Development Of Medical Devices Research Articles

Regulatory considerations of material used for medical devices and combination products in different countries: A review

Combination product can act as a medicine, medical device, or biological product that combines two or more regulated components. Combination products were originally described in 1991′s Title 21 3.2(e) of the Code of Federal Regulation i.e., CFR, under (21 CFR 3.2(e)). Combination products were originally described in 1991′s Title 21 3.2(e) of the Code of Federal Regulation i.e, CFR, under (21 CFR 3.2(e))currently enforced inthe U.S., European Union, South Korea, Malaysia, Japan, Canada.There are different regulations and approaches towards products inboth Europe and the United States. The definition differs from country to country when looking for the same term in other countries. The definition differs from country to country when looking for the same term in other countries. Contrarily, the European Union organises pharmaceutical combination products into a unit category and lacks a common definition of combination products.. As a result, the main variation in how combination products are defined across all nations is the regulatory framework.. While the US and Japan have similar definitions of combination products. The rules that should apply to combination products are outlined in the definition of a combination product. Efficacy is “the capacity of a medical instrument,” whereas safety is “Freedom from unacceptable risk. ”In products that are combinations, Interactions between various components must be taken into account first. For combination products, the biological assessment of the finished product shall be in accordance with the ISO 10993 family of standards.Countries all over the world place a high value on innovative combination items and have developed a number of strategies and directives to stimulate the development of innovative products. This article describes the Medicated Device Combination Product in various nations, along with its advantages over Medical Device and local medication therapy, the current market environment, and anticipated market trends.

Power of Parametric: Methods to Validate Ethylene Oxide Sterilization Parametric Release.

When approaching an ethylene oxide (EO) sterilization validation, medical device manufacturers traditionally have two choices. They can use biological indicators (BIs) to monitor each production run or establish a parametric release process in which sterile release is based on the monitoring and control of physical process parameters that ensure process specifications are met. In ISO 11135:2014, parametric release was brought to the forefront as an acceptable release method; however, a perception exists that implementing parametric release is challenging and time consuming. This article will demonstrate that the opposite is true. It presents a streamlined approach in which parametric release is addressed through the various stages of validation: product definition, process definition, performance qualification, routine release, and process control. Considerations for establishing specifications directly from validation versus "run and record" and trending critical process parameters (e.g., relative humidity, temperature, EO concentration) are discussed. In addition, the benefits of parametric release (active monitoring) over BI release (passive monitoring), including improvements to turnaround time, process control, risk mitigation, reduction of resource investment, and elimination of microbiological release testing, are highlighted. With multiple benefits, parametric release should be the gold standard for EO sterilization processes. It is not novel and has been widely accepted by regulatory agencies globally and notified bodies. The article further describes how the data collection and process capability that is central to process control and parametric release is more powerful than the information provided by a BI, which is merely a catastrophic indicator when used in routine processing.

MRI-based parameter inference for cerebral perfusion modelling in health and ischaemic stroke

Cerebral perfusion modelling is a promising tool to predict the impact of acute ischaemic stroke treatments on the spatial distribution of cerebral blood flow (CBF) in the human brain. To estimate treatment efficacy based on CBF, perfusion simulations need to become suitable for group-level investigations and thus account for physiological variability between individuals. However, computational perfusion modelling to date has been restricted to a few patient-specific cases. This study set out to establish automated parameter inference for perfusion modelling based on neuroimaging data and thus enable CBF simulations of groups. Magnetic resonance imaging (MRI) data from 75 healthy senior adults were utilised. Brain geometries were computed from healthy reference subjects’ T1-weighted MRI. Haemodynamic model parameters were determined from spatial CBF maps measured by arterial spin labelling (ASL) perfusion MRI. Thereafter, perfusion simulations were conducted in 75 healthy cases followed by 150 acute ischaemic stroke cases representing an occlusion and CBF cessation in the left and right middle cerebral arteries. The anatomical fitness of the brain geometries was evaluated by comparing the simulated grey (GM) and white matter (WM) volumes to measurements in healthy reference subjects. Strong positive correlations were found in both tissue types (GM: Pearson’s r 0.74, P<0.001; WM: Pearson’s r 0.84, P<0.001). Haemodynamic parameter tuning was verified by comparing the total volumetric blood flow rate to the brain in healthy reference subjects and simulations (Pearson’s r 0.89, P<0.001). In acute ischaemic stroke cases, the simulated infarct volume using a perfusion-based estimate was 197±25 ml. Computational predictions were in agreement with anatomical and haemodynamic values from the literature concerning T1-weighted, T2-weighted, and phase-contrast MRI measurements in healthy scenarios and acute ischaemic stroke cases. The acute stroke simulations did not capture small infarcts (left tail of the distribution), which could be explained by neglected compensatory mechanisms, e.g. collaterals. The proposed parameter inference method provides a foundation for group-level CBF simulations and for in silico clinical stroke trials which could assist in medical device and drug development.

