Introduction about Medical Device Regulation in Europe
Introducing the Medical Device Regulation in Europe addresses several challenges. It aims to enhance medical device regulation in Europe to ensure a higher level of safety and effectiveness. The need for the MDR arises from various factors, including shortcomings identified in the previous regulatory framework (Medical Device Directives) and the evolving landscape of medical technologies.
Rapid technological advancements in the field of medical devices have led to the development of increasingly complex and innovative products. The MDR adapts the regulatory framework to account for these technological advancements and to ensure the safety and performance of new and emerging devices.
The primary objective of the MDR is to prioritize patient safety. By introducing more stringent requirements for conformity assessment, clinical evidence, and post-market surveillance, the regulation aims to reduce the risk of harm to patients and users of medical devices. The MDR promotes transparency by introducing measures such as the European Database on Medical Devices (EUDAMED).
This database allows better traceability of medical devices in the market and facilitates communication between regulatory authorities, manufacturers, and other stakeholders. The MDR places a greater emphasis on post-market surveillance activities, ensuring that medical devices are continually monitored once they are on the market.
This enables timely identification and response to safety issues and improves overall device performance.
The MDR aims to harmonize the regulatory requirements for medical devices across EU member states. This harmonization facilitates a more consistent and predictable regulatory environment for manufacturers, streamlining the process of bringing products to market.
The MDR introduces a more refined classification system for medical devices, taking into account the potential risks associated with devices. This allows for a more accurate categorization of devices based on their characteristics and intended use. The Medical Device Regulation in Europe clarifies the roles and responsibilities of economic operators, including manufacturers, authorized representatives, importers, and distributors.
This enhances accountability throughout the supply chain, ensuring that each party plays a defined role in ensuring device compliance and safety.
The MDR aligns with global best practices and standards, contributing to international regulatory convergence. This alignment is essential for manufacturers who intend to market their devices globally. The MDR addresses identified gaps and weaknesses in the previous regulatory framework, the Medical Device Directives (MDD).
These gaps included challenges related to the classification of devices, insufficient requirements for clinical evidence, and variations in the interpretation and application of the directives among member states.
Medical Device Compliance
Medical device compliance refers to the adherence of medical devices to regulatory standards and requirements set by relevant authorities. Ensuring compliance is crucial to guarantee the safety, efficacy, and quality of medical devices, protecting both patients and healthcare providers.
The key aspects of medical device compliance are:
Regulatory Authorities
Different countries have regulatory bodies responsible for overseeing medical devices. For example, the U.S. FDA in the US, the European Medicines Agency (EMA) in the EU, and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan. Manufacturers must comply with the regulations specific to the regions where they intend to market their devices.
Classification of Devices
Medical devices are often categorized based on their risk level. The risk classifications include Class I, IIa, IIb, and III in the European Union under the MDR.
Quality Management Systems (QMS)
Compliance often involves the implementation of a QMS, such as ISO 13485. This ensures that manufacturers establish and maintain processes to consistently produce safe and effective medical devices.
Pre-market Approval (PMA) or Conformité Européenne (CE) Marking
Before marketing a medical device, manufacturers may need to obtain regulatory approval or clearance. In the U.S., this may involve the submission of a PMA application, while in the EU, devices need to be CE marked according to applicable regulations.
Post-market Surveillance
Manufacturers are required to monitor and report adverse events and product issues after a device is on the market. This involves maintaining a system for post-market surveillance and reporting to regulatory authorities.
Labelling and Instructions for Use
Compliance includes providing accurate and clear labelling for medical devices. Instructions for use must be easily understandable, and information about potential risks and proper usage should be prominently displayed.
Risk Management
Manufacturers must conduct risk assessments for their devices to identify and mitigate potential risks throughout the product lifecycle.
Clinical Data and Performance
Submission of relevant clinical data is often required for regulatory approval. This data supports claims regarding the safety and performance of the medical device.
Adherence to Standards
Compliance with relevant industry standards, such as those developed by the International Electrotechnical Commission (IEC) or ASTM International, is often necessary to demonstrate that a device meets specific criteria.
Audits and Inspections
Regulatory authorities may conduct audits and inspections to ensure that manufacturers are complying with all applicable regulations.
EU Medical Device Directive
The Medical Devices Directive (93/42/EEC) was one of the main directives governing the marketing and distribution of medical devices within the European Union. It provided the regulatory framework for the safety and performance of medical devices and outlined essential requirements that devices needed to meet.
The MDR (2017/745) came into effect in May 2021, replacing the Medical Devices Directive. It introduced more stringent requirements for the approval and surveillance of medical devices in the European Union.
The MDR emphasizes increased transparency, traceability, and the involvement of notified bodies in the conformity assessment process.
The MDR came into force on May 26, 2017, but the date of application was postponed several times. As of my last update, it was set to be fully applicable from May 26, 2021.
Key Changes and Features of Medical Device Regulation in Europe:
Stricter Scrutiny: The MDR introduces more rigorous pre-market assessment procedures, including enhanced scrutiny of high-risk devices.
Unique Device Identification (UDI): It mandates the use of a UDI system for better traceability of devices throughout their lifecycle.
EUDAMED Database: The establishment of the European Database on Medical Devices (EUDAMED) for the registration and dissemination of information about medical devices.
