Development Of Medical Products Research Articles

Review of dura mater substitutes in neurosurgical practice

AIM: This study aimed to summarize the accumulated experience and compare available materials for the plasty of dura mater (DM) defects. The growing number of patients with craniocerebral traumas and an increasing amount of neurological surgeries for tumor processes and congenital malformations resulted in an increased amount of DM defects and associated complications. Despite the development of high-efficiency medical products, the percentage of postsurgical CSF leakage remains high and reaches 32% in case the defect is in infratentorial locations. Suitable substitute materials should be developed for the repair of dural defects because of complications such as pseudomeningocele, postsurgical inflammatory processes, CSF leakage, implant rejection, and cicatrical adhesion. In this article, basic materials, including auto- and allografts, biological substances, and synthetic materials, for the repair of dural defects were reviewed. Their positive and negative properties depending on the kind and location of lesions and on the type of material used were discussed. The main characteristics to be fulfilled by an ideal dura mater substitute were analyzed. Composite materials were considered a promising trend in modern bioengineering.
 CONCLUSION: An ideal material for the repair of DM defects should have the following properties: plastic, nonimmunogenic, watertight, highly porous, high surface area of fibers, cell growth stimulating, supportive for the survival of cells until they completely integrate with host tissues, conveniently replaceable, and adhesive. No ideal transplant materials can meet all the above demands. Biological, synthetic, and host tissues only supplement one another. Relevant studies have yet to be performed to obtain a more versatile and time and cost effective material that can satisfy all the requirements of modern neurosurgery. The existing results of preclinical studies have demonstrated that composite materials are similar to synthetic materials in terms of the strength and properties of biological tissues for the migration and proliferation of cells. In the future, they may become a promising alternative to biological substitutes.

Regulatory, Legal, and Market Aspects of Smart Wearables for Cardiac Monitoring.

In the area of cardiac monitoring, the use of digitally driven technologies is on the rise. While the development of medical products is advancing rapidly, allowing for new use-cases in cardiac monitoring and other areas, regulatory and legal requirements that govern market access are often evolving slowly, sometimes creating market barriers. This article gives a brief overview of the existing clinical studies regarding the use of smart wearables in cardiac monitoring and provides insight into the main regulatory and legal aspects that need to be considered when such products are intended to be used in a health care setting. Based on this brief overview, the article elaborates on the specific requirements in the main areas of authorization/certification and reimbursement/compensation, as well as data protection and data security. Three case studies are presented as examples of specific market access procedures: the USA, Germany, and Belgium. This article concludes that, despite the differences in specific requirements, market access pathways in most countries are characterized by a number of similarities, which should be considered early on in product development. The article also elaborates on how regulatory and legal requirements are currently being adapted for digitally driven wearables and proposes an ongoing evolution of these requirements to facilitate market access for beneficial medical technology in the future.

Data Acquisition and Generative Design for a Smart Spinal Orthosis

AbstractThe design and development process of custom‐made medical devices is very complex and often requires the use of additive manufacturing to obtain a customer compliant product. One of the key stages, but also very time consuming in the development of bespoke medical products, is the data acquisition of the patients’ specific anatomy. The current research paper presents a detailed process of upper body data acquisition using 3D scanning protocols, with the goal of designing a custom smart spinal orthosis using generative design and additive manufacturing technologies. The initial captured cloud points are subjected successively to a series of surface manipulation and mesh optimization operations to generate the final working 3D model of the upper body. Each stage of the 3D model is obtained using a specific software application, as follows: *.DICOM images are generated using a 3D scanner software; *STL files are obtained by transforming initial files using MeshMixer software; *.STEP files are optimized using Fusion 360. Shape validation is done by 3D printing of a real scale upper body anatomical prototype using material extrusion. Authors also proposed a generative design process for the development of a personalized vertebral body from the construction of the smart spinal orthosis. The generative study is initialized with the following data: connection type, stress scenarios, material type (metals – Ti, Al, Steel; composites – ABS, PET, HIPS), and manufacturing technology (additive, subtractive, injection molding). A set of 49 converged outcomes is generated after running the study and three are selected for further research.

