Maximum Allowable Leakage Research Articles

Long-term sealing performance evaluation and service life prediction of O-rings under thermal–mechanical coupling conditions

In service, thermal–mechanical coupling conditions can exacerbate stress relaxation of O-rings and lead to their thermal expansion, further complicating the sealing problem. A finite element method is developed to simulate the mechanical deformation behavior of O-rings under thermal–mechanical coupling conditions, and its validity is verified by comparison with experimental data. Based on a substantial amount of simulation data, it is found that a dimensionless contact stress SG˜=SG/SG0 can be used as an indicator of the degradation of sealing performance and can be related to temperature T and time τ in the form of an aging kinetic equation. By combining this equation with the existing interfacial leakage model, an approach of predicting the long-term leakage rate of O-rings is proposed to quantitatively evaluate the effect of various factors on the performance of O-rings, and some important conclusions are drawn. Regarding the effect of temperature on O-rings, the thermal expansion effect dominates when the service time is less than 20 d, and the stress relaxation effect prevails when it is greater than 20 d. The higher the temperature, the more significant the stress relaxation, and the faster the leakage rate of O-rings. Increasing the fluid pressure enhances the relaxation effect. Using the maximum allowable leakage rate as the failure criterion, a pressure–temperature curve is plotted representing the safety boundaries, which can be used to guide the design of the sealing structures. Furthermore, an exhaustive study on the service life evaluation shows that at high temperature (T ⩾ 120 °C), the service life curves show a plunging segment near a pressure rise to 0.42 MPa.

A Leakage Prediction Model for Sealing Performance Assessment of EPDM O-Rings under Irradiation Conditions.

In this work, a model for predicting the leakage rate was developed to investigate the effect of irradiation on the sealing performance of ethylene propylene diene monomer (EPDM) O-rings. The model is based on a mesoscopic interfacial gap flow simulation and accurately predicts the sealing performance of irradiated and non-irradiated materials by utilizing the gap height as an indicator in a mechanical simulation of the O-ring under operating conditions. A comparison with vacuum test results indicates that the model is a good predictor of leak initiation. The positive pressure leakage of the O-rings was investigated numerically. The results show the following. The sealing performance of the non-irradiated O-ring is much better than that of the irradiated one. The sealing performance is the worst at 0. 713 MGy and the best at 1.43 MGy, and the seal is maintained at an absorbed dose of 3.55 MGy. A theoretical analysis of the non-monotonic variation using the proposed model shows that the leakage behavior of the O-rings depends not only on the material properties but also on the roughness and prestressing properties. Finally, a method was proposed to classify the sealing performance, using the maximum allowable leakage rate as an indicator.

Single-Use System Integrity IV: A Holistic Approach Based on Compiled Scientific Study Data.

This concluding article of the publication series provides an overarching summary of all study results presented in the three previous articles (1-3). Their interdependency in achieving a holistic approach to the integrity assurance of single-use systems (SUSs) employed in (bio)pharmaceutical manufacturing is finally illustrated. Two of those three studies were conducted to understand microbial ingress and liquid leak mechanisms in polymeric film material as determinants of the maximum allowable leakage limit (MALL) for SUSs using artificially created defects. The third study characterized gas flow through these defects-an essential variable for robust validation of physical integrity test methodologies based on gas flow. In all studies, the test samples used were 50 mm round patches of two ethylene vinyl acetate (EVA) multilayer films (300 μm and 360 µm thick) and a polyethylene (PE) multilayer film (400 μm thick). More than 1400 test samples with artificially created leaks were used in sizes ranging from 1 μm to 130 μm. The leaks were laser-drilled into the center of each patch. Microbial ingress and liquid leak testing under various process conditions resulted in a MALL of 2 µm for microbial integrity and the prevention of liquid leakages under most severe use-case conditions. The studies also demonstrated a close relationship between the occurrence of liquid leakage and microbial contamination. Different model solutions were used to evaluate the impact of liquid characteristics, mainly surface tension. The data were applied to build mathematical models for predicting the MALL under any intended use-case condition. By characterizing gas flow behavior over a broad pressure range using various defect sizes, it was possible to create formulas for three different flow regimes. These were suitable for calculating leak size in a defective product directly from the corresponding flow rate or vice versa. Finally, compilation of these different aspects enabled the authors to design and validate non-destructive physical integrity test methods having detection limits correlated to the MALL for SUSs.

