Freeze drying is a process that removes water from a product while modifying its structure and composition as little as possible. This is accomplished by freezing the product, causing the water it contains turns to ice, and then exposing it to a vacuum, so the ice is sublimed, passing directly from a solid state to a gas. This preservation and processing technique is commonly used in the food, pharmaceutical and cosmetic industries, because it offers countless advantages. Freeze-dried products:
- are significantly more stable than their liquid counterparts
- can be stored at room temperature without deterioration
- can easily be re-hydrated and restored to their original form
- undergo no structural changes (which occur when water is eliminated in other ways, such as through heat)
- are easier to handle than liquids, facilitating industrial handling steps (especially critical when working in aseptic environments)
- are easier to transport because they are less bulky and more lightweight than liquids
The main benefit of freeze drying is its ability to preserve for long periods products that are unstable and heat-sensitive and could deteriorate rapidly. Freeze-dried products are increasingly being used in different sectors. In the food industry, freeze drying continues to grow in popularity: from instant coffee or tea to infant food, more and more freeze-dried products are available on the market. In the pharmaceutical industry, freeze drying is widely used to store an extensive range of injectable products such as vaccines, increasing their shelf life and guaranteeing high safety standards.
Pharmaceutical packaging for freeze-dried products
Freeze drying facilitates the storage and transport of pharmaceutical products. However, it is a complex process that must be studied in great depth from standpoint of product formulation and the packaging in which it is to be stored. There are many essential factors:
- the product must be stable and must not undergo structural modifications in the freeze-drying or shelf life phase
- the product must be packaged in a sterile environment
- the product must be easily returned to the liquid form at the time of use
To meet these requirements, freeze-dried drugs are generally sold in vials, bottles and dual-chamber syringes or cartridges.
- Vials and bottles are relatively simple to assemble and available in a wide variety of sizes. However, they require a certain level of skill on the part of the user because the liquid needed to rehydrate the powder first needs to be added and then the product dosed for injection. Because of this, drugs packaged this way are usually administered in a hospital setting, or by specialized personnel.
- Dual-chamber syringes are a more advanced type of packaging that provides patients with both the freeze-dried powder and the solvent to rehydrate it, stored in two separate chambers that are put in contact just prior to injection. This offers countless advantages in terms of both savings of the active ingredient and the safety and ease of use for the end consumer, since no dosing is required, and patients can easily give themselves the injection. On the other hand, dual-chamber syringes are decidedly more complex to produce, since they are small and require special care during handling.
- Dual-chamber cartridges are based on the same principle as dual-chamber syringes (they provide both the freeze-dried product and the liquid needed to hydrate it), but they are designed to be used as refills for autoinjectors. They do not have their own needle and piston but are inserted into special devices that dose and inject the product. Like syringes, these devices are efficient and avoid wasting active ingredient but are rather complex to manufacture and require careful calibration, without which problems can occur when the cartridge is inserted into the injector.
Quality Control of Packaged Freeze-dried Products
For products that need to be packaged in a sterile environment, it is essential to verify packaging integrity to prevent the risk of contamination that could have very serious consequences on the health of patients. As with all injectable products, 100% of freeze-dried injectable products must be inspected according to the USP <1207>. To protect patient safety, manufacturers must ensure that every specimen placed on the market meets the quality standard, since the use of even one contaminated or improperly stored product could seriously damage a patient’s health. Automated tests provide rapid results and guarantee high accuracy and can help ensure these standards are met in every case. A variety of test methods can be used, but great care must be paid to the handling of the product to guarantee the perfect integrity of the packaging.
- Headspace Gas Analysis verifies that no potentially harmful gases like oxygen, carbon dioxide or water vapor are present in the head space of the vial or syringe containing the freeze-dried product. In the case of freeze-dried products stored in a protective nitrogen atmosphere, for example, HGA verifies that the amount of oxygen present in the head space of the vial is minimal. This confirms that the nitrogen cleaning process of the vial has been completed successfully and there is no risk of product oxidation.
- Automatic Visual Inspection: verifies that the vial containing the product is intact, free from cracks, inclusions, or dents, and that the freeze-dried powder contains no foreign particulate matter that could indicate a contamination. Special handling mechanisms are used for this test while moving the product and a series of high-resolution photographs are taken. The images are examined to inspect container integrity and understand product movement inside the packaging to highlight any non-compliant situations.
- Vacuum Decay Method uses a vacuum to confirm that the product’s packaging contains no micro-holes or leaks. The test detects both micro-holes and larger holes, which are responsible for macro-leaks
Bonfiglioli Engineering provides varied solutions for leak detection and packaging integrity of freeze-dried packaging including Vacuum and Pressure Decay testing, Headspace Gas Analysis and Automatic Visual Inspection or even a mix of these, customized to fit client requirements.
Need to speak with an expert to understand the optimal leak detection method for your container and product type? Contact us now.