As the governing regulatory document of the European Medicines Agency (EMA), EU GMP Annex 1 discusses a full host of concepts related to manufacture of sterile medicinal products. In contrast to guidance documents issued by the FDA, EU GMP Annex 1 is interpreted as law, requiring strict adherence to the regulatory expectations contained, numerous of which allude to container closure integrity testing. In fact, current proposed and ongoing revisions increase the expectations of scrutiny on package integrity.

The VeriPac 410 inspection system uses force decay technology for non-destructive seal and leak detection for blister packs, sachets, and pouches with low headspace.

Developments in non-destructive, deterministic testing technologies that can achieve optimum assurance in container closure for biologics.

Tyvek® gives the premium microbial barrier protection for sterilized medical instruments and pharmaceuticals. Apart from protecting the medical devices and pharmaceutical products from physical damages, medical and pharmaceutical packages also should provide an effective microbial barrier and help to maintain the sterility of the products. Bacteria and viruses with sizes varying from 0.002 to 100 microns are a constant threat to pharmaceuticals and medical devices which in turn can be hazardous to the patients.

Blister packaging is one of the most practical and convenient packaging formats for tablets and capsules. Blister packaging is specifically used for tablets and capsules to pack them in a convenient and controlled way for easy patient use.

Learn how these non-destructive inspection technologies verify container closure system integrity with deterministic quantitative test methods for vials, ampoules, syringes, cartridges and auto-injectors.

The pharmaceutical industry continues to bring breakthroughs in the field of new drugs and drug delivery systems amidst the increased scrutiny of the regulators. The packaging acts as the primary sterile barrier in drug delivery systems that safeguard the drug product through its life cycle. The efficiency of the primary sterile barrier and the functional components are of utmost importance to patient safety.

Packaging plays a significant role in the drug delivery system. Packaging provides information regarding the manufacturer’s name, price, date of manufacturing and expiry, dose or strength, ingredients, etc. Blister packaging is a type of packaging format specially designed for tablets and capsules made by heating and shaping a plastic sheet into the 'blister,' which is entirely covering the object, into a bubble or a pocket. Several types of plastic materials like Polyvinyl chloride (PVC), Polyethylene terephthalate (PET), Amorphous polyethylene terephthalate (APET), High-density polyethylene (HDPE), etc. and aluminum sheets or foils are used in blister packaging. Blister packages can offer barrier protection and some tamper resistance to shelf-life requirements.

The quality testing of medical device packaging is highly significant in ensuring the safe delivery of medical devices from their place of origin to the market. Guidance documents such as ISO 11607 provide a list of methods that have the capability to improve the package quality testing of today’s capability. PTI offers inspection methods that provide more reliable, sensitive, and traceable data. They offer in-depth feasibility studies, test method development, and test equipment to bring the supreme level of quality to high-value medical device applications. PTI’s inspection solutions are unique in their performance, reliability, and use of sensory technology.

The VeriPac 465 performs leak detection based on the basic principles of physics and does not require the use of trace gasses or sample preparation to perform the test. The VeriPac 465 core technology is based on the ASTM vacuum decay leak test method (F2338) recognized by the FDA as a consensus standard for package integrity testing. This test method was developed using VeriPac leak test instruments. The VeriPac 465 combines technological innovation and practical adjustments to patented dual vacuum transducer technology, PERMA-VAC, to make it the most sensitive and versatile vacuum-based leak detection technology to date. Through the introduction of unique test cycles, pneumatic controls and processing algorithms, the VeriPac 465 is establishing itself as the foremost vacuum-based leak test for parenteral products.

The most current model, the Seal Integrity Monitoring System (SIMS) 1915+, is the ideal choice for your helium-based leak detection system. Compared to conventional vacuum bubble and dye penetration test methods, packages can be quantitatively tested using helium as the tracer gas that ensures higher levels of accuracy. Such an approach allows a comparison between multiple packaging materials and forms production line settings and stability storage conditions, supporting the entire lifecycle.

There have been many advances over the past decade in terms of drug product delivery methods. As a result, key developments like unique cartridge based delivery systems have become common. It is well documented that Helium mass spectrometry is most suited for non-porous packaging such as vials and syringes. The same methodology can also be applicable to cartridge based delivery systems. In most cases the key to success is the development of a text fixture device designed and manufactured to the specific cartridge system being testing. These custom fixtures for helium leak detection can be designed to isolate specific areas of interest in the cartridge system.