Single-Use System Integrity II: Characterization of Liquid Leakage Mechanisms.

This study investigated the liquid leakage mechanism through microchannels in a flexible single-use packaging system composed of multilayer plastic film. Based on this study, a relationship between the maximum allowable leakage limit (MALL) and the loss of package integrity can be established under different use-case conditions. The MALL is defined as the greatest leak size that does not pose any risk to the product. A specifically designed liquid leak test was used to determine the leakage time, i.e., the time it takes for a package to show leakage. As a result, this method was able to determine the leak size for which no liquid leakage is observed after 30 days. This leak size varied between 2 µm and 10 µm and can be considered the MALL for liquid egress under different use-case conditions. This article also compared the MALL results of this liquid leak test with those of the microbial ingress test, showing a direct correlation between both tests. As test samples, an ethylene vinyl acetate multilayer film (300 µm thick) and a polyethylene multilayer film (400 µm thick) were cut into 50 mm patches. Before the patches were assembled in a filter holder to form a leak-tight seal, artificial leaks in sizes of 2 -25 µm were laser drilled into the center of each patch. The test units were filled aseptically with culture media and mounted vertically on the test setup. Various pressures were applied to each test unit to simulate the constraints that single-use systems may be subject to under real-world conditions. To detect the exact leakage time, electric circuits with timers were attached below each film patch. Microscopic investigations, including light microscopy and computed tomography, were used to interpret and understand the physics and geometries of the microchannels to explain any deviation from the expected results.

Performance Insulator Cover Type : YSL-70-AP Post Voltage Break Down Test

Electrical energy affect to economic, electrical energy consumption will increase and decrease likely economics. In this globalization era, electricity consumption was increased trend yearly since industrialization era. The reliability Electrical energy is very important for economic growth. The lower SAIDI and SAIFI is the bench mark for reliability of electrical energy supply. The reliable of insulator cover type: YSL-70-AP affect to the reliability electrical distribution energy on over head distribution circuit. Insulator cover protected to over head distribution circuit againt animal, bird, tree ang other temporary disturbance. Insulator cover also to protect half insulated medium voltage cable againt partial discharge and flashover.   Over voltage stress more often during operation, to impact to the material insulation performance. This quantitative research founding:  insulator cover type: YSL-70-AP still feasible to use after voltage breakdown stress. The fault current is still under the maximum allowable leakage current (11,600 micro ampere) which is 41.61 micro ampere, and breakdown voltage is still   higher than minimum that specified (24 kilo volt), which is 49.63 kilo volt. Post breakdown voltage the material insulation performance of insulator cover type: YSL-70-AP is good, and reliable to continuous operation over head distribution circuit.

Single-Use System Integrity I: Using a Microbial Ingress Test Method to Determine the Maximum Allowable Leakage Limit (MALL).

