How to make lyophilized biological agents safe pac

2022-07-31
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How to make freeze-dried biopharmaceuticals move towards safe packaging

although biopharmaceutical is a small branch of the pharmaceutical industry, its importance is increasing day by day. Biological agents are bioactive substances, which are particularly sensitive to temperature, very unstable and easy to react with each other. Due to the above characteristics, the storage life of biological agents is very short, and they usually need to be frozen for storage, otherwise they will deteriorate quickly. This article will introduce what kind of packaging should be used for biological agents produced by freeze-drying method

requirements of freeze-drying processing on packaging containers

1. The performance that the use of heat transfer carbon fiber accounts for 5% of the vehicle weight

the success of freeze-drying processing largely depends on the good heat conduction performance of the container. For this reason, the containers used in the freeze-drying process must meet the following requirements: they must be made of materials that can provide good heat conductivity, and the weaker the insulation of the containers, the better; In order to save energy, the container should have high heat conversion efficiency, which can well transfer the heat generated by the shelf of the freeze dryer to the container

vessels made of materials with low heat transfer coefficient have very low heat transfer efficiency; The shape, size or mass of the container will also affect the heat transfer efficiency of the container; If too many materials are used in the manufacture of containers, these materials will become a thermal barrier to prevent the transmission of energy into the container. Low thermal conductivity often leads to the failure of freeze-drying process

for example, we use a serum bottle to contain the medicine for freeze-drying processing. First, the surface of the frozen body should be sublimated, so that the ice in the lower layer can be vaporized into a gaseous state before it can float out of the container; With the freeze-drying process, the ice is gradually vaporized out of the container, and the sublimation surface also gradually moves down. In general, the sublimation surface will automatically move downward toward the bottom of the serum container and inward toward the center of the frozen body. If the vessel has obvious thermal insulation, the whole sublimation process cannot be controlled; If the sublimation process is not controlled, some reagents will be vacuum dried rather than freeze-dried. The medicament processed in this way does not have its due performance, and its performance such as maintaining the medicament activity, shelf life and rapid reorganization will be greatly reduced

II. Sealing performance

in the later stage of freeze-drying processing, the agent has been freeze-dried, and the equipment will create an ultra dry environment. Before taking the container containing the agent out of the ultra dry environment, the container must be sealed. This is because after the agent is dried, the advantage of the internal residual moisture reduction electric drive is indisputable: the noise is very small to less than 3%. Once exposed to the external environment with a humidity level much higher than its own, it will try to absorb moisture from the external environment. Once the medicament absorbs water, its quality will deteriorate immediately; The functions of lyophilized agents (such as long shelf life, rapid reorganization, etc.) will be weakened. The reabsorption of water by the medicament will cause the medicament to lose its due performance, thus failing to achieve the expected treatment effect, and even cause the manufacturer to recall the product

using containers that cannot be sealed in the lyophilizer is the most common mistake made by biopharmaceutical manufacturers. For example, many diagnostic reagents are packed in test tubes for freeze-drying processing. These test tubes are sealed with screw caps. However, there is no feasible method to seal these test tubes in the freeze-drying machine. Under the same conditions that meet the requirements of the construction standards, the manufacturing enterprises have to gather a large number of employees to manually seal the containers. This process is generally carried out in a workshop that does not meet the freeze-drying processing requirements. In this way, the newly freeze-dried agent will be exposed to the environment of high humidity level, and the agent will absorb a large amount of water in the environment, so its performance will become unstable

