September 2024 – Medical Devices Regulatory Insights
UK Medical Device Regulator MHRA Announces Legislative Updates
The MHRA, the UK medical device regulator, gave a progress report on the agency’s work toward completing its roadmap of medical device legislation. On September 18, Robert Reid, Ph.D. Deputy Director, Innovative Devices at the MHRA, updated the RAPS audience on the current status of the UK legislation.
In January 2024, the MHRA shared a roadmap for 2024-2025. The roadmap proposed regulatory reforms to the UK MDR 2002 based on previous reports and consultations. Three core legislations (statutory instruments (SI)) are envisioned: post-market surveillance (PMS), pre-market/core legislation, and future enhancements. Notification of the draft PMS SI was published on the WHO website at the end of July 2023, and it was expected to enter into force in June 2024, which has not yet happened.
Given the dissolution of Parliament at the end of May and the election in July, the proposed timeline was considered ambitious and was extended. Consequently, the MHRA has been reassessing, as well as focusing on the most important tenets, patient safety and patient access. Dr. Reid presented the “A refreshed roadmap” and explained that the three core SIs would still generally remain the same.
The PMS SI is expected to be presented in the next two months before Parliament. The draft SI shared in 2023 will be the version presented to Parliament. The more stringent PMS requirements aim to improve patient safety and provide clarity on PMS requirements, as well as provide a more harmonized approach and improve identification and analysis of medical device incidents. Another benefit of improving the PMS process is that it would subject medical devices to the same rigorous PMS process, including the devices that in the future would take the proposed reliance routes.
Pre-market statutory instrument – The essential changes to the core legislation are anticipated to be released in 2025. These would include the new requirements for UDI, implant cards, claims made and changes in classification. Dr. Reid reminded the audience that the legislative changes would be guided by the government’s response to the consultation on the future regulation of medical devices in the UK published in 2022.
In addition, the legislation will be updated to include the international reliance routes announced by the MHRA in May 2024. The MHRA has been testing the reliance route with manufacturers of different devices and classes to see how it would function.
Future enhancement SI- The MHRA still intends to conduct a third SI, on which they will work with stakeholders in open discussions.
While the initial roadmap has been delayed, the MHRA will still proceed with three SIs. In addition, one of the most significant updates is the inclusion of the reliance system in the pre-market stage
Original source: Emergo by UL. Published: 19 September 2024
EU Publishes its AI Act
The European Commission has published the finalized text of the Artificial Intelligence Act (AIA) which establishes a legal framework to promote the uptake of “human centric and trustworthy” AI for medical devices, in vitro diagnostic devices (IVDs) and other products. The Act also sets harmonized rules for placing products on the market, and is the world’s first comprehensive AI law, according to the European Parliament.
The AIA was published in the Official Journal on 12 July and will go into effect on 2 August, while the requirements for high-risk devices will go into effect one year later, on 2 August 2026. The text is unchanged from the AI Act adopted by the European Parliament on 13 March.
The Act aims to improve the functioning of the internal market, prohibits certain AI practices and adds specific requirements for high-risk AI systems. It does not apply to research or testing activities prior to placing products on the market. The regulation also mandates that providers and deployers of AI systems provide a “sufficient level” of AI literacy to their staff.
Devices are deemed a high risk if they are placed in the Class IIa category or higher under the Medical Devices Regulations. The regulation specifies that manufacturers of high-risk devices will have to establish a risk management system throughout the product’s lifecycle, conduct data governance to attest that data is free from errors and provide technical documentation attesting that their products comply with the Act. Manufacturers of these products will have to provide instructions for use and establish a quality management system to ensure compliance.
The regulation further specifies that high-risk systems should be designed and developed in such a way as to ensure that their operation is transparent and can enable deployers to interpret a system’s output. These systems should also be accompanied by instructions for use that provide information that is “concise, complete, correct and clear” to deployers.
The regulation also establishes other categories for those devices posing a more limited risk and manufacturers of these products are not subject to the more stringent requirements of the higher risk category.
