New Visualization Models of Designation Pathway and Group Categorization of Device-Drug and Device-Biologic Combination Products Classification in the United States: Analysis of FDA Capsular Decisions.

Objective: The developer and sponsor of new combination products in US needs to forecast which classification and designation to the regulatory scheme of drug, biological product, or device would be required for the new products by the Food and Drug Administration (FDA). To improve the predictability and acceptability of the designation of new combination products for innovators, developers, and sponsors, and to encourage the development and early access of new combination products, we proposed new visualization models of the designation pathway and group categorization.

Method: We searched the website of the FDA on 15 November, 2020 to identify the regulatory scheme of the FDA's 129 capsular decision cases of device-drug and device-biologics combination products and other publicly available cases the FDA designated to the drug/biologic or device regulatory scheme.

Diagnostic Performance and Pressure Stability of a Novel Myocardial Ischemic Diagnostic Index - The Intracoronary-Electrocardiogram-Triggered Distal Pressure/Aortic Pressure Ratio.

We hypothesized that the intracoronary-electrocardiogram (IC-ECG)-based pressure index would be more stable and precise than the instantaneous flow reserve (iFR). We investigated the usefulness of the IC-ECG-based pressure index for diagnosing myocardial ischemia. Thirty-seven consecutive patients with coronary stenosis requiring physiological assessment were enrolled in the study.

Comparative performance analysis of interventional devices for the treatment of ischemic disease in below-the-knee lesions: a systematic review and meta-analysis.

This meta-analysis aimed to evaluate the device performance of conventional balloon catheters (POBA), drug-coated balloons (DCB), bare-metal stents (BMS), and drug-eluting stents (DES) in below-the-knee (BTK) ischemic lesions with regard to lesion characteristics. Online searches of PubMed, Web of Science, and Cochrane databases (2010-2019) were conducted for each of the test devices. Primary patency rates (pp) and major amputation rates 1 year after the use of each device were analyzed using a random-effects meta-analysis model.

Aortic root geometry following valve-sparing root replacement with reimplantation or remodeling: experimental investigation under static continuous pressure.

The differences in aortic root geometry associated with various valve-sparing root replacement (VSRR) techniques have not fully been understood. We evaluated the root configuration of current VSRR techniques by developing in vitro test apparatus. Six fresh porcine hearts were used for each model.

Bicuspid aortic valve morphology and aortic valvular outflow jets: an experimental analysis using an MRI-compatible pulsatile flow circulation system.

The characteristics of aortic valvular outflow jet affect aortopathy in the bicuspid aortic valve (BAV). This study aimed to elucidate the effects of BAV morphology on the aortic valvular outflow jets. Morphotype-specific valve-devising apparatuses were developed to create aortic valve models.

Comparison of supportive regulatory measures for pediatric medical device development in Japan and the United States.

Further development of medical devices for children is required in Japan, but the development of such devices is delayed compared to that of medical devices for adults. Herein, we investigated policies for advancing the development of pediatric medical devices in Japan and the United States. Considering the achievements of each policy, we proposed a strategy to promote further development of pediatric medical devices in Japan.

A case report of myocardial ischemia improvement despite early bypass graft occlusion: Efficiency of physiological reassessment.

Patients with functional ischemia often do not complain of chest symptoms even in early occlusion after coronary artery bypass grafting (CABG). The clinical evidence indicating the necessity of revascularization for these patients is unclear. A 70-year-old man who underwent 3 stent implant procedures to treat repeated in-stent restenosis to the left anterior descending artery (LAD) felt effort-related chest pain.

Effect of QTU prolongation on hyperemic instantaneous wave-free ratio value: a prospective single-center study.

We hypothesized that in patients with QT prolongation, resistance might not decrease in the wave-free period, because QTU prolongation cannot be detected by instantaneous wave-free ratio (iFR) analysis software. We investigated whether corrected QTU (QTUc) prolongation affects the hyperemic iFR value. Forty-two consecutive patients with intermediate stenosis (≥ 50%) in the left anterior descending coronary artery (LAD) were analyzed.

Confirmation of maximal hyperemia by the incremental dose of intracoronary papaverine.

We investigated the effect of the papaverine dose increment method to confirm maximal hyperemia for fractional flow reserve (FFR) measurements. We evaluated 115 consecutive patients involving 200 lesions. FFR was measured after intracoronary papaverine injection into the left (12 mg) and right (8 mg) coronary arteries as standard doses.

Clinical efficacy of bowel perfusion assessment during laparoscopic colorectal resection using laser speckle contrast imaging: A matched case-control study.

Introduction: Disadvantages of bowel perfusion assessment with indocyanine green fluorescence angiography include the need for a fluorophore and the subjective nature of the assessment. This study was performed to evaluate the clinical efficacy of bowel perfusion assessment using laser speckle contrast imaging (LSCI) during laparoscopic colorectal surgery.

Methods: The study population comprised the first 27 consecutive patients who underwent laparoscopic left-sided colorectal resection with intraoperative perfusion assessment using LSCI.

Deployment of stent graft in an excessively higher position above the renal artery induces a flow channel to the aneurysm in chimney endovascular aortic aneurysm repair: an in vitro study.

We aimed to investigate the influences of the sealing length above the renal artery (RA) on gutter formation, non-apposed regions between the aortic wall, stent graft (SG), and chimney graft and incidence of flow channel to the aneurysm in chimney endovascular aortic aneurysm repair (Ch-EVAR) using a juxtarenal abdominal aortic aneurysm model. Neck diameter and length of the silicone model were 24 and 4 mm, respectively. In double Ch-EVAR configuration using Advanta V12, 12 combinations were tested three times with two sizes [28.