Structural Alterations of Mucins Are Associated with Losses in Functionality.

Commercial mucin glycoproteins are routinely used as a model to investigate the broad range of important functions mucins fulfill in our bodies, including lubrication, protection against hostile germs, and the accommodation of a healthy microbiome. Moreover, purified mucins are increasingly selected as building blocks for multifunctional materials, i.e., as components of hydrogels or coatings. By performing a detailed side-by-side comparison of commercially available and lab-purified variants of porcine gastric mucins, we decipher key molecular motifs that are crucial for mucin functionality. As two main structural features, we identify the hydrophobic termini and the hydrophilic glycosylation pattern of the mucin glycoprotein; moreover, we describe how alterations in those structural motifs affect the different properties of mucins-on both microscopic and macroscopic levels. This study provides a detailed understanding of how distinct functionalities of gastric mucins are established, and it highlights the need for high-quality mucins-for both basic research and the development of mucin-based medical products.

Achievements and challenges of the Sakigake designation system in Japan.

The Sakigake designation system (Sakigake) has been launched to encourage the pioneered development of innovative new medical products for the effective treatment of severe illness in Japan, which allows leveraging the several advantages in prioritized consultation, rapid review, premium drug pricing and extended data-protection period. We retrospectively analysed the Sakigake products including drugs and regenerative medical products to clarify the achievements and the future issues in this system. From April 2015 to August 2020 (the first 5-year trial period of Sakigake), 37 products were designated, and 10 of those were approved in Japan in which 7 new active substances achieved the first-in-world approvals. Oncology, neurology and cardiovascular disease were the major therapeutic areas, and those 3 accounted for 75.7% of all products. Sakigake achieved some first-in-world approvals by the Pharmaceuticals and Medical Devices Agency/the Ministry of Health, Labor and Welfare of innovative new medical products, although in some therapeutic areas, there remains room in stimulating drug development.

Does being exposed to an educational tool influence patient preferences? The influence of an educational tool on patient preferences assessed by a discrete choice experiment.

ObjectivesThere is an increased interest in patient preferences informing the development and authorisation of medical products. A requirement for robust and meaningful results of such studies is that patients adequately understand the risks and benefits associated with treatments for which their preferences are elicited. This study aims to determine the influence of an educational tool, compared with traditional written information on patient preferences elicited in a discrete choice experiment (DCE). MethodsTreatment preferences of Swedish patients with rheumatoid arthritis (RA) were assessed using a DCE. Patients were recruited via clinics, a research panel, and the Swedish Rheumatism Association. Respondents received training materials either as plain written text or as an online educational tool. The educational tool was designed to enhance understanding of the written text by using graphics, pictograms, icon arrays, spoken text, and click-on functions. Data were analysed using random parameter logit models. Results675 patients with RA were included in the analysis. The patients received either a written information (n = 358) or information via an educational tool (n = 317). Respondents receiving the educational tool placed relatively more importance on all included side effects in their decision making, compared to respondents receiving the written text, who placed greater importance on treatment effectiveness and administration methods. ConclusionCompared to the respondents receiving the written text, the decisions of respondents receiving the educational tool were more influenced by medication side effects. Further research is needed to provide guidance on how and when to use educational tools to inform and elicit patients’ preferences. Practice implicationsThe ways in which attributes are presented to patients significantly impacts preferences measured in a DCE.

