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 device 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.
Medical device testing is a crucial step in manufacturing a product. This mandatory process ensures that the medical device is safe and effective. Testing of medical devices proves that the product complies with the standards and regulations of a country. Moreover, it also sheds light on any product defects. This article discusses the testing requirements and the applicable standards.
Medical device testing applies to all medical devices, in-vitro diagnostic devices, combinational products, and active implantable devices. Some common testing of medical devices is given below:
Electrical safety tests
Functional safety tests
Performance tests
Electromagnetic compatibility (EMC) tests
Electromagnetic Interference (EMI) tests
Immunity Tests
Biocompatibility tests
Chemical testing
Cybersecurity tests (applicable to SaMDs or software that store data)
Storage and Transport
Ingress Protection
Medical device testing is crucial as the device intended for patient use must be safe. The tests a medical device must undergo depend on the device’s type. To explain further, medical equipment like a ventilator must undergo an electrical safety test. At the same time, a device such as a cannula requires appropriate biocompatibility tests. Hence, the choice for a practical device test is taken with the help of the medical device’s intended use.
The testing procedure should be logical and must begin with a risk analysis. After identifying the failure mechanisms and hazards associated with a device, testing strategies and processes can be devised to quantify the size of these risks. As a result, the purpose of a test method and procedure is to offer evidence that the hazards connected with a device are insignificant or, at the very least, acceptable when weighed against the benefits received from its use.
Types of medical device testing
Medical device testing is broadly categorized into physical, chemical/biological and cybersecurity testing. Physical testing involves the tests such as electrical testing, MRI safety, functional safety tests and EMC tests.
IEC 60601 series is a widely accepted technical standard for the safety and performance of electrical equipment. EMC/EMI tests ensure that the overall device is compatible with other medical devices and works optimally in the device environment when subjected to interference and immunity. Conformance to this standard provides that medical equipment does not create electromagnetic fields that could impair the operation of other devices in the usual environment.
Chemical or biological testing help achieve device compatibility with the surface of the skin. Medical devices that contact skin must comply with the ISO 10993 series- Biological evaluation of medical devices. For this, the manufacturer must consider the choice of material used compatibility between device materials and the biological tissues, cells, and body fluids. Testing methods like stress, shear testing, and ageing tests are performed so that the final product causes the least quality concerns.
Cybersecurity testing is crucial to medical devices so that risks such as unauthorised access to data and breaches are identified, and their occurrence minimised. A common standard followed for medical device software is IEC 62304 and ISO27001. IEC 62304 standard specifies the life cycle requirements for medical device software, whereas in ISO 27001 focuses on data and information security.
It should be noted that each of the above standards is closely related to the ISO standard for risk management of medical devices (ISO 14971). The risks associated with the medical device should be correctly identified, and appropriate tests should be done, proving that the relevant standards are met. Please read our article on global ISO requirements for a better understanding of the ISO standards.
Testing requirements around the world
To fully comply with the regulations of each country, one must also align with the testing standards accepted within each country. ISO and IEC standards are accepted across the globe. Compliance with these ensures that the devices can be marketed without any major difficulties. This article discusses the testing standards followed in major medical device markets.
In Europe, close to 80% of electrical and electronic standards follow the various IEC International Standards. Standards for electromedical equipment include IEC 60601 series standards for the requirements for high-frequency surgical instruments, short-wave therapy equipment and so on. The EU from time to time releases the harmonized standards list which are the most acceptable standards for the EU compliance.
In the US, accepts certain ISO standards however there are a list of recognized consensus standards that the FDA accepts for medical devices in the US. These include ANSI, AAMI, ATSM and so on. ANSI standards are applicable to a variety of industries like the ISO whereas AAMI testing standards are specific to medical instruments and ATSM standards are specific for materials used in medical devices.
Testing standards ensure that the medical device is fit for use not just for the patient but also for the healthcare professionals handling them. Most countries do not have stringent requirements for testing standards, but it is recommended that the devices have some form of tests done.
Why are risk management and testing standards closely linked?