A systematic review on bisphenols – Sources, health impacts, and analytical determination of bisphenol A in aqueous samples

AbstractBisphenol A and its structural analogs are used by industrial processes for the manufacture of plastics, and medical and electronic devices. When these products are disposed of, they tend to leach out causing pollution and impacting human health. Thus, many studies are focused on detecting the presence of Bisphenols in environmental matrices, especially in water and food, as it is a major route of human exposure. Advancements have been made in the preparation and detection of samples using different analytical techniques. The most widely used techniques for bisphenol detection are liquid chromatography and gas chromatography coupled with mass spectroscopy. The progress made for ultra‐trace detection of Bisphenols via the development of efficient sample extraction techniques and the benefits of each technique are highlighted. The recent advances in detection techniques using colorimetric and Raman spectroscopy are reviewed with an emphasis on the use of portable onsite techniques compared to conventional labor‐intensive and time‐consuming techniques. An overview of all the approaches to determining Bisphenols in environmental and food samples is discussed in detail to provide insight into the progress made in this field.

Quality management system: A tool for the development of the organization or an additional burden?

A quality management system constitutes one of the organizations management systems that provides for the selection of a set of processes in the organizations activities designed to ensure the stable quality of products and services provided.&#x0D; The growth of global industrial production has underscored the need for the creation of such production and management systems. These systems are designed to ensure that enterprises remains prepared to meet the constantly changing consumer value of manufactured products in accordance with consumer requirements, as well as the satisfaction of consumers themselves. As a result, attention began to focus on the production processes implemented within the organization when creating products. Regarding the production of medical devices, a quality management system can be defined as an organizational structure encompassing its functions, procedures, processes, and resources necessary for the coordinated direction and management of a manufacturing organization with respect to the quality of medical products.&#x0D; The article reflects the principles of the quality management system and management processes. Noteworthy emphasis is placed on the features of quality management systems for medical devices, including the features of the quality management system for software that is a medical device. Furthermore, the conditions under which the quality management system becomes a tool for ensuring the sustainable development of the organization are noted.

Personalized additive manufacturing of devices for the management of enteroatmospheric fistulas.

Additive manufacturing techniques allow the customized design of medical devices according to the patient's requirements. Enteroatmospheric fistula is a pathology that benefits from this personalization due to its extensive clinical variability since the size and morphology of the wound differ extensively among patients. Standard prosthetics do not achieve proper isolation of the wound, leading to a higher risk of infections. Currently, no effective personalized technique to isolate it has been described. In this work, we present the workflow for the design and manufacture of customized devices adapted to the fistula characteristics as it evolves and changes during the treatment with Negative Pressure Wound Therapy (NPWT). For each case, a device was designed with dimensions and morphology depending on each patient's requirements using white light scanning, CAD design, and additive manufacturing. The design and manufacture of the devices were performed in 230.50 min (184.00-304.75). After the placement of the device, the wound was successfully isolated from the intestinal content for 48-72 h. The therapy was applied for 27.71 ± 13.74 days, and the device was redesigned to adapt to the wound when geometrical evolutionary changes occur during the therapy. It was observed a decrease in weekly cures from 23.63 ± 10.54 to 2.69 ± 0.65 (p = 0.001). The fistulose size was reduced longitudinal and transversally by 3.25 ± 2.56 cm and 6.06 ± 3.14 cm, respectively. The wound depth also decreased by 1.94 ± 1.08 cm. In conclusion, customization through additive manufacturing is feasible and offers promising results in the generation of personalized devices for the treatment of enteroatmospheric fistula.

