Mar 2021

Why is MicroCurrent HVLD Technology a Preferred CCI Technique for Ensuring Integrity of Biologic Products

Why is MicroCurrent HVLD Technology a Preferred CCI Technique for Ensuring Integrity of Biologic Products

Often described as the driving force of pharmaceutical industry, biologic drugs have the ability to address chronic diseases, unmet medical needs and comprise of more than half of the drugs in development. These are generally large complex molecules, derived from human, animal, or microorganisms through biotechnology. Examples include blood components, cells, vaccines, tissues, and recombinant proteins. The ability of biological drugs to treat life threatening diseases coupled with aging population has lead to tremendous growth in the global biological drugs market. However, the rapid growth of biological products has also increased packaging challenges to deliver safe and effective products.

Drug contamination is a serious concern in any medical industry; however, for biologics, it amplifies several folds because they are used to treat serious illnesses and chronic conditions. Contamination has a direct impact on product stability resulting in reduced shelf life and efficacy. Along with maintaining an acceptable shelf-life, there are other challenges too. Another important factor that can affect the quality of a drug is environmental conditions. For example, if a product is exposed to extreme temperature during transit, the product quality may be compromised. A biologic can also lose its stability if it’s unable to withstand variations in light and chemicals that it might encounter. Therefore, in order to cover packaging challenges associated with biological products, ensuring its container closure integrity is crucial.

Ensuring package integrity with PTI’s MicroCurrent HVLD technology

PTI’s MicroCurrent HVLD technology is a non-destructive, non-invasive container closure integrity test method that is found to be highly effective across applications such as pre-filled syringes, vials, cartridges, ampoules, BFS, bottles and pouches. This technique can precisely detect any leak in a wide range of liquid-filled products including extremely low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions. Under this method, the sealed container is scanned using electrode probes to detect the presence of any leak. Defects in the container as well as its approximate location can be identified by analyzing a change in the current flow. MicroCurrent HVLD technology utilizes about 50% less voltage and exposes the product and environment to less than 5% of the voltage when compared to conventional HVLD solutions. It is one of the most effective CCI technologies for all parenteral and biologic products.

Benefits of PTI’s MicroCurrent HVLD technology

  • Non-destructive, non-invasive, no sample preparation
  • Highly effective across all parenteral products, including extremely low conductivity liquids (WFI)
  • Ensure higher levels of accuracy and reliability in results
  • Offline and 100% online inspection at high production speeds
  • Simplifies the inspection and validation process
  • Referenced in USP 1207 Guideline
Microcurrent HVLD, CCI, container closure integrity, container closure integrity testing, Integrity of biologic products
Dec 2020

What are the Different Seal Quality Inspection Techniques Offered by PTI?

What are the different seal quality inspection techniques offered by PTI

Seal integrity plays a vital role in ensuring the quality of packaging products. Even a minute defect in the seal can initiate a leak, which can compromise the quality of the product and directly affect its shelf life. It can also result in huge financial losses to the manufacturer. That being said, manufacturers give considerable importance to conducting appropriate seal integrity tests to ensure package integrity at every stage of its lifecycle.

Seal integrity testing methods can be classified into two- Destructive testing methods and Non-Destructive testing methods. Since under Destructive methods, the packages may get destroyed, its popularity has steadily declined over the past few decades due to this waste and high cost. “There is a huge shift in the industry towards deterministic and quantitative test methods,” says Oliver Stauffer, Chief Executive Officer at PTI - Packaging Technologies & Inspection. “This includes vacuum decay and airborne ultrasound for medical device applications. The industry is currently moving away from dye ingress and manual visual inspection because there are so many blind spots in applying them and there’s a huge false sense of assurance.”

Seal quality inspection techniques offered by PTI:

Vacuum Decay technology is a non-destructive Container Closure Integrity test method, used for seal quality inspection in nonporous, rigid or flexible packages. With the ability to detect leaks down to the sub-micron level, , Vacuum Decay technology is identified as one of the most practical vacuum-based leak detection methods. Its ability to provide quantitative, reliable and repetitive test results make it ideal solution for seal quality inspection in Pharmaceutical, Medical Device and Food and Nutrition industries.

