EU's Medical Device Expert Panels: Analysis of Membership and Published Clinical Evaluation Consultation Procedure (CECP) Results.

Background: The new EU Medical Device Regulation (MDR) places greater importance on the role of clinical evidence to establish safety and performance. Article 54 of the MDR calls for expert committees to independently review the scientific, technical, and clinical evidence supporting the market authorization of certain novel devices independently from the established process of Notified Body reviews. These experts provide a review and opinion that ultimately is taken into consideration alongside the information reviewed by the Notified Body during the review process.

Standalone Regulatory Agreements for Product-Development Collaborations in the Medical Products Industry.

Background: Medical-product companies often outsource research and manufacturing needs to contracting or partnering organizations but then must manage a challenging patchwork of regulatory activities. A standalone regulatory agreement could clarify the relationships and responsibilities between companies working jointly on a single regulated product. This study explored the need for and current use of standalone regulatory agreements.

Trends and Challenges in Access to Essential Medicines in Ethiopia and the Contributions of Local Pharmaceutical Production.

Decades ago, the United Nations declared that access to essential medicines was a key element of universal human rights. Accordingly, member states have been striving to address this issue through strategic policies and programs. Strengthening local pharmaceutical production has been a pivotal strategy adopted by many developing countries including Ethiopia.

A novel maturity index for assessing medical device startups.

Background: Startup companies in the healthcare sector often fail because they lack sufficient entrepreneurial, regulatory, and business development expertise. Maturity models provide useful frameworks to assess the state of business elements more systematically than heuristic assessments. However, previous models were developed primarily to characterize the business state of larger nonmedical companies.

Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials.

Introduction: The U.S. Food and Drug Administration (FDA)'s guidances help describe the agency's current thinking on regulatory issues and serve as a means of informal policymaking that is non-binding.

Turning Neural Prosthetics Into Viable Products.

Academic researchers concentrate on the scientific and technological feasibility of novel treatments. Investors and commercial partners, however, understand that success depends even more on strategies for regulatory approval, reimbursement, marketing, intellectual property protection and risk management. These considerations are critical for technologically complex and highly invasive treatments that entail substantial costs and risks in small and heterogeneous patient populations.

Graduate Training Capacity for Regulatory Professionals at US Universities: Are We Facing a Talent Crisis?

Background: Talent acquisition in regulatory affairs has been a continuing challenge now exaggerated by demographic shifts and expansion of regulatory requirements nationally and globally.

Methods: Survey and interview methods were used to provide information on graduation rates, graduate characteristics, and enrollment trends in the 17 US regulatory programs that could be identified to offer graduate degrees in regulatory affairs or regulatory science.

Results: US programs graduated approximately 522 MS and 4 doctoral students in 2018.

Biobank Continuity Management: A Survey of Biobank Professionals.

Academic biobanks face challenges that call for continuity and disaster planning. However, current regulations do not require such planning, so it is unclear if and how biobanks have prepared themselves to deal with future crises. This exploratory study used mixed methods to understand the state of continuity planning in U.

Validation Master Plans: Progress of Implementation in the Pharmaceutical Industry.

Background: Some international regulatory agencies require that companies develop a validation master plan (VMP) to govern their validation activities, but such a plan is not an explicit requirement of US regulations. This paper examines the progress that US pharmaceutical companies have made to implement VMPs for drug products manufactured and produced in accordance with the US FDA Good Manufacturing Practice for Finished Pharmaceuticals.

Methods: A survey instrument was developed using an established framework with a focus on behavior and capability and disseminated electronically to midlevel and senior regulatory and quality professionals concentrated in the US.

Assessing the Benefit-Risk Profile for Pediatric Implantable Auditory Prostheses.

Background/aims: Children with congenital cochleovestibular abnormalities associated with profound hearing loss have few treatment options if cochlear implantation does not yield benefit. An alternative is the auditory brainstem implant (ABI). Regulatory authority device approvals currently include a structured benefit-risk assessment.

Incentivizing Quality in the Manufacture of Pharmaceuticals: Industry Views on Quality Metrics and Ratings.

Background: An increasing number of industry-wide quality breaches and consequential drug shortages have fueled interest in finding better ways to improve the manufacturing quality of pharmaceuticals. Quality metrics offer a way of focusing FDA inspectional resources by using risk-based paradigms and communicating the quality status of different companies to other stakeholders. This exploratory study investigated industry views related to the use of quality metrics and ratings to help advance these discussions.

