Designing and Developing Medical Devices & IVDs
The design and development of medical devices and IVDs is an important part of demonstrating regulatory compliance. The processes involved in design and development must be documented and all steps of the design and development cycle documented and recorded. In this article we will look at the medical device and IVD product design and development life cycle and what is expected from a regulatory aspect.
The Design and Development Lifecycle
Medical Device and IVD Regulation
The medical device regulations will provide risk, safety and performance requirements that need to be met in order for a medical device or IVD manufacturer to demonstrate regulatory compliance. Going through these regulatory requirements as a design team should be the starting point before starting the design and development of the medical device or IVD. This is because they may have a significant impact on how the device needs to be designed based on the intended use of the medical device or IVD.
EU MDR and IVDR
In the European Union (EU), medical device need to be compliant with the Medical Device Regulations (MDR) (EU) 2017/745. IVDs need to be compliant with the In Vitro Diagnostic Regulations (IVDR) (EU) 2017/746. Within Annex I of these regulations are a list known as the General Safety and Performance Requirements (GSPR). Each of these GSPRs need to be assessed against the concept and intended use of the medical device being design and developed. This will help with the planning of the medical device in terms of what standards may need to be used to show conformity. For example there maybe a specific standard that identifies how a specific type of medical device needs to be constructed and what type of materials need to be used. If the device is electronic then there will be standards specific for electrical safety and so on. Using standards is how to demonstrate that the design of the device meets the GSPRs.
UK Medical Device Regulations 2002
In the UK, medical devices need to be compliant with the Medical Device Regulations 2002 (as amended), the UK MDR 2002 refers to the Medical Device Directives 93/42/EEC for medical devices and 98/79/EC for IVDs. Within Annex I of the directives are a list known as the Essential Requirements (ER). Each of these ERs need to be assessed against the concept and intended use of the medical device being design and developed. This will help with the planning of the medical device in terms of what standards may need to be used to show conformity. For example there maybe a specific standard that identifies how a specific type of medical device needs to be constructed and what type of materials need to be used. If the device is electronic then there will be standards specific for electrical safety and so on. Using standards is how to demonstrate that the design of the device meets the ERs.
Medical Device Harmonised Standards
One way harmonisation of safety has been developed is through the use and acceptance of international standards. The use of standards ensures that medical devices meet agreed minimum levels of safety which are accepted within the regulations. Based on the applicable regulatory requirements the design and development team need to choose standards that will allow them to demonstrate that the design and development of the medical device or IVD meets the regulatory requirements. Here are some examples of medical device-related standards that are accepted internationally.
Standards required to be used for all medical device types:
- ISO 14971 – Medical devices. Application of risk management to medical devices
- ISO 20417 – Medical devices. Information to be supplied by the manufacturer
- ISO 15223 – Medical devices. Symbols to be used with information to be supplied by the manufacturer – General requirements
- ISO 13485 – Medical devices. Quality management systems. Requirements for regulatory purposes
- ISO 62366 – Medical devices – Application of usability engineering to medical devices
Standards that cover medical devices containing software or software as a standalone medical device:
- IEC 62304 – Medical device software. Software life-cycle processes
Electrical devices:
- ISO 60601-1 series – Medical electrical equipment. General requirements for safety – Collateral standard. Safety requirements for medical electrical systems
- ISO 60601-2 series – Medical electrical equipment – Particular requirements for the basic safety and essential performance of magnetic resonance equipment for medical diagnosis
Sterilised medical devices:
- ISO 11135 – Sterilization of health care products. Ethylene oxide – Requirements for development, validation and routine control of a sterilization process for medical devices
- ISO 11137 – Sterilization of health care products – Radiation – Requirements for development, validation and routine control of a sterilization process for medical devices
- ISO 17665 – Sterilization of health care products – Moist heat – Requirements for the development, validation and routine control of a sterilization process for medical devices
- ISO 11607-1 – Packaging for terminally sterilized medical devices – Requirements for materials, sterile barrier systems and packaging systems
- ISO 11607-2 – Packaging for terminally sterilized medical devices – Validation requirements for forming, sealing and assembly processes
Specific Standards for Specific Equipment:
- ISO 60601-2-24 – Medical electrical equipment – Particular requirements for the basic safety and essential performance of infusion pumps and controllers
- ISO 3826-4 – Plastics collapsible containers for human blood and blood components – Aphaeresis blood bag systems with integrated features
There are hundreds of different standards which apply to different groups or to specific medical devices. When you start to design and develop a medical device or IVD it is important to review the regulatory requirements specific to your medical device based on its intended use.
Design and Development Plan
Planning Medical Device Design and Development of a medical device is a requirement of regulatory systems. All manufacturers of Medical Devices are required to maintain a Quality Management System, in the USA this is determined under the CFR Title 21 part 820. Within the European Union, it is placed within demonstrating certificated compliance with international standard EN ISO 13485. The USA has recently indicated that they will also use the ISO 13485 standard for the requirements of manufacturers being compliant for QMS purposes.
Within the QMS requirements of the standard, manufacturers are to perform Design and Development inline with the requirements set out within the standard. Design and Development planning should cover as a minimum the following:
- the design and development stages;
- the review(s) needed at each design and development stage;
- the verification, validation, and design transfer activities that are appropriate at each design and development stage;
- the responsibilities and authorities for design and development;
- the methods to ensure traceability of design and development outputs to design and development inputs;
- the resources needed, including necessary competence of personnel.
