Although biopharmaceuticals is a small branch of the pharmaceutical industry, its importance is increasing. Biopharmaceuticals are biologically active substances that are particularly sensitive to temperature, very unstable, and susceptible to reaction with each other. Due to these characteristics, the storage life of biopharmaceuticals is very short, and it is usually required to be stored frozen, otherwise it will deteriorate quickly. This article will introduce you to what kind of packaging should be used for biological agents produced by lyophilization.
Freeze-drying processing requirements for packaging containers
First, thermal transfer performance
The success of lyophilization depends largely on the good thermal conductivity 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 provide good heat transfer properties, and the weaker the insulation of the containers, the better; in order to save energy, the containers should have high heat conversion efficiency. The heat generated by the lyophilizer shelf can be transferred well into the container.
Containers made of materials with low heat transfer coefficient have very low heat transfer efficiency; the shape, size or quality of the container also affects the heat transfer efficiency of the container; if too much material is used in the manufacture of the container, these materials become a hot A barrier that blocks energy from being conducted into the container. Low heat conductivity often leads to product freeze-drying failure.
For example, we use a serum bottle to fill the drug and freeze-dry it. First, the surface of the frozen body should be sublimated, so that the lower layer of ice vaporizes into a gaseous state before it can float out of the container; as the freeze-drying process progresses, the ice gradually vaporizes out of the container, and the sublimation surface gradually moves downward. In general, the sublimation surface will automatically face down towards the bottom of the serum container and inward toward the center of the frozen body. If the container is clearly insulated, the entire sublimation process cannot be controlled; and if the sublimation process is not controlled, some of the agent will be vacuum dried rather than freeze dried. The agent thus processed does not have the performance it deserves, and its performance of drug retention, shelf storage life, and rapid reorganization are greatly compromised.
Second, sealing performance
In the latter part of the freeze-drying process, the agent has been lyophilized and the device creates an ultra-dry environment. The container must be sealed before it can be removed from the ultra-dry environment. This is because after the agent is dried, the internal residual moisture drops below 3%. Once exposed to a humidity level far greater than its own external environment, it will absorb moisture from the external environment. As soon as the drug is absorbed, the quality will degenerate immediately; the functions that the lyophilized drug should have (such as long shelf storage life, rapid reorganization, etc.) will be weakened. Re-absorption of water by the agent can result in loss of performance of the agent, which in turn can not achieve the desired therapeutic effect, and may even cause the manufacturer to recall the product.
The use of containers that cannot be sealed in the lyophilizer is a mistake often made by the biopharmaceutical manufacturing company. For example, many diagnostic agents are stored in test tubes for lyophilization. These tubes are sealed with a cap. However, there is no feasible way to seal these tubes in the lyophilizer, so the manufacturer must not. Do not assemble a large group of employees to manually seal the container. This process is generally carried out in a workshop that does not meet the freeze-drying requirements. As a result, the lyophilized processed agent will be exposed to high humidity levels, and the agent will absorb a large amount of moisture in the environment. Therefore it will become unstable.
Third, waterproof vapor permeability
The water vapor permeability is related to the amount of water vapor that permeates into the vessel. In general, the higher the permeability of the packaging material, the less secure the package seal, the more water vapor that penetrates, and the greater the likelihood that the freeze-dried agent will degrade. Once the lyophilized agent is exposed to an environment with a humidity of more than 3%, its stability is threatened. High water vapor permeability can compromise the stability of the product and the therapeutic effect of the product.
Packaging container for lyophilization
First, the glass serum bottle
When lyophilizing the test tube diagnostic reagent, the glass serum bottle with the grooved rubber plug is the ideal packaging container for the Zui, because the container meets the three requirements that should be met: First, the container is made of glass material. It has good heat transfer performance. The serum bottle is specially designed to meet the heat transfer requirements of the freeze dryer. The good thermal conductivity of the glass material makes it the best choice for the production of serum bottles. Secondly, it has a trough shape. The glass serum bottle of the rubber stopper can be sealed in the lyophilizer to avoid exposing the lyophilized agent to a high humidity environment. After sealing the glass serum bottle in an ultra-dry environment, the water content of the lyophilized drug can reach a level equal to or even less than 3%; again, the glass serum bottle can effectively block the penetration of water vapor into the bottle, thereby protecting the lyophilized drug. Eroded by moisture or other pollutants.
For these reasons, glass serum bottles have become the traditional choice for manufacturers of diagnostic reagents.
However, glass serum bottles with grooved rubber plugs do not meet all the needs of pharmaceutical companies. Because serum bottles are single in form, they do not provide a diverse and unique form. The medicament is stored in a serum bottle for lyophilization, which means that the serum bottle is also used as a delivery device for the product after lyophilization. There is currently no viable way to extract the lyophilized product from the serum bottle, let alone repackage it into another delivery device. It's like a canned spaghetti. The jar of spaghetti makes the cooking of spaghetti more convenient and effective, but the package doesn't look good.
