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Parenteral products, such as pre-filled syringes, vials, and cartridges require stringent quality control to ensure sterility and product integrity. A compromised container closure can lead to contamination, posing severe risks to patient safety. To address this, automated Container Closure Integrity Testing (CCIT) solutions like the E-Scan RTX offer a highly reliable and efficient approach.

Understanding Parenteral Products

Parenteral products are sterile pharmaceuticals, mainly liquid form, administered via injection, including pre-filled syringes, vials, cartridges, and ampoules. These products bypass the body's natural defense mechanisms, making sterility and container closure integrity critical to patient safety.

Ensuring their container closure integrity (CCI) is critical to maintaining sterility and preventing microbial contamination, oxidation, or loss of potency. Given the delicate nature of biologic drugs, traditional destructive test methods like dye ingress are inadequate. Instead, non-destructive methods such as HVLDmc technology provide reliable and repeatable testing.

Automated Container Closure Integrity Testing (CCIT) is a non-destructive method used to test the integrity of pharmaceutical packaging, ensuring it remains sealed and free from contamination. Unlike traditional probabilistic methods such as dye ingress or microbial ingress tests, automated CCIT provides precise, repeatable, and high-throughput testing, making it ideal for large-scale production. It eliminates human error, increases sensitivity to micro leaks, and complies with regulatory guidelines such as USP Chapter 1207, which recommends deterministic testing methods. By integrating advanced technologies like MicroCurrent High Voltage Leak Detection (HVLDmc), automated CCIT ensures that parenteral products, including pre-filled syringes and vials, meet the highest quality and safety standards while maintaining efficiency in manufacturing.

Automated CCI Testing Using E-Scan RTX

The E-Scan RTX platform is PTI’s fully automated, modular container closure integrity (CCI) testing solution designed specifically for pre-filled syringes. Engineered with a dynamic robotic system, the RTX delivers a practical, reliable, and adaptable approach to CCI testing, seamlessly integrating with your production requirements.

This advanced platform features MicroCurrent HVLD technology, an innovative form of high-voltage leak detection (HVLD) optimized for high-risk, delicate biologic liquids. The RTX ensures fast and accurate PASS/FAIL results within seconds, making it ideal for batch release testing, inline production environments, or laboratory applications.

Unlike conventional HVLD methods, PTI’s MicroCurrent HVLD operates with a unique DC voltage mode, using no more than 50% of the voltage typically applied in traditional high-voltage testing. This enables precise leak detection even in low-conductivity liquids, such as sterile water. Additionally, the reduced voltage minimizes product exposure to high electrical stress, making it the preferred CCI solution for parenteral and biologic products.

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).
• Robust CCI technology, MicroCurrent HVLD offers bi-lateral scalability from the lab to production line.
• Listed in USP Chapter 1207 as the 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.

Transdermal patches have become an increasingly popular drug delivery system due to their ability to provide controlled drug release, improved patient compliance, and reduced systemic side effects. However, ensuring the integrity of the packaging is essential to maintaining the stability, potency, and sterility of the patch throughout its shelf life. Any compromise in packaging can lead to contamination, drug degradation, or unintended drug exposure, posing significant risks to both patients and handlers.

To mitigate these risks, advanced package integrity testing methods are required. Traditional methods like the Bubble Emission and Dye Ingress have limitations in detecting leaks in transdermal patch packaging. Instead, quantitative and deterministic approaches such as Helium Leak Detection and Force Decay Technology have emerged as reliable solutions for ensuring package integrity.

What Are Transdermal Patches?

Transdermal patches are adhesive patches that deliver medication through the skin into the bloodstream. They provide controlled drug release over an extended period, making them a preferred option for medications requiring consistent dosing. Common examples of transdermal patches include those used for pain relief (fentanyl), hormone replacement therapy, nicotine cessation, and cardiovascular treatments.

Since these patches contain potent drugs, it is crucial to ensure that their packaging remains intact. A compromised package could lead to accidental drug exposure, degradation due to environmental factors, or microbial contamination, which could reduce efficacy and increase health risks.

Challenges Associated with Ensuring Transdermal Patch Integrity

Transdermal patch packaging presents unique challenges when it comes to integrity testing. Some key difficulties include:

• Small Headspace: The limited air volume inside the patch sachet makes it challenging to create sufficient pressure differentials for traditional vacuum-based testing methods.
• High Barrier Materials: Many patches are sealed in foil-based laminates, which require highly sensitive testing to detect microleaks.
• Potent Drug Risks: Drugs like fentanyl require secure containment, as accidental exposure can be fatal.
• Environmental Protection: The packaging must provide a complete barrier against moisture, oxygen, and contaminants to prevent degradation.