An aerosol microbial ingress test was specifically designed and used to create a predictive model in order to determine the maximum allowable leakage limit (MALL) of single-use systems (SUSs). The MALL is defined as the greatest leak size that does not pose any risk to the product. The procedure involved taking test samples of film material from single-use bags. As test samples, an ethylene vinyl acetate multilayer film (300 μm thick) and a polyethylene multilayer film (400 μm thick) were cut into 50 mm patches. Artificial defects of 1-100 µm were laser-drilled in the middle of each film patch. The patch was assembled on a holder and properly sealed. The test units were filled aseptically with culture media and placed inside an aerosol chamber. Various pressures were applied to the test unit to simulate the constraints that single-use systems may be subject to under real-world conditions. After an aerosolization cycle with spores of Bacillus atrophaeus, a minimum concentration of 106 CFU/cm2 was reached on the film surface. The test units were incubated for 14 days at 30°C-35°C and visually inspected for bacterial ingress. Thirty samples per defect size were tested. Logistic regression was used to indicate the MALL for a single-use system according to the required risk level. With this method, the probability of the occurrence or absence of ingress for a specific defect size was reported according to the experimental data. In addition to physical parameters, such as the pressure applied and the film material, the effect of the probabilistic nature of the microorganisms in determining the MALL is considered. Although finding an experimental model to predict the MALL for real-life process conditions was the ultimate objective, this paper also presents the microbial ingress test data obtained so far for two extreme conditions. Potential constraints, such as vibration, shock, acceleration, liquid movement, and pressure differentials, observed during normal usage were simulated using two extreme differential pressures, 0 mbar and 300 mbar. The estimated MALL for typical use-case conditions are 10-20 µm for storage applications and 2-10 µm for shipping conditions. The microbial integrity test method used in this article was able to detect bacterial ingress down to 3 µm defect size.LAY ABSTRACT: As use of single-use systems (SUSs) is increasingly expanding into all process steps of commercial manufacturing, integrity failure can significantly impact drug safety, availability, and costs. Consequently, growing industry scrutiny on single-use system integrity (SUSI) is raising the need to develop good science behind reliable determinations of liquid leakage and microbial ingress as well as the appropriate physical integrity testing technologies. In the current study, microbial ingress testing by the aerosol method is used to determine the maximum allowable leakage limit (MALL) for SUSs. To define the MALL, it is generally assumed that a system or product will not show any microbial ingress or leakage at a certain defect size. Statistical analysis of the experimental data in this study indicated the MALL with probability at a certain defect size for each system. As a result, the method studied provides a more accurate way of predicting ingress and increasing safety down the line for drug manufacturers and patients alike.

Natural tracing for concentrated leakage detection in a rockfill dam

During two field visits to the Renzonghai dam at the southeast edge of the Qinghai-Tibet Plateau in China, a large amount of leaking water was observed downstream of the dam. In particular, at the high reservoir water level, the leakage amount reached 754.33 L/s, >10 times the maximum allowable leakage limit, which seriously threatens the dam safety. Therefore, it is essential to identify the leakage paths quickly and efficiently, so that they can be stopped. The natural tracers of temperature and conductivity are combined with water stable isotope and chemistry compositions for dam leakage investigation. For comparison analysis, in-situ measurements and sample collections were completed in September 2015 at a high water level and in April 2016 at a low water level. The results obtained from temperature and conductivity logging are improved by measuring the water stable isotope and chemistry compositions, which showed at least three concentrated leakage paths. Two of them were located on each side of the dam abutment through the developed faults, and the other one went through the concrete cut-off wall and dam foundation. Due to the low cost, efficiency, and simple operation of this natural tracer technique, it is suggested that the technique should be utilized by engineers for dam leakage investigation, especially for concentrated leakage path delineation, at least at the preliminary stage.

Mathematical analysis of the effect of the constant temperature assumption in the leak test of PTB Testing Instructions, Volume 25

<p class="Abstract">"PTB Testing Instructions, Volume 25: Gas meters – Test rigs with critical nozzles" (PTB 25) includes a detailed description of a test to evaluate the tightness of the rig (leak test). The mathematical modeling of this test assumes that temperature remains constant, and it is established a maximum allowable change of 0.1 K during the test. PTB 25 defines a maximum value of the leak flow rate as criteria for approval of the test.</p><p class="Abstract">In this work, the effect of the assumption of constant temperature over the leak test result was analyzed. Different processes in which the real leak flow rate was zero and there was a change in the temperature of the system equal to the maximum permissible (according to PTB 25) were simulated, and the leak flow rate calculated by PTB 25’s model was determined. The assumption of constant temperature does not simplifies drastically the mathematical model. It is concluded that PTB 25’s maximum allowable temperature change is too high for most practical situations, leading to errors that exceeds the maximum allowable leakage rate. The factors “test time” and “enclosed volume” have a high effect over the magnitude of the error given by PTB 25’s leak flow rate model.</p>

Holistic Considerations in Optimizing a Sterile Product Package to Ensure Container Closure Integrity.