The Effect of Titanium Dioxide Nanoparticle Composites as an Antibacterial in Synthesizing Polyurethane Biopolymers

Abstract. In the health sector, the use of polyurethane (PU) as a basic material for the manufacture of medical devices also creates problems related to local and systemic infections. One of the most appropriate ways to overcome this problem is to add titanium dioxide (TiO2) nanoparticles to the urethane polymer to produce a biodegradable polymer and bacterial decontamination. In synthesizing decontaminating polyurethane bacteria, several characterization techniques were carried out, including polymer test, namely strain and stress, functional group analysis using Fourier Transform Infra-Red (FTIR), and antibacterial test. Based on the results of the FTIR test analysis, shows a change in the functional group. At wave number 1724.36 cm-1, the N-H functional group appears, this absorption is the absorption of the urethane group and TiO2 is in the range of 513.07 cm-1. Mechanical properties test showed strain (28.92 - 21.88% GL) and young modulus at intervals (5,484-3,268 MPa). and the antibacterial test showed that the inhibitory power of test samples A1 and A4 with resistance diameters of 8mm and 8mm proved to be very effective in killing E.Coli bacteria while A1¹, A2¹, A3¹, and A4 killed could not kill S. Aureus bacteria inhibitors. The characterization results show that the polyurethane biopolymer can be used as a medical device with bacterial decontamination properties.

Patient Engagement and Patient Experience Data in Regulatory Review and Health Technology Assessment: A Global Landscape Review

BackgroundWorking with patients through meaningful patient engagement (PE) and incorporating patient experience data (PXD) is increasingly important in medicines and medical device development. However, PE in the planning, organization, generation, and interpretation of PXD within regulatory and health technology assessment (HTA) decision-making processes remains challenging. We conducted a global review of the PE and PXD landscape to identify evolving resources by geography to support and highlight the potential of integration of PE and PXD in regulatory assessment and HTA.MethodsA review of literature/public information was conducted (August 2021–January 2023), led by a multistakeholder group comprising those with lived or professional experience of PE and PXD, to identify relevant regulatory and HTA initiatives and resources reviewed and categorized by geography and focus area.ResultsOverall, 53 relevant initiatives/resources were identified (global, 14; North America, 11; Europe, 11; Asia, nine; UK, six; Latin America, one; Africa, one). Most focused either on PE (49%) or PXD (28%); few (11%) mentioned both PE and PXD (as largely separate activities) or demonstrated an integration of PE and PXD (11%).ConclusionsOur analysis demonstrates increasing interest in PE, PXD, and guidance on their use individually in decision-making. However, more work is needed to offer guidance on maximizing the value of patient input into decisions by combining both PE and PXD into regulatory and HTA processes; the necessity of integrating PE in the design and interpretation of PXD programs should be highlighted. A co-created framework to achieve this integration is part of a future project.

The significance of ternary hybrid cross bio-nanofluid model in expanding/contracting cylinder with inclined magnetic field

Significance: Bio-nanofluids have achieved rapid attention due to their potential and vital role in various fields like biotechnology and energy, as well as in medicine such as in drug delivery, imaging, providing scaffolds for tissue engineering, and providing suitable environments for cell growth, as well as being used as coolants in various energy systems, wastewater treatment, and delivery of nutrients to plants.Objective: The present study proposes a novel mathematical model for the ternary hybrid cross bio-nanofluid model to analyse the behaviour of blood that passes through a stenosed artery under the influence of an inclined magnetic field. The model considers the effect of expanding/contracting cylinder, infinite shear rate viscosity, and bio-nanofluids.Methodology: The considered model of the problem is bounded in the form of governing equations such as PDEs. These PDEs are transformed into ODEs with the help of similarity transformations and then solved numerically with the help of the bvp4c method.Findings: The results show that the flow rate and velocity decrease as the inclination angle of the magnetic field increases. Additionally, research has found that the presence of nanoparticles in the bio-nanofluid has a significant impact on the velocity and flow rate. Therefore, the flow rate decreases, in general, as the stenosis becomes more severe.Advantages of the study: The results obtained from this study may provide insights into the behaviour of blood flow in stenosed arteries and may be useful in the design of medical devices and therapies for the treatment of cardiovascular diseases.