According to a recent blog post from the consultancy IQVIA, a large segment of AI’s use in healthcare would be classified as ‘high-risk’ under the Act and thus subject to multiple requirements.
At RAPS Euro Convergence meeting in Berlin earlier this year, European regulators and health authorities sought to provide assurance that AIA is compatible with the Medical Device Regulation (MDR). These assurances were prompted by concerns expressed by MedTech Europe earlier this year that AIA would conflict Medical Device Regulations and the In Vitro Diagnostic Directive.
Besides medical devices and IVDs, the scope of the Act covers machinery, toys, lifts, equipment and protective systems intended for use in potentially explosive atmospheres, radio equipment, pressure equipment, recreational craft equipment, cableway installations, appliances burning gaseous fuels, automotive and aviation products.
Original source: RAPS. Published: 15 July 2024
Amending Regulation (EU) 2024/1860 and EUDAMED gradual roll-out
On 9th July 2024, the amending Regulation (EU) 2024/1860 was published in the Official Journal of the European Union (OJEU) with immediate effect.
The objective of the amending Regulation is to further mitigate the risk of shortages of medical devices on the market by:
- Extending the transitional periods for certain in vitro diagnostic medical devices (IVDs) if certain conditions are met.
- Obliging manufacturers to inform the relevant national competent authorities in case of their intention to interrupt/withdraw the supply of certain critical medical devices and IVDs.
- Implementing a gradual roll-out of the EUDAMED database, through making mandatory, the use of those EUDAMED modules that are already available for voluntary use once they are declared to be functional; instead of waiting for all the modules to become available and be declared functional before their mandated use.
The first three of the six EUDAMED modules are already available for voluntary use (Actor registration; UDI and device registration; Notified Bodies and certificates). As per the recent updates from the European Commission, two other modules (vigilance and post-market surveillance; market surveillance) are expected to be completed in 2024 and these five modules are anticipated to be declared functional around mid 2025. The module covering clinical investigation / performance studies is not expected to be completed before Q3 2026. Details are in the updated roadmap published by the EC.
The amending Regulation (EU) 2024/1860 makes the use of the available EUDAMED modules mandatory as per the timelines, that apply after a notice is published in the Official Journal of the European Union (OJEU) that the relevant modules are functional and meet the specifications.
Original source: BSI. Published: 9 July 2024.
European Commission Proposes Common Specifications for IVDs for Parasites, Viruses
The European Commission has proposed updating common specifications for certain class D in vitro diagnostic devices to consider tests for certain parasites and viruses that are of public health concern.
On 19 August, the Commission published the proposed amendments that, if finalized, would update the In Vitro Diagnostic Medical Devices Regulation (Regulation (EU) 2017/746). The Commission said the amendments are intended to include certain viruses and parasites not already considered in the regulation that are of public health importance.
“For class D devices intended for detection of hepatitis E virus, Toxoplasma gondii, Plasmodium spp., as well as four types of arboviruses (Chikungunya virus, dengue virus, West Nile virus and Zika virus), harmonized standards do not exist as regards certain requirements of Annex I to Regulation (EU) 2017/746, and there is a need to address public health concerns, as the risk associated with the use of those devices is significant for public health and patient safety,” said the Commission. “The experience with the use of common specifications laid down in Implementing Regulation (EU) 2022/1107, has demonstrated that there is a need to clarify some of those specifications or, where necessary, update them to reflect the state of the art.”
While the Commission said sponsors, manufacturers, notified bodies, and other stakeholders need time to transition to the new regulations, they may also voluntarily start complying with the changes before they have been finalized. It also noted that it had consulted with the Medical Device Coordination Group (MDCG) and the changes comply with the opinion of the Committee on Medical Devices.
The Commission also published an Annex detailing qualitative and quantitative requirements for Nucleic Acid Amplification Technique (NAT) devices for detecting hepatitis E and several arboviruses.
