scholarly journals Maximizing Regulatory Review Efficiency: The Evolution of the FDA OCE RTOR Pilot

2022 ◽  
Author(s):  
Ya Grace Gao ◽  
Samantha Roberts ◽  
Allison Guy
Keyword(s):  
Real Time ◽  
Drug Application ◽  
Priority Review ◽  
Pilot Program ◽  
Regulatory Review ◽  
Oncology Review ◽  
The Us ◽  
Complex Features ◽  
Study Designs ◽  
Oncology Center

AbstractTo promote the efficient review of oncology drug applications, the US Food and Drug Administration (FDA) Oncology Center of Excellence (OCE) launched the Real-Time Oncology Review (RTOR) pilot program in 2018. RTOR allows FDA to review individual sections of eCTD modules of a drug application for oncology drugs in contrast to requiring the applicant to submit complete modules or the complete application before review is initiated. Initially, the program accepted only supplemental applications with simple study designs and easily interpretable endpoints, but the scope has since been expanded to include applications for New Molecular Entities (NME), and other applications with more complex features. Though many applicants experience faster approvals under RTOR, it is difficult to isolate the effect of the RTOR program on review timelines as its contribution is masked by other expedited programs like priority review and breakthrough therapy designation (BTD). This article discusses the expanded scope of RTOR, its interplay with other OCE initiatives to modernize regulatory review, summarizes Genentech’s experiences in planning RTOR submissions from February 2019 to July 2021, and provides considerations for the future of the program.

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies

2019 ◽  
Vol 143 (1) ◽  
pp. 73-77
Author(s):  
Anat Gafter-Gvili ◽  
Ariadna Tibau ◽  
Pia Raanani ◽  
Daniel Shepshelovich
Keyword(s):  
Hematological Malignancies ◽  
New Drugs ◽  
Priority Review ◽  
Regulatory Review ◽  
Regulatory Pathways ◽  
The Us ◽  
Black Box Warnings ◽  
Accelerated Approval ◽  
Drug Approvals ◽  
Approved Drugs

The prevalence of safety-related postmarketing label modifications of medications for hematological malignancies is unknown. We identified 35 new drugs indicated for hematological malignancies approved by the US Food and Drug Administration between January 1999 and December 2014. Characteristics of supporting trials and safety-related label modifications from approval to December 2017 were collected from drug labels. Regulatory review and approval pathways were also collected. New drug approvals were supported by trials with a median of 167 patients (interquartile range 115–316). All drugs were approved based on surrogate endpoints. Twenty-seven drug approvals (77%) were not supported by randomized controlled trials. All drugs received orphan drug designation, and most were granted fast track designation, priority review, and accelerated approval (83, 74, and 60%, respectively). A total of 28 drugs (80%) had postmarketing safety-related label modifications. Additions to black box warnings, contraindications, warnings and precautions, and common adverse reactions were identified in 31, 11, 77, and 46% of drugs, respectively. Five drugs (14%) were permanently or temporarily withdrawn from the US market. Drugs for hematological malignancies are often approved based on limited evidence through expedited regulatory pathways with incomplete safety profiles. Hematologists should be vigilant for unrecognized side effects when prescribing newly approved drugs.

FDA’s Oncology Center for Excellence Pilots Project Orbis: A framework for concurrent submission and review of oncology products among international partners.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14125-e14125
Author(s):  
Dianne Spillman ◽  
Shaily Arora ◽  
Rajesh Venugopal ◽  
Bradley Scott ◽  
Sarah Golding ◽  
...  
Keyword(s):  
Cancer Therapeutics ◽  
The United States ◽  
Lymphocytic Leukemia ◽  
Health Science ◽  
Therapeutic Good Administration ◽  
Pilot Program ◽  
Regulatory Review ◽  
Regulatory Pathways ◽  
Health Canada ◽  
Oncology Center

e14125 Background: Cancer therapeutics often receive FDA approval months to years before regulatory submission to other countries. [i] Registrational trials in oncology are increasingly international, with many patients enrolled outside of the United States. Harmonizing access to new global standards of treatment may facilitate optimal design and conduct of global clinical trials. Methods: In May 2019, the Oncology Center for Excellence launched Project Orbis in collaboration with the Australian Therapeutic Good Administration (TGA) and Health Canada. The aim of this initiative is to provide a framework for concurrent submission and review of oncology products among international partners to facilitate global access. Results: The first Project Orbis was a collaborative review of a supplemental application for lenvatinib and pembrolizumab for patients with advanced endometrial cancer. This review also deployed other OCE regulatory review tools including the Real-Time Oncology Review (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire application, and its accompanying Assessment Aid, to facilitate discussions among regulatory agencies. Lenvatinib and pembrolizumab was approved on September 17, 2019, in conjunction with the TGA and Health Canada, three months prior to the FDA goal date. FDA, TGA, and Health Canada issued a second action under Project Orbis on November 21, 2019, with the approval of acalabrutinib for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Several other products are under international review as part of this pilot program and a summary of timelines and outcomes will be described. Conclusions: Project Orbis is an innovative OCE initiative that leverages the Center’s longstanding communication and collaboration with international regulators. This pilot program facilitates concurrent submission and review of oncology products among global regulatory health agencies. Continued efforts under Project Orbis will build on the initial success to incorporate additional global partners including Swissmedic and Singapore’s Health Science Authority. [i] The Centre for Innovation in Regulatory Science (CIRS). R&D Briefing 70 New drug approvals in six major authorities 2009-2018: Focus on Facilitated Regulatory Pathways and Orphan Status