Laser Speckle Contrast Imaging for Intraoperative Quantitative Assessment of Intestinal Blood Perfusion During Colorectal Surgery: A Prospective Pilot Study.

Background: The main limitation of perfusion assessment with indocyanine green fluorescence angiography during colorectal surgery is that the surgeon assesses the quality of perfusion subjectively. The ideal intestinal viability test must be minimally invasive, objective, and reproducible. We evaluated the quantitativity and reproducibility of laser speckle contrast imaging for perfusion assessment during colorectal surgery.

Underfilled Balloon-Expandable Transcatheter Aortic Valve Implantation With Ad Hoc Post-Dilation - Pulsatile Flow Simulation Using a Patient-Specific Three-Dimensional Printing Model.

Background: Underfilled transcatheter aortic-valve implantation with ad hoc post-dilation is a therapeutic option for patients with borderline annuli to avoid acute complication. The effects of this technique on valve leaflet behavior, hydrodynamic performances, and paravalvular leakage (PVL) using patient-specific three-dimensional (3D) aortic-valve models were investigated.

Methods and results: A female octogenarian patient was treated with this technique by using a 23-mm Sapien-XT.

Mechanical Ventilation-Related Safety Incidents in General Care Wards and ICU Settings.

Background: Although the ICU is the most appropriate place to care for mechanically ventilated patients, a considerable number are ventilated in general medical care wards all over the world. However, adverse events focusing on mechanically ventilated patients in general care have not been explored.

Methods: Data from the Japan Council for Quality Health Care database were analyzed.

Four Food and Drug Administration draft guidance documents and the REGROW Act: A litmus test for future changes in human cell- and tissue-based products regulatory policy in the United States?

Modern regenerative medicine research has expanded well past the development of traditional drugs and medical devices with many promising new therapies encompassing an increasingly diverse range of substances, notably cell-based therapies. These substantial recent developments and the progress in the health care and therapeutics fields necessitate a new regulatory framework agile enough to accommodate these unique therapies and acknowledge their differences with traditional pharmaceuticals. In the United States, recent proposed changes in the regulatory framework for autologous human cells, tissues, and cellular and tissue-based products (HCT/Ps) and their perceived risk-benefit analysis for patients remain controversial in the scientific field.

Quantitative assessment of paravalvular leakage after transcatheter aortic valve replacement using a patient-specific pulsatile flow model.

Background: Quantitative assessment of post-transcatheter aortic valve replacement (TAVR) aortic regurgitation (AR) remains challenging. We developed patient-specific anatomical models with pulsatile flow circuit and investigated factors associated with AR after TAVR.

Methods: Based on pre-procedural computed tomography (CT) data of the six patients who underwent transfemoral TAVR using a 23-mm SAPIEN XT, anatomically and mechanically equivalent aortic valve models were developed.

Investigation of adverse events associated with an off-label use of arterial stents and CE-marked iliac vein stents in the iliac vein: insights into developing a better iliac vein stent.

We analyzed the adverse events associated with an off-label use of arterial stents and CE-marked iliac vein stents for the treatment of iliac venous thromboembolism and investigated their relationships with the anatomical features of the iliac vein, to gain insights into the development of a better iliac vein stent. Reports of adverse events following the use of stents in the iliac vein were retrieved from the Manufacturer and User Facility Device Experience (MAUDE) database that contain suspected device-associated complications reported to the Food and Drug Administration. Data from 2006 to 2016 were investigated.

Comparison of the new Japanese legislation for expedited approval of regenerative medicine products with the existing systems in the USA and European Union.

Legislation for expedited-approval pathways and programmes for drugs, biologics or medical devices has been enacted for rapid commercialization of innovative products in the United States of America (USA) and the European Union (EU). However, less innovative products are increasingly benefitting from these expedited-approval pathways, and obligations to collect and report post-marketing data on approved products are being bypassed frequently. The Japanese government recently enacted legislation for a new conditional and time-limited approval pathway dedicated to regenerative medicine products.

A Comparative Safety Profile Assessment of Oncolytic Virus Therapy Based on Clinical Trials.

Oncolytic virus therapy (OVT) represents a new class of therapeutic agents in cancer treatment. The molecular and cellular mechanisms of action of OVTs have been evaluated in nonclinical/clinical phase trials. Various genetically modified viruses have been developed as oncolytic agents, and the first approval of an OVT for clinical use was issued by the US Food and Drug Administration in 2015.

Bayesian statistics and clinical trial designs for human cells and tissue products for regulatory approval.

Introduction: In order to obtain premarket approval for medical products derived from human cells or tissues in the United States (US), the European Union (EU), and Japan, data from clinical trials are typically required to evaluate product efficacy and safety. Clinical investigators or study sponsors often face challenges when designing clinical trials on human cells and tissue products with the goal of obtaining premarket approval owing to the unique characteristics of products in this category. The methods used to administer, infuse and transplant these products vary more widely than the methods used for pharmaceuticals.

Analysis of the safety evaluation for premarketing clinical trials of hemodialyzer and of postmarketing safety reports of hemodialyzer in Japan and the US: insights into the construction of a sophisticated premarketing evaluation.

Our aim was to conduct a scoping review of the regulations for hemodialyzers in the safety evaluation in Japan and the United States, and to evaluate the criteria for premarketing clinical trials and postmarketing safety reports to inform the development of a sophisticated premarketing evaluation in Japan. Regulations for approval of hemodialyzers were identified from the databases of the Ministry of Health, Labor and Welfare in Japan and the Federal Drug Agency (FDA) in the United States (US). The criteria for premarket clinical trials and postmarketing safety reports were evaluated for both countries.