scholarly journals Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 928
Author(s):  
Barbara Bolgiano ◽  
Eilís Moran ◽  
Nicola J. Beresford ◽  
Fang Gao ◽  
Rory Care ◽  
...  
Keyword(s):  
Drug Product ◽  
Quality Attributes ◽  
Drug Substance ◽  
Reactive Material ◽  
Critical Quality Attributes ◽  
Freeze Dried ◽  
Quality Control Testing ◽  
Specific Igg ◽  
Key Indicators ◽  
Endotoxin Content

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM197), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India.

scholarly journals Comparison of Techniques to Control Ice Nucleation during Lyophilization

Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1439
Author(s):  
Jacob Luoma ◽  
Erika Ingham ◽  
Carmen Lema Martinez ◽  
Andrea Allmendinger
Keyword(s):  
Drug Product ◽  
Quality Attributes ◽  
Ice Nucleation ◽  
Residual Moisture ◽  
Critical Quality Attributes ◽  
Stability Behavior ◽  
Drug Products ◽  
Ice Fog ◽  
Comparison Of Techniques ◽  
Enzyme Formulation

Controlling ice nucleation during lyophilization of parenteral drug products increases the homogeneity of critical quality attributes, such as residual moisture, across drug product batches and shortens lyophilization cycle time. In the present study, we compare three mechanistically different techniques to control ice nucleation during the freezing step of lyophilization, which are referred to as “depressurization”, “partial vacuum”, and “ice fog” techniques. The techniques are compared with respect to their operational limitations and challenges. Installation considerations are also discussed. Using the aforementioned nucleation techniques, we investigated a monoclonal antibody formulation and an enzyme formulation at different protein concentrations using feasible nucleation temperatures and different vial formats and fill volumes. Samples were compared for solid state properties and other critical quality attributes on stability. When nucleated at the same temperature, the three techniques produced products with the same quality attributes and stability behavior. Under conditions resulting in micro-collapse, stability behavior can be different. We found that each technology had considerations for achieving robust nucleation. The present comparison may serve as guidance in selecting a nucleation method.

Correlation of Drug Substance Particle Size Distribution with Other Bulk Properties to Predict Critical Quality Attributes

2014 ◽  
Vol 19 (9) ◽  
pp. 1076-1081 ◽  
Author(s):  
Henry G. Morrison ◽  
Wenle Tao ◽  
William Trieu ◽  
Shawn D. Walker ◽  
Sheng Cui ◽  
...  
Keyword(s):  
Particle Size ◽  
Particle Size Distribution ◽  
Size Distribution ◽  
Quality Attributes ◽  
Drug Substance ◽  
Bulk Properties ◽  
Critical Quality Attributes

Quality by Design in Pharmaceutical Formulation

2019 ◽  
pp. 221-239
Author(s):  
Sundaramurthy Vivekanandan
Keyword(s):  
Quality By Design ◽  
Drug Product ◽  
Quality Attributes ◽  
Pharmaceutical Products ◽  
Design Approach ◽  
Critical Quality Attributes ◽  
Quality Product ◽  
Product Profile ◽  
Critical Material Attributes ◽  
Quality By Design Approach

Quality by design (QbD) is a systematic, scientific, risk-based approach to product development and manufacturing process to consistently deliver the quality product. In this chapter, application, benefits, opportunities, regulatory requirements involved in quality by design of pharmaceutical products are discussed. In quality by design approach, during development, the developer defines quality target product profile (QTPP) and identifies critical quality attributes (CQA). Critical process parameters (CPP) of unit operations which impacts critical quality attributes need to be identified to understand the impact of critical material attributes (CMA) on quality attributes of the drug product. Quality by design approach is defined in ICH guidelines Q8 – Pharmaceutical Development, Q9 – Quality Risk Management, Q10 – Pharmaceutical Quality System. This chapter describes the implementation of new concepts in quality by design like design of experiments to achieve design space, control strategy to consistently manufacture quality product throughout the product lifecycle.

scholarly journals Current hurdles to the translation of nanomedicines from bench to the clinic

2021 ◽  
Author(s):  
Snežana Đorđević ◽  
María Medel Gonzalez ◽  
Inmaculada Conejos-Sánchez ◽  
Barbara Carreira ◽  
Sabina Pozzi ◽  
...  
Keyword(s):  
Drug Product ◽  
Early Stage ◽  
Regulatory Agencies ◽  
Important Process ◽  
Close Collaboration ◽  
Critical Quality Attributes ◽  
Research Areas ◽  
Physical Chemical ◽  
Clinical Models ◽  
Further Development

AbstractThe field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further development of this field will face significant challenges at the regulatory level if related guidance remains unclear and unconsolidated. This review describes those features and pathways crucial to the clinical translation of nanomedicine and highlights considerations for early-stage product development. These include identifying those critical quality attributes of the drug product essential for activity and safety, appropriate analytical methods (physical, chemical, biological) for characterization, important process parameters, and adequate pre-clinical models. Additional concerns include the evaluation of batch-to-batch consistency and considerations regarding scaling up that will ensure a successful reproducible manufacturing process. Furthermore, we advise close collaboration with regulatory agencies from the early stages of development to assure an aligned position to accelerate the development of future nanomedicines. Graphical abstract

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.

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