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.
Keywords Results for Isothermal
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.).
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 …
Kinetic analysis of solids of the quasi-autocatalytic decomposition type: SADT determination of low-temperature polymorph of AIBN
Simulations of SADT values based on the heat balance of the system are presented for azobisisobutyronitrile (AIBN). These simulations used kinetic parameters obtained from heat flow calorimetry experiments performed at temperatures in the stability range of low-temperature (L-T) polymorph of AIBN. Thermal Activity Monitor (TAM) data were collected in the range of 55-70 °C. The simulated SADT value for L-T AIBN amounts to 46 °C. This is very similar to the computed results obtained in the BAM project for the high-temperature (H-T) form of AIBN which amounts to 47 °C and is also in full agreement with the large scale experimentally found SADT of AIBN (47 °C) …
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) …
Thermal decomposition of AIBN, Part B: Simulation of SADT value based on DSC results and large scale tests according to conventional and new kinetic merging approach
The paper presents the results of the common project performed with the Federal Institute for Materials Research and Testing, Berlin, Germany (BAM) concerning the comparison of the experimental results with simulations based on the application of the kinetic-based method and heat balance of the system for the determination of the self accelerating decomposition temperature (SADT). The substantial potential of the kinetic-based method is illustrated by the results of the simulation of SADT of azobisisobutyronitrile (AIBN) …
Determination of Thermal Hazard from DSC measurements. Investigation of Self-Accelerating Decomposition Temperature (SADT) of AIBN
The method of determination of the thermal hazard properties of reactive chemicals from DSC experiments is illustrated by the results of SADT simulations performed with azobisisobutyronitrile (AIBN). The kinetics of decomposition of AIBN in the solid state was investigated in a narrow temperature window of 72-94 °C, just below the sample melting. The kinetic parameters of the decomposition were evaluated by differential isoconversional method. The very good fit of the experimental results by the simulation curves, based on the determined kinetic parameters, indicated the correctness of the kinetic description of the process …
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% …
Technical note in Japanese based on HPLC data (limited amount of data points)
Technical note in Japanese based on HPLC data (limited amount of data points)
Kinetic Evaluations for the Transportation of Dangerous Chemical Compounds
Current legislation about goods carriage (ADR – Agreement Concerning the International Carriage of Dangerous Goods by Road) sets the determination of several parameters related to the conditions of the used containers. Several of these parameters are required for the substance classification and the definition of the precautions to be adopted during transportation. One of the main potential hazards during freight is related to the thermal decomposition of the substance. Testing for the identification of decomposition in the carriage conditions can be time consuming and expensive, therefore different solutions have been attempted to simulate thermal behaviour of chemical compounds during transportation …
Optimization of Modeling of Propellants Aging Investigated According to NATO AOP-48 Ed.2 Test Procedure
The stability test procedure according to NATO-AOP 48 Ed. 2 commonly applied for the explosives and nitrocellulose-based propellants is based on the assumption that the kinetic description of the process of stabilizer depletion can be done by applying the reaction-order (RO) model for the fitting experimental data. In the present paper another procedure is proposed by application more general Prout-Tompkins (PT) model based on the autocatalytic character of the reaction. Presented computer simulations indicate that PT model allows much better fit of the processes which kinetics is not fully determined …
Estimation of Time to Maximum Rate under Adiabatic Conditions(TMRad) using Kinetic Parameters derived from DSC – Investigation of Thermal Behavior of 3-Methyl-4-Nitrophenol
Kinetic parameters of the decomposition of hazardous chemicals can be applied for the estimation of their thermal behavior under any temperature profile. Presented paper describes the application of the advanced kinetic approach for the determination of the thermal behavior also under adiabatic conditions occurring e.g. in batch reactors in case of cooling failure. The kinetics of the decomposition of different samples (different manufacturers and batches) of 3-methyl-4-nitrophenol were investigated by conventional DSC in non-isothermal (few heating rates varying from 0.25 to 8.0 K/min) and isothermal (range of 200-260°C) modes …
The Simulation of the Thermal Behavior of Energetic Materials based on DSC and HFC Signals
Two small calibre and four medium calibre types of propellants were investigated non-isothermally (0.25-4 K min-1) by differential scanning calorimetry (DSC) in the range of RT-260-C and isothermally (60-100°C) by heat flow calorimetry (HFC). The data obtained from both techniques were used for the calculation and comparison of the kinetic parameters of the decomposition process. The application of HFC allowed to determine the kinetic parameters of the very early stage of the reaction (reaction progress below 0.02) what, in turn, made possible the precise prediction of the reaction progress under temperature mode corresponding to real atmospheric changes according to STANAG 2895 …
Advanced Simulation of the Lifetime of Energetic Materials based on HFC Signals
The prediction of the shelf life of energetic materials requires the precise determination of the kinetics of their decomposition. Due to the fact that energetic materials decompose with the evolution of heat, the thermoanalytical methods such as Differential Scanning Calorimetry (DSC) and Heat Flow Calorimetry (HFC) are often used for the monitoring the reaction rate and the evaluation of the kinetic parameters of these reactions. In the present paper we describe the precise, advanced method of the evaluation of the kinetic parameters from HFC signals …
Prediction of the Progress of Solid-State Reactions under Different Tempreature Modes
Using a computational method (AKTS-TA-Software) for solid-state kinetic analysis, the calculations of the progress of solid-state reactions were achieved employing temperature conditions different from those at which the experiments were carried out. The prediction of the solid-state reaction extent is illustrated by the results obtained during decomposition of hydromagnesite (component of some pharmaceuticals) …
Computational aspects of kinetic analysis: Part A: The ICTAC kinetics project-data, methods and results
Part A of this series of papers (Parts B to E follow) presents the data and methods used, as well as the results obtained by participants in the ICTAC Kinetics Project. The isothermal and non-isothermal data sets provided were based on a hypothetical simulated process as well as on some actual experimental results for the thermal decompositions of ammonium perchlorate and calcium carbonate. The participants applied a variety of computational methods. Isoconversional and multi-heating rate methods were particularly successful in correctly describing the multi-step kinetics used in the simulated data …
Computational aspects of kinetic analysis.: Part E: The ICTAC Kinetics Project—numerical techniques and kinetics of solid state processes
The hyphenated thermal analysis-mass spectrometry technique (TA-MS) was applied for the investigation of the thermal behavior of reference and aged parchment samples. The kinetic parameters of the process were calculated independently from all recorded TA and MS signals. The kinetic analysis showed the distinct dependence of the activation energy on the reaction progress. Such behavior is characteristic for the multistage mechanism of the reaction …