08
Feb 2022

Head Space Analyzer Module for Quality Control Leak Testing

Head Space Analyzer Module for Quality Control Leak Testing

Helium leak testing is a non-destructive method to verify the presence of a leak in a component or device by using helium as a tracer gas. Being a highly sensitive method, it measures the amount of helium escaping through the package and is stated as a leak rate. Helium leak detection using Seal Integrity Monitoring System (SIMS) 1915+ is widely used in pharmaceutical and medical device product package systems for quality checking. SIMS 1915+ enable quantitative CCI analyses of packages at a sensitivity level as low as 1 x 10-10 mbar/L/sec. This quantitative method enables direct comparison across multiple packaging materials and formats, production line settings, and stability storage conditions. Each SIMS 1915+ Helium Leak Testing device is custom-built to meet the specifications and packaging configurations of the client. The following are the SIMS 1915+ configurations for CCI.

  • Headspace Analyzer Module (HSAM)
  • Helium Leak Detector Module
  • External Calibrated Helium Leak Standard
  • Dual Test Port Manifold
  • Vacuum Test Fixture Model (VTFM)

Quality Control Leak Testing using LDA's Head Space Analyzer Module

The Head Space Analyzer Module (HSAM) is a critical component of a Leak Detection Associates (LDA) custom helium leak testing system. The Model VM-2, created by Leak Detection Associates, is the most recent version of this unique device. The HSAM includes a probe, which is essential for determining the helium concentration in the headspace of the container system. This system is simple to use and operate since it has an Integral Calibration Chamber with a Calibrant Gas Flow Control Valve and a Universal Holder that allows multiple diameter systems to be evaluated. Leak Detection Associates will provide three (3) Puncture Probes (two spares) with each unit.

The optional vial filling component enables the test preparation of already-sealed vials by replacing the headspace gas with 100% helium. This module can be used to prepare samples at the moment of testing, after capping, or to prepare samples that have been stored for a period of time prior to testing. When combined with the VM-2, these unique attachments enable accurate and sample-specific readings that may be integrated into flexible study designs.

Uses of Helium Leak Detection

  • Ensuring container closure integrity.
  • Seal integrity monitoring during stability studies.
  • Verify and predict shelf-life seal integrity.
  • Useful in the early-stage drug product package system development.
  • Selecting closure formulation and configuration.

LDA's Head Space Analyzer Module (HSAM) - SIMS 1915+ configuration ensures highly sensitive leak detection of pharmaceutical pouches. Cold form blister cards, parenteral vials, cartridges, pre-filled syringes, bottles, combination product systems, and medical device products are other applications.

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helium leak detector, helium leak testing, helium leak detection, helium mass spectrometry, sims 1915+
238
03
Feb 2022

How to Evaluate Helium Leak Rate Method for Pharmaceutical Containers?

How to Evaluate Helium Leak Rate Method for Pharmaceutical Containers?

Pharmaceutical containers can be tested for Container Closure Integrity (CCI) in a variety of ways. Blue dye test and bacterial or microbial immersion test come under traditional, probabilistic methods. Whereas Vacuum Decay, Airborne Ultrasound, MicroCurrent HVLD, and Helium Leak Detection belong to the deterministic group of test methods. Each approach has advantages and disadvantages that should be considered while selecting a test method for a certain container type. All the methods are not appropriate for all sample configurations. Some succeed in certain applications while failing in others. Nowadays, the pharmaceutical industry is moving away from the traditional blue dye and bacterial immersion test methods and approaching deterministic methods for CCI testing.

The helium leak rate method is proven to be a strong contender for many applications. Helium leak testing is described as the process of detecting leaks in various enclosed or sealed systems by utilizing helium as a "tracer" gas and measuring its concentration as it leaves due to leakage. Like most CCI methods, Helium Leak Detection is deterministic. This method is more sensitive and not prone to contamination as compared to traditional dye or bacterial immersion methods. Due to its highly sensitive nature, it is possible to detect extremely small leaks, which are not possible with other leak testing methods.

