1. Interference factors in the development of freeze-dried reagents
The performance of freeze-drying reagents, stable form is a necessary condition, which can ensure long-term stability at room temperature.
Crystal morphology, crystallization process, and the formation of crystal nuclei are all related to solute, outer wall of packaging material, and external particles. The environment has a greater impact on product performance. The moisture content of the product is a quality indicator of freeze-dried products. Exceeding the standard will cause the product to shrink. However, the shrinkage after being out of the box may also be due to the failure of the auxiliary material protection agent, and whether the moisture content is caused by the freeze-drying process or other sources, this is what we must figure out when researching and developing.
Excipient types, concentrations, protective properties, and morphological stability, if the experimental design is carried out according to the orthogonal method, a simple reagent development, there are dozens of freeze-drying experiments in a conventional way. Therefore, the primary consideration for laboratory freeze dryer equipment in the research and development stage is high efficiency. High-efficiency features, small water vapor resistance, large water vapor gradient pressure difference, that is, low cold trap temperature.
2. Development of freeze-drying process of freeze-drying machine
The environment and cross-contamination result in great differences in the crystallization process. Once particles and pollutants form nuclei, the crystallization process will undergo major changes.
Therefore, the temperature value measured by the product temperature probe is not the true "eutectic point" during the rapid experiment. This point actually makes a big difference in production line construction.
In fact, during process development, we pay more attention to the temperature at which all ingredients are frozen, and at what temperature, the resistance of the product changes. Of course, it is necessary to pay attention to some details to determine the resistance change. The potential difference of the collected power supply will also be affected. To influence.
The product form of the freeze-dried reagent is not only related to the auxiliary materials, but also has a greater impact on the pre-freezing and sublimation process. In addition, the dust in the environment and the surface of the packaging material will affect the crystallization of the reagent process. The experimental design must ensure that the interference factors are eliminated one by one during the development. The freeze-drying process developed and the scale-up freeze-drying process are different, and the environmental factors of the two processes are very different.
Most freeze-drying process development units neglected environmental control during the development process. If the newly developed product does not have any reference products, then an environmentally controlled laboratory freeze dryer with an isolator is recommended.
3. Sample trial production
We need to produce some samples for performance testing, development and verification of instruments.
Eliminate all interference factors to determine the performance of the lyophilized reagent. After completing the first step of reagent formulation development, it is necessary to enter the second step of trial production. For diagnostic reagents, it must be combined with kits or chips/cards to verify the entire process. In this process, the environmental requirements are even higher. Therefore, when choosing to develop a freeze dryer, it is necessary to clarify the research and development goals. When configuring, it is necessary to consider the connection of upstream and downstream processes and configure appropriate protection devices.
4. Apparatus and equipment: verification
The freeze dryer alternates between cold and heat, and the temperature range is 80°C~-65°C. It is closely related to the environment. The performance of the freeze dryer equipment may vary depending on the environment. Moreover, the position of the temperature probe designed for the freeze dryer is different from the position of our products. When starting the research and development, we must have a comprehensive understanding of the freeze dryer equipment, so basic verification of the equipment must be carried out.
Judging from the customers we have contacted, most of the R&D departments have neglected to verify the instrument or have no reasonable verification program. Design a reasonable lyophilizer equipment verification program, which can eliminate the interference factors of the equipment and obtain a stable formula.