Post-Market Surveillance (PMS) and Post-Market Clinical Follow-up (PMCF): Strengthened requirements for post-market surveillance and clinical follow-up to monitor and report on device performance.
According to the MDR 2017/745, a ‘medical device’ means any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:
Diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,
Diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,
Investigation, replacement or modification of the anatomy or of a physiological or pathological process or state,
Providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations.
Medical Device Certification in Europe
The CE marking is a certification mark that indicates conformity with health, safety, and environmental protection standards for products sold within the European Economic Area (EEA). The CE marking is mandatory for various product categories, including Medical Device Regulation in Europe.
For medical devices, obtaining the CE marking signifies compliance with the applicable European regulations, such as the Medical Device Regulation (MDR) or the In Vitro Diagnostic Regulation (IVDR).
The CE marking demonstrates that a product meets the essential requirements outlined in European Union (EU) directives or regulations, ensuring a high level of safety and performance. Medical devices that are intended to be placed on the market within the EEA must bear the CE marking.
This includes a wide range of products, from simple devices to complex technologies. The CE marking allows a medical device to be legally placed on the market and sold within the EEA. Various economic operators in the supply chain, including manufacturers, importers, distributors, and authorized representatives, have specific responsibilities related to the CE marking process.
As part of the new regulatory framework, information about medical devices, including their CE certificates, will be registered in the European Database on Medical Devices (EUDAMED).
Manufacturers must continuously ensure that their devices remain in compliance with regulatory requirements. This includes monitoring post-market surveillance data and promptly addressing any safety concerns.
Manufacturers of Medical Device Regulation in Europe must follow a series of steps to affix the CE marking:
Conformity Assessment: The manufacturer assesses the device’s conformity with applicable EU regulations. This assessment can involve self-certification or the involvement of a Notified Body, depending on the device’s risk classification.
Technical Documentation: The manufacturer prepares comprehensive technical documentation that demonstrates compliance with essential requirements, including design, manufacturing, and performance data.
Quality Management System (QMS): Manufacturers must implement and maintain a QMS in accordance with relevant standards, such as ISO 13485.
Declaration of Conformity: Once the conformity assessment is successful, the manufacturer issues a Declaration of Conformity, declaring that the device meets the requirements of applicable EU regulations.
Affixing the CE Mark: The CE marking is affixed to the product, packaging, or accompanying documentation, indicating that the device complies with EU regulations.
Europe healthcare device standards
European healthcare device standards are a set of technical specifications and criteria that provide a common language and framework for the design, manufacturing, and performance of healthcare devices within the European Union (EU).
These standards are developed by various standardization organizations, and compliance with these standards helps manufacturers meet regulatory requirements and ensure the safety and efficacy of their devices.
Some of these standards are:
ISO Standards: cover various aspects, including quality management, risk management, and specific requirements for different types of medical devices.
Electromagnetic Compatibility (EMC) Standards: Healthcare devices, especially electronic and electrical equipment, must comply to ensure that they do not interfere with other devices and are not susceptible to interference. Common standards include EN 60601-1-2 for medical electrical equipment.
Biocompatibility Standards: ensure that materials used in devices do not cause adverse reactions when in contact with the human body. EN ISO 10993 is a series of standards addressing biocompatibility.
Quality Management System (QMS) Standards: Compliance with quality management system standards is essential for medical device manufacturers. ISO 13485 is an international standard, and compliance with it is often required for the CE marking of medical devices in Europe.
Risk Management Standards: Risk management is a critical aspect of medical device design and manufacturing. EN ISO 14971 is the standard that outlines the principles for risk management.
Sterilization Standards: standards like EN ISO 11135 for ethylene oxide sterilization and EN ISO 17665 for moist heat sterilization provide guidelines for ensuring the effectiveness of the sterilization process.
Software Standards: As software plays an increasingly important role in healthcare devices, standards like IEC 62304 provide guidance on the software life cycle processes.
Usability and Human Factors Standards: Standards in this category address the design and usability of healthcare devices to ensure that they are user-friendly and safe. EN ISO 14971 and IEC 62366 are relevant standards.
Labelling Standards: Standards related to labelling provide guidance on the information that should be included on medical device labels. EN 980 and EN ISO 15223-1 are examples.
It’s important for manufacturers and stakeholders in the healthcare industry to stay updated on the latest standards and ensure compliance with relevant regulations, as these standards play a crucial role in demonstrating conformity to essential requirements for medical devices in the European market.
Additionally, the specific standards applicable to a particular device depend on its type, classification, and intended use.
Conclusion
In conclusion, the unveiling of the Medical Device Regulation in Europe represents a significant milestone in the evolution of regulatory standards for Medical Device Regulation in Europe. The comprehensive changes introduced by the MDR are driven by a commitment to advancing patient safety, fostering innovation, and adapting to the rapidly evolving landscape of healthcare technologies.
The MDR addresses critical shortcomings identified in the previous regulatory framework, offering a more robust and transparent system for the approval and surveillance of medical devices.
With a heightened focus on risk management, clinical evidence, and post-market surveillance, the MDR aims to ensure that medical devices entering the European market meet the highest standards of safety and efficacy.
Key elements of the MDR include an enhanced classification system, stricter conformity assessment procedures, and the implementation of a Unique Device Identification (UDI) system. These features contribute to a more sophisticated and nuanced approach to regulatory compliance, tailored to the diverse range of Medical Device Regulation in Europe and their associated risks.