The Annex notes that target sequence amplification devices used to detect the RNA of the viruses in question will require a functionality control for each specimen that is considered the state of the art and used throughout the test process including during extraction, amplification, and detection. The ability to detect genotype and/or subtype should be demonstrated with the right primer or probe design validation and be validated by testing characterized genotyped specimens.
“Potential cross-reactivity of non-target nucleic acid sequences shall be analyzed by appropriate primer or probe design validation and shall also be validated by testing selected specimens,” said the Commission. “Results of quantitative NAT devices shall be traceable to international standards or reference materials calibrated against those international standards, if available, and be expressed in international units utilized in the specific field of application.”
The Annex also details requirements for devices used to detect certain parasites, such as Plasmodium spp., which causes malaria. It includes performance characteristic requirements for the tests, including their diagnostic and analytical sensitivities, diagnostic specificity, and cross-reactivity.
Original source: RAPS. Published: 26 August 2024
Guidance Documents Issues By the Medical Device Coordination Group (MDCG)
July 2024
MDCG 2021-5 Rev.1: Guidance on standardisation for medical devices.
MDCG 2020-16 Rev.3: Guidance on Classification Rules for in vitro Diagnostic Medical Devices under Regulation (EU) 2017/746.
Q&A: Q&A on practical aspects related to the implementation of the extended transitional period provided for in the IVDR, as amended by Regulation (EU) 2024/1860
Q&A Rev. 2: Q&A on practical aspects related to the implementation of Regulation (EU) 2023/607 – Extension of the MDR transitional period and removal of the “sell off” periods.
FDA Issues Draft Guidance on Predetermined Change Control Plans for Medical Devices
On August 22, 2024, the U.S. Food and Drug Administration (“FDA”) released a draft guidance entitled “Predetermined Change Control Plans for Medical Devices” (the “PCCP Draft Guidance”), which details FDA’s approach to implementing its statutory authority to clear or approve PCCPs as part of device premarket submissions. A PCCP authorized as part of a marketing submission provides device manufacturers with advanced clearance or approval for certain pre-specified modifications that would otherwise require a new marketing submission. The PCCP Draft Guidance discusses the types of modifications appropriate for PCCPs and the categories of information to include in a PCCP.
The PCCP Draft Guidance sets forth five guiding principles for PCCPs:
- A PCCP should contain sufficient information to enable FDA to assess the reasonable assurance of safety and effectiveness or substantial equivalence of the device.
- While PCCPs are optional, PCCPs may in some cases be the least burdensome means for bringing device modifications to market.
- A PCCP becomes part of the marketing authorization of a device and will be included in FDA’s letter of authorization. Manufacturers must implement device modifications in a manner consistent with the authorized PCCP.
- A PCCP “should include only a few, specific modifications that can be verified and validated” and not “a list of any/all modifications that a manufacturer may possibly make.” FDA cautions that it may not be able to authorize a PCCP that includes “numerous” modifications or modifications “that range across various aspects of the device.”
- PCCPs are intended to harmonize with FDA’s existing guidance documents that address when a new marketing submission is required for device modifications
By enabling manufacturers to obtain pre-authorization for certain defined modifications to their devices, PCCPs present a valuable opportunity for manufacturers to deploy innovative modifications to devices more quickly while continuing to ensure the safety and effectiveness of marketed devices. Conversely, PCCPs also have the potential to increase submission complexity, which in some cases could delay an initial marketing authorization and potential launch. Disclosure of PCCPs in public documents could also have implications for manufacturers vis-à-vis competitive positioning and awareness in the marketplace of potential future product changes.
Original source: Ropesgray. Published: 9 September 2024
FDA’s Final Guidance on DCTs Adds Clarity on HCP Task Log, Inspection Requirements, Data Variability
The US Food and Drug Administration’s (FDA) final guidance on decentralized clinical trials (DCTs) addresses some key issues from the draft guidance raised by clinical experts and industry groups, including providing more information on requirements to keep a task log of healthcare providers (HCPs), physical inspection requirements, and clarifying challenges around data variability in DCTs.