Validating Helium Leak Rate Method for Pharmaceutical Containers

Validation of a Helium leak rate method for pharmaceutical container closure integrity assurance required proof that this physical testing method was as excellent as, if not better than, microbial immersion challenge testing in detecting potential integrity problems. Helium leak rate and microbial challenge tests were performed on one lot of rubber-stopper, broth-filled glass vials, which include faulty vials with known leaks. Glass micropipettes (0.1 to 10 microns) were fitted into the sidewalls of the vials to prepare defective vials. A 10% seeded defect rate was present in the validation lot, with nearly 50% of the leaks having a predicted probability of failing a microbial challenge (> 10%). The test units were charged for 4 hours under 40 psi helium pressure to implant the helium tracer in them. After charging, the crucial leak rate was found to be 10(-7) standard cc/second, and test units with measured leak rates exceeding this value were considered helium leak rate failures.

Microbial immersion challenge was performed by immersing the test units for 24 hours in a bath containing 10(9-10) viable E. coli and B. diminuta organisms, followed by a 13-day incubation period at 35°C. Visually, microbial failures were identified. The mean failure rates of the helium and microbial leak test techniques were compared statistically. The average helium failure rate was 6.9%, whereas the average microbial failure rate was 2.8%. There was a considerable difference between helium and microbial failure rates. As a result, helium leak rate testing has been shown to be an acceptable pharmaceutical container/closure integrity method for container quality assurance.

The helium leak detection method is chosen to be one of the best techniques for ensuring the integrity of pharmaceutical containers. This technique may be used to test the inherent package integrity and the Maximum Allowable Leakage Limit (MALL) during package development. It is applicable to a wide range of package types, can locate leaks, and can measure leak flow rates directly.

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helium-based leak detection systems, helium leak testing, helium leak detection, helium mass spectrometry, helium leak detector
226
27
Jan 2022

Role of Helium Leak Detection in Vial Leak Testing

Role of Helium Leak Detection in Vial Leak Testing

Container Closure Integrity Testing (CCIT) is essential for maintaining the sterility and stability of sterile injectable products. The optimal test method varies depending on the product. CCI testing is used to determine if there is a leak between the contents of a container and its external environment. This can be done by identifying whether communication can be established between the contents of the container and its surroundings.

Pharmaceutical containers such as vials, syringes, cartridges, and blister packs are frequently tested as part of a stability study to ensure that the closure of the container can maintain a sterile barrier. As part of a stability testing methodology, the Food and Drug Administration (FDA) suggests performing a container closure integrity test instead of a sterility test. Primary packaging methods based on vials for sterile pharmaceutical products must provide protection over the shelf life. This necessitates the demonstration of Container Closure Integrity (CCI), which should be done early in the pharma product development process. Helium leak testing is the most chosen CCI test method due to its high sensitivity when compared to other leak test methods.

What is Helium Leak Testing and How it Evaluates Vial Integrity?

Helium leak testing is one of the Container Closure Integrity (CCI) test methods for testing the leakage of pharmaceuticals and medical devices. This method uses helium and the change in concentration is detected when it exits owing to leakage. The applications of helium leak testing include vials, pre-filled syringes, foil pouches, or cold form blister cards. Each of these packaging types is meant to keep out harmful environmental pollutants such as dirt, microorganisms, or even gases while maintaining the sterility of the medicinal product enclosed. The package is filled with helium and subjected to vacuum in this method. A helium leak detector is used to quantify the amount of helium that escapes the package. The result is expressed as a leak rate.

Why Use Helium as a Tracer Gas?

Due to the following reasons, helium is considered an ideal choice for this type of testing:

  • Helium is inert, and it is one of the smallest gas molecules.
  • Small atomic size allows it to breach pathways reliably and easily.
  • Helium is non-toxic, non-condensable, non-flammable.
  • Safe to use as it will not interact with the components being tested.
  • Helium is less expensive and readily available when compared to other tracer gases.
  • The presence of helium in the atmosphere is not more than 5ppm.

As a highly sensitive quantitative test technique, helium leak testing evaluates Container Closure System (CCS) components for parenteral applications. It offers quantitative leak rate data that significantly exceeds the detection limitations of conventional approaches. The method has proven to analyze the impact of processing factors on container closure systems, such as parenteral vial capping applications, elastomeric closure selection, or changing sealing parameters.