The regulation’s emphasis on transparency is evident in the establishment of the EUDAMED, providing stakeholders with a centralized platform for information sharing and increased traceability. This marks a crucial step towards creating a harmonized regulatory environment across EU member states.
As manufacturers navigate the complexities of compliance, understanding the requirements of the MDR becomes paramount. The alignment of the MDR with global standards fosters a seamless transition for manufacturers looking to market their devices internationally, reinforcing the EU’s commitment to global regulatory convergence.
In essence, the EU MDR sets a new benchmark for the medical device industry, demanding higher standards of quality, safety, and accountability. While the transition may present challenges for manufacturers, the long-term benefits lie in a safer and more innovative landscape that ultimately benefits patients and healthcare systems across Europe.
Staying informed about the intricacies of the MDR and collaborating with regulatory experts will be crucial for industry players aiming to navigate this transformative regulatory landscape successfully.
Recent amendments to Regulation (EU) 2017/745, also known as the Medical Devices Regulation (MDR), have introduced significant changes to the timelines and conditions for placing certain medical devices on the market or putting them into service. This comprehensive analysis explores the key points of these amendments, focusing on the intricate timeline considerations.
Paragraph 3 Amendments
Paragraph 3 has undergone crucial revisions, introducing new provisions (3a to 3g) that outline conditions and timelines for the placement of medical devices on the market or into service.
Let’s delve into the details of these Regulation (EU) 2017/746 amendments:
3a. Derogation and Conditions
By derogation from Article 5, devices falling under paragraphs 3b and 3c may be placed on the market or put into service, subject to the fulfilment of conditions specified in paragraph 3d.
3b. Placing Devices with Certificates
Devices with certificates issued under Directive 90/385/EEC or Directive 93/42/EEC, valid by virtue of paragraph 2, can be placed on the market until specific dates:
– Until 31 December 2027 for class III devices and class IIb implantable devices (excluding specific items).
– Until 31 December 2028 for class IIb devices (excluding those covered by the previous point), class IIa devices, and class I devices in sterile condition or with a measuring function.
3c. Conformity Assessment Procedure
Devices with conformity assessment procedures under Directive 93/42/EEC, not involving a notified body, may be placed on the market or put into service until 31 December 2028, provided certain conditions are met.
3d. Conditions for Placement
Devices can be placed on the market until the specified dates (3b and 3c) if the following conditions are met by 26 May 2024:
– Continued compliance with relevant directives.
– No significant changes in design and intended purpose.
– No unacceptable risk to health or safety.
– Implementation of a quality management system by the manufacturer.
– Lodgement of a formal application for conformity assessment by 26 May 2024 and a written agreement signed with a notified body by 26 September 2024.
3e. Application of MDR Requirements
In derogation from paragraph 3a, devices in paragraphs 3b and 3c are subject to MDR requirements for post-market surveillance, market surveillance, vigilance, and registration of economic operators and devices.
3f. Responsibilities of Notified Bodies
The notified body issuing the certificate in paragraph 3b remains responsible for surveillance unless agreed otherwise. A transition of surveillance responsibilities is outlined in agreements between manufacturers and notified bodies.
3g. Derogation for Class III Custom-made Implantable Devices
Class III custom-made implantable devices can be placed on the market until 26 May 2026 without a certificate, provided a formal application is lodged by 26 May 2024, and a written agreement with a notified body is signed by 26 September 2024.
Paragraph 4 Replacement
Paragraph 4 stipulates that device lawfully placed on the market before 26 May 2021, and those placed afterward under paragraphs 3a, 3b, 3c, and 3g, may continue to be made available or put into service.
Article 122 Amendments
Article 122 outlines amendments related to the repeal of Directives 90/385/EEC and 93/42/EEC, effective from 26 May 2021. Noteworthy points include the continuation of Directives’ application for devices in specific paragraphs of Article 120(3a) to (3f) and (4).
Article 123 Amendments
In Article 123(3), point (d), the amendment includes a reference to Article 120(3e), further emphasizing the continued application of certain requirements from the repealed Directives.
Regulation (EU) 2017/746 Amendments
The amendments to Regulation (EU) 2017/746, also known as the In Vitro Diagnostic Devices Regulation (IVDR), focus on Articles 110 and 112.
Article 110 Amendment
Devices lawfully placed on the market under Directive 98/79/EC before 26 May 2022, and those placed afterward under paragraph 3 of this Article, may continue to be made available or put into service.
Article 112 Amendment
For devices referred to in Article 110(3) and (4) of the IVDR, Directive 98/79/EC shall continue to apply to the extent necessary for the application of those paragraphs.
Conclusion
The recent amendments to MDR and IVDR introduce a complex framework of conditions and timelines for the placement of medical devices on the market. Stakeholders, including manufacturers and notified bodies, must carefully navigate these provisions to ensure compliance and a smooth transition to the new regulatory landscape.
As technology advances across all healthcare fields, Software plays a significant role in all products. It is widely integrated into digital platforms serving both medical and non-medical purposes. Medical device software is one of three types of Software related to medical devices.
The other two types of medical device software include Software that is an integral part of the medical device (medical device software) and Software used in manufacturing or maintaining the medical device.