The final guidance provides recommendations for using decentralized components in clinical trials. This includes elements like such as use of decentralized health technologies and software, roles and responsibilities for sponsors and investigators, using local healthcare providers as well as remote clinical trial visits, and trial design, conduct, and oversight. The final guidance also outlines informed consent and institutional review board oversight, what investigational products can use a DCT, how to package and ship investigational products, and patient safety processes and procedures.
Changes from draft guidance
Large portions of the final guidance have been rewritten, and FDA said they made editorial changes in the final guidance to improve clarity. In addressing comments raised in response to the draft guidance, FDA removed all mentions of a requirement to create and maintain a local task log of HCPs contracted for trial-related services in routine clinical practice.
FDA also provided more specific examples surrounding the challenges of data variability in DCTs. They noted the trial design should limit variability from trial-related activities performed by HCPs and trial personnel as well as activities that can performed by participants at home, such as spirometry tests. To reduce the potential for data variability, stakeholders should consider training and video supervision in the case of participant activities performed independently, and to specify what activities are permitted remotely, at trial sites, or can be based on participants’ preference.
The agency also updated its responsibilities for sponsors in DCTs that use local HCPs, noting that networks of local HCPs can be used for contracted services. “Sponsors should ensure these networks of local HCPs are qualified to perform the contracted activities,” FDA said. “Sponsors should also keep a record of these networks and other contracted service providers, including their roles and assigned activities.”
Concerning physical inspections for DCTs, FDA clarified that there needs to be a physical location where FDA inspectors can access records related to the trial, whether paper records or electronic access for “participants under the clinical investigator’s care” and to coordinate remote or in-person interviews with trial personnel. This physical location is usually the inspection location for clinical investigators in section 1 and section 3 of Form 1572 in the case of an investigational new drug, or included in an investigational device exemption, but can be another location, FDA said.
Original source: RAPS. Published: 17 September 2024.
FDA: Voluntary Malfunction Summary Reporting Program
On August 29, 2024, the FDA issued the Voluntary Malfunction Summary Reporting (VMSR) Program for Manufacturers guidance document to describe and clarify several aspects of the VMSR Program, including the FDA’s approach to determining the eligibility of product codes for the program and the conditions for submitting MDRs for device malfunctions in summary format under the program. This guidance is consistent with the modification notice (89 FR 70096).
Under the VMSR program, manufacturers submit separate summary reports for each unique combination of brand name, device model, and problem code(s). Each summary report identifies the total number of reportable malfunctions, and the summary reports are available to the public in MAUDE. Importantly, mandatory submission of individual reports of death or serious injury events continues to be required, under sections 803.50 and 803.52, or 803.53, as applicable.
Manufacturers of devices in the referenced product code(s) may submit summary reports of reportable malfunction events for those devices in accordance with the conditions described in the August 17, 2018 Federal Register notice (83 FR 40973) and republished in the August 29, 2024 FR Notice (89 FR 70096), which announced a minor, technical modification to the VMSR program. Information regarding the product codes eligibility for participating in the VMSR Program is made available in the FDA Product Classification Database.
It is manufacturer’s responsibility to take the steps necessary to ensure compliance with the applicable laws and regulations administered by the FDA and the conditions of the VMSR Program. If a manufacturer does not submit summary reports for reportable malfunction events in accordance with the conditions described in the FR notices (83 FR 40973 and 89 FR 70096), including the reporting schedule and format, then the manufacturer must submit individual malfunction reports in compliance with all requirements under CFR Part 803, unless the manufacturer has been granted a different exemption, variance, or alternative that applies. Additional information regarding the VMSR Program can be found in the Voluntary Malfunction Summary Reporting (VMSR) Program for Manufacturers guidance.
The manufacturers of devices of product codes ineligible to participate in the VMSR Program must submit individual reports that comply with all applicable requirements of 21 CFR part 803 for reportable malfunction events
Original source: FDA. Published: 29 August 2024.