The Use of 3D Printing and Nanotechnologies to Prevent and Inhibit Biofilms on Medical Devices

Biofilms remain one of the most pervasive complications of the medical field, representing 50–70% of all nosocomial infections and up to 80% of total microbial infections. Since biofilms contain intricately small matrices, different microenvironments, and accumulations of biodiverse microorganisms of different resistances, these structures end up being difficult to target. As we review in this paper, 3D printing and nanotechnology help overcome these unique challenges of targeting biofilms, especially within the medical field. These technologies bring versatility and more precise control to personalized reusable medical device development and implants, with enhanced antimicrobial characteristics. They allow for decreased surface roughness of the implants, smaller pores, more targeted topography, and even added antibiotic or drug-releasing abilities for the medical devices. Furthermore, combining 3D with nanoparticles allows for the creation of anodized nanosurfaces of medical implants with increased osseointegration and reduced polymerization while promoting cost efficiency, durability, and biocompatibility. In this review, we explore the potentially valuable antimicrobial consequences of applying 3D technology and nanoengineering to dental and orthodontic implants, oral prostheses, hearing aids, joint replacements, catheters, stents, endotracheal tubes, prosthetics, and bone scaffolds.

On government regulation of the market of medical devices

Subject. This article discusses the expansion of the range of medical devices manufactured in Russia and import substitution in the healthcare sector. Objectives. The article aims to determine the subjects and objects of the market of medical devices and analyze the regulatory legal acts governing the circulation of medical devices in Russia. Methods. For the study, we used statistical and content analyses. Results. The article finds that the concepts of medical market, market of medical services, and market of medical devices are not clearly defined in Russian legislation, and many State and interstate standards for medical devices need to be updated. Conclusions. It is necessary to draft and adopt a Federal law On the Production and Circulation of Medical Devices in the Russian Federation, which, in particular, will regulate the issues of import substitution in the healthcare sector.

Limitation of the migration of plasticizers from medical devices through treatment with low-pressure cold plasma, polydopamine coating, and annealing

Poly(vinyl chloride) (PVC) is widely used in the manufacture of medical devices. The plasticizers added to PVC are potentially toxic for humans, likely to migrate, and thus unintentionally administered to patients. The objective of the present study was to reduce the migration of plasticizer (1,2-cyclohexanedicarboxylic acid, diisononylester (DINCH) or trioctyltrimellitate (TOTM)) from PVC by implementing a three-step surface treatment process: (i) pretreatment with low-pressure argon cold plasma, (ii) polydopamine coating, and (iii) post-treatment with cold plasma exposure or thermal treatment at 140 °C.Samples were then characterized in terms of the water contact angle (WCA) and the aspect in scanning electron microscopy. Plasticizer migration (n = 5) was measured using an HPLC technique with ultraviolet detection and found to depend on the treatment and the plasticizer.Plasticized PVC was hydrophobic, with a measured mean ± standard deviation WCA of 96.7 ± 3.6° for PVC-DINCH and 110.2 ± 5.8° for PVC-TOTM. Plasma post-treatment and thermal post-treatment were respectively associated with a mean decrease in migration of 38.3 ± 1.9% for DINCH and 61.5 ± 4.4% for TOTM.Our results are promising with regard to limiting the migration of plasticizers into the patient’s blood and thus enabling the development of safer medical devices.

Development of new surgical mesh geometries with different mechanical properties using the design freedom of 3D printing

AbstractThe emergence of new rapid prototyping techniques such as melt electrowriting and their application in the development of medical devices, enables new geometries for surgical meshes that were previously limited by current conventional manufacturing methods. The change in geometry allows a direct impact on the mechanical behavior of surgical meshes using identical polymers. The adaptation of the mechanical properties of surgical meshes, based on sinusoidal auxetic design with varying amplitude and number of waves per total fiber length, aims to improve biocompatibility by mimicking and matching the mechanical properties of vaginal soft tissue, which is not provided by current polypropylene nondegradable meshes. The auxetic design of the meshes can supply dimensionally stable pores under tensile load, which is a limitation of the current meshes. The mechanical properties can be controlled with mesh deformations up to 100%, Young's modulus ranging from 50 to 400 N/mm2 and a variable toe region. The printed meshes show an effective porosity of over 70% and are lightweight or ultra‐lightweight. By combining matching mechanical properties with good porosity and weight, 3D printed sinusoidal meshes, made of biodegradable Poly‐ε‐caprolactone, show promising results to improve surgical meshes for use in pelvic organ prolapse repair.

