Integrated Devices: A New Regulatory Pathway to Promote Revolutionary Innovation.

Policy Points Current medical device regulatory frameworks date back half a century and are ill suited for the next generation of medical devices that involve a significant software component. Existing Food and Drug Administration efforts are insufficient because of a lack of statutory authority, whereas international examples offer lessons for improving and harmonizing domestic medical device regulatory policy. A voluntary alternative pathway built upon two-stage review with individual component review followed by holistic review for integrated devices would provide regulators with new tools to address a changing medical device marketplace.

Regulatory perspectives on next-generation sequencing and complementary diagnostics in Japan.

INTRODUCTION: The 'one biomarker/one drug' scenario is unsustainable because cancer is a complex disorder that involves a number of molecular defects. In the past decade, major technological advances have lowered the overall cost and increased the efficiency of next-generation sequencing (NGS). AREAS COVERED: We review recent regulations on NGS and complementary diagnostics in Japan, mainly focusing on high-quality studies that utilized these new diagnostic modalities and were published within the last 5 years. We highlight significant changes in regulation, and explain the direction of efforts to translate the results of NGS and complementary diagnostics into clinical practice. EXPERT OPINION: NGS holds a number of advantages over conventional companion and complementary diagnostics that enable simultaneous analyzes of multiple cancer genes to detect actionable mutations. Parallel technological developments and regulatory changes have led to the rapid adoption of NGS into clinical practice. NGS-based genomic data have been leveraged to better understand the characteristics of a disease that affects its patient's response to a given therapy. As NGS-based tests become more widespread, however, Japanese authorities will face significant challenges particularly with respect to the complexity of genomic data, which will have to be managed if NGS is to benefit patients.

FDA Perspectives on the Regulation of Neuromodulation Devices.

The United States Food and Drug Administration (FDA) ensures that patients in the United States have access to safe and effective medical devices. The division of neurological and physical medicine devices reviews medical technologies that interface with the nervous system, including many neuromodulation devices. This article focuses on neuromodulation devices and addresses how to navigate the FDA's regulatory landscape to successfully bring devices to patients.

Medical Devices; Neurological Devices; Classification of the Percutaneous Nerve Stimulator for Substance Use Disorders. Final order.

The Food and Drug Administration (FDA or we) is classifying the percutaneous nerve stimulator for substance use disorders into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the percutaneous nerve stimulator for substance use disorders' classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

[In search of a travel guide-results from a survey of E­health startup companies]. / Reiseführer gesucht ­ Ergebnisse einer Umfrage bei E­Health-Start-ups.

As is the case in other sectors, innovative digital products have started to enter the health market, too. If digital products like apps are considered medical devices, startups are often confronted with regulatory procedures that they deem to be slow and with which they are not familiar. This applies to both the certification procedures and the requirements and procedures for reimbursement, where problems could occur. The aim of this article is to better understand the startups' experience in navigating through these procedures, the hurdles they encounter, and their need for support. Therefore, the digital association Bitkom e. V. and the Federal Institute for Drugs and Medical Devices (BfArM) conducted a web-based survey on five themes with a total of 23 questions. These questions focused inter alia on the composition of the team, product planning, familiarity with regulatory requirements, experience with institutions and different sources of information, the assessment of challenges in the process, and the resulting need for support.The analysis on the basis of 18 complete replies has shown that startups work on products with documentation and communications functions, but also integrate diagnostic and therapeutic features. The latter are characteristics of medical devices. Startups consider themselves to be relatively familiar with regulatory requirements regarding medical devices. The largest hurdles are associated with reimbursement: long and costly processes until the startups' products could be reimbursed.Both with regard to reimbursement and certification, startups see a need for low-threshold, cost-efficient advisory services and a simplification and acceleration of existing procedures with regard to medical devices.

[Handling of retrieved implants in orthopedic surgery : Results of a survey within the framework of the EndoCert initiative]. / Bestandsaufnahme zum Umgang mit ausgebauten Implantaten in der orthopädischen Chirurgie : Ergebnisse einer Umfrage im Rahmen der EndoCert-Initiative.

BACKGROUND: Although investigations of retrieved medical implants can provide valuable information about the cause of the revision, there is a lack of information, which could be avoided by consequent failure analyses. In the framework of the EndoCert certification system it is obligatory to record and report incidents. OBJECTIVES: The present work examines how the willingness to report has developed in certified arthroplasty centers and which method of handling retrievals is preferred and actually used. MATERIALS AND METHODS: On the basis of a questionnaire for handling retrievals, all 508 arthroplasty centers that were certified till June 1, 2016, were included (return rate = 97.2%). RESULTS: A total of 93.3% of the centers have established an algorithm for handling of retrievals and 83.0% of the centers prefer to hand out the retrieval to the patient, while only 25.7% wish to store it in the center for research purposes. In the case of a potential incident as the cause of revision, centers prefer to forward the retrieval to damage analysis, whereby the centers act in different ways, depending on the case. An implant fracture is, e.g., considered a reportable event in most cases without temporal limitation. On the other hand, breakage or failure of surgical instruments is considered not to be reported in the case of more than half of the centers. In 2014 and 2015, approximately 71% of EPZs reported no incidents. CONCLUSIONS: According to our survey, many certified arthroplasty centers are sensitized to careful handling of retrievals. The treatment of the explanted components is conducted in different ways. The assessment of whether an incident is to be reported shows large differences. In view of the relatively high number of revision surgeries, the number of reports to the authorities appears to be low.