Software as a Medical Device Introduction
The International Medical Device Regulators Forum (IMDRF) defines SaMD as “software intended for one or more medical purposes that perform those purposes without being part of a hardware medical device.”
FDA defines SaMD as “Software that meets the definition of a device in 181 section 201(h) of the FD&C Act and is intended to be used for one or more medical purposes without being part of a hardware device.”
The use of SaMD is experiencing a steady rise, with its application extending to various technology platforms such as medical device platforms, commercial “off-the-shelf” platforms, and virtual networks, among others.
This kind of software was previously referred to as “standalone software,” “medical device software,” or “health software” by industry professionals, international regulators, and healthcare providers, often leading to confusion with other software categories.
How Do I Know if My Product is SaMD?
As a member of the International Medical Device Regulatory Forum (IMDRF), the FDA recognizes the structural similarity between the two organizations’ definitions of SaMD. The definitions provided by the FDA and IMDRF highlight two criteria that must be satisfied for software to be designated as SaMD.
To evaluate if the Software is a medical device, it is important to assess its compliance with the regulatory authority’s definition. The IMDRF emphasizes that the Software must be “intended for one or more medical purposes”. On the other hand, the FDA references FD&C, or the Federal Food, Drug, and Cosmetic Act, Section 201(h), which outlines the definition of a device. This section defines a device as follows:
According to Section 201(h) of the FD&C, a device encompasses various articles such as tools, implements, instruments, machines, devices, appliances, in vitro reagents and other similar or related items, including components and accessories.
An article must also be legally recognised in the National Formulary, the United States Pharmacopoeia, or an analogous revision in order to meet the requirements of Section 201(h) of the FD&C Act’s definition of a device.
The product is intended to be used in the diagnosis of disease or other conditions as well as in the treatment, mitigation, treatment, or prevention of disease in people or animals, according to the definition of a device under FD&C Section 201(h).
In addition, a product must be intended to change any structure or function of the human or animal body without compromising its primary function for it to qualify as a device under Section 201(h) of the FD&C Act.
In addition, the definition of a device in Section 201(h) of the FD&C Act states that it must not achieve its primary purpose by chemical action in or on the human or animal body, nor must it rely on metabolism to achieve its purpose.
Note that the term “device” does not include software features that are excluded by Section 520(o). To apply this definition, it is essential to establish the intended use and indications for the use of your product. To refresh your understanding,
The intended use of a device refers to its designated purpose or the specific function for which the device is intended to be utilised. In other words, it defines the intended or intended application of the device
Indications for use pertain to the diseases or conditions that a device is designed to diagnose, treat, prevent, cure, or mitigate. These indications specify the target patient population and provide insights into why the device would be used on individuals with those diseases or conditions
Once the intended use and indications for the use of your product are defined, the second and third points in the FDA’s definition of a medical device will help determine whether your product falls under the regulatory scope of a medical device. These criteria will clarify whether your product meets the requirements for medical device regulation.
If you intend to market your software product in the United States, I recommend carefully reviewing the FDA’s guidance on Policy for Device Software Functions and Mobile Medical Applications.
This guidance provides valuable insights into the specific software functions that the FDA classifies as medical devices and functions that are not considered medical devices and, therefore, not subject to FDA regulation. Familiarizing yourself with this guidance will provide you having a thorough awareness of the regulatory environment for software products in the medical field.
If you’re still unsure about whether your product qualifies as a medical device, contacting the FDA directly for clarification is safest. Contacting the FDA now will provide reliable advice and ensure you receive accurate information tailored to your specific product and situation.
Is My Software Considered SaMD or SiMD?
When a product is found to fit the definition of a medical device, the second portion of the IMDRF and FDA definition of software as a medical device (SaMD) must be taken into account.
According to the IMDRF definition, Software must be used for its intended purpose only and must not be an integral part of a physical medical device.
According to the IMDRF, the FDA makes it clear that Software as a Medical Device (SaMD) is not a part of a hardware device and is instead intended for standalone usage for one or more medical purposes.
This further limit the scope of Software as a medical device (SaMD), as the Software used to operate or control a hardware device does not fulfil the requirements to be categorised as a SaMD. Instead, this type of Software is referred to as SiMD or “software in a medical device.”
Here are some examples of Software that assist in operating a hardware medical device, which falls under the category of Software in a Medical Device (SiMD) and not Software as a Medical Device (SaMD):
Software that controls the inflation or deflation of a blood pressure cuff
Software that controls the delivery of insulin on an insulin pump
Software used in the closed-loop control of a pacemaker.
“firmware,” or “micro-code,” indicating their classification as SiMD rather than SaMD.
To qualify as SaMD, a product must have standalone Software that independently carries out the functions defining it as a medical device, distinct from any associated hardware. The IMDRF guidance on “Possible Framework for Risk Categorization and Corresponding Considerations” further provides additional insights and clarifications regarding the SaMD definition.
1. SaMD is a medical device, including in-vitro diagnostic (IVD) medical devices.
2. SaMD can run on general-purpose computing platforms not specifically designed for medical purposes.
3. “Without being part of” means the Software is unnecessary for a hardware medical device to achieve its intended medical purpose.
4. Software intended to drive a hardware medical device does not meet the definition of SaMD.
5. SaMD can be combined, such as being integrated as a module, with other products, including medical devices.
6. SaMD can interface with other medical devices, including hardware medical devices, other SaMD software, and general-purpose Software.
