On the Suitability of Vibration Acceptance Criteria of Process Pipework

The risk of vibration-induced fatigue in process pipework is usually assessed through vibration measurements. For small-bore pipework, integrity personnel would measure the vibration of the pipework and refer to widely used charts to quantify the risk of vibration-induced fatigue. If the vibration levels are classified as OK, no action is required on behalf of the operators. However, if it is a CONCERN or PROBLEM vibration level, strain measurements are required to adequately quantify the risk through a fatigue life assessment. In this paper, we examine the suitability of a widely used vibration acceptance criteria through finite element models. A total of 4,800 models are used to study the suitability of this vibration acceptance criteria by monitoring both the vibration and dynamic stress. The model comprises a small-bore pipe (2″ SCH 40) that is fitted on a mainline size 5″ SCH 40 using a weldolet; the length of the mainline takes three values resulting in three models. The mainline supporting conditions will be varied using translational and rotational springs. The finite element models will be excited using a point load resembling flow-induced forces (with varying flow velocity and fluid composition). These excitations are obtained from the literature and are based on experimental studies as power spectral density functions. The results show that the studied vibration acceptance criterion is suitable in 99.73% of all the studied models with 68.27% confidence level. For the models with a shorter mainline pipe, the criterial is suitable in 76.5% of the time with 68.27% confidence level.

Mitigating Safety Concerns of SRU Stack Using Advanced Analytical/Optical Technologies

Objective/Scope (25-75 word) In SRU, Tail gas exhaust stacks are provided with external cladding, preventing condensation beneath refractory surfaces. External cladding is made of individual Aluminium sheet panels, each 1.7mx1.5mx3mm thk, weighing 60Kg, attached by screws / rivets. Stack size is 6.5mdia × 90m height. Due to high wind, panel sometimes detaches from stack, falling down from 90m height, posing serious HSE threat to plant personal safety. This paper details an analytical design approach, supported with high resolution, remote controlled drone inspection technic to resolve one such issue. Methods, Procedures, Process (75-100 word) Initially, detached and dropped screws were observed, due to wind loads & vibration, which lead to falling of a clad panel from 80m height, fortunately, when no personal was below. Detailed finite element analysis of external cladding was performed, considering wind loads and thermal loads on panels with stack to panel joint configuration. Periodic inspection of the joints is vital to confirm reliability of the joints, which is not possible during operation with conventional inspection methods in an SRU exhaust stack. Hence, a latest technology, high-resolution, optical camera assisted, drone, controlled & monitored by remote computers were employed to assess the panel integrity. Results, Observations & Conclusions (100-200 words) Analysis Results Finite element analysis was performed for the stack cladding. As this analysis was non-conventional, there is no well-established industry acceptance criteria for the analysis results. Hence, an acceptance criteria was jointly developed with Contractor, which is fundamentally the minimum number of screws per panel, required to be intact, during the 2 year period, to confirm the panel integrity. Distance Drone inspection Manned inspection was not feasible in a running plant. Also, conventional aerial survey drones could not be engaged, as it was unsafe to fly the drone above live plant. Hence, an aerial drone with high-resolution optical camera, with overlapping method was employed. Advanced post processing software was used to analyse the images for best results. Conclusion To ensure clad panels integrity and 100% personal safety, Based on Finite element analysis, the original screws have been replaced with rivets with the following acceptance criteria. The integrity of the cladding remains intact even if 20% of the screws / rivets are lost whether it is consecutive or random. Above 20% there may be impact and further investigation is advised. Panels were monitored three times periodically in 2 year span to assess the fasteners intactness. The images from the optical camera, after software processing confirmed the fasteners integrity. Novel/Additive Information (25-75 words) 100% Plant and personal safety is ADNOC's principal objective. Occasionally, achieving this target require unorthodox analysis and acceptance criteria development. Most of all, the conventional monitoring technics, due to their limitations, pushes us to explore alternate technologies. The new high-resolution, optical camera assisted, drone technic can be engaged in a running plant and the images are processed using proprietary software to achieve best results of minute details.

