proteins, given their impacts on the efficacy and safety of biologics drugs. Recent reports on the conjugates of N-acetyl-galactosamine and mannose-6-phosphate for lysosomal degradation, Fab glycans for antibody diversification, as well as sialylation therapeutic modulations and O-linked applications, have been fueling the continued interest in glycoengineering. The current advancements of the human glycome and the development of a comprehensive network in glycosylation pathways have presented new opportunities in designing next-generation therapeutic proteins.

scholarly journals The evidence base for psychotropic drugs approved by the European Medicines Agency: a meta-assessment of all European Public Assessment Reports

2020 ◽  
Vol 29 ◽  
Author(s):  
Florian Erhel ◽  
Alexandre Scanff ◽  
Florian Naudet
Keyword(s):  
Effect Size ◽  
Psychotropic Drugs ◽  
Comparative Effectiveness ◽  
Data Retrieval ◽  
European Medicines Agency ◽  
Positive Trial ◽  
Active Comparator ◽  
European Public ◽  
Meta Analyses ◽  
Assessment Reports

Abstract Aims To systematically assess the level of evidence for psychotropic drugs approved by the European Medicines Agency (EMA). Methods Cross-sectional analysis of all European Public Assessment Reports (EPARs) and meta-analyses of the many studies reported in these EPARs. Eligible EPARs were identified from the EMA's website and individual study reports were requested from the Agency when necessary. All marketing authorisation applications (defined by the drug, the route of administration and given indications) for psychotropic medications for adults (including drugs used in psychiatry and addictology) were considered. EPARs solely based on bioequivalence studies were excluded. Our primary outcome measure was the presence of robust evidence of comparative effectiveness, defined as at least two ‘positive’ superiority studies against an active comparator. Various other features of the approvals were assessed, such as evidence of non-inferiority v. active comparator and superiority v. placebo. For studies with available data, effect sizes were computed and pooled using a random effect meta-analysis for each dose of each drug in each indication. Results Twenty-seven marketing authorisations were identified. For one, comparative effectiveness was explicitly considered as not needed in the EPAR. Of those remaining, 21/26 (81%) did not provide any evidence of superiority against an active comparator, 2/26 (8%) were based on at least two trials showing superiority against active comparator and three (11%) were based on one positive trial; 1/26 provided evidence for two positive non-inferiority analyses v. active comparator and seven (26%) provided evidence for one. In total, 20/27 (74%) evaluations reported evidence of superiority v. placebo with two or more trials. Among the meta-analyses of initiation studies against active comparator (57 available comparisons), the median effect size was 0.051 (range −0.503; 0.318). Twenty approved evaluations (74%) reported evidence of superiority v. placebo on the basis of two or more initiation trials and seven based on a single trial. Among meta-analyses of initiation studies against placebo (125 available comparisons), the median effect size was −0.283 (range −0.820; 0.091). Importantly, among the 89 study reports requested on the EMA website, only 19 were made available 1 year after our requests. Conclusions The evidence for psychiatric drug approved by the EMA was in general poor. Small to modest effects v. placebo were considered sufficient in indications where an earlier drug exists. Data retrieval was incomplete after 1 year despite EMA's commitment to transparency. Improvements are needed.

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