7. Mobile apps that meet the defined criteria are considered SaMD.
Although it is crucial to distinguish between Software as a Medical Device (SaMD) and Software in a Medical Device (SiMD), both types of Software adhere to many common standards for development, including the global standard for software lifecycle procedures is IEC 62304. lifecycle processes.
If your Software falls under the category of SiMD, you will still find the guidance documents and standards outlined in this guide valuable and applicable.
What are Some Examples of SaMD?
1. Software that enables a mobile device to view diagnostic images from MRI, ultrasound, or X-ray scans.
2. Software that utilizes image processing techniques to aid in detecting breast cancer.
3. Software that diagnoses a medical condition by analyzing data from the tri-axial accelerometer on a smartphone.
4. Software that collects real-time patient data monitored by a healthcare professional and utilized to develop treatment plans.
Clinical Evaluation
Clinical evaluation is a methodical and well-organized process that creates clinical evidence by continuously creating, collecting, analyzing and evaluating clinical data on SaMD to create clinical trials that review the clinical context and performance indicators of SaMD.
The quality and scope of the clinical assessment is based on the SaMD function for the clinical objective, which also ensures that the SaMD score is clinically valid and can be used consistently and predictably.
3 Clinical Evaluation Software
To qualify the software, the following three criteria must be met. To qualify your software, you must meet the three criteria outlined below.
Valid Clinical Association of a SaMD
Analytical/Technical Validation of a SaMD
Clinical Validation
1. Valid Clinical Association of a SaMD
Verifying that your software’s output corresponds to the targeted clinical conditions is the main goal here. Use of secondary data analysis, clinical trials (new data generated), professional society guidelines, original clinical research, literature searches, and/or secondary data analysis are all options for carrying out that task. All SaMD should show a reliable clinical association.
2. Analytical/Technical Validation
Does your software correctly process input data to generate accurate, dependable, and precise output data?” is the question we are attempting to answer in this context. Develop supporting documentation that demonstrates your SaMD’s output met your expectations in terms of technicality.
This action is being assessed by a manufacturer as part of the software’s validation and verification phase (V&V).
3. Clinical Validation
SaMD has been evaluated in your target population and for your intended use; users are able to achieve clinically significant results through consistent and dependable use.
Medical device apps are increasingly growing these days. MHRA has issued new guidance on the stand-alone software medical devices, including apps. This guidance is a crucial document for manufacturers and users of such medical devices.
In the UK, medical devices are subject to UKCA marking. The UKCA marking is no exception to software medical devices.
Software Medical Devices or not
Classifying software or a mobile app as a medical device can be challenging. If the software or app has a well-defined intended medical purpose, it is essential to mark CE or UKCA on the product.
This ensures that the device conforms to the requirements of the regulation of the EU and UK and is safe for use. The flow chart provided below helps determine if the software is a medical device, in vitro diagnostic device, active implantable, or accessory.
Flowchart on the classification of software into medical device Source: MHRA Software flowchart
Intended purpose
A medical device is defined by the intended purpose on the device labelling, Instructions for use and any promotional materials, including brochures.
Depending on the intended purpose, the device can be classified as a device with a medical purpose if it:
Prevents disease
Diagnoses a disease, injury or handicap
Monitoring a disease, injury or handicap
Treats or alleviation of a disease, injury or handicap
Compensates an injury or handicap
Investigates replaces or modifies anatomy or physiological process
Controls conception
A software device is considered to have a medical purpose if it has one of the following features and looks into in vitro data:
Concerning a physiological or pathological state
Concerning a congenital abnormality
To determine the safety and compatibility with potential recipients
To monitor therapeutic measures
Software Medical device classification and essential requirements
Rule 9 includes active therapeutic devices intended to administer or exchange energy
Rule 10 includes active devices intended for the diagnosis
Rule 12 includes all other active class I devices
Rule 14 includes devices used for contraception or the prevention of the transmission of sexually transmitted diseases
One of the essential requirements for software apps is for the benefit to outweigh any risks. Essential requirements also state the risks of ergonomic features and the intended use environment.
Manufacturers of such devices must ensure that the user interface must be consistent, and graphics and text must be clear and legible. The software or app must be designed with safety in mind.
In addition, the clinical evaluation following Annex X of the UK MDR must be done. A similar set of requirements applies to IVDs.
Labelling requirements
The software labelling must be clear and visible to the user. Manufacturers must ensure the app meets relevant requirements and displays UKCA marking on the landing page itself.
The following particulars must be present on the software label:
App name
Version number
Date of manufacture
Manufacturer name and address
UKRP name and address
Purpose of software
Warnings and precautions
UKCA or CE marking
Labelling for an app with medical purpose
Examples of Software with a medical purpose
Software with a medical purpose may be devices that:
Provide information for the calculation of drug dose using IVD data such as blood
Enables therapeutic drug monitoring
Monitor blood glucose levels
Provides medical conditions based on input user data
Indicate potential developing disease based on the entered data
Automate the pathway for treatment for an individual
Enables people with visual or hearing disabilities to read or listen by magnifying text or amplifying sounds
Software or app without an intended medical use would include:
General apps for recording patient images which later require the diagnosis of a clinician
Apps that give general recommendations instead of user-specific advise
Software that is intended to record heart rates, such as fitness or sports apps
Apps that remind patients of drug intake
Apps to treat non-medical conditions
Software that provides tips or advice
Disclaimer: Regulations/legislations are subjected to changes from time to time and the author claims no responsibility for the accuracy of information.