A new major chapter dealing with container closure integrity was released by the United States Pharmacopeial Convention. Chapter <1207> provides a significant amount of education and guidance concerning test methodologies to prove that a system is integral and safe for use. The test method used is only one of the major considerations in approaching the challenge of proving an integral system. This paper takes a holistic review of all the major considerations needed in qualifying a new vial system for container closure integrity. There is substantial interplay among many aspects in the process of sealing a vial. This review helps to define major risks that need to be considered and mitigated and reinforces the need to understand the maximum allowable leakage limit that is acceptable for a specific drug application. A typical risk-based approach considers materials, test methods, process, people, environment, and equipment. Each of these aspects is considered in some detail along with a recommended process flow for building a best practice, science-based approach. This approach will inform decision making for evaluating the correct combination of components and assuring they are assembled and tested in an appropriate manner. This work, once completed, can be the basis for a vial system platform or specific drug application qualification.LAY ABSTRACT: Container closure integrity is a fundamental requirement of every sterile drug package. With recent upgrading of compendia standards and guidance around this issue, there is an opportunity to better define a best practice approach to a complicated subject. It is important to recognize that there is substantial interplay among the components of the system, the process of assembly, and the test methods that are used. This paper takes a holistic approach to discussing these issues and identifying the risks that must be considered in assuring an integral container over the shelf life of a drug product.

Method Development for Container Closure Integrity Evaluation via Headspace Gas Ingress by Using Frequency Modulation Spectroscopy.

USP <1207.1> Section 3.5 states that "A deterministic leak test method having the ability to detect leaks at the product's maximum allowable leakage limit is preferred when establishing the inherent integrity of a container-closure system." Ideally, container closure integrity of parenteral packaging would be evaluated by measuring a physical property that is sensitive to the presence of any package defect that breaches package integrity by increasing its leakage above its maximum allowable leakage limit. The primary goals of the work presented herein were to demonstrate the viability of the nondestructive, deterministic method known as laser-based gas headspace analysis for evaluating container closure integrity and to provide a physical model for predicting leak rates for a variety of container volumes, headspace conditions, and defect sizes. The results demonstrate that laser-based headspace analysis provides sensitive, accurate, and reproducible measurements of the gas ingress into glass vial-stopper package assemblies that are under either diffusive or effusive leak conditions. Two different types of positive controls were examined. First, laser-drilled micro-holes in thin metal disks that were crimped on top of 15R glass vials served as positive controls with a well-characterized defect geometry. For these, a strong correlation was observed between the measured ingress parameter and the size of the defect for both diffusive and effusive conditions. Second, laser-drilled holes in the wall of glass vials served as controls that more closely simulate real-world defects. Due to their complex defect geometries, their diffusive and effusive ingress parameters did not necessarily correlate; this is an important observation that has significant implications for standardizing the characterization of container defects. Regardless, laser-based headspace analysis could readily differentiate positive and negative controls for all leak conditions, and the results provide a guide for method development of container closure integrity tests.LAY ABSTRACT: The new USP 39 <1207>, "Package Integrity Evaluation-Sterile Products", states in section 3.4.1: "tracer gas tests performed using … laser-based gas headspace analysis [have] been shown to be sensitive enough to quantitatively analyze leakage through the smallest leak paths found to pose the smallest chance of liquid leakage or microbial ingress in rigid packaging." In addition, USP <1207> also states that "for such methods, the limit of detection can be mathematically predicted on the basis of gas flow kinetics." Using the above statements as a foundation, this paper presents a theoretical basis for predicting the gas ingress through well-defined defects in product vials sealed under a variety of headspace conditions. These calculated predictions were experimentally validated by comparing them to measurements of changes in the headspace oxygen content or total pressure for several different positive controls using laser-based headspace analysis. The results demonstrated that laser-based headspace analysis can, by readily differentiating between negative controls and positive controls with a range of defect sizes on the micron scale, be used to assess container closure integrity. The work also demontrated that caution must be used when attempting to correlate a leak rate to an idealized defect-size parameter.