Techniques to Ensure Package Integrity

To overcome these challenges, advanced deterministic testing methods like Helium Leak Detection and Force Decay Technology offer precise and reliable leak detection.

1. Helium Leak Detection

Helium leak testing is a highly precise Container Closure Integrity Testing as (CCIT) method that detects microleaks in sealed packaging. Due to helium's small atomic size and inert properties, it serves as an ideal tracer gas for identifying defects.

The process involves filling the package with helium, applying a vacuum, and measuring helium escape using a sensitive detector. The quantified leak rate provides critical insights into sealing integrity. Widely used in pharmaceutical and parenteral packaging, helium leak testing ensures sterile barriers, supports design validation, quality control, failure analysis, and aids in manufacturing process qualification.

2. Force Decay Technology

Force Decay is a quantitative, non-destructive leak detection method ideal for low-headspace packaging made from non-porous materials like films, laminates, or foils. It enables package testing without damage, allowing tested samples to be returned to the batch.

The system employs nested tooling for consistent package positioning and controlled expansion. During testing, a vacuum is applied, causing package expansion, which is monitored using ASTM F2338 vacuum decay principles. The VeriPac force measurement system detects defects based on force decay or vacuum level changes.

PTI’s VeriPac 410 utilizes force decay technology for non-destructive leak detection in blister packs, sachets, and pouches. It accurately identifies defective packages within multi-cavity formats by measuring surface deflection during vacuum testing, making it highly effective for low-headspace applications.

Ensuring the integrity of transdermal patch packaging is critical to maintaining drug efficacy, safety, and regulatory compliance. Traditional methods often fall short in detecting microleaks, making advanced deterministic testing methods like Helium Leak Detection and Force Decay Technology indispensable. As the demand for transdermal patches continues to grow, investing in high-precision package integrity testing solutions will be essential for pharmaceutical companies to uphold quality standards and ensure patient safety.

Medical device packaging plays a crucial role in maintaining product sterility, stability, and functionality. However, two of the most overlooked yet destructive environmental contaminants in medical device packaging are moisture and oxygen. While many packaging strategies focus on microbial contamination, the gradual ingress of oxygen and moisture can have severe implications for product performance and shelf-life.

For certain medical devices—such as drug-coated stents, moisture-sensitive bone cement, and oxygen-critical diagnostic kits—even minimal exposure to moisture or oxygen can result in degradation, rendering the product ineffective or unsafe. The key to mitigating these risks lies in ensuring package integrity through advanced testing methodologies like Vacuum Decay Technology

Moisture and Oxygen: Invisible Threats in Medical Device Packaging

Medical devices are often packaged in either porous or non-porous materials, each with distinct vulnerabilities:

• Porous packaging allows for equalization of partial pressures, reducing microbial contamination risks but potentially increasing exposure to environmental contaminants like moisture and oxygen.
• Non-porous packaging, on the other hand, creates a sealed environment but is susceptible to microleaks—tiny defects that permit oxygen and moisture ingress over time.

Unlike bacteria, moisture and oxygen ingress is more predictable and gradual, occurring through microleaks that might not be large enough for microbial entry. As pressure fluctuations and environmental conditions change, these contaminants steadily penetrate the packaging, compromising sterility, chemical stability, and device performance.

Medical Device Package Integrity Testing Using Vacuum Decay Technology

The VeriPac Vacuum Decay Technology, compliant with ASTM F2338 standards, is an advanced, deterministic, and non-destructive Container closure integrity test method (CCIT)for identifying microscopic leak. packaging. Designed for versatility, this technology is suitable for both rigid and flexible containers, making it an ideal solution for the pharmaceutical industry.

This innovative system follows a simple yet highly effective process. The primary packaging is placed inside a testing chamber, which is designed to accommodate various packaging formats. Once secured, a controlled vacuum is applied. A highly sensitive pressure transducer then monitors any vacuum decay, which may result from gas escaping or liquid vaporizing within the package—both clear indicators of potential leaks. Capable of detecting leaks as small as 5 microns or even smaller, this precise and reliable method ensures the highest level of package integrity.

Benefits of the VeriPac Series

• High Sensitivity: Detects microscopic leaks with precision.
• Non-Destructive: Allows manufacturers to test without damaging the product.
• Adaptability: Suitable for both rigid and flexible packaging formats.
• Efficiency: Provides fast, accurate, and quantitative results.

Moisture and oxygen pose silent but significant risks to medical device packaging. These contaminants can penetrate microleaks, degrading products and compromising patient safety. By integrating Vacuum Decay Technology into quality control processes, manufacturers can extend product shelf-life, enhance safety, and ensure the highest standards of medical device integrity.