Global Regulatory Dissonance: A Case Study of Industry Views on the Development of Drugs for Postmenopausal Osteoporosis.

Background: The footprint of drug distribution is multinational, but the regulatory frameworks supporting drug development, review, and approval remain largely regional. As a result, industry faces regulatory standards that may be complementary, additive, or contradictory, resulting in global regulatory dissonance (GRD).

Methods: Global regulatory dissonance was explored through a case study of drug development (postmenopausal osteoporosis) using survey methodology.

Management of Clinical Trial Agreements: Current Practices of Investigators in the United States.

The clinical trial agreement (CTA) is a key but often underappreciated document governing the relationship between a study site and a sponsor. Previous anecdotal materials have suggested that investigators may not often be involved in the review or negotiation of the CTA and may attach little importance to it. To provide more systematic current information, survey methods were used to explore the level of engagement, knowledge, and perceptions of investigators in the United States.

The Role of Universities in the Commercialization of Medical Products: A Survey of Industry Views.

Survey methods were used to explore the expectations and recommendations of senior business development professionals with respect to the roles, activities, and interactions with US universities in the development of new medical products. This target group was chosen because it was judged to be most likely to interact with university faculty and technology transfer services and seek and acquire university assets. The survey instrument was first reviewed by a focus group of individuals with experience both in technology transfer and in academic or industry policy, then distributed to a selected subset of 80 business development professionals, of whom 72 responded.

Percutaneous fiber-optic sensor for chronic glucose monitoring in vivo.

We are developing a family of fiber-optic sensors called Sencils (sensory cilia), which are disposable, minimally invasive, and can provide in vivo monitoring of various analytes for several weeks. The key element is a percutaneous optical fiber that permits reliable spectroscopic measurement of chemical reactions in a nano-engineered polymeric matrix attached to the implanted end of the fiber. This paper describes its first application to measure interstitial glucose based on changes in fluorescence resonance energy transfer (FRET) between fluorophores bound to betacyclodextrin and Concanavalin A (Con A) in a polyethylene glycol (PEG) matrix.

The BION devices: injectable interfaces with peripheral nerves and muscles.

Object: The purpose of this study was to describe a novel technology for implantable neuromuscular stimulation to treat complications of paralysis and disuse atrophy, including shoulder subluxation, hand contractures, drop foot, and osteoarthritis. The authors review the results so far of several pilot clinical studies of these muscle stimulation devices.

Methods: Miniature wireless stimulators received power and individually addressed command signals from an external radiofrequency transmission coil.

First Clinical Experience with BION Implants for Therapeutic Electrical Stimulation.

The objective of this study was to assess the usability and safety of BION injectable neuromuscular microstimulators for therapeutic electrical stimulation (TES) to treat two conditions involving disuse atrophy: poststroke shoulder subluxation in hemiplegic subjects and knee osteoarthritis. Clinicians were provided with PC-based software to track implants and to design the exercise programs. Subjects self-administered TES (3 sessions/day, 10-30 min/session) for 6 or 12 weeks.

Prevention of muscle disuse atrophy by low-frequency electrical stimulation in rats.

When muscles lose neural drive, they atrophy rapidly. Neuromuscular electrical stimulation (NMS) has been used in attempts to prevent or reverse the atrophy, but optimal stimulation programs and parameters are not well defined. In this study, we investigated the effects of four different stimulation patterns on disuse atrophy produced in the tibialis anterior, lateral gastrocnemius, and soleus muscles of rats paralyzed with tetrodotoxin for seven days.

Effects of muscle immobilization at different lengths on tetrodotoxin-induced disuse atrophy.

Previous studies have shown that immobilization causes muscle atrophy and that the rate of atrophy depends on the length at which the muscle is immobilized. However, most studies have been carried out in neurologically intact animals that were capable of generating at least some voluntary muscle activation. In this study, tetrodotoxin was applied chronically to the rat sciatic nerve to produce complete paralysis of distal muscles for seven days, and the ankle was immobilized to hold the muscles at long or short lengths.

Morphometry of Macaca mulatta forelimb. II. Fiber-type composition in shoulder and elbow muscles.

The present study examined the fiber-type proportions of 22 muscles spanning the shoulder and/or elbow joints of three Macaca mulatta. Fibers were classified as one of three types: fast-glycolytic (FG), fast-oxidative-glycolytic (FOG), or slow-oxidative (SO). In most muscles, the FG fibers predominated, but proportions ranged from 25-67% in different muscles.