General Risks of CRM&amp;N Product Development Process: A Case Study of a Medical Device Manufacturing Company

Nowadays, every new product development process is bound to have certain risks. This study will analyze the identification and control risks in the Cardiac Rhythm Management &amp; Neuromodulation (CRM&amp;N) product development process of a medical device manu-facturing company in the United States and summarize and analyze the common risks dur-ing New Product Development Process (PDP). CRM&amp;N system of medical industry prod-uct and service institutions, namely the CRM&amp;N system used by medical devices, medical equipment, medical consumables, biotechnology and other medical products/services en-terprises. The medical industry is facing many problems in transportation and terminal sales. This study adopts the case analysis method, through the analysis of a new product development case of a company, the research results of this study are obtained: (1) Risk should be controlled at every step of a new product from the preparation before production to the end of production. Therefore, the company needs to establish a complete risk man-agement system to reduce the existence of some risks as far as possible. (2) Large sample size and heavy testing workload in the process of new product development led to in-creased costs. Therefore, companies need to use new statistical methods to analyze large sample data and reduce development costs. This study makes an in-depth analysis of the risks that may occur in the process of the company's new product development and draws some useful conclusions and strategies.

Utilizing Linear Regression for Predicting Sales of Top-Performing Products

PT Ajidarma Delta Medika is a company engaged in the sale of medical devices in the city of Bekasi. This company markets a variety of medical device products. Judging from the large number of consumer requests for medical device products based on sales data for the last 3 years, predictions are needed for the best-selling product sales, in order to facilitate the company in planning the supply of stock. To find out the best-selling medical device product sales, data prediction techniques are used with the Linear Regression algorithm. By using the Linear Regression algorithm, the results are obtained to predict the best-selling sales of several products sold at PT Ajidarma Delta Medika. This research produces an accuracy value with the MAPE formula for predicting the best-selling product sales of 14.2%. This shows that the linear regression method is good at predicting sales of medical devices in the following year.

Risk Management in Medical Device Industry

In spite of the fact that risk management has developed into an essential component of the process of developing medical devices, as mandated by both domestic and international regulations and standards, there is still no all-encompassing model that describes how risk management in the development of medical devices ought to be approached, particularly in terms of the types of risks that ought to be addressed. This is due to the fact that risk management has developed into an essential component of the process, which is mandated by both domestic and international regulations and standards. The present focus of risk management in the industry of developing medical devices is on technical risks, such as product, usability, and development process hazards. This is done in compliance with the norms and laws of standards. On the other hand, non-technical risks, such as those associated with businesses and projects, are not given nearly enough consideration. This review focuses on the risk management in medical device industry.

Electrothermal transport of water conveying copper, silver and alumina nanoparticles through a vertical wavy microchannel

This study emphasizes the significance of optimizing heat transmission, energy conversion, and thermal management in electronic devices, renewable energy systems, and emerging technologies like thermoelectric devices and energy storage systems. The aim is to enhance heat transfer efficiency for improved performance and lifespan of electronic equipment. The research utilizes a mathematical flow analysis to study a water-based ternary nanofluid’s flow and thermal characteristics in a vertical microfluidic channel driven by peristalsis and electroosmosis. The ternary-hybrid nanofluid (THNF), comprising copper, silver, and alumina nanoparticles dissolved in water, is examined considering induced magnetic fields. The study delves into fluid flow, heat absorption, and mixed convection, using Debye–Hückel, lubrication, and long wavelength approximations. Results show that THNF exhibits superior heat transmission compared to pure water. Increasing solid volume fraction of nanoparticles decreases THNF’s temperature. Induced magnetic fields impact the system. This research could influence thermal pipe heat sinks and bioengineered medical devices design.