Adalimumab and anti-adalimumab LISA-TRACKER immunoassays performance criteria for therapeutic drug monitoring of adalimumab-amgen biosimilar (ABP501)

Background ABP501 is a biosimilar to Reference Adalimumab (HUMIRA®) produced by AMGEN. Adalimumab (ADA) has a marketing authorization for Crohn's disease, ulcerative colitis and other inflammatory or autoimmune diseases. The aim of this study was to evaluate the LISA-TRACKER assays developed by Theradiag (France), for the monitoring of ABP501 and anti-ABP501 antibodies in human serum. Results 68 ABP501 clinical samples were measured with the LISA TRACKER Duo Adalimumab assay. LISA TRACKER has been validated as suitable for quantification of ABP501 in human serum samples. Accuracy of the LISA-TRACKER was measured using 3 human serum matrices spiked with known levels of biosimilar, 3 levels spanning the dynamic range. Percentages of recovery were ranged from 90 to 120% for biosimilar batch1, and between 93 and 105% for biosimilar batch2. The acceptance criteria (CV < 20%) were met for intra-run (from 3.8 to 16.5%) and inter-run imprecision (from 4.4 to 13.9%) including the two batches. All results were comprised within ± 20% from results, obtained with the kit and sample unexposed in order to evaluate stability of the sample, stability of the kit and consistency of the results. In any case, but two, all percentages of inhibition were > 50% for specificity. Specificity was tested with Biosimilar spiked samples, Biosimilar with Humira® spiked samples, and clinical samples from patients treated with adalimumab biosimilar. All of these samples were spiked with polyclonal antibodies directed against Humira®. Specificity inhibition and specificity detection steps were also part of the validation parameters. Reagents made with ABP501 gave similar results than reagents made with Humira® meeting acceptance criteria. Conclusions LISA-TRACKER ADA and anti-ADA assays are reliable for the monitoring of patients treated with ABP501.

Annulus Perforate, Wash and Cement : Establishing Barrier Verification Process for Deepwater Subsea Wells Abandonment and Its Lessons Learnt

Wells plug & abandonment was carried out in a deepwater field (Field C) offshore West Africa. There were 15 deepwater subsea wells, in this field. Thirteen of the wells were completed with Open Water Vertical Xmas Tree (OXT) while remaining two were completed with Enhanced Vertical Xmas Tree (EVXT). All the wells were permanently abandoned with permanent barriers established in accordance to Norsok D-010, rev. 2013. This involved establishing well barriers which would both horizontally and vertically effective. The operator evaluated several methods in establishing well barriers for the permanent abandonment purpose of these 15 wells. The barriers placement for areas with good annulus cement were straightforward as an internal cement plug could be spotted as a permanent barrier. For this particular field, it is noted that all of the 15 wells have hydrocarbon bearing and permeable formations above the top of expected annulus lead cement which is designed basically to manage ECD during cementing job rather than giving good annular isolation. Due to this, it is important for the operator to employ the best technique that could establish a permanent cement barrier both inside the casing and in the annulus at the same time. Operator learned that Section Milling was the widely accepted method to establish barrier in cases where there is poor cement or the annulus cement is not present particularly in land and offshore wells. However, this technique poses severe operational risk especially in a deepwater operation mode. Upon review, it was determined that Perforate, Wash and Cement (PWC) technology has been proven and it would become a valuable technique in establishing well barrier which complies with abandonment requirement as per the industry guidelines. High risk activities for deepwater operations such as section milling could be avoided by employing this method. Nonetheless, the Perforate, Wash and Cement (PWC) technology has its own set of risks especially with its method of establishing the well barrier immediately upon setting it. This involves drilling and re-logging the well immediately after setting the cement in annulus to prove the barrier. Upon discussion with PWC contractor, it was agreed that the verification technique may create additional hazards as it could jeopardize the integrity of the installed barrier in the annulus. The additional requirement for cement verification process will also prolong the project duration, hence is an additional cost to the project too. Operator worked together with the Perforate Wash and Cement (PWC) Contractor and Well Examiner to determine the best verification method for PWC plugs with the objective to comply with regulation on cement verification while at the same time, resulting in most cost-efficient and time-efficient operation. The establishment of Element Acceptance Criteria as an alternative Barrier Verification Process for PWC technology is necessary to improve the reliability of the system as well as reducing associated risks. In total, 18 PWC operations were successfully carried out throughout the campaign. An extensive after action review was conducted at the completion of each job to capture the valuable lessons learnt. These lessons learnt are shared in this paper as well which could add value for future operations with similar settings. It is expected that this paper will serve as a reference in the establishment of Element Acceptance Criteria as well as its implementation during the P&A campaign. It is hoped that the lessons learnt shared in the paper could assist other Operators on planning for similar campaigns in the future.