TGA: New Regulatory Changes for Medical Devices Containing Medicinal Substances, Animal, Microbial, or Recombinant Materials
As of 1 July 2024, new regulatory requirements for medical devices containing medicinal substances, or materials derived from animal, microbial, or recombinant sources will take effect. TGA has released draft guidance to help sponsors and manufacturers navigate these changes, which aim to align with international standards while ensuring continued access to safe, high-quality medical devices in Australia.
The changes, which amend the Therapeutic Goods (Medical Devices) Regulations 2002, are designed to modernise Australia’s medical device regulatory framework. Some of the notable changes include:
- Classification Rule 5.5: Devices containing non-viable tissues or cells of animal origin (except those derived from hair, wool, or other low-risk materials) will remain classified as Class III. However, materials of microbial or recombinant origin, such as hyaluronic acid, have been reclassified to lower classes, reflecting their reduced risk.
- Labelling Requirements: Medical devices that include animal-derived substances will now need to include specific information on their labels and instructions for use (IFU). However, it is no longer necessary to include details about microbial or recombinant origin substances unless required for safety reasons.
- Changes for Specified Medical Devices: These changes allow the TGA to recognise approvals from a broader range of overseas regulators for devices containing these substances, simplifying the approval process.
Sponsors with medical devices already included in the Australian Register of Therapeutic Goods (ARTG) before 1 July 2024 have until 1 July 2026 to submit a reclassification application. This will allow you to continue supplying your device while aligning with the new classification requirements. For new applications lodged after 1 July 2024, the TGA will assess them based on the updated classification rules.
To comply with the new requirements, sponsors and manufacturers should:
- Review your device portfolio to identify products impacted by the changes.
- Submit reclassification applications before 1 July 2026 for any existing ARTG entries.
- Update labelling and IFUs to ensure compliance with the new requirements for materials of animal origin.
- Monitor critical suppliers: While suppliers of microbial and recombinant materials are no longer considered “critical,” manufacturers must continue managing supplier risks within their quality management systems.
Original source: Kd&a. Published: 4 September 2024.
TGA Seeks Feedback on Clarifying and Strengthening the Regulation of AI
Australia’s Therapeutic Goods Administration (TGA) has proposed changes to ensure the drug and device legislative frameworks align with proposed “guardrails” on the use of artificial intelligence (AI).
The Department of Industry, Science and Resources is leading the Australian government’s work on the safe and responsible use of AI. The department has proposed establishing guardrails on using AI in high-risk settings while allowing the use of the technology in low-risk settings under existing laws. The guardrails include strategies for regulatory compliance, risk management and human control.
In parallel, TGA is collecting feedback on plans to revise therapeutic goods legislation to reflect AI safety measures. The administration believes the regulatory framework already broadly aligns with the guardrails, but some changes may be needed. TGA is accepting feedback until 13 October.
Original source: RAPS. Published: 16 September 2024.
WHO Creates Medical Device Database to Encourage Data Consistency across Borders
World Health Organization (WHO) has introduced an online platform called MeDevIS (Medical Devices Information System), the first global open access clearing house for information on medical devices. It is designed to support governments, regulators and users in their decision-making on selection, procurement and use of medical devices for diagnostics, testing and treatment of diseases and health conditions.
MeDevIS replaces paper-based literature search across multiple publications with non-standard device names which can add to the complexity. Along with providing a single platform, MedevIS also aims to help make the naming of the medical devices simpler.
MeDevIS references two international naming systems for medical devices – the European Medical Device Nomenclature (EMDN), mostly used in European countries for registration in the European database, and the Global Medical Device Nomenclature (GMDN) used in regulatory agencies in Australia, Canada, the United Kingdom and the USA and other Member States. The naming systems include coding and definitions and can be used in every country to facilitate registration for regulatory approval, procurement and supply, inventories in health facilities, tracking and pricing
Original source: TRPMA. Published: 11 July 2024.
References
Image 1: Array
Image 2: Emergo
Image 3: Medenvoy
Image 4: RAPS
Image 5: Comvita
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