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Container closure integrity (CCI) testing of intravenous (IV) bags is an important quality control measure to ensure the safety and efficacy of the products. CCI testing helps verify that the container closure system, including the bag and its closure, maintains its integrity throughout the product's shelf life and prevents any leakage or contamination.

Various methods, including visual inspection, dye immersion testing, bubble emission testing, headspace gas analysis, and Vacuum decay testing can be employed to assess the integrity of the container closure system. These methods help to identify any defects or breaches that may compromise the sterility and stability of the IV bags. Manufacturers should select an appropriate method based on their specific requirements and regulatory guidelines to ensure the quality and safety of the IV bags.

Vacuum Decay Technology for CCI Testing of Intravenous Bags

Vacuum decay technology is an FDA-approved leak detection technique that can be used for CCI testing of high-risk package applications. The non-destructive nature of the process allows for greater understanding of packages, testing at a greater frequency with more accuracy and with less waste. Vacuum decay technology is capable of detecting leaks in sealed rigid, semi-rigid and flexible packaging made of non-porous or porous materials and has been proven to provide repeatable, reliable and quantitative test results.

VeriPac testing systems using Vacuum decay leak testing are highly effective for leak testing of IV bags. Using a differential pressure transducer leak test system, the test method is capable of detecting package leaks and invisible defects in the IV bag body and also in seams, welds and port areas. This method is non-invasive, non-subjective and does not require sample preparation.

The test method works by connecting the VeriPac test systems to a manually operated test chamber containing an IV bag. The next step is to draw a vacuum on the IV bag in the test chamber and observe any changes in the vacuum level. If there is any damage to the package, air or liquid will flow from the package into the chamber, causing pressure fluctuations. On the other hand, defect-free packages do not leak any pressure into the chamber, keeping the chamber vacuum level constant. Regardless of the location of the defect, the vacuum decay system can pick up both large and small defects. It takes about 30 seconds for testing IV bags, repeatable and sensitive to 15 microns for liquid and gas leaks.

Benefits of Vacuum Decay Technology

• Eliminates destructive, subjective testing methods.
• Non-destructive technology.
• Accurate, repeatable results.
• Pass/fail results backed by quantitative test data.
• Eliminates destructive, subjective testing methods.
• ASTM Test Method F2338, FDA Consensus Standard and referenced in USP 1207 Guidelines.
• Meets Annex 1 regulatory guidelines.

Recent regulatory changes have shifted requirements and strategies for container closure integrity. IV bags and flexible parenteral presentations have experienced the greatest impact from these new perspectives on quality. IV bags have always presented a significant risk. New provisions to Annex 1 have made the requirements for quality risk management (QRM) clear, and USP guidance documents outline the need for greater control. Based on the regulatory requirements and guidance, practical solutions for IV bag container closure integrity should offer non-destructive, practical and deterministic approaches to assure integrity. There are critical considerations for IV bag QRM, and strategic approaches to assuring integrity of IV bags and flexible parenteral presentations to satisfy the shifting regulatory environment.

Parenteral preparations are sterile medicinal products that are administered by injection, infusion or implantation into the body. They are used to deliver medications directly into the bloodstream, bypassing the digestive system and providing a rapid onset of action. There are different types of parenteral preparations, including intravenous (IV) injections, intramuscular (IM) injections, subcutaneous (SC) injections, and intradermal (ID) injections. Each type of administration is chosen based on the specific medication being delivered and the patient's condition.

Parenteral preparations can be single-dose or multi-dose and are usually packaged in vials, ampoules, or pre-filled syringes. These products must be sterile, pyrogen-free, and free from any particulate matter to prevent infections and other adverse reactions in patients. Parenteral preparations can include a wide range of medications, including antibiotics, anticoagulants, vaccines, chemotherapy drugs, and many others. They are typically prepared in a controlled environment, such as a hospital or pharmacy, and are subject to strict quality control measures to ensure their safety and efficacy.

Overall, parenteral preparations play a critical role in modern medicine, allowing for the delivery of life-saving medications directly into the bloodstream.

Overview of Automated Parenteral CCI Solutions

1. E-Scan MicroCurrent RTX

E-Scan RTX is a practical, reliable and entirely automated container closure integrity test (CCIT) approach for pre-filled syringes. The dynamic robotic design of the RTX platform can be customized to meet your manufacturing requirements. The E-Scan RTX uses MicroCurrent HVLD technology, a ground-breaking variation of HVLD, the optimal CCI solution for high-risk biological fluids. It can be used for batch release testing in the lab, on the production line, or in both environments. The test cycle only lasts for a short period of time. The HVLDmc test method checks the entire package for small pinholes, microcracks and defects in the closing seal. This ensures the integrity of the product seal. The HVLDmc has proven to be a highly sensitive leak test method for a variety of liquid-filled pharmaceutical packaging types, including pre-filled syringes, vials, blow-fill-seal containers, and other liquid-filled packages.