Diagnostic tests generally require simple operation, ease of use, and error-free, while serum bottles are less convenient to use. From the manufacturer's point of view, the packaging should enhance the usability of the product, and the reagent delivery package cannot be limited by the processing and packaging of the reagent. Therefore, test tube diagnostic reagent manufacturers began to look for other kinds of containers to process and deliver lyophilized drugs.
Second, non-standard freeze-dried containers
In fact, other containers with grooved rubber plugs can be defined as non-standard freeze-dried containers. Some test tube diagnostic reagent manufacturers are experimenting with these non-standard containers to freeze-process processed products, but none of the containers they have developed so far have been able to freeze-dry, seal and store the agents. Many of these containers have too low heat transfer properties and cannot be sealed in freeze dryers; some have too high water vapor permeability. Due to these deficiencies, products processed through non-standard freeze-dried containers do not have the stability and quality that should be achieved.
As with serum bottles, other containers used for lyophilized packaging must also provide good heat transfer properties, can be sealed in a lyophilizer, and provide a high quality water vapor barrier for lyophilized agents. Many test tube diagnostic reagent manufacturers have begun to use non-freeze-dried special design containers to process and package their agents, such as sample cups, foil seal pockets, and screw caps or lid containers.
Companies that develop new products need to reduce the cost of existing products, using new diagnostic equipment to differentiate products from competitors' products, which encourage biopharmaceutical manufacturers to develop and use non-standard freeze-dried containers. However, manufacturing companies must achieve the desired dryness, cleanliness, and environmental friendliness to protect product integrity and stability. Many companies believe that they can handle product quality problems and use non-standard conveyors. However, if a non-standard lyophilized container is used, the overall quality of the product will definitely be affected.
New technology will bring packaging container revolution
The advent of precision freeze-dried beads technology (freezing the drug into beads) may lead to a packaging revolution in freeze-dried biopharmaceuticals. The lyophilized beads are very stable and do not react with each other, and multiple freeze-dried beads can be packaged in the same delivery device. This gives the product a great deal of flexibility compared to the previous use of a single glass serum bottle as a packaging container. Biolyph has developed LyoSpheres processing equipment and programs for precise freeze-dried bead processing.
Precision freeze-dried beads technology eliminates traditional packaging restrictions, allowing lyophilized pharmaceuticals to be used in a variety of delivery packaging formats, and corporate brands are thus differentiated. At the same time, product development and marketing personnel can realize the optimization design of the conveyor according to the requirements of special tests and end users.
Source: China Packaging Network
Freeze-drying processing requirements for packaging containers
First, thermal transfer performance
The success of lyophilization depends largely on the good thermal conductivity 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 provide good heat transfer properties, and the weaker the insulation of the containers, the better; in order to save energy, the containers should have high heat conversion efficiency. The heat generated by the lyophilizer shelf can be transferred well into the container.
Containers made of materials with low heat transfer coefficient have very low heat transfer efficiency; the shape, size or quality of the container also affects the heat transfer efficiency of the container; if too much material is used in the manufacture of the container, these materials become a hot A barrier that blocks energy from being conducted into the container. Low heat conductivity often leads to product freeze-drying failure.
For example, we use a serum bottle to fill the drug and freeze-dry it. First, the surface of the frozen body should be sublimated, so that the lower layer of ice vaporizes into a gaseous state before it can float out of the container; as the freeze-drying process progresses, the ice gradually vaporizes out of the container, and the sublimation surface gradually moves downward. In general, the sublimation surface will automatically face down towards the bottom of the serum container and inward toward the center of the frozen body. If the container is clearly insulated, the entire sublimation process cannot be controlled; and if the sublimation process is not controlled, some of the agent will be vacuum dried rather than freeze dried. The agent thus processed does not have the performance it deserves, and its performance of drug retention, shelf storage life, and rapid reorganization are greatly compromised.
Second, sealing performance
In the latter part of the freeze-drying process, the agent has been lyophilized and the device creates an ultra-dry environment. The container must be sealed before it can be removed from the ultra-dry environment. This is because after the agent is dried, the internal residual moisture drops below 3%. Once exposed to a humidity level far greater than its own external environment, it will absorb moisture from the external environment. As soon as the drug is absorbed, the quality will degenerate immediately; the functions that the lyophilized drug should have (such as long shelf storage life, rapid reorganization, etc.) will be weakened. Re-absorption of water by the agent can result in loss of performance of the agent, which in turn can not achieve the desired therapeutic effect, and may even cause the manufacturer to recall the product.