Biostatistical Considerations When Using RWD and RWE in Clinical Studies for Regulatory Purposes: A Landscape Assessment

Real-world evidence (RWE), derived from data from “real-world” clinical practice and medical product utilization, is an increasingly important source of evidence that holds great potential to increase efficiency and improve clinical development and life cycle management of medical products. Regulatory agencies, public-private partnerships, and health technology assessment organizations have launched major initiatives and released guidance to address considerations in the use of RWE to inform regulatory decision making. However, many challenges remain on how RWE could be best used for various types of regulatory decisions from statistical perspectives. To address the relevant statistical challenges, a working group under the auspices of the ASA Biopharmaceutical Section was established. This article reviews the biostatistical challenges and methods for the use of RWE for medical product development. There are two companion articles as the output from the same working group that address focused topics. The article by Chen et al. provides the current landscape on the use of RWE to inform clinical study design and analysis, and the article by Ho et al. presents a review of causal inference framework for design and analysis of studies using RWE.

Interaction of Differently Coated Silver Nanoparticles With Skin and Oral Mucosal Cells.

Silver nanoparticles (AgNP) can be found in different consumer products and various medical devices due to their excellent biocidal properties. Despite extensive scientific literature reporting biological effects of AgNP, there is still a lack of scientific evidence on how different surface functionalization affects AgNP interaction with the human skin and the oral epithelium. This study aimed to investigate biological consequences following the treatment of HaCaT and TR146cells with AgNP stabilized with negatively charged sodium bis(2-ethylhexyl)-sulfosuccinate (AOT), neutral polyvinylpyrrolidone (PVP), and positively charged poly-l-lysine (PLL). All AgNP were characterized by means of size, shape and surface charge. Interactions with biological barriers were investigated invitro by determining cell viability, particle uptake, oxidative stress response and DNA damages following AgNP treatment. Results showed a significant difference in cytotoxicity depending on the surface coating used for AgNP stabilization. All three types of AgNP induced apoptosis, oxidative stress response and DNA damages in cells, but AOT- and PVP-coated AgNP exhibited lower toxicity than positively charged PLL-AgNP. Considering the number of data gaps related to the safe use of nanomaterials in biomedicine, this study highlights the importance of particle surface functionalization that should be considered during design and development of future AgNP-based medical products.

Patent Protection and Access to COVID-19 Medical Products in Developing Countries

Several new vaccines that have been developed for COVID-19 are patent protected. The patentees control the production, supply and pricing of these vaccines. Most people in low-income countries have been unable to access the vaccines. India and South Africa supported by a large number of developing countries have submitted a proposal to the TRIPS Council of the WTO requesting a temporary waiver to eliminate patent and other intellectual property barriers for the development, production and supply of all COVID-19 medical products. Nine months have passed since the proposal was first made in October 2020 but still no decision could be taken because of the opposition from developed countries. The disagreements essentially revolve around four issues: whether suspension of patent rights will act as a disincentive for the development of new medical products; whether patented products can be manufactured in the absence of manufacturing capacities; whether voluntary initiatives are better than a patent waiver; and whether a waiver is necessary in view of compulsory licensing and other measures which TRIPS permits. The paper briefly reviews these issues and also provides some suggestions about what developing countries can do to make COVID-19 medical products affordable and accessible.

The Effect of Medical Artificial Intelligence Innovation Locus on Consumer Adoption of New Products

The purpose of this study is to explore the effect of innovation locus on consumers’ adoption of artificial intelligence products in healthcare. Across three experiments, we demonstrate that consumers are more likely to accept medical artificial intelligence for peripheral products than for core products. This effect is mediated by individual uniqueness neglect and moderated by medical risk. Specifically, individual uniqueness neglect significantly mediates the effect of innovation loci on consumers’ adoption of medical artificial intelligence for high-risk products. In contrast, the mediating effect of individual uniqueness neglect becomes weaker for low-risk products. These findings make important theoretical contributions to the artificial intelligence and healthcare literature. We also provide some practical implications to promote the future development of medical artificial intelligence products and improve consumers’ acceptance of medical artificial intelligence.

