Container Closure Integrity Testing Solutions Throughout the Product Lifecycle
Developments in non-destructive, deterministic testing technologies that can achieve optimum assurance in container closure for biologics.
Biotechnology and pharmaceutical companies both produce medicines to treat conditions and save lives, but the medicines made by biotechnology companies are derived from living organisms while those made by pharmaceutical companies generally are produced using a synthetic process and are chemical based. Biotech and pharma markets are important industry sectors, sharing many broad similarities. The research & development of the fast growing Biotech industry accounts for many breakthrough life-saving treatments and vaccines for common diseases and conditions.
Cell & gene therapies encompass a wide range of therapeutic treatments that have emerged in recent years including stem cell treatments, genetic editing, tissue regeneration, among many others. These treatments emerging from the Biotechnology industry have fundamentally different properties than traditional medicines. They are often “live active product” or living drugs that can heal and replace diseased or damaged organs. Consequently, cell and gene therapy products are transforming the treatment of cancers and genetic diseases. Additionally, cell and gene therapies are rapidly expanding into other areas of medicine including autoimmune diseases, cardiovascular diseases, musculoskeletal disease, dermatological diseases and many others.
Packaging and drug delivery methods for these products are commonly parenteral packaging - pre-filled syringes, vials, cartridges, IV bags and other single use bags.
Moving toward deterministic technologies for more reliable container closure integrity testing
PTI’s technologies are the most sensitive and most reliable solutions for pharmaceutical and biotech packaging applications where the results have a significant impact on stability studies, clinical trials, production performance and patient safety.
Inspection solutions include the following applications:
- Liquid-filled containers such as vials, ampoules, syringes, bottles, etc.
- Containers filled with lyophilized product.
- Flexible packaging - pouches, single-use bags, IV bags
- Combination products: inhalers and autoinjectors
- Blister packaging for oral/solid dose products
When assuring the quality of all packaged products, testing container closure integrity (CCI) is critical, especially for parenteral products. If there is a breach in the seal, even a microscopic defect, it affects the sterility and the stability of the products – the drug may not be as effective due to oxidation or moisture ingress impacting the active ingredient.
More importantly, a sealing or closure defect can lead to patient safety concerns. Parenterals are sterile preparations intended to be administered directly into the system circulation in humans or animals. A compromised parenteral container can act as a vehicle for microbial transmission and pose a significant risk to the patient.
PTI’s solutions cover container closure integrity from the R&D Laboratory to fully automated solutions for production and manufacturing.
E-Scan MicroCurrent HVLD technology can be used to quantitatively detect leaks without destroying the sample. When it is applied to a non-conductive package material that contains a semi-conductive product inside, a spike in the voltage reading would indicate a defect in the packaging. MicroCurrent technology can be applied for containers with liquids including proteinaceous products, products with suspensions or emulsions and sterile water for injection (WFI).
Vacuum decay is another deterministic technology that is known to provide reproducible and reliable results for CCI testing of high-risk package applications. The ASTM Test Method F2338 was developed using PTI VeriPac instruments and is also an FDA recognized standard. The test involves placing a package in a test chamber, applying vacuum, and monitoring the vacuum level for any change, which would indicate the presence of a leak.
Scalable CCI solutions from Laboratory to Automated Production Inline Testing
With PTI’s decades of experience and expertise in providing CCI solutions to the pharmaceutical and biotechnology industries, we understand the challenges and are ready to support you. We help to design a strategy for CCI testing according to regulatory requirements.
Our benchtop laboratory systems are scalable to fully automated testing on the production line and at-line small batch testing.
Helium Leak Detection and Low Temperature/Cold Storage Package Test Solutions
Complex drug and biologic formulations have resulted in a continuous drive toward deeper cold storage in an effort to maintain product quality attributes, requiring life science companies to drive toward deeper cold storage. Since these products are often cell or gene or proteinaceous in nature, they are required to be stored at below -20°C, and also needs storage and distribution environment that include dry ice (~-78.5°C), or even liquid nitrogen (~-200°C).
While the products demanding such intense cold storage may be complex, oftentimes, the package systems in which the products are placed are rather traditional in nature, such as a screw or crimp top vial. However, at these temperatures, many of the materials used in these package systems and responsible for maintaining package integrity are not typically assessed at these temperatures. When such packages are exposed to deep-cold or ultra-cold temperatures, materials reach or exceed their glass transition state. This particularly causes physical changes to elastomeric components and creates leaks at low temperatures that would otherwise not be observed while at room temperature. Common areas where such type of leakages are observed include primary seal areas, primarily between an elastomeric closure and glass vial being used below -60C. If manufacturers are able to test container closure integrity while at these low temperatures, they gain a number of benefits with regard to optimal package choice and design, assembly parameters, minimizing leakages as well as have a clear understanding of a package system’s performance in accordance with USP 1207.
PTI offers a line of low temperature add-on options that enable helium leak testing to as low as -150C for individual package samples. When using helium as a tracer gas, packages can be quantitatively tested to levels far exceeding bubble and dye penetration tests, pressure decay, mass extraction, and high voltage leak detection. The LDA systems follow the guidelines set forth by the USP 1207 general chapter test requirement and more specifically by ASTM F2391-05, standard leak test method for helium technology.