The MDR reinforces the clinical data and evaluation process (article 61 and Annex XIV), and the manufacturer must confirm the device’s conformity to fundamental health and safety requirements using reliable clinical data and evaluation.
The clinical evaluation establishes the device’s safety and capacity to fulfil its intended function. It also evaluates adverse side effects and determines whether the benefit-risk ratio is acceptable.
Manufacturers must plan, carry out, and document a clinical evaluation in line with Article 61 and Part A of Annex XIV.
Clinical data for the medical device are created, compiled, examined, and ultimately evaluated through a systematic and organised process called a clinical evaluation.
The Clinical Evaluation Report (CER), which the manufacturer uses to show that the medical device complies with the general safety and performance requirements specified in Annex I of the MDR, is the end result of the clinical evaluation.
The Clinical Evaluation Report (CER) is an essential component of a manufacturer’s quality management system and an essential component of the technical documentation for the medical device (MDR Article 10 (3)). It must be actively updated on a regular basis utilising information from the post-market clinical follow-up and post-market surveillance of the medical device (PMCF).
Thus, clinical evaluation is a continuous procedure throughout a medical device’s life cycle.
The Objective of Clinical Evaluation
The clinical evaluation aims to show that the medical device can be used as intended while still being safe and effective, including in terms of its clinical advantages.
The clinical evaluation can also be used to reevaluate risks and find previously overlooked hazards or dangers. The acceptability of hazards must be reevaluated by manufacturers using the most recent clinical evidence.
The objectives of the clinical examination include:
The product’s use for its intended purpose under normal circumstances demonstrates conformity with the general safety and performance requirements listed in Annex I of the MDR
Evaluating or excluding undesirable side effects
Proof of the validity of the risk-benefit ratio
Proving the makers’ medical claims.
Alternative product methods and technologies that can be used in place of the treatment being evaluated are evaluated and documented as part of the clinical study.
The clinical evaluation must ensure that the tested product is not worse than the potential substitutes. The clinical evaluation needs to describe and assess the state of the art.
When assessing state of the art, clinical benefits, safety, and performance should be taken into account. When designing and producing their products, medical device makers must take the latest technological advancements into account.
Clinical Evaluation Data
Clinical information gathered while using the medical device forms the basis of the clinical evaluation. The following are some potential sources for these:
Clinical trial(s) conducted by the manufacturer of the medical device
Clinical trial(s) or other research on a known similar product from the scientific literature
Data from post-market surveillance (PMS) are clinically significant, particularly from post-market clinical follow-up (PMCF).
Reports regarding additional clinical trials using the product under review or a comparable product that has been published in the peer-reviewed scientific literature
Manufacturers must consider preclinical data in addition to clinical data when making their clinical evaluations.
For instance, this comprises the outcomes of the following tests: Testing for biocompatibility, electrical and mechanical safety electromagnetic compatibility in accordance with IEC 60601-1-2, usability, software, animal, simulation, and laboratory testing, as well as testing for durability and stability.
For absolutely non-critical products (stand-alone software, dental drills, oral spatulas, etc.) and must be justified by the manufacturer based on risk management, in accordance with MDR Article 61 “Clinical Evaluation” Section 10.
The manufacturer’s claims, the anticipated clinical performance, and the precise interactions the device has with the human body are all taken into account in this explanation.
According to Annex II of the MDR, the manufacturer in this situation must explain in the technical documentation why they believe it is appropriate to show compliance with the general safety and performance requirements based solely on the outcomes of non-clinical test methods, including performance evaluation, technical testing, and pre-clinical evaluation.
Clinical Evaluation Plan (CEP)
A medical device’s clinical evaluation is a continuous process for developing, collecting, analysing, and evaluating clinical data. It is systematic and well-planned.
Manufacturers are required to create and update a clinical evaluation plan in accordance with Article 61 (paragraph 12) and Annex XIV Part A “Clinical Evaluation” of the MDR (CEP).
Basic ideas like the goals and format of the clinical evaluation are already stated in this strategy. The manufacturer establishes the fundamental performance and safety standards that relevant clinical data in the CEP must back up.
With detailed clinical outcome metrics, it outlines the desired clinical advantages for the patient and specifies the intended purpose, intended target groups, and explicit indications and contraindications.
A new required component of the clinical evaluation plan is a clinical development plan (CDP) for organising pertinently planned clinical trials, including a post-market clinical follow-up plan (PMCF plan).
These adjustments give clinical findings more weight. The Clinical Development Plan (CDP) explains how the manufacturer will gather new or extra clinical data through clinical trials or observational studies to solve open “gap analysis” problems at the beginning of the development phase.
Human volunteers are used in clinical trials to assess the clinical effectiveness and safety of medical equipment.
Class III Devices and Implantable Devices
Clinical investigations must always be carried out in the case of implanted devices and class III devices, with the following exceptions:
The already marketed device has been altered by the same manufacturer, who has also shown that the altered device is equivalent to the marketed one.
The notified body has approved of this demonstration, and the clinical assessment of the marketed device is sufficient to show that the altered device complies with the necessary safety and performance requirements.