Benefits of E-Scan MicroCurrent RTX

• MicroCurrent HVLD technology is effective across all parenteral products, including biologics and extremely low conductivity liquids including sterile water (WFI).
• Listed in USP Chapter 1207 as recommended method for parenteral liquid package inspection.
• Robust method and good Signal-Noise-Ratio between good and defective products.
• Low voltage exposure reduces production of ozone.

2. VeriPac LPX Technology

VeriPac LPX is an automated inspection solution for CCI testing of parenteral products. The VeriPac LPX series is a line of fully automated instruments for 100% inline testing of package quality inspection. The performance of the packing line may be highly assured due to the enhanced automated testing accessible by LPX. The dynamic robotic design of the VeriPac LPX can be customized according to manufacturing needs. The LPX series offers flexible and scalable solutions to satisfy manufacturing line needs. Rigid containers, parenteral products, and flexible packaging are some applications of LPX technology. Systems using VeriPac LPX use Vacuum Decay technology and ASTM Test Method F2338. The FDA recognizes the test technique as a consensus standard for pharmaceutical package testing and is listed in ISO 11607 and USP Chapter 1207 guidelines.

Benefits of VeriPac LPX Technology

• Automated testing enables the highest level of container quality assurance.
• Deterministic, quantitative test method.
• ASTM Test Method F2338 and FDA standard, ISO 11607.
• Non-destructive, non-subjective, no sample preparation.
• Pick-and-Place option back into the production line.
• Auto reject option of defects removed from the production line.
• USP <1207> compliant.

Parenteral products are typically tested for their container closure integrity (CCI) to ensure that the product remains sterile and safe for use. Automated CCI solutions can provide a fast and reliable method for testing CCI in parenteral products. These solutions offer several benefits over traditional manual testing methods, including increased efficiency, consistency, and accuracy. Automated CCI solutions typically use non-destructive testing methods, such as vacuum decay or high voltage leak detection, to identify any leaks or defects in the container closure system. These methods are highly sensitive and can detect even the smallest leaks that may compromise the sterility of the product.

Automated Container Closure Integrity Testing (CCIT) is a specialized form of testing that focuses on verifying the integrity of the container closure systems of several types of containers used to store and transport products. This can include vials, pre-filled syringes, bottles, pouches, and other types of containers. The container closure system includes the closure device (such as a stopper or cap) and the container or package itself (such as a glass or plastic vial or bottle), and it is essential to ensure that it is properly sealed so that it does not allow any leaks or contaminants to enter the container.

Automated CCI testing of pre-filled syringes involve using specialized testing equipment and techniques to simulate real-world conditions and test the container closure system's integrity. This testing process can be done in the laboratory by an operator or fully automated to increase efficiency and accuracy.

Testing Pre-filled Syringes Using E-Scan RTX

The E-Scan RTX platform is a modular, fully automated container closure integrity solution for pre-filled syringes. The RTX is a practical and dependable CCI solution with a dynamic robotic design that is adjusted to meet your production needs. This robust, flexible platform uses MicroCurrent HVLD technology, a revolutionary form of HVLD that is the optimal CCI solution for fragile, high-risk biologic liquids. It is appropriate for batch release testing at the production line, in the lab, and provides a quick PASS/FAIL result with a test cycle of only seconds.

A robotic arm will track and pick up nested syringe trays from a standard single lane conveyor. The robot removes the syringes from the nested tray and rotates the syringes through two test stations, one to detect needle shield defects and the other to inspect the rest of the syringe body. The test starts automatically and gives a fixed PASS/FAIL signal on completion of the test. An adjustable failure reference can be set to allow PASS/FAIL based on a predetermined LOD (limit of detection) setting in the initial recipe. After testing, syringes are automatically loaded back into the syringe tray, defective syringes are collected in the reject tray.

Benefits of E-Scan RTX

• MicroCurrent HVLD technology is effective across all parenteral products, including biologics and extremely low conductivity liquids including sterile water (WFI).
• Listed in USP Chapter 1207 as a recommended method for parenteral liquid package inspection.
• Robust method and good Signal-Noise-Ratio between good and defective products.
• Low voltage exposure reduces the production of ozone.

Automated pre-filled syringe testing is critical to ensuring the safety and efficacy of pre-filled syringes used in the pharmaceutical industry. By using automated testing techniques, manufacturers can ensure that the container closure system is reliable and free from defects, reducing the risk of contamination or other safety concerns.