Risk analysis is a crucial step in designing a medical device. Certain identified risks can be managed with a minor change in the initial stages of the manufacture and these can be identified with the help of an appropriate test.
Disclaimer: Regulations/legislations are subjected to changes from time to time and the author claims no responsibility for the accuracy of information.
Medical devices conforming with the medical device regulations must have a conformity marking. Medical devices that do not conform may still be placed in the market, provided they apply through the exceptional use devices pathway. This article discusses the exceptional use requirements to be satisfied to gain access to EU and UK markets.
In the UK, the UKCA marking displays that the device conforms to UK Medical Device Regulations 2002. Without UKCA marking, the devices can only be placed in the market under certain circumstances. Similarly, CE marking is accepted throughout the EU, which denotes that medical device conforms to the EU MDR 2017/745. This procedure may also apply to custom-made devices that have not complied with standard conformity procedures. These devices are called special-purpose devices in the EU and are mentioned in Article 21 of EU MDR 2017/745.
A manufacturer may place a medical device if the following conditions are met:
The clinician supports the application for the treatment of the patient
No alternative to this medical device is available on the market
Justification on how the medical device can improve the patient’s health with the device
The manufacturer is responsible for placing the device on the market, but the manufacturer and clinician must fill out the Humanitarian use of device-application form and submit to [email protected] . The application form must be submitted for each different patient. MHRA approves the case-by-case application basis and may request more information if the application details are deemed unclear.
The application form for exceptional use devices requires the following details:
Risk analysis, hazard identification and estimation of risks
Name and address of the consultant
Patient’s medical condition details
Device necessity and
Other relevant information
Devices for special purposes in the EU
Devices under this category do not require a CE mark. Still, they must meet the conditions mentioned in EU MDR that the device is evaluated for its safety and effectiveness by the manufacturer. Articles 62-82 of EU MDR describe the requirements to be met by manufacturers of investigational devices.
Firstly, for investigational devices, a proper clinical investigation plan is required. Read our detailed article on Clinical investigation in the EU for more information regarding this topic. In short, the clinical investigation has a different technical file and application form than the CE-marked medical devices.
The application form should be submitted with the following documents.
Clinical investigation plan
Investigator’s brochure
Name and address of the manufacturer
Patient information sheet
Detailed risk analysis and test reports
Informed consent document
Other available technical documentation
Custom-made devices
As per EU MDR, ‘custom-made devices’ means as any device specifically made in accordance with a written prescription of any person authorised by national law by virtue of that person’s professional qualifications which gives, under that person’s responsibility, specific design characteristics, and is intended for the sole use of a particular patient exclusively to meet their conditions and needs. However, the definition does not include ‘mass produced’ devices that need to be adjusted per user requirements. UK MDR 2002 5 (1) has a similar definition for custom-made medical devices. The provisions in Great Britain (England, Wales and Scotland) can be accessed in Guidance on Custom-made devices in GB. Medical devices like dental appliances and prosthetics all come under custom-made devices as these are designed specifically for an individual and are not mass-produced.
Custom-made devices require technical documentation following Annex II and III of EU MDR. In addition to the documents, the manufacturer or authorised representative should draw a statement containing crucial information like that the device is intended for exclusive use by a particular user and data allowing unique identification of the medical device.
An important point to remember is that custom-made devices must conform to general safety and performance requirements in Annex I of EU MDR and essential requirements in Annex I Schedule 2A of the UK MDR 2002, and the devices are not exempt from these requirements.
FAQs
What devices come under custom-made devices?
Medical devices that come under Custom-made devices are specifically designed for an individual patient. Some great examples include dental crowns, fillings, elastics and retainers for dental structure or health. Other devices such as artificial eyes and maxillofacial implants like craniofacial implants, auricular, nasal implants, hearing aids and orthopaedic footwear fall into this category. The healthcare professionals must take accurate impressions of patients so that the device is a custom fit for the end-user or patient.
What is the difference between a custom-made device and an investigational device?