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helium leak testing, helium leak detection, helium leak detector, leak test, parenteral vials
256
24
Jan 2022

Understanding Pre-Filled Syringes Leak Detection Using Helium Mass Spectrometry

Understanding-Prefilled-Syringes-Leak-Detection-Using-Helium-Mass-Spectrometry

The use of pre-filled syringes (PFS) as a container solution for pharmaceutical products has increased significantly in recent years. It is expected that this trend will accelerate in the future decades. Pre-filled syringes have the benefit of reducing pharmaceutical waste and extending the life of the product for the pharmaceutical industry. In general, pre-filled syringes are recognized as an effective, reliable, and convenient way to dispense drugs. In addition, many injections can be self-administered without worrying about being completely transferred from a vial. It provides a safe and effective option for patients in need of long-term pharmaceutical therapies.

When compared to the conventional vial, pre-filled syringes provide extra complexity in the field of container closure integrity (CCI) inspection. The advantages of pre-filled syringes include ease of use compared to conventional vial packaging. Pre-filled syringes eliminate the necessary procedures before you use the drug in a vial. In addition, since pre-filled syringes contain the correct dose, it helps to avoid dosing errors.

Leak Testing Pre-Filled Syringes Using Helium Mass Spectrometry

The device that detects and monitors leaks within and outside a product is called Mass Spectrometer Leak Detector. This approach makes use of helium as a tracer gas, which is utilized to fill a product coupled to a detector. Helium mass spectrometry is widely known for its suitability for non-porous packaging like vials and pre-filled syringes.

The leak detector works on the basis of a sector field mass spectrometer. In a vacuum, analyzed entering gases (Helium) are ionized. Helium ions are accelerated and separated in a magnetic field using increased voltage. Using a specific detector, the ion current is converted to an electric current. The current is accelerated and displayed on the screen by leak detection units. The current measured is proportional to both, the helium concentration and the measured leakage.

Benefits of Helium Leak Testing

  • Leaks may be detected and quantified with a high degree of sensitivity.
  • Due to the inert properties of helium, it does not affect the substances under test.
  • The testing is mostly conducted in a dry, temperature-independent environment.
  • Helium leak testing has a shorter cycle time, which lowers the cost and overall processing time.

For non-porous packaging including vials, pre-filled syringes, and cartridges, helium mass spectrometry has emerged as the new leak detection standard. Unlike probabilistic traditional methods, helium leak detection methods are preferred by manufacturers and regulators for their high sensitivity, fast test time, and detection capability. Pharmaceutical industries usually choose this process during the evaluation and eligibility stages of a new packaging process, where MALL plays an important role.

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helium mass spectrometry, helium leak testing, helium leak detection, helium leak detection methods, helium leak detector
269
15
Dec 2021

An Overview of Helium Leak Detection Services

An-Overview-of-Helium-Leak-Detection-Services

Helium Leak Testing is used to locate and identify extremely tiny leaks in any component that can produce a differential pressure. Helium Leak Rate can be expressed quantitatively (the quantity of leak rate). The helium leak testing method is also used to examine the performance of a component or system, as well as to study or evaluate the lifetime of a product. Helium gas is primarily utilized as a leak testing medium due to its ability to detect and quantify leak rates at very low levels.

LDA offers various helium leak testing services for pharmaceuticals and medical devices. The services are as follows:

Leak Testing Services

  • Installation & Quality Assurance of Helium Leak Detector
  • Leak Detection Associates guarantees that each custom instrument comes with comprehensive service delivery, installation, and validation program that is appropriate for the regulated environments in which the instruments will be used. Prior to delivery, the LDA Engineering Technician will collaborate with delivery site personnel to confirm that the location has the appropriate gas and electrical supplies for instrument functioning. Once the instrument is on-site and in the position specified by the customer, the Engineering Technician will perform a formal Installation Qualification (IQ), Operation Qualification (OQ), and Performance Qualification (PQ). Prior to execution, these can be pre-approved by local Quality Assurance.