Under this method, the sample packages are first placed in a close fitting evacuation test chamber that contains an external vacuum source. The vacuum levels and changes in vacuum over a pre-determined time are closely monitored. The single or dual vacuum transducer technology is used to monitor the test chamber for both the level of vacuum as well as the change in vacuum over a predetermined test time. The changes in the absolute and differential vacuum indicate the presence of leaks and defects within the package.Over the past few years, Vacuum Decay technology has seen great advancements in the form of PTI’s PERMA-VAC technology and VeriPac FLEX Series.

The next generation PERMA-VAC technology is a single or dual vacuum transducer technology that has made the VeriPac line of test systems the most sensitive vacuum-based leak tests available in the market. It has higher test sensitivity for providing accurate and reliable results and can be applied to rigid and semi-flexible packages alike. PTI’s PERMA-VAC technology ensures the most stable test measurement ever achieved through vacuum decay.

VeriPac FLEX series is an ideal package inspection solution for dry filled pouches and flexible packaging. To accommodate different package formats and test sensitivity requirements, VeriPac FLEX series is available in several configurations with multiple test chamber sizes.


2.Airborne Ultrasound technology:

Airborne Ultrasound technology is yet another seal quality inspection technique, which is capable of non-destructively conducting advanced seal quality inspection of pouches and flexible packaging. It is capable of accommodating multiple packaging materials like Tyvek, paper, foil, film, aluminum, plastic and poly and is also proven to provide deterministic, reliable and accurate test results.

As the name suggests, this method utilizes ultrasound waves to detect defects in package seals. Ultrasound waves are passed through the material as the package seal moves along the sensor head. This causes reflections of sound waves. Such signal strength variations are closely monitored to identify defects if any. Its ability to evaluate seal quality even under conditions where the defect may not result in a leak, makes Airborne Ultrasound technology a practical choice for seal quality inspection across different industries.

PTI’s Seal-Scan (Offline) and Seal-Sensor (Online) are the latest advancements to the ultrasound test series. Both these technologies make use of non-contact airborne ultrasonic testing technology and have been established as one of the most effective methods for inspection of flexible package seals. Airborne ultrasound is also an ASTM Test Method F3004 for seal quality inspection.


seal quality inspection, airborne ultrasound technology, vacuum decay technology, container closure integrity testing, ccit, container closure integrity
Dec 2020

Role of MicroCurrent HVLD Technology in Parenteral Product Container Closure Integrity (CCI) Testing

Role of MicroCurrent HVLD Technology in parenteral product container closure integrity (CCI) testing

Ensuring pharmaceutical package integrity has always been a priority for drug product manufacturers. However, over the past few decades, innovations in health care sector have also accelerated pharmaceutical package integrity challenges. Although testing package quality of all healthcare products is important, in the case of parenteral products it is amplified significantly. Parenteral products are defined as injectible products that can be either liquid or powders. Solutions can contain suspensions, emulsions and be proteinaceous in nature. ”. Since these drugs are directly administered into human bodies, ensuring complete integrity of such packages is crucial. Common packaging formats for parenteral products include Liquid-filled containers such as vials, ampoules, syringes, BFS and auto injectors; Lypholized (powder) products are often packaged in vials. Even a minute breach in the package can cause microbial contamination leading to product deterioration. Hence ensuring container closure integrity is a critical process in the life cycle of parenteral products.

What is HVLD Methodology?

