Vaccine is an economical and effective means to prevent and control infectious diseases. Vaccination is a routine method to prevent and control human and animal diseases by inducing a protective immune response in the body. Although the vaccine is highly effective, there are still some challenges in the production and use process——
① The structure is unstable;
② It is easy to be degraded and destroyed by enzymes that are ubiquitous in the environment;
③ It needs to be stored between -20°C and -70°C below zero.
This means that the vaccine needs to be stored in the freezer and transported in the cold chain throughout the whole process, and distribution and use will become very difficult. These problems can be solved by vacuum freeze-drying. At present, due to its advantages, freeze-drying technology has been widely used in biopharmaceuticals such as vaccines and antibodies.
Freeze-dried vaccines use the method of passage or genetic modification of pathogenic microorganisms to make the pathogenic microorganisms non-pathogenic without destroying the original immunogenicity. The pathogenic microorganisms that have lost their pathogenicity will be amplified and cultured liquid into a freeze dryer. After low temperature and increasing the vacuum degree in the freeze dryer, the water in the culture solution is separated by sublimation to make a dry powder that maintains the original microbial immunogenicity, which is the freeze-dried vaccine.
Vaccine freeze-drying process
Freeze-drying technology is the key technology in the preparation process of freeze-dried dosage forms of vaccines. In the process of freeze-drying and storage of vaccines, the chemical composition, freezing temperature and rate, drying temperature and residual moisture in dry solids, temperature and humidity of storage environment, etc. All factors will affect the activity of the vaccine, thereby affecting the vaccine, so it is necessary to optimize the freeze-drying process of the vaccine.
1. Freezing and drying have an impact on the characteristics of the vaccine, which in turn affects the stability of the vaccine. Slow freezing leads to the formation of a small number of large crystals, which can be harmful to vaccines; while rapid freezing reduces the time for permeable water to be released, but creates a greater risk of internal icing. Therefore the choice between fast or slow freezing is difficult, so it is critical to consider the freezing rate during vaccine lyophilization development for vaccine stability.
2. Product temperature is critical in the whole sublimation drying step, it will affect drying time, sublimation rate and stability. When optimizing the main drying parameters for vaccine lyophilization, it is worth considering the cost-effectiveness of reducing drying time and product stability.
3. Removing moisture during analytical drying will reduce product stability, and excessive residual moisture will also lead to collapse, aggregation and degradation. Therefore, optimal residual moisture content and analytical drying conditions should also be part of the freeze-drying process for vaccine development.
The in-situ freeze dryer is suitable for vaccine freeze-drying R&D and production. It can explore the freeze-drying process, explore the eutectic point, and obtain a better freeze-drying curve.
[In-situ Freeze Dryer Freeze-drying Process]
1. It can optimize the process of pre-freezing, sublimation drying and analytical drying;
2. Up to 60 programs can be stored, and 30 temperature gradients can be set for each program, and parameters such as sample partition temperature, heating and cooling rate, holding time and vacuum setting can be set independently for each gradient;
3. High-speed magnetic pump is used to eliminate heat, with better temperature control uniformity and better freeze-drying effect;
4. High-precision temperature sensor, the minimum adjustment value of temperature control accuracy is 0.5°C;
5. Intelligent freeze-drying endpoint judgment system to avoid vaccine contamination and shorten freeze-drying time;