Investigational devices are those that are research devices that are developed that have no market equivalent. These devices are subjected to a clinical study to check product effectiveness. On the other hand, custom-made devices are not subject to clinical research but are customised according to the patient’s requirements. Both investigational devices and custom-made devices do not require CE/UKCA marking and require exceptional devices regulatory approvals to enter the respective markets.
Disclaimer: Regulations/legislations are subjected to changes from time to time and the author claims no responsibility for the accuracy of information.
A Label is the written, printed, or graphic information that goes on the packaging of the medical device.
Instructions For Use (IFUs) or Package Insert is the essential information accompanying the medical device for its safe and effective use by the user. It can be a single to multiple-page document.
Labelling is the content that goes on the Label or IFUs.
What are the minimum requirements for labeling?
The ISO has published many standards applicable to the medical device industry. Some of them are as below:
Standard Number
Standard Name
ISO 18113
In vitro diagnostic medical devices – Information supplied by the manufacturer (labelling) – Part 1, 2, 3, 4 and 5
ISO 28219
Packaging – Labelling and direct product marking with linear bar code and two-dimensional symbols
Medical devices – Information to be supplied by the manufacturer
ISO 14025
Environmental labels and declarations – Type III environmental declarations – Principles and procedures
ISO 14021
Environmental labels and declarations – Self-declared environmental claims (Type II environmental labelling)
ISO 14020
Environmental labels and declarations – General principles
ISO 22742
Packaging – Linear barcode and two-dimensional symbols for product packaging
There are more specific product-oriented labelling standards available.
ISO 20417 has defines information to be disclosed by the manufacturer. Every medical device manufacturer, distributor, importer, or Authorized Representative is bound to comply with the standard before placing the device on market. The requirements are as follows:
Information on Label
Manufacturer details – Trade Name, address, country
Product description.
Product identification – model or catalogue number, Lot number, serial number, expiry date, UDI,
Storage instructions
Operating instructions
Warning or precautions
Presence of any harmful substances (>0.1% w/w), biological origin substances, medicinal substances, nanotechnology materials
Electronic IFUs (if available)
Mention of: Single-use/ Single patient multiple-use / Reuse / Limitation on reuse
If Sterile and method of sterilization
Explanation of safety-related colours
Information on Packaging
Name and address of the manufacturer or an authorized representative
UDI
Production controls – lot number, serial number, expiry date
Model number, catalog number, commercial name
Mention of: Single-use/ Single patient multiple-use / Reuse / Limitation on reuse
Storage or special handling requirements
Any special requirements for battery-powered medical device
Contraindications, warnings, or precautions
Information in IFUs
General information (as above)
Intended Use of the medical device
Safety information
Performance of the medical device
Any residual risk associated with the use of the medical device or its accessory
Any known contraindications
Document control number of the IFU
Safe disposal information
Any specific instructions for handling or preparatory treatment
Any warnings, precautions, or limitations
If any accessories or indicators are provided along with the device, instructions on their use to be provided in the IFU.
Technical description
The harmonized ISO standard makes sure true and uniform information is conveyed to a lay/common person.
Global Labelling Requirements
Most countries have a mandatory requirement for the IFUs or Labels in their local language. To streamline this requirement, ISO 15223 standard provides a list of signs and symbols that depict common terms such as Manufacturer, Lot number, storage conditions, Expiry, eIFU and many more.
The uniform symbols help in identifying the necessary information without the language barrier. Another advantage is it saves significant label space.
FAQs
Is it necessary to follow the ISO standards?
It is advisable to develop a medical device in compliance with the applicable harmonized standards. This shall favor in smooth marketing of the product along with its competitors.
Is it necessary to brief the symbols in IFU when symbols from standards are used?
Yes, it is required to brief every symbol in the IFU that is used on the label of the product.
Can a distributor or an importer label be affixed separately apart from the main label?
Yes, it is also allowed to affix these labels separately on the product. This is because one manufacturer may have several distributors or importers within EEA.
Is it necessary to create dedicated labels for accessories of medical devices?
Yes, it is. Not every time the accessory is shipped along with the medical device and it is required to identify them with appropriate labels.
