Is read-across for chemicals comparable to medical device equivalence and where to use it for conformity assessment?

Novel medical devices must conform to medical device regulation (MDR) for European market entry. Likewise, chemicals must comply with the Registration, Evaluation, Authorization and Restriction of Chemicals (REACh) regulation. Both pose regulatory challenges for manufacturers, but concordantly provide an approach for transferring data from an already registered device or compound to the one undergoing accreditation. This is called equivalence for medical devices and read-across for chemicals. Although read-across is not explicitly prohibited in the process of medical device accreditation, it is usually not performed due to a lack of guidance and acceptance criteria from the authorities. Nonetheless, a scientifically justified read-across of material-based endpoints, as well as toxicological assessment of chemical aspects, such as extractables and leachables, can prevent failure of MDR device equivalence if data is lacking. Further, read-across, if applied correctly can facilitate the standard MDR conformity assessment. The need for read-across within medical device registration should let authorities to reconsider device accreditation and the formulation of respective guidance documents. Acceptance criteria like in the European Chemicals Agency (ECHA) read-across assessment framework (RAAF) are needed. This can reduce the impact of the MDR and help with keeping high European innovation device rate, beneficial for medical device patients.

The consequences of the new European reclassification of non-invasive brain stimulation devices and the medical device regulations pose an existential threat to research and treatment: An invited opinion paper.

A significant amount of European basic and clinical neuroscience research includes the use of transcranial magnetic stimulation (TMS) and low intensity transcranial electrical stimulation (tES), mainly transcranial direct current stimulation (tDCS). Two recent changes in the EU regulations, the introduction of the Medical Device Regulation (MDR) (2017/745) and the Annex XVI have caused significant problems and confusions in the brain stimulation field. The negative consequences of the MDR for non-invasive brain stimulation (NIBS) have been largely overlooked and until today, have not been consequently addressed by National Competent Authorities, local ethical committees, politicians and by the scientific communities. In addition, a rushed bureaucratic decision led to seemingly wrong classification of NIBS products without an intended medical purpose into the same risk group III as invasive stimulators. Overregulation is detrimental for any research and for future developments, therefore researchers, clinicians, industry, patient representatives and an ethicist were invited to contribute to this document with the aim of starting a constructive dialogue and enacting positive changes in the regulatory environment.

[Critical Control Points and Case Studies in the Production of Metal Additive Manufacturing Medical Device].

The critical control points in the production quality management of metal additive manufacturing medical devices, including personnel, hardware, design and development, procurement control, production management and quality control are summarized from the perspective of supervision. The typical cases are analyzed to provide reference for medical device regulatory authorities and enterprises.

Delivery Device Patents on GLP-1 Receptor Agonists.

This study analyzed the US Food and Drug Administration­listed patents on glucagon-like peptide 1 (GLP-1) receptor agonists to determine their claim characteristics and the potential barriers they pose to generic entry.

Approaching 3D printing in oral and maxillofacial surgery - suggestions for structured clinical standards.

PURPOSE: With respect to the European Union 2017 amendment of the Medical Device Regulations (MDR), this overview article presents recommendations concerning medical 3D printing in oral and maxillofacial surgery (OMFS). METHODS: The MDR were screened for applicability of the rules to medical in-house 3D printing. Applicable regulations were summarized and compared to the status of medical use of 3D printing in OMFS in Germany. Recommendations were made for MDR concerning medical 3D printing. RESULTS: In-house printed models, surgical guides, and implants fall under the category of Class I-III, depending on their invasive and active properties. In-house medical 3D printing for custom-made medical devices is possible under certain prerogatives: (1) the product is not being used in another facility, (2) appropriate quality systems are applied, (3) the reason for omitting commercial products is documented, (4) information about its use is supplied to the responsible authority, (5) there is a publicly accessible declaration of origin, identification, and conformity to the MDR, (6) there are records of manufacturing site, process and performance data, (7) all products are produced according to the requirements proclaimed before, and (8) there is an evaluation of clinical use and correction of possible issues. CONCLUSION: Several aspects must be addressed for in house medical 3D printing, according to the MDR. Devising MDR related to medical 3D printing is a growing challenge. The implementation of recommendations in OMFS could help practitioners to overcome the challenges and become aware of the in-house production and application of 3D printed devices.

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.

The value of using real-world evidence as a source of clinical evidence in the European medical device regulations: a mixed methods study.