The use of containers that cannot be sealed in the lyophilizer is a mistake often made by the biopharmaceutical manufacturing company. For example, many diagnostic agents are stored in test tubes for lyophilization. These tubes are sealed with a cap. However, there is no feasible way to seal these tubes in the lyophilizer, so the manufacturer must not. Do not assemble a large group of employees to manually seal the container. This process is generally carried out in a workshop that does not meet the freeze-drying requirements. As a result, the lyophilized processed agent will be exposed to high humidity levels, and the agent will absorb a large amount of moisture in the environment. Therefore it will become unstable.
Third, waterproof vapor permeability
The water vapor permeability is related to the amount of water vapor that permeates into the vessel. In general, the higher the permeability of the packaging material, the less secure the package seal, the more water vapor that penetrates, and the greater the likelihood that the freeze-dried agent will degrade. Once the lyophilized agent is exposed to an environment with a humidity of more than 3%, its stability is threatened. High water vapor permeability can compromise the stability of the product and the therapeutic effect of the product.
Packaging container for lyophilization
First, the glass serum bottle
When lyophilizing the test tube diagnostic reagent, the glass serum bottle with the grooved rubber plug is the ideal packaging container for the Zui, because the container meets the three requirements that should be met: First, the container is made of glass material. It has good heat transfer performance. The serum bottle is specially designed to meet the heat transfer requirements of the freeze dryer. The good thermal conductivity of the glass material makes it the best choice for the production of serum bottles. Secondly, it has a trough shape. The glass serum bottle of the rubber stopper can be sealed in the lyophilizer to avoid exposing the lyophilized agent to a high humidity environment. After sealing the glass serum bottle in an ultra-dry environment, the water content of the lyophilized drug can reach a level equal to or even less than 3%; again, the glass serum bottle can effectively block the penetration of water vapor into the bottle, thereby protecting the lyophilized drug. Eroded by moisture or other pollutants.
For these reasons, glass serum bottles have become the traditional choice for manufacturers of diagnostic reagents.
However, glass serum bottles with grooved rubber plugs do not meet all the needs of pharmaceutical companies. Because serum bottles are single in form, they do not provide a diverse and unique form. The medicament is stored in a serum bottle for lyophilization, which means that the serum bottle is also used as a delivery device for the product after lyophilization. There is currently no viable way to extract the lyophilized product from the serum bottle, let alone repackage it into another delivery device. It's like a canned spaghetti. The jar of spaghetti makes the cooking of spaghetti more convenient and effective, but the package doesn't look good.
Diagnostic tests generally require simple operation, ease of use, and error-free, while serum bottles are less convenient to use. From the manufacturer's point of view, the packaging should enhance the usability of the product, and the reagent delivery package cannot be limited by the processing and packaging of the reagent. Therefore, test tube diagnostic reagent manufacturers began to look for other kinds of containers to process and deliver lyophilized drugs.
Second, non-standard freeze-dried containers
In fact, other containers with grooved rubber plugs can be defined as non-standard freeze-dried containers. Some test tube diagnostic reagent manufacturers are experimenting with these non-standard containers to freeze-process processed products, but none of the containers they have developed so far have been able to freeze-dry, seal and store the agents. Many of these containers have too low heat transfer properties and cannot be sealed in freeze dryers; some have too high water vapor permeability. Due to these deficiencies, products processed through non-standard freeze-dried containers do not have the stability and quality that should be achieved.
As with serum bottles, other containers used for lyophilized packaging must also provide good heat transfer properties, can be sealed in a lyophilizer, and provide a high quality water vapor barrier for lyophilized agents. Many test tube diagnostic reagent manufacturers have begun to use non-freeze-dried special design containers to process and package their agents, such as sample cups, foil seal pockets, and screw caps or lid containers.
Companies that develop new products need to reduce the cost of existing products, using new diagnostic equipment to differentiate products from competitors' products, which encourage biopharmaceutical manufacturers to develop and use non-standard freeze-dried containers. However, manufacturing companies must achieve the desired dryness, cleanliness, and environmental friendliness to protect product integrity and stability. Many companies believe that they can handle product quality problems and use non-standard conveyors. However, if a non-standard lyophilized container is used, the overall quality of the product will definitely be affected.
New technology will bring packaging container revolution
The advent of precision freeze-dried beads technology (freezing the drug into beads) may lead to a packaging revolution in freeze-dried biopharmaceuticals. The lyophilized beads are very stable and do not react with each other, and multiple freeze-dried beads can be packaged in the same delivery device. This gives the product a great deal of flexibility compared to the previous use of a single glass serum bottle as a packaging container. Biolyph has developed LyoSpheres processing equipment and programs for precise freeze-dried bead processing.
Precision freeze-dried beads technology eliminates traditional packaging restrictions, allowing lyophilized pharmaceuticals to be used in a variety of delivery packaging formats, and corporate brands are thus differentiated. At the same time, product development and marketing personnel can realize the optimization design of the conveyor according to the requirements of special tests and end users.
Source: China Packaging Network
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