If the manufacturer wants to provide an eIFU how to indicate this on the label?
Firstly, not all the medical devices are eligible for eIFU provision. Regulation 207/2012 states what are the categories of MDs that are eligible for eIFU.
What is the deadline to implement UDI carrier on device labelling?
Article 123.3.f states these timelines as:
Disclaimer: Regulations/legislations are subjected to changes from time to time and the author claims no responsibility for the accuracy of information.
With the UKCA deadline fast approaching and updating the existing regulation UK MDR 2002, MHRA has conducted a public opinion forum,
Some of the key highlights are stated below, for your quick review.
Transition Timeline
The significant update on this forum discussion is the Transition timeline of July 2023 has been moved.
The revised timeline is an extra 5 years for CE-marked products issued against EU MDR/IVDR, and an extra 3 years for CE marked under EU MDD and 5 years under EU IVDD.
There are a couple of caveats to this, but these are expected.
Devices that are subject to significant changes in design or intended purpose will be excluded from these provisions
All post-market requirements applicable to the new regulatory framework must be complied with for all products which benefit from the transitionary arrangements
MDSAP consideration:
Additional to CE certification, UK MHRA will consider MDSAP certification as an alternative route to market to UK.
Caveat:
UK MHRA will require UK Approved bodies to consider MDSAP assessments.
Domestic assurance routers will allow an abridged assessment with scrutiny and Approved bodies will be able to reject if they consider sufficient evidence is not provided.
Classification:
Under the upcoming new regulation, MHRA is considering updating the Classification of Medical devices as well as In Vitro Devices(IVD) and Assisted reproductive technologies(ART)
And devices with nanoparticles will be moved between Class IIa -III depending on the risk involved.
Traceability:
MHRA will be bringing our requirements for economic operators to identify and record the following information:
Any economic operator to whom they have directly supplied a medical device
Any economic operator who has directly supplied them with a medical device
Any public or private sector health institution or healthcare professional to which they have directly supplied a medical
This will provide more traceability of the product.
Currently, this doesn’t state where and how the record needs to be maintained so we would ask the manufacturers to maintain this record and provide the same to us (UKRP) on a monthly basis for our records.
On the whole, MHRA is considering its new regulation to be in line with EU MDR/IVDR in certain aspects, we will know more when the new regulation is released and consider the above as MHRA’s view on changes to be made based on the public opinion.
Disclaimer: Regulations/legislations are subjected to changes from time to time and the author claims no responsibility for the accuracy of information.
ISO – International Organization for Standardization, is the international, non-governmental body for drafting and establishing technical and non-technical standards. These standards are developed by different committees within the ISO. Having around 165 member states, with one representative from each, ISO is a global entity catering to the needs of industry requirements.
Are ISO standards important?
The ISO medical device standards are the Bible for many countries, especially ones which do not have predefined regulations or processes. For regulated countries, in addition to their respective regulations and guidance, ISO standards are also preferred. The most popularly referred ISO standard is the ISO 13485:2016 Medical devices — Quality management systems — Requirements for regulatory purposes. In addition to general standards, ISO also publishes product-specific guidance such as for Implants, Orthopedic, Medical Electric Equipment, and many more.
Global ISO Requirements
In Europe, the European Commission has the Medical Device Regulation MDR 2017/745 and In-vitro Diagnostic Device Regulation IVDR 2017/746. These regulations provide a detailed framework for introducing a medical device in the European market. However, in addition to that, certain ISO standards may also be referred to for ensuring a better-quality product. Some of the many popularly used standards include:
ISO 14971:2019 Medical Devices – Application of Risk Management to medical devices
ISO 15223-1:2021 Medical devices – Symbols to be used with information to be supplied by the manufacturer – Part 1: General requirements
IEC 60601-2-83 Medical electrical equipment – Part 2-83: Particular requirements for the basic safety and essential performance of home light therapy equipment
IEC 60601-1 Medical electrical equipment – Part 1: General requirements for basic safety and essential performance
The European Commission also has Harmonized Standards, developed by European Standards Organization CEN, CENELEC, or ETSI, per the international standards. It provides a list of the applicable harmonized standards for enhanced product safety and quality.