Implantable polypyrrole bioelectrodes inducing anti-inflammatory macrophage polarization for long-term in vivo signal recording.

Bioelectrodes are critical components of implantable electronic devices that enable precise electrical signal transmission in close contact with living tissues. However, their in vivo performance is often compromised by inflammatory tissue reactions mainly induced by macrophages. Hence, we aimed to develop implantable bioelectrodes with high performance and high biocompatibility by actively modulating the inflammatory response of macrophages. Consequently, we fabricated heparin-doped polypyrrole electrodes (PPy/Hep) and immobilized anti-inflammatory cytokines (interleukin-4 [IL-4]) via non-covalent interactions. IL-4 immobilization did not alter the electrochemical performance of the original PPy/Hep electrodes. In vitro primary macrophage culture revealed that IL-4-immobilized PPy/Hep electrodes induced anti-inflammatory polarization of macrophages, similar to the soluble IL-4 control. In vivo subcutaneous implantation indicated that IL-4 immobilization on PPy/Hep promoted the anti-inflammatory polarization of host macrophages and significantly mitigated scarring around the implanted electrodes. In addition, high-sensitivity electrocardiogram signals were recorded from the implanted IL-4-immobilized PPy/Hep electrodes and compared to bare gold and PPy/Hep electrodes, which were maintained for up to 15 days post-implantation. This simple and effective surface modification strategy for developing immune-compatible bioelectrodes will facilitate the development of various electronic medical devices that require high sensitivities and long-term stabilities. STATEMENT OF SIGNIFICANCE: To fabricate highly immunocompatible conductive polymer-based implantable electrodes with high performance and stability in vivo, we introduced the anti-inflammatory activity to PPy/Hep electrodes by immobilizing IL-4 via non-covalent surface modification. IL-4-immobilized PPy/Hep could significantly mitigate inflammatory responses and scarring around implants by skewing macrophages to an anti-inflammatory phenotype. The IL-4-immobilized PPy/Hep electrodes could successfully record in vivo electrocardiogram signals for up to 15 days with no substantial sensitivity loss, retaining their superior sensitivity compared to bare gold and pristine PPy/Hep electrodes. Our simple and effective surface modification strategy for developing immune-compatible bioelectrodes will facilitate the development of various electronic medical devices that require high sensitivities and long-term stabilities, such as neural electrode arrays, biosensors, and cochlear electrodes.

Usability testing of Healthcare Devices: A review of the current UX methods used for usability testing of healthcare devices

This literature review examines the state of usability testing in medical device design, focusing on techniques and instruments used for assessing user-centered design. The analysis includes 30 studies from various fields, such as telemedicine, assistive technology, and healthcare devices. The review discusses different UX analysis techniques, their benefits and their drawbacks. Usability testing is critical in healthcare equipment design, utilizing various approaches and metrics. However, the analysis also highlights significant obstacles that need to be addressed, such as the need for more rigorous testing procedures and the application of user-centered design concepts. Overall, the review underscores the importance of usability testing in creating user-friendly, secure, and efficient medical equipment that benefits both patients and medical professionals.

Strain-rate dependence of mechanical characteristics of PLLA with different MW

Abstract Dynamic mechanical properties of polymers for biomedical applications are crucial parameters for development and engineering of new medical devices. Here, the time-dependent material behavior is a key factor for durability. Varying the strain rate is a convenient implementation of time-dependency for uniaxial testing. This study investigates time-dependence of Poly(L-Lactide) (PLLA) through uniaxial testing with different strain rates and PLLA with different molecular weight. The results show strain dependence for elongation at break and yield stress, Young’s modulus however is not rate dependent. An increase in elongation at break is also seen with increasing molecular weight of PLLA. Plastic strain increases significantly only for PLLA with an intermediate inherent viscosity. Results show distinct time dependencies regarding strain rate for PLLA with slightly different inherent viscosities. For stent-related mechanical material characteristics, higher molecular weight PLLA seems to be advantageous. This study only considers base materials, although appropriate thermal, mechanical as well as chemical post processing approaches for further adjustment of different properties have already been shown. A combination of the best possible base material and a suitable post-processing should be targeted.