Additionally, there is no requirement for clinical testing for class III and implantable devices if a manufacturer can show that its product is functionally equivalent to a product that has already been marketed, provided that the notified body has approved the demonstration and the following requirements are met.
The two manufacturers have a contract in place that expressly grants the manufacturer of the second product full access to the technical documentation on a continuing basis, and the original device manufacturer is still in business.
Additionally, No obligation for clinical investigation for Class III and implantable devices:
If the devices have been legitimately marketed under previous directives, the clinical evaluation is supported by enough clinical data, and they adhere to Common specifications where they are available.
Annex XIV
A clinical evaluation must be planned, continually carried out, and documented by manufacturers in order to:
Create and maintain a clinical evaluation plan,
Utilising a systematic, scientific literature study, determine the clinical data that is available that is pertinent to the device and its intended use, as well as any gaps in the clinical evidence;
Evaluate each relevant clinical study’s applicability for proving the device’s performance and safety;
To produce any additional or new clinical data required to address unresolved problems through adequately conducted clinical research in accordance with the clinical development strategy; and
In order to conclude the safety and clinical performance of the device, including its clinical advantages, all pertinent clinical data must be examined.
Equivalence
Equivalence for the EU MDR clinical evaluation must be proven in two distinct ways.
Clinical
Used for the same clinical condition (with equivalent severity and stage of disease).
Utilised for the same medicinal purpose, and utilised for the same intended purposes, and
Utilised at the same body location, and used in a population with similar features (e.g., age, gender, anatomy, physiology, etc.), and not anticipated to produce noticeably differing performances (in the relevant critical performances such as the expected clinical effect, the specific intended purpose, the duration of use, etc.).
Technical
Have similar specifications and properties (e.g., physicochemical properties such as type and intensity of energy, tensile strength, viscosity, surface characteristics, wavelength, surface texture, porosity, particle size, nanotechnology, specific mass, atomic inclusions such as nitrocarburising, oxidability),
Similar design
Used under the same conditions, similar deployment methods (if applicable), and similar operating principles).
Biological
Use the same tools or substances when in contact with the same body fluids or human tissues.
FAQs
What do you mean by clinical evaluation?
A clinical evaluation is a systematic and well-planned procedure used to acquire, gather, analyse, and ultimately evaluate clinical data for a medical device.
What is clinical evidence?
Clinical evidence is defined as clinical data and clinical evaluation results about a device of sufficient amount and quality to permit a qualified assessment of whether the device is secure and provides the expected clinical benefit(s) when used in accordance with the manufacturer’s instructions.
The amended ‘Blue Guide’ on the application of the product rules 2022’ (“Blue Guide”) was released by the European Commission on June 29, 2022.
The Blue Guide allows a better understanding of EU product regulations and their uniform and coherent application across various sectors throughout the EU single market.
The Blue Guide has undergone significant changes, including the definition of new terms, the addition of information on which economic actors will be responsible for compliance in a complicated product supply chain, and the incorporation of Regulation (EU) 2019/1020 on market surveillance and product compliance.
Technical Documentation of The ‘Blue Guide’
The manufacturer must compile the technical documentation, including details proving the product complies with all relevant specifications.
If the law mandates a conformity assessment process based on a quality system, this paperwork may be a component of the quality system documentation.
Regardless of the product’s origin or location, technical documentation must be available when the product is put on the market.
The technical documentation must be preserved for ten years following the date the product was placed on the market. The manufacturer or the authorised representative based in the Union oversees this.
The documentation must include
Description of the product
Intended use of the product
Design and manufacture of the product
Operation of the product
The requirements in Annex II of Decision No. 768/2008/EC concern the technical documentation necessary to demonstrate the product’s compliance with the relevant harmonisation legislation.
If only part of the harmonised standard is applied or does not cover all relevant essential requirements, then the way applicable essential requirements not covered by it are dealt with should be documented in the technical documentation.
The technical documentation must reflect all versions of the product, including the changes made, information on how the various conformity assessments can be identified, and information on how the different versions of the product can be identified to avoid scenarios in which, during a product’s life, a market surveillance authority must deal with product versions for which the technical documentation given to it does not apply.
Even if it isn’t explicitly stated in the Union harmonisation legislation, the documentation must always be in a language the notified body can understand.
EU Declaration of Conformity
As part of the conformity assessment process outlined in the Union harmonisation legislation, the manufacturer or the authorised representative formed within the Union must prepare and sign an EU Declaration of Conformity.
This document is required to show the product’s compliance with the applicable legislation requirements.
Unless the legislation specifies otherwise, the manufacturer must maintain the EU Declaration of Conformity for 10 years after the product is placed on the market. The importer is accountable for the Declaration of Conformity for products they have brought in.
It is necessary to keep the EU Declaration of Conformity updated. Even if they are produced in series, each product has its own EU Declaration of Conformity.
The version of the EU declaration of conformity must be updated for products put on the market after any modifications have been made to any elements of the EU declaration of conformity.
Either the model declaration found in Annex III of Decision No. 768/2008/EC or a model declaration directly annexed to the in question sectoral Union harmonisation legislation have to be referred to understand the contents in the EU Declaration of Conformity.
The declaration must include enough details to allow the identification of all the products it covers, whether in the form of a document, label, or equivalent.