III. water vapor permeability

water vapor permeability is related to the amount of water vapor penetrating into the container. Generally speaking, the higher the permeability of packaging materials, the less firm the packaging seal, and the more water vapor penetrated, the greater the possibility of degradation of freeze-drying agents. Once the lyophilized agent is exposed to the humidity of more than 3%, its stability will be threatened. High water vapor permeability will endanger the stability of the product and the therapeutic effect of the product

packaging containers that can be used for freeze-drying processing

1. Glass serum bottles

when freeze-drying test tube diagnostic reagents, the glass serum bottles with grooved rubber plugs are the most ideal packaging containers, because they meet the three requirements that should be met: first, the containers are made of glass materials and have good heat conductivity. The serum bottles are specially designed to meet the heat transfer needs of the freeze-drying machine, The good thermal conductivity of glass material makes it the best choice for manufacturing serum bottles; Secondly, the glass serum bottle with grooved rubber stopper can be sealed in the lyophilizer to avoid exposing the lyophilized agent to high humidity. After sealing the glass serum bottle in the ultra dry environment, the water content of the lyophilized reagent can reach the level of equal to or even less than 3%; Thirdly, the glass serum bottle can effectively prevent water vapor from penetrating into the bottle, so it can protect the lyophilized agent from moisture or other pollutants

for these reasons, the glass serum bottle has become the traditional choice of diagnostic reagent manufacturers

however, the glass serum bottle with grooved rubber stopper can not meet all the needs of pharmaceutical enterprises. Because the form of serum bottle is single, it can not provide diverse and unique forms. The reagent is loaded in the serum bottle for freeze-drying processing, which means that the serum bottle will also be used as the product delivery device after freeze-drying processing. At present, there is no feasible way to extract the lyophilized products from the serum bottle, let alone repackage them into another conveying device. It's like canning spaghetti. The canning of spaghetti makes the cooking of spaghetti more convenient and efficient, but the package is not good-looking

diagnostic tests generally require simple operation, convenient use and no error, while the use of serum bottles is not very convenient. From the perspective of the manufacturer, the packaging should enhance the usability of the product, and the reagent delivery packaging should not be limited by the reagent processing packaging. Therefore, test tube diagnostic reagent manufacturers began to look for other types of containers to process and transport lyophilized reagents

II. Nonstandard freeze-drying containers

in fact, other containers with grooved rubber plugs can be defined as nonstandard freeze-drying containers. Some test tube diagnostic reagent manufacturers are trying to use these non-standard containers to freeze-dry their products, but so far these containers they have developed can not effectively freeze-dry, seal and store the reagents. The heat transfer performance of many containers is too low to be sealed in the lyophilizer; Others have high water vapor permeability. Due to these shortcomings, the products processed by non-standard freeze-drying containers do not have the stability and quality they should have

like serum bottles, other containers used as freeze-drying processing packaging must also provide good heat transfer performance, be able to seal in the freeze-drying machine, and provide high-quality water vapor barrier for freeze-drying agents. Many test tube diagnostic reagent manufacturers have begun to use specially designed containers for non freeze-drying processing to process and package their reagents, such as sample cups, foil sealed bags, and containers with screw caps or flip caps

when developing new products, enterprises need to reduce the cost of existing products and adopt new diagnostic equipment to distinguish products from competitors' products. These urge biopharmaceutical manufacturers to develop and use non-standard freeze-drying containers. However, the manufacturing enterprise must make the products reach the required dryness, cleanliness and environmental protection, and protect the integrity and stability of the products. Many enterprises believe that they can handle product quality problems and use non-standard conveying devices. However, if non-standard freeze-drying containers are used, the overall quality of their products will certainly be affected

new technology will bring about a revolution in packaging containers

the emergence of freeze-drying bead technology (freeze-drying agents into beads) may bring about a revolution in the packaging of freeze-dried biological agents. Lyophilized beads are very stable and do not react with each other. Multiple lyophilized beads can be packaged in the same conveyor. Compared with the previous use of a single glass serum bottle as a packaging container, this brings great flexibility to the product design. Biolyph has developed lyospheres processing equipment and programs for precise lyophilized bead processing. The precise freeze-drying bead technology eliminates the traditional packaging restrictions, so that the freeze-drying agent can use a variety of transportation packaging forms, so the enterprise brands can be distinguished. At the same time, product development and marketing personnel can realize the optimal design of conveying device according to special tests and end-user requirements

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