Retracted] Artificial Intelligence Imaging to Observe the Protective Effect of Hydrogen Sulfide on Acute Kidney Injury Caused by Urinary Sepsis

With the development of medical technology products and the rapid development of computer technology, medical AI has become a hotbed in scientific research and clinical practice. Some medical AI‐assisted diagnosis has been applied to the clinic to assist doctors in formulating treatment plans. The traditional method of clinical diagnosis and treatment is that the physician makes an intentional diagnosis and then performs ancillary tests. The clinician performs diagnosis and treatment by identifying clinical symptoms and analyzing auxiliary examination results. Modern medical AI is based on big data collection and analyzes the test results through artificial intelligence and computer algorithms. It can output diagnostic results with high sensitivity and specificity for clinical tests. Acute kidney injury (AKI) is a common clinical emergency. The main clinical features are elevated blood creatinine, decreased urine output, and sharp decline in renal function within a short period of time, and it is a hot spot worldwide. In this experiment, a rabbit sepsis model was replicated by inoculating E. coli bacteria into the rabbit’s unilateral ureteral lumen and ligation. NaHS was used as an exogenous hydrogen sulfide donor to observe the effects of hydrogen sulfide on UTIs. The protective effect of oxidative stress and inflammatory response in acute kidney injury with hyperemia. In the experiment, the production of endogenous hydrogen sulfide was decreased in the Sepsis group, and the renal CSE activity was decreased, while the content of endogenous hydrogen sulfide in the NaHS group was higher than that of the Sepsis group, and the CSE activity of renal tissue was increased. It can be seen that the plasma hydrogen sulfide and renal tissue SCE levels in septic acute kidney injury increased after NaHS intervention, and the renal tissue damage was reduced, suggesting that hydrogen sulfide is mainly generated endogenously through the action of CSE, which causes damage to the kidneys. The expressions of iNOS and HO‐1 in renal tissues of urinary sepsis are increased. H2S can play a certain protective effect on acute kidney injury in urinary sepsis by down‐regulating iNOS and up‐regulating the expression of HO‐1.

Global Pandemic and Rapid New Product Development of Medical Products

New product development is a strenuous and long process for companies. When the COVID-19 disease turned into a global pandemic, governments announced the need for various medical products that were scarce and at the same time imposed lockdowns and trade restrictions. During this period, rapid new product development of medical products was attempted by many companies worldwide using their existing supply chains. Data of 240 companies from non-medical product-segment background launching new medical products were collected and analyzed. Two case studies of Indian companies responding to shortages of ventilators and PPE are presented. A critical reflection of a new way of new product development and cooperation across firms is discussed.

Characteristics of Medical Products Comprising Human Cells, Genes, or Tissues Developed in Japan and the European Union Compared via Public Assessment Reports.

Medical products comprising human cells, genes, and tissues have been developed for clinical applications worldwide, and their developmental environment has been established. These products can be imported and exported, but marketing authorization regulations are complicated among regions. This investigation was conducted to identify the characteristics of medical products comprising human cells, genes, and tissues. We used website data, books from survey companies, and reports from public agencies to conduct two investigations. We used website data to conduct a general information survey of 143 cell-therapy and gene-therapy products sold in 24 countries and public assessment reports to individually survey non-clinical and clinical developments of 18 cell-therapy and gene-therapy products developed in Japan and the European Union (EU). The first survey revealed that the numbers of products used in orthopedic surgery and dermatology have increased since 2000, and the numbers of hematological products have increased since 2011. The second investigation revealed that fewer orphaned products were developed in Japan than in the EU. The most appropriate dose was 1.2 × 108 cells per injection per adult. Clinical trials to determine the most appropriate dose were conducted in the EU but not in Japan. No non-clinical immunogenicity tests for autogenous products were conducted in Japan or the EU. Pharmacokinetics tests were not individually performed for sheet-form products. Both in vivo and in vitro pharmacological tests were more likely to be conducted in the EU, while only one or the other was conducted in Japan. Furthermore, in Japan, carcinogenicity tests were performed based on non-clinical technical guidance, while in the EU, these tests were determined according to each product's features. Fewer clinical trials were performed, and fewer subjects per product were used in Japan than in the EU. Many aspects of the clinical and non-clinical development of medical products comprising human cells, genes, and tissues differ between Japan and the EU. Analyzing these differences will enable the safe and rapid distribution of these products to clinical sites.