To ease the administrative burden on economic operators, where multiple pieces of Union harmonisation legislation apply to a product, the manufacturer or the authorised agent must produce a single declaration of conformity.
The surveillance authority must access the EU declaration of conformity upon request. The declaration must always be made in the language(s) that the Member state(s) where the product is marketed requires.
Marking requirements
Before many products may be marketed on the European market, a CE Mark must be affixed to them. The label identifies a product as:
Complies with the relevant standards of European product directives
Satisfies all requirements outlined in Europe’s applicable, recognised, and harmonised performance and safety standards.
Appropriate for its intended use and won’t threaten people or property
The CE Mark is mandated conformity marking used by the European Union (EU) to control the sale of goods inside the European Economic Area (EEA).
A manufacturer certifies that their products conform with the EU’s New Approach Directives by placing the CE mark on them. These directives include products made in or intended for sale in the EEA and those sold in the EU. As a result, the CE symbol is identifiable everywhere, even by those unfamiliar with the EEA.
The manufacturer is ultimately in charge of the product’s compliance with the provisions of the Union harmonisation legislation and the use of the CE marking, regardless of whether they are based inside or outside the Union.
The manufacturer has the right to direct an authorised agent to apply the CE marking on his behalf. By placing the CE marking on a product, a manufacturer certifies that it complies with all applicable regulatory requirements for CE marking, on his sole responsibility.
Suppose the importer or distributor or another operator places products on the market under his name or trademark or modifies them. In that case, he then takes over the manufacturer’s responsibilities, including the responsibility of affixing the CE marking.
The definition, the format, and the general guidelines governing the CE marking are outlined in Regulation (EC) No. 765/2008. Procedures for conducting conformity assessments that result in its affixing are outlined in Decision No. 768/2008/EC.
The Regulation (EC) No 765/2008 and Decision No 768/2008/EC’s guiding principles are primarily upheld by the sectoral Union harmonisation legislation requiring the application of the CE marking.
If a notified body participates in the production control phase following the appropriate Union harmonisation law, its identification number must come after the CE marking.
If the legislation so demands, the manufacturer or the authorised agent must attach the identifying number under the supervision of the notified authority.
A notified body may participate in the production stage depending on the conformity evaluation techniques. Only if it engages in manufacturing must the notified body’s identification number come after the CE marking.
CE marking appears on products without an identification number
CE marking appears on products with an identification number
Either no notified body intervened in the design or production phase (module A)
Either upon manufacturer’s choice, a notified body intervened in the production phase (modules A1, A2)
Upon manufacturer’s choice, the in-house accredited body intervened in the production phase (modules A1, A2)
A notified body intervened in the design phase (module B), and upon the manufacturer’s choice, a notified body (not necessarily the same one but the one whose identification number appears) intervened in the production phase (modules C1, C2 following module B)
A notified body intervened in the design phase (module B), but no notified body intervened in the production phase (module C following module B);
A notified body intervened in the design phase (module B), and a notified body (not necessarily the same one but the one whose identification number appears) intervened in the production phase (modules C1, C2, D, E, F following module B)
A notified body intervened in the design phase (module B), and upon the manufacturer’s choice, the in-house accredited body intervened in the production phase (modules C1, C2 following module B)
A notified body intervened in the design and production phase (modules D1, E1, F1, G1 H, H1)
Modules for Conformity Assessment
A conformity assessment is any procedure by the manufacturer to evaluate a product, system, service, or perhaps even a person’s compliance with the standards and specifications outlined in a standard or specification.
Testing or inspection is frequently used for verification. Conformance assessments are performed on products during the design and manufacturing phases.
A conformity assessment procedure’s primary goal is to show that products that have been put on the market adhere to the standards set out in the existing legislation.
Conformity assessment processes comprise one or two conformity assessment modules under Union harmonisation legislation. A conformity assessment encompasses both the design and production phases since products are subject to conformity evaluation during both phases.
In contrast, a module may cover just one of the two phases or both. A “horizontal menu” of conformity assessment modules and how processes are constructed from modules is outlined in Decision No. 768/2008/EC.
Union harmonisation legislation creates conformity assessment processes either by foreclosing on the manufacturer’s options or by defining a range of options from which the manufacturer must select.
The manufacturer is responsible for conformity evaluation. However, a third party must be included in the compliance evaluation process if required by the applicable legislation.
FAQs
What is the significance of CE marking?
By applying the CE marking to a product, the manufacturer declares solely on his responsibility that the product complies with the essential requirements of the applicable Union harmonisation legislation requiring its application and that the relevant conformity assessment procedures have been completed. Products bearing the CE mark are presumed to comply with the applicable Union harmonisation legislation and thus have free circulation in the European Union.
Can I, as a manufacturer, personally affix the CE marking to my products?
After the required conformity assessment procedure has been completed, the manufacturer or his authorised representative can apply the CE marking. This means that the product must go through the conformity assessment procedure outlined in one or more of the relevant Union harmonisation acts before being given the CE marking and put on the market. The latter determines whether the manufacturer himself may conduct the conformity assessment or whether the involvement of a third party (the notified body) is necessary. The published ‘Blue guide’ helps product manufacturers understand how to place their products in conformity with the applicable product regulation.
Disclaimer: Regulations/legislations are subjected to changes from time to time and the author claims no responsibility for the accuracy of information.