scholarly journals Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria

2019 ◽  
Vol 10 ◽  
pp. 204062071987472 ◽  
Author(s):  
Robert M. Stern ◽  
Nathan T. Connell
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Failure ◽  
Phase Iii ◽  
The European Union ◽  
Regulatory Review ◽  
Dosing Schedule ◽  
The Us ◽  
United States Food ◽  
States Food ◽  
Us Fda

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare stem cell disorder characterized by hemolytic anemia, bone marrow failure, and thrombosis. Until recently, the complement inhibitor, eculizumab, was the only United States Food and Drug Administration (US FDA)-approved therapy for the treatment of PNH. Although effective, eculizumab requires a frequent dosing schedule that can be burdensome for some patients and increases the risk of breakthrough intravascular hemolysis. Ravulizumab, an eculizumab-like monoclonal antibody engineered to have a longer half-life, is intended to provide the same benefits as eculizumab but with a more convenient and effective dosing schedule. In two recently published phase III non-inferiority trials, ravulizumab was found to be non-inferior to eculizumab both in efficacy and safety for the treatment of patients with PNH. Based on these results, ravulizumab was approved by the US FDA on 21 December 2018 and is currently under regulatory review in both the European Union and Japan.

Improving Operational Efficiency Using Automated Time Analysis for Multi-Well Pad Fracturing

2021 ◽  
Author(s):  
Fahd Siddiqui ◽  
Mohammadreza Kamyab ◽  
Michael Lowder
Keyword(s):  
Real Time ◽  
Operational Efficiency ◽  
Permian Basin ◽  
Potential Cost ◽  
Time Period ◽  
Cloud Server ◽  
The Us ◽  
Single Well ◽  
Complete Automation

Abstract The economic success of unconventional reservoirs relies on driving down completion costs. Manually measuring the operational efficiency for a multi-well pad can be error-prone and time-prohibitive. Complete automation of this analysis can provide an effortless real-time insight to completion engineers. This study presents a real-time method for measuring the time spent on each completion activity, thereby enabling the identification and potential cost reduction avenues. Two data acquisition boxes are utilized at the completion site to transmit both the fracturing and wireline data in real-time to a cloud server. A data processing algorithm is described to determine the start and end of these two operations for each stage of every well on the pad. The described method then determines other activity intervals (fracturing swap-over, wireline swap-over, and waiting on offset wells) based on the relationship between the fracturing and wireline segments of all the wells. The processed data results can be viewed in real-time on mobile or computers connected to the cloud. Viewing the full operational time log in real-time helps engineers analyze the whole operation and determine key performance indicators (KPIs) such as the number of fractured stages per day, pumping percentage, average fracture, and wireline swap-over durations for a given time period. In addition, the performance of the day and night crews can be evaluated. By plotting a comparison of KPIs for wireline and fracturing times, trends can be readily identified for improving operational efficiency. Practices from best-performing stages can be adopted to reduce non-pumping times. This helps operators save time and money to optimize for more efficient operations. As the number of wells increases, the complexity of manual generation of time-log increases. The presented method can handle multi-well fracturing and wireline operations without such difficulty and in real-time. A case study is also presented, where an operator in the US Permian basin used this method in real-time to view and optimize zipper operations. Analysis indicated that the time spent on the swap over activities could be reduced. This operator set a realistic goal of reducing 10 minutes per swap-over interval. Within one pad, the goal was reached utilizing this method, resulting in reducing 15 hours from the total pad time. The presented method provides an automated overview of fracturing operations. Based on the analysis, timely decisions can be made to reduce operational costs. Moreover, because this method is automated, it is not limited to single well operations but can handle multi-well pad completion designs that are commonplace in unconventionals.

scholarly journals Internet of medical things – integrated, ultrasound-based respiration monitoring system for incubators

2020 ◽  
Author(s):  
◽  
Tareq Abdulqader
Keyword(s):  
Real Time ◽  
Respiration Rate ◽  
Surface Measurement ◽  
Time Interval ◽  
Portable Devices ◽  
Important Indicator ◽  
The Us ◽  
Respiratory Signal ◽  
Central Apnoea ◽  
Respiration Signal