Integrity testing of foil pouches offers a unique set of challenges. In most packaging processes that involve foil as the product barrier there is a concern about the incidence of punctures in the foil. These defects (typically called micro-voids) can be created as the foil is being rolled in thin sheets and tiny particles are inadvertently rolled into the foil. The most common defect is caused from the handling of the packages during the assembly of the foil and insertion of the drug product.

A helium based test method for verifying the integrity of a blister card holding drug product has been proven to be the most effective approach due to the extreme sensitivity offered. The test method relies on detecting helium sealed in the package system as it escapes through micro-channels in the package. A test sequence begins by placing the package in the test fixture and a vacuum is quickly drawn. The resulting pressure differential causes helium to escape through potential holes or cracks in the package.

Bottles come in a wide array of sizes and configurations, reflective of their diverse use in the health sciences industry. Typically, they exhibit a screw top closure threaded onto the bottle mouth, though sealing properties ranges from elastomeric liners, to o-rings, to induction seals and reliance on plastic-to-plastic contact and compression. One specific trend is the increase in need to test sterile bulk containers or sterile API containers. As the industry continues to move toward outsourcing or even insourcing through a network of suppliers or sites, transport of sterile drug product or API is becoming increasingly common. These types of containers are traditionally challenging to test, but can be qualified prior to use or as a proof of concept using helium leak detection.

With the advent of more advanced drug development for a wide variety of injectable compounds and an increasing preference for self-administration, prefilled syringes are the largest parenteral package growth sector. In many ways, the prefilled syringe is more complex and intricate in comparison to a traditional vial, a sealed ampoule, or bottles with screw top closures. They have multiple sealing sites that require integrity, but there is also a functionality piece associated: the syringe plunger must be able to deliver a dose, and thus, is movable.

Parenteral products, specifically vials, both glass and, increasingly, polymeric vials, represent one of the most common package systems historically tested by helium leak detection, largely due to their continued dominance as a package system for high-potency drugs requiring utmost protection. The primary sealing interface of a traditional vial system is between the elastomeric closure and land seal of a vial, physically compressed together by a crimped aluminum seal.

Helium leak detection (HeLD) is routinely used and widely accepted for applications that require the utmost leak sensitivity.

The pharmaceutical industry continues to bring breakthroughs in the field of new vaccines and drug delivery systems amidst the increased scrutiny of the regulators. The packaging acts as the primary sterile barrier in drug delivery systems that safeguard the drug product through its life cycle. The efficiency of the primary sterile barrier and the functional components are of utmost importance to patient safety.

The ongoing R&D of PTI continues to build a powerful set of leading-edge inspection technologies that will bring patented and unique solutions to high risk packaging applications. There is continuous development in the field of creating new test methods for container closure integrity, seal integrity testing and package integrity testing.

PTI Inspection Systems are scientific instruments being deployed for high risk packaging applications. The environments in which these systems operate is often highly regulated with test results having a significant impact on operational decisions. The reliability and sensitivity of a CCI test method is critical to assure that correct decisions are made to maintain product quality and patient safety. If PTI’s equipment is going to test your packaging, we aim to deliver the most effective solution. Feasibility studies offer a detailed glimpse into the technological capabilities ahead of critical purchasing decisions. Feasibility studies can also act as a preliminary test method for an application. The results from feasibility or method development testing can be rolled out to the production environment for rapid validation and deployment.

A variety of test methods exist to challenge package quality and performance. The objective of a feasibility study is to evaluate if a recommended CCI solution works and establish the optimal test parameters and Limit of Detection (LoD).

Airborne ultrasound is a referenced technology in the new USP <1207> Chapter Guidance as a deterministic test method for seal quality testing, is an ASTM Test Method F3004 and FDA Recognized Standard for seal quality integrity testing.

Tyvek® gives the premium microbial barrier protection for sterilized medical instruments and pharmaceuticals. Apart from protecting the medical devices and pharmaceutical products from physical damages, medical and pharmaceutical packages also should provide an effective microbial barrier and help to maintain the sterility of the products. Bacteria and viruses with sizes varying from 0.002 to 100 microns are a constant threat to pharmaceuticals and medical devices which in turn can be hazardous to the patients.

Non-destructive package testing of multi-cavity blisters – completely tool-less for different blister formats.

The United States Pharmacopeia USP 1207 guidance has been revised, encouraging the preference to deterministic, quantitative, and reliable non-destructive technologies to comply with quality standards.