Adapting a Hyper-heuristic to Respond to Scalability Issues in Combinatorial Optimisation

<p>The development of a heuristic to solve an optimisation problem in a new domain, or a specific variation of an existing problem domain, is often beyond the means of many smaller businesses. This is largely due to the task normally needing to be assigned to a human expert, and such experts tend to be scarce and expensive. One of the aims of hyper-heuristic research is to automate all or part of the heuristic development process and thereby bring the generation of new heuristics within the means of more organisations. A second aim of hyper-heuristic research is to ensure that the process by which a domain specific heuristic is developed is itself independent of the problem domain. This enables a hyper-heuristic to exist and operate above the combinatorial optimisation problem “domain barrier” and generalise across different problem domains. A common issue with heuristic development is that a heuristic is often designed or evolved using small size problem instances and then assumed to perform well on larger problem instances. The goal of this thesis is to extend current hyper-heuristic research towards answering the question: How can a hyper-heuristic efficiently and effectively adapt the selection, generation and manipulation of domain specific heuristics as you move from small size and/or narrow domain problems to larger size and/or wider domain problems? In other words, how can different hyperheuristics respond to scalability issues? Each hyper-heuristic has its own strengths and weaknesses. In the context of hyper-heuristic research, this thesis contributes towards understanding scalability issues by firstly developing a compact and effective heuristic that can be applied to other problem instances of differing sizes in a compatible problem domain. We construct a hyper-heuristic for the Capacitated Vehicle Routing Problem domain to establish whether a heuristic for a specific problem domain can be developed which is compact and easy to interpret. The results show that generation of a simple but effective heuristic is possible. Secondly we develop two different types of hyper-heuristic and compare their performance across different combinatorial optimisation problem domains. We construct and compare simplified versions of two existing hyper-heuristics (adaptive and grammar-based), and analyse how each handles the trade-off between computation speed and quality of the solution. The performance of the two hyper-heuristics are tested on seven different problem domains compatible with the HyFlex (Hyper-heuristic Flexible) framework. The results indicate that the adaptive hyper-heuristic is able to deliver solutions of a pre-defined quality in a shorter computational time than the grammar-based hyper-heuristic. Thirdly we investigate how the adaptive hyper-heuristic developed in the second stage of this thesis can respond to problem instances of the same size, but containing different features and complexity. We investigate how, with minimal knowledge about the problem domain and features of the instance being worked on, a hyper-heuristic can modify its processes to respond to problem instances containing different features and problem domains of different complexity. In this stage we allow the adaptive hyper-heuristic to select alternative vectors for the selection of problem domain operators, and acceptance criteria used to determine whether solutions should be retained or discarded. We identify a consistent difference between the best performing pairings of selection vector and acceptance criteria, and those pairings which perform poorly. This thesis shows that hyper-heuristics can respond to scalability issues, although not all do so with equal ease. The flexibility of an adaptive hyper-heuristic enables it to perform faster than the more rigid grammar-based hyper-heuristic, but at the expense of losing a reusable heuristic.</p>

Adapting a Hyper-heuristic to Respond to Scalability Issues in Combinatorial Optimisation