High Voltage Leak Detection (HVLD)) is a non-destructive Container Closure Integrity technique used primarily to evaluate closure integrity of parenteral product packaging. HVLD technology makes use of quantitative electrical conductivity measurement principles. This method operates by passing high voltage micro current signals through sample packages. Under the presence of a leak, the electrical resistance of the sample declines, causing an increase in current. Applications of High Voltage Leak Detection Technology include testing of the following package formats:

  • Pre-filled Syringes
  • Ampoules
  • Drug Product Cartridges
  • Liquid Filled Vials
  • Blow-Fill-Seal (BFS) Container

PTI’S MicroCurrent HVLD technology has revolutionized the conventional HVLD method. MicroCurrent HVLD is a non-destructive, non-invasive CCI technique that can be applied to a wide range of liquid filled products including low conductivity sterile water for injection (WFI) and highly proteinaceous drug products within suspensions. PTI’s E-scan HVLD, a highly sensitive CCI testing process uses electrode probes to scan sealed non-conductive containers. Under the presence of a leak, there will be a change in current flow indicating a defect in the container along with its approximate location. This unique technique uses about 50% less voltage and exposes the product and environment to less than 5% of the voltage. An important feature of E-scan HVLD is its ability to easily shift from the laboratory offline to 100% inline testing applications. With the capability to accommodate multiple packaging formats including glass, plastic or poly laminates, it is an ideal solution for parenteral package testing.

Benefits of MicroCurrent HVLD:

  • Deterministic, non-destructive, non-invasive
  • High level of repeatability and accuracy
  • Ideal package integrity solution for parenteral products
  • Low voltage exposure to the product and environment
  • Offline and 100% online inspection at high production speeds
CCIT, container closure integrity, container closure integrity testing, parenteral product leak testing, MicroCurrent HVLD, CCI testing
Sep 2020

CCIT - A risk mitigation tool for parenteral products

CCIT - A risk mitigation tool for parenteral products

Today’s healthcare industry assures treatments that were unimaginable a few years ago. As pharmaceutical industry grows in importance, the techniques of primary packaging for healthcare products, especially parenteral products has taken on new prominence. Common parenteral packaging methods include Liquid-filled containers such as vials, ampoules, syringes, blow-fill-seals and auto-injectors and containers filled with lyophilized products. Since these drugs are directly administered into human bodies, high sensitivity integrity tests are required to ensure product quality throughout its shelf life. For reasons of safety, packaging material, integrity and design are regulated by Food And Drug Administration as strictly as the product itself.

Container Closure Integrity Testing is a leak detection test conducted using a non-destructive packaging inspection system to protect the drug from any possible contamination. It is a crucial step in evaluating safety and integrity of the primary packaging so as to maintain a sterile barrier and to avoid leakage resulting in contamination of the drug. Packaging components like bottles, vials, syringes that are in direct contact with the product are called primary components while aluminum caps, cardboard boxes are secondary components as they are not in direct contact with the product. Proper packaging should be a priority for all drug products, but in case of parenteral products, these concerns amplifies several folds as they are directly injected. Hence initiating a proper container closure system is vital for product and consumer safety.

Although Container Closure Integrity Testing can be performed in many different ways, it can be broadly classified into Probabilistic methods and Deterministic methods. Probabilistic test methods including Microbial Challenge by Immersion, Tracer Liquid Tests (e.g. Dye Ingress), Bubble Tests etc. are traditional test methods where result accuracy may be uncertain. On the other hand, Deterministic test methods like Electrical Conductivity and Capacitance Test (HVLD), Laser-based Gas Headspace Analysis, Mass Extraction, Pressure Decay provide quantitative results with high accuracy. The United States pharmacopeia released guidance in 2016 stating that deterministic methods are preferred over probabilistic test methods.Packaging Technologies And Inspection (PTI’s) Microcurrent HVLD technology and vacuum decay technology are the latest inventions in package integrity testing of parenteral products.

1. Microcurrent HVLD Technology: Microcurrent HVLD is a unique High Voltage Leak Detection Technology, highly effective across all parenteral products. Its Applications include liquid-based products ranging from extremely low conductivity sterile water for injection (WFI) to proteinaceous products with suspensions. Its ability to detect small pinholes, micro cracks and seal defect detection down to single-digit microns makes it an ideal choice for testing parenteral products.