The study's aim was to develop a non-contact, ultrasound (US) based respiration rate and respiratory signal monitor suitable for babies in incubators. Respiration rate indicates average number of breaths per minute and is higher in young children than adults. It is an important indicator of health deterioration in critically ill patients. The current incubators do not have an integrated respiration monitor due to complexities in its adaptation. Monitoring respiratory signal assists in diagnosing respiration rated problems such as central Apnoea that can affect infants. US sensors are suitable for integration into incubators as US is a harmless and cost-effective technology. US beam is focused on the chest or abdomen. Chest or abdomen movements, caused by respiration process, result in variations in their distance to the US transceiver located at a distance of about 0.5 m. These variations are recorded by measuring the time of flight from transmitting the signal and its reflection from the monitored surface. Measurement of this delay over a time interval enables a respiration signal to be produced from which respiration rate and pauses in breathing are determined. To assess the accuracy of the developed device, a platform with a moving surface was devised. The magnitude and frequency of its surface movement were accurately controlled by its signal generator. The US sensor was mounted above this surface at a distance of 0.5 m. This US signal was wirelessly transmitted to a microprocessor board to digitise. The recorded signal that simulated a respiratory signal was subsequently stored and displayed on a computer or an LCD screen. The results showed that US could be used to measure respiration rate accurately. To cater for possible movement of the infant in the incubator, four US sensors were adapted. These monitored the movements from different angles. An algorithm to interpret the output from the four US sensors was devised and evaluated. The algorithm interpreted which US sensor best detected the chest movements. An IoMT system was devised that incorporated NodeMcu to capture signals from the US sensor. The detected data were transmitted to the ThingSpeak channel and processed in real-time by ThingSpeak’s add-on Matlab© feature. The data were processed on the cloud and then the results were displayed in real-time on a computer screen. The respiration rate and respiration signal could be observed remotely on portable devices e.g. mobile phones and tablets. These features allow caretakers to have access to the data at any time and be alerted to respiratory complications. A method to interpret the recorded US signals to determine respiration patterns, e.g. intermittent pauses, were implemented by utilising Matlab© and ThingSpeak Server. The method successfully detected respiratory pauses by identifying lack of chest movements. The approach can be useful in diagnosing central apnoea. In central apnoea, respiratory pauses are accompanied by cessation of chest or abdominal movements. The devised system will require clinical trials and integration into an incubator by conforming to the medical devices directives. The study demonstrated the integration of IoMT-US for measuring respiration rate and respiratory signal. The US produced respiration rate readings compared well with the actual signal generator's settings of the platform that simulated chest movements.

scholarly journals Robotic Ultrasound Scanning With Real-Time Image-Based Force Adjustment: Quick Response for Enabling Physical Distancing During the COVID-19 Pandemic

2021 ◽  
Vol 8 ◽  
Author(s):  
Mojtaba Akbari ◽  
Jay Carriere ◽  
Tyler Meyer ◽  
Ron Sloboda ◽  
Siraj Husain ◽  
...  
Keyword(s):  
Quality Assessment ◽  
Real Time ◽  
Close Contact ◽  
Image Features ◽  
Svm Classifier ◽  
Quick Response ◽  
Robot Arm ◽  
Noise Characteristics ◽  
The Us

During an ultrasound (US) scan, the sonographer is in close contact with the patient, which puts them at risk of COVID-19 transmission. In this paper, we propose a robot-assisted system that automatically scans tissue, increasing sonographer/patient distance and decreasing contact duration between them. This method is developed as a quick response to the COVID-19 pandemic. It considers the preferences of the sonographers in terms of how US scanning is done and can be trained quickly for different applications. Our proposed system automatically scans the tissue using a dexterous robot arm that holds US probe. The system assesses the quality of the acquired US images in real-time. This US image feedback will be used to automatically adjust the US probe contact force based on the quality of the image frame. The quality assessment algorithm is based on three US image features: correlation, compression and noise characteristics. These US image features are input to the SVM classifier, and the robot arm will adjust the US scanning force based on the SVM output. The proposed system enables the sonographer to maintain a distance from the patient because the sonographer does not have to be holding the probe and pressing against the patient's body for any prolonged time. The SVM was trained using bovine and porcine biological tissue, the system was then tested experimentally on plastisol phantom tissue. The result of the experiments shows us that our proposed quality assessment algorithm successfully maintains US image quality and is fast enough for use in a robotic control loop.

scholarly journals Automating Terrain Texturing in Real-Time Using a Rule-Based Approach

2010 ◽  
Vol 9 (4) ◽  
pp. 21-28
Author(s):  
John Ferraris ◽  
Christos Gatzidis ◽  
Feng Tian
Keyword(s):  
Real Time ◽  
Rule Based ◽  
Novel Approach ◽  
Great Performance ◽  
Rule Set ◽  
Complex Features ◽  
Rule Based Approach

This publication proposes a novel approach to automatically colour and texture a given terrain mesh in real time. Through the use of weighting rules, a simple syntax allows for the generation of texture and colour values based on the elevation and angle of a given vertex. It is through this combination of elevation and angle that complex features such as ridges, hills and mountains can be described, with the mesh coloured and textured accordingly. The implementation of the approach is done entirely on the GPU using 2D lookup textures, delivering a great performance increase over typical approaches that pass colour and weighting information in the fragment shader. In fact, the rule set is abstracted enough to be used in conjunction with any colouring/texturing approach that uses weighting values to dictate which surfaces are depicted on the mesh

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