  • Helium Leak Detector Service Agreement
  • Leak Detection Associates recognizes that maintaining instrument performance is an important part of the business’s success. While the instruments offered by LDA are simple to use and maintain, it helps to improve productivity by proactively guaranteeing performance with an LDA Annual Service Agreement. Leak Detection Associates provides service contract plans that are customized to the unique needs and specifications. The following are examples of key components of any service program:

    1. Repair and replacement parts are available on-site at no additional charge

    2. Annual On-Site Preventative Maintenance

    3. Detailed Annual Requalification & Calibration

  •  Helium Leak Detector Calibration Services
  • Annual calibration services for all components of the test system, including internal and exterior leak standards and HSAM probes, are also available as an alternative to a full-service contract. Failure to calibrate the leakage criteria may result in a decrease in the accuracy and validity of the results over time, as well as concerns of individuals working in a CGMP or other controlled environment. A complete calibration program at regular intervals is designed to ensure proper instrument readings for the life of the device with minimal instrument downtime. LDA can set reminders when service is required once in our calibration database, ensuring that SIMS 1915+ does not skip a beat.

  • Training for Helium Leak Testing
  • Leak Detection Associates offers on-site training relevant to how the SIMS 1915+ Helium Leak Testing device will be utilized, with the objective of being a comprehensive solutions provider to the clients. More sophisticated parts of leak testing, as well as system care and maintenance, can be covered in training programs. The Leak Detection team has over 20 years of hands-on expertise and can help the organization with anything from basic knowledge and understanding of leak testing basics to specialized leak test method development and validation.

  • Helium Leak Detection Feasibility Studies
  • LDA offers dependable feasibility and method development services. Prior to procuring an instrument or moving on with outsourcing solutions, feasibility services can provide proof of concept for its intended usage, or they can assist to expand existing capabilities by designing solutions for new package systems. LDA also provides full method development utilizing industry-standard positive control techniques in the cases where clients do not have internal resources experience in the development of helium leak detection tests, or where current resources need to be expanded. Methods created at LDA can be transferred and verified at the client site, or they can be utilized frequently at LDA for lab-scale, non-cGMP research.

  • Onsite or In-House CCI for Package Systems
  • LDA offers testing capabilities at both the client's site and our location. A SIMS 1915+ purchased and installed in a controlled context can be used for client onsite testing. With hands-on expertise in cGMP and regulated laboratory and production environments, documentation procedures are quite often in line with internal and external quality standards. LDA also provides the option of bringing one of our test units to a client's site for particular investigations. In-house testing is an alternative for clients looking to analyze package systems or designs on a contract basis.

LDA provides its customers with the highest quality of services. We are the world's leading manufacturer of high sensitivity helium-based leak detection systems for the pharmaceutical and biologic industries. Our engineers and support staff are highly trained and certified, allowing us to provide professional services across a wide range of testing domains.

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helium leak detector, helium leak testing, helium leak detection, mass spectrometry, helium mass spectrometry
468
30
Mar 2021

Evaluating Integrity of Pre-Filled Syringes with Helium Leak Testing

Evaluating Integrity of Pre-Filled Syringes with Helium Leak Testing

What is helium leak detection?

The pharmaceutical industry has seen a significant rise in the use of pre-filled syringes in recent years. This demand is expected to accelerate over the coming decades. Pre-filled syringes offer benefits to the pharmaceutical industry in the form of reduced drug waste and increased product life span. Health care workers consider pre-filled syringes as an efficient, convenient and reliable drug administration method. However, they pose several challenges in manufacturing and require extensive testing.

Just like any other drug product, pre-filled syringes should be free from pyrogens and should be sterile. Not just that, they are expected to be biologically, chemically and physically stable throughout its shelf life. Considering the complex nature of these products, it isn’t surprising that there are many opportunities for it to fail to meet quality requirements. Defects in pre-filled syringes mainly depend on drug product design and syringe process design. Additionally, patient related issues are also an area of concern. Therefore, it is important for manufacturers to have knowledge and understanding of various tests involved to ensure patient safety.

Container Closure Integrity testing of pre-filled syringes

Sterility is the most important quality attribute associated with any pharmaceutical/ parenteral drug product. Container Closure Integrity (CCI) testing is one of the key tests performed by manufacturers so that the product is guaranteeing sterility and microbiological quality until point of use. Container closure integrity testing evaluates the ability of container closure systems to maintain a sterile barrier against possible contaminants that can deteriorate the quality of final pharmaceutical and biological products. There are multiple methods to conduct container closure integrity tests, each with its own set of benefits and limitations. For instance, techniques like dye ingress and microbiological ingress are destructive to the samples being tested. Such tests rely on statistically representative number of samples from the batch and assume that defects are uniformly present throughout the batch. On the other hand, deterministic methods are non-destructive in nature and can be used to test every unit from the batch.