2. VeriPac Vacuum Decay Technology: VeriPac Vacuum Decay Technology, based on the ASTM vacuum decay leak test method (F2338-09) and accredited by the FDA for package integrity testing, is a non-destructive inspection system, capable of defect detection down to 0.002 cc/min. This system is applicable for empty and pre-filled syringes, liquid-filled and lyophilized vials and other flexible and rigid liquid-filled packaging. Depending on the package type and leak test sensitivity needed, appropriate VeriPac model can be selected.

PTI’s next generation PERMA- VAC technology addresses vacuum decay detection at the very core of physical test measurement by controlling the test system volume and maximizing the SNR between good and defective samples. This makes PERMA-VAC the most reliable vacuum-based leak test available in the market.
CCIT, parenteral product leak testing, container closure integrity testing, container closure integrity, package integrity testing, ccit pharmaceutical, hvld
Sep 2020

Container Closure Integrity Testing (CCIT) - An Ideal Solution for the Pharmaceutical Industry

Container closure integrity testing - An ideal solution for pharmaceutical industry

The global pharmaceutical industry has seen tremendous growth over the last few decades. The complex nature of the industry coupled with frequent breakthroughs has made it a favorite subject of scrutiny. Since any defect in the packaging of drugs can have serious consequences, assuring the quality of the packaging is of prime interest for every manufacturer. Pharmaceutical products are expected to be free from microbial contamination and safe to use right from production throughout their shelf-life. The drug’s stability can be adversely affected through contamination in the form of oxygen, humidity or microbiological ingress. In order to prevent such risks, integrity tests with high sensitivity are required.

Previously, only sterility testing was conducted on pharmaceutical packaging. However, when it was realized that sterility testing alone is not sufficient to hold the integrity of the medical products, the US FDA published Guidance for Industry for Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products. This emphasised the importance of verification of microbial barrier properties of a pharmaceutical product package (i.e., CCI). FDA defines Container Closure Integrity Testing (CCIT) “as the sum of packaging components that together contain and protect the dosage form”.

Container Closure Integrity Testing is a method of leak detection using a non-destructive packaging inspection system to prevent possible contamination. Such a test is essential since any defect in the container can cause external particles to enter the product, thereby reducing its shelf life. Implementing right Container Closure System has been of prime importance for a manufacturer as it affects both the product and the patient. Hence, the relevance of CCI Testing in the pharmaceutical industry has steadily increased over the years. Contaminants that can enter a product include micro-organisms, reactive gases, and other substances. CCIT ensures product quality is maintained from the point of manufacture throughout its distribution and use. Container closure systems include primary packaging components and secondary packaging components. Components such as a glass vial or syringe, which come into direct contact with the product, are primary packaging components. On the other hand, components that are crucial to ensure correct package assembly, such as aluminum caps, over stoppers etc. are the secondary packaging components

CCI Testing Methods

Container closure integrity testing can be performed in many different ways. Each method has its own merits and demerits. A number of factors have to be considered while selecting appropriate testing methods. These factors include, but are not limited to; the reliability of the test method, material of the primary package and inline versus an offline testing requirement. CCI testing methods can also be selected depending on specific desired outcomes. Examples of desired outcome include: identifying the presence of leak paths, understanding leak path’s location, evaluating leak rate for the whole package, and measuring potential for microbial ingress. The United States pharmacopeia released guidance in 2016 stating that deterministic methods are preferred over probabilistic test method.

1. Probabilistic methods: Here, the testing methods are more traditional, and the accuracy of the result is uncertain. The probabilistic methods include the following:
  • Microbial Challenge by Immersion
  • Tracer Liquid Tests (e.g. Dye Ingress)
  • Bubble Tests
  • Tracer Gas (Sniffer Mode)
2. Deterministic methods: Such methods provide quantitative results with a higher level of accuracy. The chances of errors are also minimal. The deterministic methods include the following:
  • Electrical Conductivity and Capacitance Test (HVLD)
  • Laser-based Gas Headspace Analysis
  • Mass Extraction
  • Pressure Decay
  • Tracer Gas (vacuum mode)
  • Vacuum Decay
CCIT, container closure integrity, container closure integrity testing, pharmaceutical product leak testing, pharmaceutical package testing, package integrity testing

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