The pharmaceutical industry continues to lead industries in terms of quality requirements and the value of data. The shift to more automated processes is less about the cost of human capital, but more about the pursuit of quality. The European Medicines Agency (EMA) updated Annex 1, driving for 100% inspection on fused containers and appropriate quality test measures for applications based on level of risk. The United States Pharmacopeia (USP) revamped Chapter 1207 on container closure integrity (CCI) to be prescriptive of deterministic technologies and encourages a deeper understanding of a container’s CCI requirements. The FDA continues to drive a ‘quality culture’ agenda versus a ‘compliance culture’, and the FDA has been explicitly targeting data integrity as a campaign for assuring quality. Every regulatory and guidance body is driving towards more reliable and accurate test methods.

Container Closure Integrity (CCI) is defined as whether the container is maintaining a sterile barrier. Intravenous (IV) bags are crucial in delivering fluids or medication quickly. Leaking parenteral packages are considered an extremely high risk as they deliver fluid directly into the bloodstream and have a high potential for microbial growth, requiring the need for sensitive and reliable CCI testing.

PTI has developed a new standard for protecting, storing and presenting data generated from its line of non-destructive leak testers in the form of a software package called PTI Ethos.

VeriPac FLEX Systems are versatile non-destructive package inspection systems designed for pouches and other flexible packaging.

VeriPac 355 is a non-destructive micro leak detection system for container closure integrity and package integrity testing for a wide range of products and packaging formats. This system is specifically designed to test containers for gas leaks for dry products (lyophilized vials, powder filled) as well test for liquid leaks (non-protein based liquid filled vials, prefilled syringes). The VeriPac 355 can be incorporated into protocols at any point in the handling process as it is non-destructive and requires no sample preparation. With the capability to detect leak rates as low as 0.2 cc/min, depending on packaging specifications, the VeriPac 355 is the optimal non-destructive quantitative test method for many pharmaceutical and food applications.

This poster presentation explains a new technology for integrity testing/leak detection for all parenteral and biologic products including low conductivity liquids such as sterile water for injection (WFI).

Multicavity blister packs and low headspace packaging use a variety of test methods to determine package integrity, with most being destructive, subjective, and unreliable.

PTI’s E-Scan 655 patent pending technology uses a unique mode of MicroCurrent HVLD which applies less than 50% of the voltage used with conventional high voltage technologies. 

VeriPac 455 is a non-destructive inspection system used for highly sensitive micro leak detection of empty and pre-filled syringes, liquid filled and lyophilized vials and other pharmaceutical packaging formats.

The E-Scan 655 is a revolutionary, deterministic offline microleak testing instrument that utilizes a new class of HVLD technology to inspect vials, syringes, and other liquid-filled parenteral products for container closure integrity.

The VeriPac 410 inspection system offers non-destructive seal and leak detection for blister packs, sachets, and pouches with low headspace including transdermal patch packaging

The E-Scan 655 is a deterministic offline micro leak test instrument that utilizes a new class of HVLD technology to inspect vials, syringes, and other liquid filled parenteral products for container closure integrity.

The VeriPac 310 is a non-destructive, non-invasive inspection system for leak detection and package integrity testing.

The VeriPac 410 utilizes a combination of vacuum decay technology and differential force measurement to identify defective packages. Multiple packages can be tested in a single test cycle, and the 410 identifies which package or cavity is defective. 

Complementing the high cost of medical device manufacturing, there is a high value placed on the sterility and quality of the final product which are the main reasons for successful integration of Seal-Scan® airborne ultrasound seal inspection for medical device packaging.

Seal-Sensor™ utilizes ultrasound technology that provides non-contact seal inspection solutions for offline laboratory use and high speed 100% online applications. Seal-Sensor is a very rapid, reliable method that provides an instant reading of seal presence and quality.

VeriPac 455 is a non-destructive inspection system that offers unique integrity testing approaches, permitting highly sensitive micro leak detection of empty and pre-filled syringes, liquid filled and lyophilized vials, and other rigid containers. Testing these types of products demands the highest level of sensitivity, repeatability, and accuracy, and the VeriPac 455 is up to the task.

VeriPac 455 is a non-destructive inspection system that offers unique integrity testing approaches, permitting highly sensitive micro leak detection of empty & pre-filled syringes, liquid filled & lyophilized vials and other types of liquid filled packaging.

VeriPac micro leak testers evaluate and analyze the integrity of vials and ampoules with precision and repeatability. Test components are optimized for high sensitivity applications and high resolution requirements of the pharmaceutical industry.