In the USA, the US Food and Drug Administration (FDA) has a Code of Federal Regulations (CFR) and Guidance.
CFRs are legally binding. Manufacturers must comply with the requirements of CFR
The guidance provides Agency’s thinking on regulatory issues. They are NOT legally binding
In addition to these, the FDA also accepts certain recognized consensus standards from different organizations such as ISO, CLSI, ANSI, IEC, CEN, etc. These standards may be used to justify a Declaration of Conformity for a product. The widely accepted medical device ISO standards are, but are not limited to:
ISO 10993 – Biological Evaluation for Medical Devices
ISO 14160 – Sterilization of Healthcare Products
ISO 11737 – Sterilization of Medical Devices
In Canada, the Standards Council of Canada (SCC) is the ISO member body. Similar to the US FDA, the Therapeutic Products Directorate (TPD) of Health Canada periodically releases a list of acceptable international or national standards for medical devices. Manufacturers can use these recognized standards in conjunction with the Health Canada’s Medical Devices Regulations (SOR-98/282) and the Guidance Documents, to prove product conformity and safe use in the market.
China‘s National Medical Products Administration (NMPA) is developing indigenous standards that more closely align with those of ISO. Biocompatibility testing is one avenue where the scope and requirements for China are more than that of the US/EU. Hence, NMPA has developed various biocompatibility testing standards which are to be used in addition to the ISO standard.
For the rest of the world’s medical device industry,
India encourages ISO certification for all its industries. The medical sector must be ISO 13485 compliant while the pharmaceutical sector must be ISO 9001 compliant for Quality Management Systems, in addition to other relevant and applicable ISO standards.
Japan’s The Japanese Industrial Standards Committee (JISC) is an ISO member body. The regulatory authority, Pharmaceutical and Medical Device Agency (PMDA) revised its Ordinance No. 169 in 2021 to closely align with the ISO 13485:2016 standard. The transition period is 3 years and must comply by March 25, 2024
For the Korean regulatory authority, aligning the requirements of Korean Good Manufacturing Practice (GMP) to that of ISO 13485:2016 is believed to be a step closer to entering the Medical Device Single Audit Program (MDSAP)
Russia’s Federal Service for Surveillance in Healthcare (Roszdravnadzor) is known to accept ISO 13485:2016 certification. Information on acceptance of other ISO standards cannot be confirmed. It does not accept market approvals in the US, EU, or other countries as a reference for market authorization in Russia
Australia’s Standard Australia is a member of the ISO, IEC, and ICSID. It strongly encourages the use of international standards, except where their use is ineffective or inappropriate and does not develop any national Australian standard for which there is already an international standard in existence. In 2019, TGA published Therapeutic Goods (Conformity Assessment Standard for Quality Management Systems) Order 2019which provides a list of applicable conformity assessment standards.
Brazil’s ANVISA accepts Good Manufacturing Practices (GMP) along with the ISO 13485
FAQs
Can QMS be established solely based on ISO standards?
For countries that do not have their own QMS regulations, the ISO standard can be used as a reference. For countries with established local regulations, and that accepts ISO, both ISO standard and local/national regulations must be considered.
Are ISO standards freely available?
No. ISO standards are available for purchase from the ISO official website. However, they do have FREE read-only formats available.
Comparing ISO standards to local regulations, which one takes precedence?
The local or national regulation always takes precedence over the ISO standard.
Can the manufacturer use an older version of an ISO standard for compliance?
No. Manufacturers must make sure they comply with the active or most recent version of the ISO standard. This is not restricted just to ISO standards but applies to National regulations too. Manufacturers must keep their QMS up to date with the latest requirements of the industry. The ideal way to be updated is to refer to the latest version of any Standard or Regulation.
Disclaimer: Regulations/legislations are subjected to changes from time to time and the author claims no responsibility for the accuracy of information.