<p>The development of a heuristic to solve an optimisation problem in a new domain, or a specific variation of an existing problem domain, is often beyond the means of many smaller businesses. This is largely due to the task normally needing to be assigned to a human expert, and such experts tend to be scarce and expensive. One of the aims of hyper-heuristic research is to automate all or part of the heuristic development process and thereby bring the generation of new heuristics within the means of more organisations. A second aim of hyper-heuristic research is to ensure that the process by which a domain specific heuristic is developed is itself independent of the problem domain. This enables a hyper-heuristic to exist and operate above the combinatorial optimisation problem “domain barrier” and generalise across different problem domains. A common issue with heuristic development is that a heuristic is often designed or evolved using small size problem instances and then assumed to perform well on larger problem instances. The goal of this thesis is to extend current hyper-heuristic research towards answering the question: How can a hyper-heuristic efficiently and effectively adapt the selection, generation and manipulation of domain specific heuristics as you move from small size and/or narrow domain problems to larger size and/or wider domain problems? In other words, how can different hyperheuristics respond to scalability issues? Each hyper-heuristic has its own strengths and weaknesses. In the context of hyper-heuristic research, this thesis contributes towards understanding scalability issues by firstly developing a compact and effective heuristic that can be applied to other problem instances of differing sizes in a compatible problem domain. We construct a hyper-heuristic for the Capacitated Vehicle Routing Problem domain to establish whether a heuristic for a specific problem domain can be developed which is compact and easy to interpret. The results show that generation of a simple but effective heuristic is possible. Secondly we develop two different types of hyper-heuristic and compare their performance across different combinatorial optimisation problem domains. We construct and compare simplified versions of two existing hyper-heuristics (adaptive and grammar-based), and analyse how each handles the trade-off between computation speed and quality of the solution. The performance of the two hyper-heuristics are tested on seven different problem domains compatible with the HyFlex (Hyper-heuristic Flexible) framework. The results indicate that the adaptive hyper-heuristic is able to deliver solutions of a pre-defined quality in a shorter computational time than the grammar-based hyper-heuristic. Thirdly we investigate how the adaptive hyper-heuristic developed in the second stage of this thesis can respond to problem instances of the same size, but containing different features and complexity. We investigate how, with minimal knowledge about the problem domain and features of the instance being worked on, a hyper-heuristic can modify its processes to respond to problem instances containing different features and problem domains of different complexity. In this stage we allow the adaptive hyper-heuristic to select alternative vectors for the selection of problem domain operators, and acceptance criteria used to determine whether solutions should be retained or discarded. We identify a consistent difference between the best performing pairings of selection vector and acceptance criteria, and those pairings which perform poorly. This thesis shows that hyper-heuristics can respond to scalability issues, although not all do so with equal ease. The flexibility of an adaptive hyper-heuristic enables it to perform faster than the more rigid grammar-based hyper-heuristic, but at the expense of losing a reusable heuristic.</p>

Tisagenlecleucel Leukapheresis and Manufacturing Outcomes in Patients Less Than 3 Years of Age with Relapsed/Refractory Acute Lymphoblastic Leukemia

Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR)-T cell therapy approved for patients (pts) ≤25 years of age with B-cell acute lymphoblastic leukemia (B-ALL) that is refractory or in second or later relapse. Pts &lt;3 years of age were excluded from tisagenlecleucel clinical trials in relapsed/refractory (r/r) ALL (NCT02435849 [ELIANA]; NCT02228096 [ENSIGN]). We present leukapheresis and tisagenlecleucel manufacturing outcomes in pts &lt;3 years old with r/r B-ALL in the US commercial setting since regulatory approval. Methods: Qualified pts were &lt;3 years of age at time of request for commercial tisagenlecleucel, with manufacturing data after August 30, 2017 (date of first FDA approval of tisagenlecleucel). Only pts whose tisagenlecleucel was manufactured and administered in the US were included; tisagenlecleucel was manufactured at Morris Plains, NJ, USA. Pt leukapheresis and manufacturing outcome data are presented for all pts and stratified by weight (&lt;10 kg and ≥10 kg) and age (&lt;1 year old and 1-3 years old). These data provide an extended analysis (cut-off March 31, 2021) from the previous report (Eldjerou, 2019). Results: Among 65 pts, the median age was 15.6 months (range, 3.6-36); median body weight was 10.4 kg (range, 6-20) at leukapheresis; 105 leukaphereses were performed in 65 pts (49 &lt;10 kg and 56 ≥10 kg). A median of 1 leukapheresis day was required to meet adequate cell counts (range, 1-4 &lt;10 kg and 1-6 ≥10 kg). The median total blood volume reported in 53/65 pts was 3.5 L (range, 1.3-14.3). The acceptance criteria for tisagenlecleucel manufacture (total nucleated cells: ≥2.0 × 10 9, CD3+ count: ≥1.0 × 10 9, CD3%: ≥3%) were met in 59/66 (26 &lt;10 kg and 33 ≥10 kg) leukapheresis materials; 7/66 did not meet acceptance criteria but proceeded to manufacturing. Following leukapheresis, median percent cell populations were: T cells 55.1% (58% &lt;10 kg and 54.8% ≥10 kg), B-cells 16.9% (20.3% &lt;10 kg and 14.6% ≥10 kg), natural killer cells 4% (3.8% &lt;10 kg and 4.7% ≥10 kg), and monocytes 3.9% (2.6% &lt;10 kg and 4.9% ≥10 kg). Manufacturing success is the formulation of a final product within approved specifications. Out of 66 manufacturing batches (23 batches &lt;1 year old and 43 batches 1-3 years old; 29 batches &lt;10 kg and 37 batches ≥10 kg), 55 (83.3%) were successful. Of the 59 manufacturing batches that met acceptance criteria, 50 were within specification, 2 were terminated, and 7 were out-of-specification due to cell viability (n=4), CAR+% expression (n=2), or another reason (n=1). One pt who experienced manufacturing failure was remanufactured successfully with a second attempt. Of the 7 batches that did not meet the acceptance criteria, 5 were within specifications and 2 were terminated. The median manufactured cell dose was 2.3x10 6 CAR+ viable T cells/kg [range, 0.23-4.6x10 6 (2.5x10 6 &lt;10 kg and 2.1x10 6 ≥10 kg)], median percent cell viability was 90.6% [range, 66.7%-98.3% (91.9% &lt;10 kg and 90% ≥10 kg)], median CAR+ percent expression was 12.0% [range, 2.1%-37.2% (12.2% &lt;10 kg and 11.8% ≥10 kg)]. From 2017 to 2021, the frequency of CD3+ cells present in the leukapheresis material was greatest in 2021 (Figure, left panel). The percentage of in-specification products was 69%-83% in 2017 to 2019 and increased to 89% and 100% in 2020 and 2021, respectively. Additionally, the number of terminations decreased over time (Figure, right panel). Measures for successful leukapheresis in low-weight infant/toddler pts include verification of absolute lymphocyte and/or CD3+ counts on the day prior to the leukapheresis procedure, maintenance of hematocrit levels at 40%, adequate venous access, blood prime of the leukapheresis instrument, prevention of hypocalcemia, and consideration for allowing for &gt;1 day of leukapheresis for the pt to meet the acceptance criteria when medically feasible/safe. During leukapheresis, hypothermia must be prevented, and the pt must be monitored for hypocalcemia, hypomagnesemia, and alkalosis. Conclusions: Leukapheresis and tisagenlecleucel manufacturability in pediatric pts with r/r B-ALL &lt;3 years old and low weight (lowest 6 kg, youngest 3.6 months) continues to be feasible and leukapheresis and manufacturing outcomes show an improvement over time. Communication among cross-functional teams within and between the institution and manufacturer have been key for achieving these advancements. Clinical outcome data for these pts are currently being explored. Figure 1 Figure 1. Disclosures Willert: Novartis Pharmaceuticals Corporation: Current Employment. Fong: Novartis Pharmaceuticals Corporation Canada: Current Employment. Clough: Novartis Pharmaceuticals Corporation: Current Employment. Magley: Novartis Pharmaceuticals Corporation: Current Employment. Shojaee: Novartis Pharmaceuticals Corporation: Current Employment. Tiwari: Novartis Healthcare Pvt. Ltd: Current Employment. Acker: Novartis Pharmaceuticals Corporation: Current Employment.

Risk-Acceptance Criteria in Occupational Health and Safety Risk-Assessment—The State-of-the-Art through a Systematic Literature Review

The utilization of risk acceptance criteria (RAC) can help a business to judge whether the risk level concerning any process involved in its working environment is acceptable or not, especially when the risk has a significant societal impact. Thus, the main intention of this study is to make known the current state-of-the-art concerning RACs and to propose new interpretations of it by surveying, for first time, the scientific literature about the RACs associated with the occupational health and safety (OHS) risk-assessment methodologies (RAA). A second objective of this work is the attainment of a prediction for the evolution of the quantity of the publications concerning OHS-RACs, and a third one is the derivation of an algorithm (via a flow-chart) in order to illustrate the process of the formation of new OHS-RACs. The work consists of two parts, (a) exploring and presenting methods of developing RACs in OHS; (b) classifying, analyzing, and benchmarking relevant published scientific articles by surveying the Scopus data base with proper search-hints, through a time interval of 20 years (January2000–December 2019). The review has defined a plethora of RAC-papers with reference to OHS, which is a remarkable percentage in comparison with the other fields aggregated, and this outcome proves that the issue of utilizing RACs is fundamental for the field of OHS. Additionally, it has been deduced that, day after day, there is an increasing tendency for the scientific community to develop and use RACs in the field of occupational safety, as this is evident by their frequent reference to the risk analysis and assessment (RAA) process. Our specific research methodology has been compatible with the PRISMA protocol. A prediction for the evolution of the quantity of the OHS-RAC publications is also given by confirming the Poisson stochastic process. Finally, we propose a generic guideline framework that can contribute to the establishment of new empirically-generated OHS-RACs.