OBJECTIVES: This study investigates the benefits, limitations and awareness of using Real World Evidence and Real World Data for post-market clinical follow-up studies and clinical evaluation reports in the European Medical Device Regulations. METHODOLOGY: A mixed methods study was utilized with qualitative interviews and a quantitative survey. RESULTS: The findings from the study demonstrate that in the case of the Medical Device Regulations, opportunities exist for manufacturers of legacy devices to conduct Real World Evidence studies to bridge gaps in clinical evidence. The primary value of Real World Evidence lies in its ability to provide an accurate and, therefore, more reliable measure of device safety and performance. As a measure of safety and performance, it supplements clinical evidence generated from pre and post-market clinical investigations, reducing the costs associated with these studies and supporting the manufacturer's benefit: risk conclusion. CONCLUSION: This study provides insight into how the medical device industry could utilize Real World Evidence and have an initiative in the EU similar to the FDA-sponsored NESTcc partnership. This would aid medical device manufacturers in transitioning to the MDR clinical evaluation requirements and mitigate the impact on medical device availability in the EU.

Cervical pessary to prevent preterm birth and poor neonatal outcome: An integrity meta-analysis of randomized controlled trials focusing on adherence to the European Medical Device Regulation.

BACKGROUND: Findings from randomized trials (RCTs) on cervical pessary treatment to prevent spontaneous preterm birth are inconsistent. OBJECTIVES: Our hypothesis suggests that adhering to the European Medical Device Regulation (MDR) and following the instructions for use are essential prerequisites for successful therapy. Conversely, the non-adherence to these guidelines will probably contribute to its failure. SEARCH STRATEGY AND SELECTION CRITERIA: Based on validated criteria from integrity assessments we performed a systematic review identifying 14 RCTs evaluating the effect of cervical pessaries. DATA COLLECTION AND ANALYSIS: We analyzed the implications of 14 criteria each accounting for 0-2 points of a score reflecting the clinical evaluation plan (CEP) as proposed by the MDR to evaluate the risk-benefit ratio of medical devices. MAIN RESULTS: Seven RCTs in each singleton and twin pregnancies (5193 "cases") were included, detecting a high heterogeneity within control groups (I2 = 85% and 87%, respectively, P < 0.01). The CEP score varied from 11 to 26 points for all studies. The most common reasons for low scores and potential data compromise were poor recruitment rates, no (completed) power analysis, and no pre-registration, but mainly non-adherence to technical, biological, and clinical equivalence to the instructions for use as required by the MDR. All trials with score values greater than 20 had applied audit procedures. Within this group we found significantly reduced rates of spontaneous preterm birth at less than 34 weeks within the pessary group in singleton (odds ratio 0.28; 95% confidence interval 0.12-0.65) and twin pregnancies (odds ratio 0.30; 95% confidence interval 0.13-0.67). Similarly, there was a significant reduction in the composite poor neonatal outcome in singleton (odds ratio 0.25; 95% confidence interval 0.10-0.61) and twin pregnancies (odds ratio 0.54; 95% confidence interval 0.35-0.82) after a pessary as compared with controls. CONCLUSION: Non-audited RCTs and meta-analyses mixing studies of different clinical quality as pre-defined by a CEP and the MDR pose the risk for erroneous conclusions.

[Introduction and Discussion of IMDRF Personalized Medical Device Regulatory Pathways].

OBJECTIVE: To interpret the key contents of the guidance of Personalized Medical Device Regulatory Pathways issued by the IMDRF, and provide reference for the improvement of China's medical device regulatory system. METHODS: The regulatory requirements of personalized medical devices and point-of-care manufacture of medical device were described respectively, and the feasibility of implementing the regulation of point-of-care manufacture of medical device in China was analyzed. RESULTS: The different regulatory pathways of medical devices produced at point-of-care are feasible and have different regulatory risks. CONCLUSIONS: In combination with the recommendations provided by the IMDRF guidance and the clinical and regulatory realities in China, we should accelerate the improvement of the regulations and supporting documents for point-of-care manufacture of medical device in China.

[Introduction and Reflection on Novel Medical Device Regulatory Science Tool MDDT].

In recent years, emerging technology medical devices have developed rapidly. How to more scientifically and more efficiently regulate these novel medical devices so as to improve access to advanced medical technology while ensuring safety and effectiveness is a new challenge faced by regulatory authorities, and is also the core topic of regulatory science. New tools, new standards and new methods are important means to achieve regulatory science. "Medical Device Development Tool" proposed by the U.S. FDA is a novel medical device regulatory science tool, which can help medical device developers to predict and evaluate product performance more efficiently. It is also helpful for regulatory authorities to make regulatory decisions more efficiently. This study introduces the concept, qualification process, role of MDDT in medical device regulation and MDDT examples, and makes some discussion on the device evaluation from the perspective of reliability and validity. MDDT can facilitate the developing of novel medical device.

[Analysis of Factors Affecting Effectiveness of Medical Device Registration Self-inspection from Perspective of Technical Evaluation].