[Qualification and classification of medical apps : What should be noted and what is BfArM's contribution?] / Abgrenzung und Klassifizierung von Medical Apps : Was ist zu beachten und welche Unterstützung bietet das BfArM?

Smartphones and tablets with their nearly unlimited number of different applications have become an integral part of everyday life. Thus, mobile devices and applications have also found their way into the healthcare sector.For developers, manufacturers, or users as well, it is often difficult to decide whether a mobile health application is a medical device.In this context, it is extremely important for manufacturers to decide at an early stage of the development whether the product is to be introduced into the market as a medical device and is therefore subject to the legislation on medical devices.This article first presents the regulatory framework and subsequently introduces the reader to the Federal Institute for Drugs and Medical Devices' (BfArM) view of the criteria for differentiating between apps as non-medical products and apps as medical apps as well as the classification thereof. Various examples are presented to demonstrate how these criteria are applied practically and options that support developers and manufacturers in their decision making are shown. The article concludes with a reference to current developments and offers a perspective on the new European medical device regulations MDR/IVDR (Medical Device Regulation/In-Vitro Diagnostic Regulation) as well as on future challenges regarding medical apps.

Public Regulatory Databases as a Source of Insight for Neuromodulation Devices Stimulation Parameters.

OBJECTIVE: The Shannon model is often used to define an expected boundary between non-damaging and damaging modes of electrical neurostimulation. Numerous preclinical studies have been performed by manufacturers of neuromodulation devices using different animal models and a broad range of stimulation parameters while developing devices for clinical use. These studies are mostly absent from peer-reviewed literature, which may lead to this information being overlooked by the scientific community. We aimed to locate summaries of these studies accessible via public regulatory databases and to add them to a body of knowledge available to a broad scientific community. METHODS: We employed web search terms describing device type, intended use, neural target, therapeutic application, company name, and submission number to identify summaries for premarket approval (PMA) devices and 510(k) devices. We filtered these records to a subset of entries that have sufficient technical information relevant to safety of neurostimulation. RESULTS: We identified 13 product codes for 8 types of neuromodulation devices. These led us to devices that have 22 PMAs and 154 510(k)s and six transcripts of public panel meetings. We found one PMA for a brain, peripheral nerve, and spinal cord stimulator and five 510(k) spinal cord stimulators with enough information to plot in Shannon coordinates of charge and charge density per phase. CONCLUSIONS: Analysis of relevant entries from public regulatory databases reveals use of pig, sheep, monkey, dog, and goat animal models with deep brain, peripheral nerve, muscle and spinal cord electrode placement with a variety of stimulation durations (hours to years); frequencies (10-10,000 Hz) and magnitudes (Shannon k from below zero to 4.47). Data from located entries indicate that a feline cortical model that employs acute stimulation might have limitations for assessing tissue damage in diverse anatomical locations, particularly for peripheral nerve and spinal cord simulation.

Integration of new technology into clinical practice after FDA approval.

Development of new medical technology is a crucial part of the advancement of medicine and our ability to better treat patients and their diseases. This process of development is long and arduous and requires a significant investment of human, financial and material capital. However, technology development can be rewarded richly by its impact on patient outcomes and successful sale of the product. One of the major regulatory hurdles to technology development is the Food and Drug Administration (FDA) approval process, which is necessary before a technology can be marketed and sold in the USA. Many businesses, medical providers and consumers believe that the FDA approval process is the only hurdle prior to use of the technology in day-to-day care. In order for the technology to be adopted into clinical use, reimbursement for both the device as well as the associated work performed by physicians and medical staff must be in place. Work and coverage decisions require Current Procedural Terminology (CPT) code development and Relative Value Scale Update Committee (RUC) valuation determination. Understanding these processes is crucial to the timely availability of new technology to patients and providers. Continued and better partnerships between physicians, industry, regulatory bodies and payers will facilitate bringing technology to market sooner and ensure appropriate utilization.

Medical Devices; Neurological Devices; Classification of the Thermal System for Insomnia. Final order.

The Food and Drug Administration (FDA) is classifying the thermal system for insomnia into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the thermal system for insomnia's classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.

New technology in electrophysiology: FDA process and perspective.

The Food and Drug Administration (FDA) is a large regulatory agency that monitors everything from food, tobacco, and veterinary medicine to pharmaceutical drugs and medical devices. The Mission statement of the CDRH, one of the Centers of the FDA, in its most succinct form is to protect and promote public health. This is accomplished through timely and continued access to safe, effective, and high quality medical devices. This paper aims to review the overarching principles of the Agency's review process for cardiac devices as well as highlight some of the newer programs that FDA has engaged in to facilitate innovation, device development, research, and timely market approval.

Dental Devices; Reclassification of Electrical Salivary Stimulator System. Final order.