Helium Leak Testing for Pre-Filled Syringes

Helium leak testing refers to the act of finding leaks in some type of enclosed or sealed system using helium as a “tracer” gas and measuring its concentration as it escapes due to leakage. Under this technique, the package is helium filled and subjected to vacuum. The amount of helium escaping the package is quantitatively measured with the help of a helium leak detector. The result is stated as a leak rate. Apart from being an effective container closure integrity test method, helium leak testing is also applicable in product design, product quality analyses, failure analyses and validation.

Why use helium as a tracer gas?

Helium is considered as an ideal choice of tracer gas because of the following reasons:

  • Helium is non-toxic, non-condensable, non-flammable.
  • It is inert, making it safe for use as it will not interact with the components being tested.
  • The atom size of helium is really small, allowing it to breach pathways reliably and easily.
  • Compared to other tracer gases, helium is less expensive and readily available.
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helium leak testing, pre filled syringes, container closure integrity testing, helium leak detector
826
05
Nov 2020

History of Helium Leak Detection

History of Helium Leak Detection

The First Helium Leak Detectors

The genesis for the use of helium as a method for leak detection can be traced back to the 1940’s and the Manhattan Project. The first atomic bomb created used uranium isotope 235, which is taken by way of separation from uranium-238. The separation was accomplished in a huge “diffusion” plant using microporous tubing as the diffusion medium and this process needed to be done in a manner that prevented any trace of moist ambient air in the process chambers. In essence, it was imperative that all the equipment be free of any leaks. Equipment of this size and magnitude had never before been tested to such and extreme leak detection specification. A number of various leak detection devices were tried, and they all proved unsuccessful as they could not meet the required standard for sensitivity. Eventually, a simplified mass spectrometer based on the Nier 60 spectrometer tube was chosen for leak detection and helium was the gas of choice used with it. It was determined that helium flow as sensitive as 10−6 std cm3 could easily be detected.

Major Improvements in Helium Leak Detection

In the 70+ years since the inception of the Manhattan Project, helium leak detectors have understandably been drastically improved. The size of an actual helium detector that in 1945 required a large scale, multi-story warehouse building, can now fit on a standard laboratory benchtop and the level of detection has been improved to levels that meet or exceed flows rates of 10−10–10−11 std cm3. With the inception of computers, operation of a helium detector has been fully automated. Based upon these developments, the use of helium as a medium for leak detection has become common and wide-spread practice and thus has a presence in almost every conceivable industry from refrigeration, semi-conductors, automotive and food and drug packaging components.

Modes of Operations using Helium Leak Detection

Conceptually, the principle of operations has not changed much in the past 50 years although, as noted, the size has been drastically reduced. The central piece of the helium leak detector is the cell in which the residual gas is ionised and the resulting ions accelerated and filtered in a mass spectrometer. Most of the current detectors use, as in the original design, a magnetic sector to separate the helium ions from the other gases. Permanent magnets are generally used to generate the magnetic field. The adjustment needed for the selection of the helium peak is made by varying the ion energy. At the highest sensitivity range, currents as low as femtoamperes have to be measured. This is achieved with the use of an electron multiplier in the most modern detectors. If the cell of a leak detector is not much different from the original design, the pumping system has considerably changed with the original diffusion pumps now being replaced by turbomolecular pumps or dry molecular-drag pumps. The sensitivity of the helium leak detector is given by the ratio between the helium flow through the leak and the partial pressure increase in the cell. In order to increase the sensitivity, the pumping speed of the tracer gas has to be reduced. This must be done without diminishing the pumping speed for the other gases (mainly water as leak detection usually takes place in unbaked systems) in order to keep the appropriate operating pressure for the filament emitting the ionising electrons. Selective pumping is therefore needed to provide a high pumping speed for water and a low pumping speed for helium

We hope that you have learned something regarding the history of helium leak detectors. In future installments, we will address various test methods and case studies that will provide more specific insight into the use of helium applied to the package leak testing needs of the pharmaceutical and life sciences industries.

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helium leak detection, helium leak detector, operations using helium leak detection
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