Type inspection is a necessary precondition of technical evaluation of medical device. The implementation of The Provisions for Administration of Self-Test for Medical Device Registration facilitates the registration pathway for applicants. How to improve the effectiveness of registration self-test has drawn attention from many stakeholders. In this study, we analyzed and discussed the factors affecting the validity of registration self-test from technical evaluation perspective, and proposed suggestions for improvement accordingly. The aim of this article is to boost the reliability and effectiveness of registration self-test and offer a reference for applicants to carry out registration self-test.

Medical device regulatory challenges in the UK are affecting innovation and its potential benefits.

The increase in regulatory challenges on medical technology developed and deployed in the UK is having a negative impact on innovation. In this paper we show how the limited capacity of Approved and Notified Bodies is one more barrier in the innovation pipeline, that could push more teams to consider applying for FDA approval instead of UKCA marking, potentially limiting how much our patients benefit from the world-leading research undertaken in UK universities.

[Risk Management Analysis of Medical Device Registration Self-inspection].

Through the analysis of laws and policies related to registration self-inspection, visiting and researching enterprises, holding symposiums, and issuing nationwide questionnaires, the risks in the registration self-inspection process were summarized, analyzed, and evaluated. From the aspects of regulatory departments and manufacturing enterprises, we suggest to improve China's medical device registration regulations system and reduce the risks of all parties in the registration self-inspection work.

Evaluating Aseptic Presentation of Different Medical Device Packaging Configurations.

The Medical Device Regulation (MDR) of the European Union (EU) places greater emphasis on the usability of medical devices, with the goal of eliminating or reducing the risk of infection to patients. As this goal also is applicable to sterile packaging, ANSI/AAMI/ISO 11607-1:2019 introduced a usability evaluation requirement for aseptic presentation of terminally sterilized medical devices. In an effort to reduce contamination risks, this requirement focuses specifically on the sterile barrier system (SBS). However, research is limited on evaluating the usability of SBSs and their performance, from an aseptic presentation standpoint, in clinical settings. To address this research gap, we assessed 14 sterile medical devices with five different SBS configurations to elucidate how SBS configuration (type, size, and number of SBS layers) and user satisfaction levels affect usability. A total of 40 experienced clinical nurses participated in 280 individual trials (20 per SBS configuration), which were conducted in a simulated operating room. Ultraviolet fluorescent powder was used to simulate the contamination process and to evaluate the success or failure of the aseptic presentation. Pouch and tray configurations exhibited the best overall performance, while vent bags performed poorly and were considered less acceptable. Double SBS configurations outperformed single SBS configurations. The study highlighted the importance of appropriate SBS symbols to identify SBS layers, which is another patient safety-related requirement of the EU MDR. The current work also includes an analysis of the powder contamination method used in conducting the usability evaluation.

P14-A117†Assessment of performance and safety of corneal chamber hypothermic storage and PSS-L corneal rinsing in human and porcine corneas.

PURPOSE: To prove the safety and performance of the hypothermic corneal storage medium Corneal Chamber, containing Eusol-C solution (AL.CHI.MI.A. S.r.l.) and of the rinsing solution PSS-L (AL.CHI.MI.A. S.r.l.) in support to the new CE certification process in accordance to the EU 2017/745 Medical Device Regulation METHODS: Fifteen (n=15) human donor corneas unsuitable for transplantation and n=11 porcine corneas were evaluated for the following quality parameters: ECD, HEX%, CV%, endothelial morphology, endothelial mortality and transparency at day 0 and after 14±1 days (day 14) of storage in Corneal Chamber at 2-8°C. Then, corneas were rinsed in PSS-L for 1' at room temperature (RT) and the same parameters were assessed Post Rinsing (Day 14PR). In order to evaluate the antimicrobial carryover after the corneal storage in Corneal Chamber(14 days at 4°C), gentamicin sulphate was quantified in human and porcine corneas homogenates by UHPLC. RESULTS: Human and porcine corneas stored in Corneal Chamber at 2-8°C for 14 days showed a good overall quality of the tissue according to quality parameters evaluated. In particular, mean ECD, HEX% and CV% did not show statistically significant changes at the end of storage and endothelial mortality increased of 3.1±3.3% in human corneas and 7.8±3.5% in porcine corneas. Slight variations in endothelial morphology score and corneal transparency were observed. Rinsing with PSS-L did not negatively affect the quality parameters evaluated before and after rinsing and gentamicin sulfate residues were completely removed. CONCLUSION: The storage of corneal tissues in Corneal Chamber at 2-8°C for 14 days and the corneal rinse with 30 ml of PSS-L at RT for 1 min are safe and effective procedures allowing the preservation of the corneal quality parameters including ECD, endothelial mortality, endothelial morphology, HEX%, CV%, and corneal transparency and the elimination of gentamicin sulfate from the tissues before transplantation.