Сlinical Case of Successful Lumbar Sympathectomy in the Treatment of Complex Regional Pain Syndrome

ABSTRACT. A 53-year-old male patient had extensive traumatic damage to the right lower limb in a car accident that happened 17 years ago, which subsequently led to a large amputation at the hip level. Later, adduction contracture in the right hip joint with a complex regional pain syndrome developed. Due to the ineffectiveness of various methods of conservative treatment, it was decided to perform right-sided lumbar sympathectomy. Ten days later, the patient was discharged for outpatient treatment. The result of the operation was a complete relief of pain syndrome both in the early postoperative and in the long-term periods of time. Despite the large number of types of conservative therapy in modern clinical practice, none of them is perfect. Doctors decide to operate less often, trying to minimize the intervention. However, therapeutic effects are not always possible as monotherapy, often requiring additional treatments. Due to the wide development and distribution of medical products, doctors often neglect or forget about such a method as lumbar sympathectomy. Therefore, the problem of complex regional pain syndrome remains relevant today.

Artificial Intelligence and Machine Learning in Computational Nanotoxicology: Unlocking and Empowering Nanomedicine.

Advances in nanomedicine, coupled with novel methods of creating advanced materials at the nanoscale, have opened new perspectives for the development of healthcare and medical products. Special attention must be paid toward safe design approaches for nanomaterial-based products. Recently, artificial intelligence (AI) and machine learning (ML) gifted the computational tool for enhancing and improving the simulation and modeling process for nanotoxicology and nanotherapeutics. In particular, the correlation of in vitro generated pharmacokinetics and pharmacodynamics to in vivo application scenarios is an important step toward the development of safe nanomedicinal products. This review portrays how in vitro and in vivo datasets are used in in silico models to unlock and empower nanomedicine. Physiologically based pharmacokinetic (PBPK) modeling and absorption, distribution, metabolism, and excretion (ADME)-based in silico methods along with dosimetry models as a focus area for nanomedicine are mainly described. The computational OMICS, colloidal particle determination, and algorithms to establish dosimetry for inhalation toxicology, and quantitative structure-activity relationships at nanoscale (nano-QSAR) are revisited. The challenges and opportunities facing the blind spots in nanotoxicology in this computationally dominated era are highlighted as the future to accelerate nanomedicine clinical translation.

Challenging Precedent: Critical Care Nursing and Medical Product Innovation.

In this presentation, I will share my unconventional journey, starting from my first job as a critical care staff nurse to my current role as tenure-track faculty at the University of Massachusetts Amherst, where I hold a joint position with the Institute for Applied Life Sciences and the College of Nursing. Throughout this journey, I have had many opportunities to participate in interdisciplinary clinical outcomes research and medical product development as a staff nurse, clinical nurse specialist, and project lead from the clinical, industry, and academic perspectives. While passionate about my central clinical research interests in technology innovation and its responsible use in critical and acute care, the foundation of my approach is dedicated to the values and lessons of my earliest experiences in critical care bedside nursing: supporting and preserving the dignity and humanity of person-centered patient care. Early in my career as a critical care nurse, I realized how vitally important a critical care nursing perspective could be in the design of technology for meeting the critical care needs of patients, nurses, and other professionals who provide this care. As the nation's largest group of health care professionals, nurses use more products than any other health care professional, and thus nurses have a uniquely practical and care-sensitive perspective on the development and design of medical products. Nurses, especially critical care nurses, are in a unique position to identify and address everyday health care issues, challenge assumptions and the status quo, address unrecognized and unarticulated needs, and ensure that clinical outcomes research serves as the foundation for validating the effectiveness of medical product innovation. My goal is to share lessons learned and to help participants to see the many different ways that critical care nursing knowledge can be used to improve patient care.