The Food and Drug Administration (FDA) is issuing a final order to reclassify the salivary stimulator system, a postamendments Class III device, into class II (special controls) and to rename the device the "electrical salivary stimulator system." The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.

Physical Medicine Devices; Reclassification of Shortwave Diathermy for All Other Uses, Henceforth To Be Known as Nonthermal Shortwave Therapy. Final order; technical correction.

The Food and Drug Administration (FDA) is issuing a final order to reclassify shortwave diathermy (SWD) for all other uses, a preamendments class III device, into class II (special controls), and to rename the device "nonthermal shortwave therapy'' (SWT). FDA is also making a technical correction in the regulation for the carrier frequency for SWD and SWT devices.

Regulation of Peripheral Nerve Stimulation Technology.

The number of peripheral nerve stimulation (PNS) indications, targets, and devices is expanding, yet the development of the technology has been slow because many devices used for PNS do not have formal regulatory approval. Manufacturers have not sought Food and Drug Administration (FDA) approval for PNS devices because of a perceived lack of interest amongst practitioners and patients. Without FDA approval, companies cannot invest in marketing to educate the implanters and the patients about the benefits of PNS in the treatment of chronic pain. Violation of this has resulted in governmental investigation and prosecution. Most of the PNS devices currently used to treat chronic pain are FDA approved for epidural spinal cord stimulation. Many of the complications seen in PNS surgery can be attributed to the lack of purpose-built hardware with FDA approval. Despite the lack of regulatory approval, there are insurance companies that approve PNS procedures when deemed medically necessary. As the targets and indications for PNS continue to expand, there will be an even greater need for customized technological solutions. It is up to the medical device industry to invest in the design and marketing of PNS technology and seek out FDA approval. Market forces will continue to push PNS into the mainstream and physicians will increasingly have the choice to implant devices specifically designed and approved to treat chronic peripheral nerve pain.

Medical devices; neurological devices; classification of the limited output transcutaneous piezoelectric stimulator for skin reactions associated with insect bites. Final order.

The Food and Drug Administration (FDA) is classifying the limited output transcutaneous piezoelectric stimulator for skin reactions associated with insect bites into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the limited output transcutaneous piezoelectric stimulator for skin reactions associated with insect bites' classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.

Medical devices; neurological devices; classification of the transcutaneous electrical nerve stimulator to treat headache. Final order.

The Food and Drug Administration (FDA) is classifying the transcutaneous electrical nerve stimulator to treat headache into class II (special controls). The special controls that will apply to the device are identified in this order, and will be part of the codified language for the transcutaneous electrical nerve stimulator to treat headache classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.

Pediatric cardiovascular safety: challenges in drug and device development and clinical application.

Development of pediatric medications and devices is complicated by differences in pediatric physiology and pathophysiology (both compared with adults and within the pediatric age range), small patient populations, and practical and ethical challenges to designing clinical trials. This article summarizes the discussions that occurred at a Cardiac Safety Research Consortium-sponsored Think Tank convened on December 10, 2010, where members from academia, industry, and regulatory agencies discussed important issues regarding pediatric cardiovascular safety of medications and cardiovascular devices. Pediatric drug and device development may use adult data but often requires additional preclinical and clinical testing to characterize effects on cardiac function and development. Challenges in preclinical trials include identifying appropriate animal models, clinically relevant efficacy end points, and methods to monitor cardiovascular safety. Pediatric clinical trials have different ethical concerns from adult trials, including consideration of the subjects' families. Clinical trial design in pediatrics should assess risks and benefits as well as incorporate input from families. Postmarketing surveillance, mandated by federal law, plays an important role in both drug and device safety assessment and becomes crucial in the pediatric population because of the limitations of premarketing pediatric studies. Solutions for this wide array of issues will require collaboration between academia, industry, and government as well as creativity in pediatric study design. Formation of various epidemiologic tools including registries to describe outcomes of pediatric cardiac disease and its treatment as well as cardiac effects of noncardiovascular medications, should inform preclinical and clinical development and improve benefit-risk assessments for the patients. The discussions in this article summarize areas of emerging consensus and other areas in which consensus remains elusive and provide suggestions for additional research to further our knowledge and understanding of this topic.

Bad medicine: prescription drugs, preemption, and the potential for a no-fault fix.

For decades, federal regulation of pharmaceutical drugs and medical devices has worked hand in hand with state tort claims to protect the health and safety of the American public. Now, a new trend toward preemption endangers this scheme. In recent years, the Supreme Court has given increasing deference to agency assertions about their preemptive authority and has found preemption in an increasing number of cases. In the process, the Supreme Court has preempted claims for medical device injuries and left claims for pharmaceutical harms in a precarious position. The elimination of common law claims for drug and device harms will leave holes in the FDA's regulatory scheme, endangering the health and safety of Americans. It will also prevent ordinary Americans from seeking compensation for their injuries--even those injuries caused by manufacturer malfeasance. This Article proposes that Congress create a no-fault compensation scheme for drugs and medical devices to close these gaps. Such a scheme could be both practical and politically possible, satisfying manufacturers, tort reformers, patients, and plaintiffs' lawyers alike.