Good till the last drop: How much is too much valve leakage?

Validating the effectiveness of safety instrumented systems (SISs) is an integral and vitally important part of maintaining protection layers and preventing a hazardous condition. However, deciding on the basis for what constitutes “sufficiently safe” can be difficult. For example, when considering valves used as the final element in SISs, many in industry are basing the Maximum Allowable Leakage Rate (MALR) on the valve tightness specification instead of the hazardous condition that is being prevented when these valves are closed. This article will review a pilot conducted at The Dow Chemical Company to compare using the valve tightness class as a basis for MALR versus a safety‐based calculated MALR. Economics and safety aspects are evaluated and the general types of safety based calculations used are reviewed. Key questions answered include: (1) what exactly is the requirement for estimating MALR, (2) how is MALR calculated using a safety basis, (3) are there differences in cost when basing MALR on valve tightness class versus a safety based calculation, (4) are time efficiencies realized when basing MALR on the safety case versus on the valve tightness class, and (5) which is usually more conservative, a valve tightness class‐based MALR or a safety‐based MALR? © 2015 American Institute of Chemical Engineers Process Saf Prog 35: 26–31, 2016

CO2 storage monitoring: leakage detection and measurement in subsurface volumes from 3D seismic data at Sleipner

Demonstrating secure containment is a key plank of CO2 storage monitoring. Here we use the time-lapse 3D seismic surveys at the Sleipner CO2 storage site to assess their ability to provide robust and uniform three-dimensional spatial surveillance of the Storage Complex and provide a quantitative leakage detection tool. We develop a spatial-spectral methodology to determine the actual detection limits of the datasets which takes into account both the reflectivity of a thin CO2 layer and also its lateral extent. Using a tuning relationship to convert reflectivity to layer thickness, preliminary analysis indicates that, at the top of the Utsira reservoir, CO2 accumulations with pore volumes greater than about 3000 m3 should be robustly detectable for layer thicknesses greater than one metre, which will generally be the case. Making the conservative assumption of full CO2 saturation, this pore volume corresponds to a CO2 mass detection threshold of around 2100 tonnes. Within the overburden, at shallower depths, CO2 becomes progressively more reflective, less dense, and correspondingly more detectable, as it passes from the dense phase into a gaseous state. Our preliminary analysis indicates that the detection threshold falls to around 950 tonnes of CO2 at 590 m depth, and to around 315 tonnes at 490 m depth, where repeatability noise levels are particularly low. Detection capability can be equated to the maximum allowable leakage rate consistent with a storage site meeting its greenhouse gas emissions mitigation objective. A number of studies have suggested that leakage rates around 0.01% per year or less would ensure effective mitigation performance. So for a hypothetical large-scale storage project, the detection capability of the Sleipner seismics would far exceed that required to demonstrate the effective mitigation leakage limit. More generally it is likely that well-designed 3D seismic monitoring systems will have robust 3D detection capability significantly superior to what is required to prove greenhouse gas mitigation efficacy.

Does TFT Mobility Impact Pixel Size in AMOLED Backplanes?

Recent advances in organic light emitting diode (OLED) device efficiencies are making the amorphous silicon (a-Si) backplane a viable solution for a large range of display sizes. This paper presents the possibilities and design challenges of a-Si active-matrix organic light-emitting-diode (AMOLED) backplanes for applications ranging from small full color cell phone displays to HDTV screens. An analytical model for the minimum pixel-area, and hence the maximum resolution for both bottom and top emitting AMOLED architectures is presented in terms of the a-Si thin-film transistor (TFT) device parameters, the process design-rules, and the pixel circuit parameters. It is established that the lower device mobility of a-Si TFTs is no longer the limiting factor. For instance, in a 20'' W/SXGA panel with full color red-green-blue subpixels, the state-of-the-art TFT processes yield a square pixel size of /spl sim/266 /spl mu/m. Further, quantitative analysis of charge-injection/charge-feedthrough error in the pixel, and the maximum allowable leakage current for the TFT is also presented.