Technical Comments
Novel methods using kinetic analysis of DSC, ARC, sparse data and datalogger inputs to determine TMRad24h and SADT, improving the reliability of simulation of energetic material behaviour.
References: https://unece.org/fileadmin/DAM/trans/danger/publi/unrec/rev21/ST-SG-AC10-1r21e_Vol1_WEB.pdf Roduit et al., Therm. Anal. Calorim., 93 (2008) 153-161. Roduit...
Stability modeling to predict vaccine shelf-life and evaluate impact of temperature excursion from the ‘cold chain’
The stability of vaccines is of great interest industries and government institutions. Accelerated stability studies are designed to determine the rate of vaccine degradation over time as a result of exposure to temperatures higher than those recommended for product storage. However, commonly applied stability predictions based on application of zero- or first order kinetics are very often too simplified for description of the degradation of biological products, which frequently undergo complex and multistep degradation reactions. We used an advanced kinetic approach mixing with statistical analysis to fit the forced degradation data (ELISA, NTA … ) by computed kinetic parameters, and finally, to predict valuable the long term stability of vaccine. The modeling approach is based on the selection of the most appropriate kinetic equations which fit the degradation rate of compounds subjected to elevated temperatures, accelerating the rate of the reaction.
Predictive modeling for assessing the long-term thermal stability of a new fully-liquid quadrivalent meningococcal tetanus toxoid conjugated vaccine
Establishing product stability is critical for pharmaceuticals. We used a modeling approach to predict the thermal stability of a fully-liquid quadrivalent meningococcal (serogroups A, C, W, Y) conjugate vaccine (MenACYW-TT; MenQuadfi®) at potential transportation and storage temperatures. Vaccine degradation was determined by measuring the rate of hydrolysis through an increase of free polysaccharide (de-conjugated or unconjugated polysaccharide) content during six months storage at 25°C, 45°C and 56°C. A procedure combining advanced kinetics and statistics was used to screen and compare kinetic models describing observed free polysaccharide increase as a function of time and temperature for each serogroup.
Accelerated Predictive Stability for Vaccines
The main challenge for the formulation of biologically derived products is to control the rate of degradation of their constituents to ensure an acceptable lifetime during storage and transport around the world [1-3]. The concept of stability of biological compounds (proteins, viruses, bacteria) is complex to understand, involving theoretically, concepts of both thermodynamics and advanced kinetics. one way of estimating protein stability is to study the denaturation when a protein is subjected to chemical stress (denaturing agents, pH) or physical stress (temperature, pressure…, etc.).
A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate
The stability of live-attenuated viruses is very challenging due to thermal sensitivity; therefore, solid form is usually required (often freeze-dried products). Micropellet technology is a lyophilization technology that has the potential to provide greater flexibility in the presentation of a given vaccine particularly in multi-dose format or in combination of different vaccines. As a novel vaccine alternative process, this spray freeze-dried (SFD) micropellet technology was evaluated using as a model a yellow fever virus produced in Vero cells (vYF) …
Continous Monitoring of Shelf Lives of Materials by Application of Data Loggers With Implemented Kinetic Parameters
The evaluation of the shelf life of, for example, food, pharmaceutical materials, polymers, and energetic materials at room or daily climate fluctuation temperatures requires kinetic analysis in temperature ranges which are as similar as possible to those at which the products will be stored or transported in. A comparison of …
Biophysical virus particle specific characterization to sharpen the definition of virus stability
Vaccine thermostability is key to successful global immunization programs as it may have a significant impact on the continuous cold-chain maintenance logistics, as well as affect vaccine potency. Modern biological and biophysical techniques were combined to in-depth characterize the thermostability of a formulated rabies virus (RABV) in terms of …
Accurate prediction of vaccine stability under real storage conditions and during temperature excursions
Due to their thermosensitivity, most vaccines must be kept refrigerated from production to use. To successfully carry out global immunization programs, ensuring the stability of vaccines is crucial. In this context, two important issues are critical, namely: (i) predicting vaccine stability and (ii) preventing product damage due to excessive temperature excursions outside of the recommended storage conditions (cold chain break) …
Advanced Kinetic Analysis as a Tool for Formulation Development and Prediction of Vaccine Stability
We have used a protein-based vaccine, a live virus vaccine, and an experimental adjuvant to evaluate the utility of an advanced kinetic modeling approach for stability prediction. The modeling approach uses a systematic and simple procedure for the selection of the most appropriate kinetic equation to describe the degradation rate of compounds subjected to accelerated conditions. One-step and two-step reactions with unlimited combinations of kinetic models were screened for the three products under evaluation. The most appropriate mathematical model for a given product was chosen based on the values of residual sum of squares and the weight parameter w. A relatively simple n-th order kinetic model best fitted the degradation of an adjuvanted protein vaccine with a prediction error lower than 10% …
Prediction of Thermal Stability of Materials by Modified Kinetic and Model Selection Approaches based on Limited Amount of Experimental Points
The experimental data collected in the discontinuous mode are often used for the computation of reaction kinetics and, further, for the simulation of the thermal stability of materials. However, the kinetic calculations based on limited amount of sparse points require specific criteria allowing correct choice of the best kinetic model. We present the modified kinetic computations allowing considering one, two or even more reaction stages by applying unlimited amount of combinations of different kinetic models for the best description of the reaction course. The kinetic parameters are calculated using the truncated Šestâk-Berggren (SB) approach and further verified by using the Akaike and Bayesian information criteria (AIC and BIC, respectively) …