COVID-19: Regulatory Landscape of Medicinal and Medical Device Products for Human Use

Against the backdrop of the COVID pandemic, the scientific and medical communities are working with all deliberate speed with state-of-the-art technologies to develop diagnostic and therapeutic products that can identify, treat, and prevent infection with SARS-CoV-2. These activities may only be legally conducted with the necessary statutes and regulations in place to facilitate the timely development, manufacturing, evaluation, and distribution of products that meet quality standards. The present regulatory landscape for medicinal and medical products for human use has been shaped by nearly 12 decades of statutory history that followed in reaction to disasters and tragedies. Five distinct, closely woven threads of statutory history have led to the regulatory infrastructure we have in place: (1) standardized processes for routine development of medicinal and medical device products for human use; (2) processes for expedited development to shorten time frames and expand patient populations; (3) mechanisms of Expanded Access to make medicinal products available to patients prior to approval of the US Food and Drug Administration; (4) Emergency Use Authorization during public health emergencies; and (5) the development of pathways for bringing generic drugs and biosimilar biologics to market. These mechanisms are being brought to bear to facilitate the defeat of infection with SARS-CoV-2.

Challenging Precedent: Critical Care Nursing and Medical Product Innovation

In this presentation, I will share my unconventional journey, starting from my first job as a critical care staff nurse to my current role as tenure-track faculty at the University of Massachusetts Amherst, where I hold a joint position with the Institute for Applied Life Sciences and the College of Nursing. Throughout this journey, I have had many opportunities to participate in interdisciplinary clinical outcomes research and medical product development as a staff nurse, clinical nurse specialist, and project lead from the clinical, industry, and academic perspectives. While passionate about my central clinical research interests in technology innovation and its responsible use in critical and acute care, the foundation of my approach is dedicated to the values and lessons of my earliest experiences in critical care bedside nursing: supporting and preserving the dignity and humanity of person-centered patient care. Early in my career as a critical care nurse, I realized how vitally important a critical care nursing perspective could be in the design of technology for meeting the critical care needs of patients, nurses, and other professionals who provide this care. As the nation’s largest group of health care professionals, nurses use more products than any other health care professional, and thus nurses have a uniquely practical and care-sensitive perspective on the development and design of medical products. Nurses, especially critical care nurses, are in a unique position to identify and address everyday health care issues, challenge assumptions and the status quo, address unrecognized and unarticulated needs, and ensure that clinical outcomes research serves as the foundation for validating the effectiveness of medical product innovation. My goal is to share lessons learned and to help participants to see the many different ways that critical care nursing knowledge can be used to improve patient care.

INVESTIGATION ON METHODS AND CHARACTERISTICS IN MEDICAL DEVICE DEVELOPMENT

AbstractA targeted development of safe medical products can be supported by design methods. This paper analyses which design methods are applied in the development of medical devices and whether they are adapted for considering medical devices’ special features (legal, human and technical issues). In particular, variety management, risk assessment and user-centered design for medical devices are examined. Typically, interdisciplinary risk assessment is methodically supported. Additionally, user-centered design methods for requirements assessment, design verification and design validation are applied.

Emerging Standards and Analytical Science for Nanoenabled Medical Products.

Development and application of nanotechnology-enabled medical products, including drugs, devices, and in vitro diagnostics, are rapidly expanding in the global marketplace. In this review, the focus is on providing the reader with an introduction to the landscape of commercially available nanotechnology-enabled medical products as well as an overview of the international documentary standards and reference materials that support and facilitate efficient regulatory evaluation and reliable manufacturing of this diverse group of medical products. We describe the materials, test methods, and standards development needs for emerging medical products. Scientific and measurement challenges involved in the development and application of innovative nanoenabled medical products motivate discussion throughout this review.