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Design and Development Process
Design processes are indicated within ISO 13485 and as a minimum should cover the following:
Design Inputs:
- functional, performance, usability and safety requirements, according to the intended use;
- applicable regulatory requirements and standards;
- applicable output(s) of risk management;
- as appropriate, information derived from previous similar designs;
- other requirements essential for design and development of the product and processes.
Design outputs:
- meet the input requirements for design and development;
- provide appropriate information for purchasing, production and service provision;
- contain or reference product acceptance criteria;
- specify the characteristics of the product that are essential for its safe and proper use.
Medical Device Design and Development Review:
At suitable stages, systematic reviews of design and development shall be performed in accordance
with planned and documented arrangements to:
- evaluate the ability of the results of design and development to meet requirements;
- identify and propose necessary actions.
Participants in such reviews shall include representatives of functions concerned with the design and development stage being reviewed, as well as other specialist personnel.
Medical Device Design and Development Verification:
Design and development verification shall be performed in accordance with planned and documented arrangements to ensure that the design and development outputs have met the design and development input requirements.
The organization shall document verification plans that include methods, acceptance criteria and, as
appropriate, statistical techniques with rationale for sample size.
If the intended use requires that the medical device be connected to, or have an interface with, other medical device(s), verification shall include confirmation that the design outputs meet design inputs when so connected or interfaced.
Design Validation:
Medical Device Design and Development validation shall be performed in accordance with planned and documented arrangements to ensure that the resulting product is capable of meeting the requirements for the specified application or intended use.
The organization shall document validation plans that include methods, acceptance criteria and, as appropriate, statistical techniques with a rationale for sample size.
Design validation shall be conducted on representative product. Representative product includes initial production units, batches or their equivalents. The rationale for the choice of product used for validation shall be recorded.
As part of design and development validation, the organization shall perform clinical evaluations or performance evaluations of the medical device in accordance with applicable regulatory requirements. A medical device used for clinical evaluation or performance evaluation is not considered to be released for use to the customer.
If the intended use requires that the medical device be connected to, or have an interface with, other medical device(s), validation shall include confirmation that the requirements for the specified application or intended use have been met when so connected or interfaced.
Validation shall be completed prior to release for use of the product to the customer.
Medical Device Design and Development Transfer:
The organization shall document procedures for transfer of design and development outputs to manufacturing. These procedures shall ensure that design and development outputs are verified as suitable for manufacturing before becoming final production specifications and that production capability can meet product requirements.
Control of Design and Development changes:
The organization shall document procedures to control design and development changes. The organization shall determine the significance of the change to function, performance, usability, safety and applicable regulatory requirements for the medical device and its intended use.
Design and development changes shall be identified. Before implementation, the changes shall be:
- reviewed;
- verified;
- validated, as appropriate;
- approved.
The review of design and development changes shall include evaluation of the effect of the changes on constituent parts and product in process or already delivered, inputs or outputs of risk management and product realization processes.
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Medical Device Design and Development - Risk Management
Risk Management is the overriding factor in Medical Device Design and Development. Risk management should be applied as per international standard ISO 14971. Risk should be evaluated at every phase of the design and development of a medical device and then continue throughout the life cycle of the medical device via post market surveillance and obsolescence, with the data being captured within the risk management file.
Risk Management Plan
Risk management activities are required to be planned in accordance with ISO 14971. Each medical device should have its own risk management plan in accordance with the risk management process. The plan should sit within the risk management file.
As a minimum the risk management plan should consider the following:
- the scope of the planned risk management activities, identifying and describing the medical device and the life cycle phases for which each element of the plan is applicable;
- assignment of responsibilities and authorities;
- requirements for review of risk management activities;
- criteria for risk acceptability, based on the manufacturer’s policy for determining acceptable risk, including criteria for accepting risks when the probability of occurrence of harm cannot be estimated;
- a method to evaluate the overall residual risk, and criteria for acceptability of the overall residual risk based on the manufacturer’s policy for determining acceptable risk;
- activities for verification of the implementation and effectiveness of risk control measures; and
- activities related to collection and review of relevant production and post-production information.
Risk Identification
Risk Identification should occur at the beginning of the design and development process and at each stage of the design and development process thereafter. The purpose of risk identification is to understand all of the possible known risks and foreseeable risks associated with the device and its use, these should also include all possible user error risks or device misuse risks.
These should be analysed for their likely frequency of happening and the likely severity should they happen. This is usually done by giving each identified risk a risk score, such as 1-5 for likelihood of occurrence and 1-5 for severity (with 1 being low and 5 being high), these scores are then multiplied to give the risk score.
The group leading the risk management should establish what is considered to be an acceptable risk score (green), what is a moderate risk score (amber) and what is a high-risk score (red).
Risk control
Identified risks during the Medical Device Design and Development phase need to be mitigated to as “low as practically possible” according to the requirements of ISO 14971. Risk control measures should ensure that they have either fully mitigated and therefore removed the risk, reduced the risk to an acceptable level or be considered to be a residual risk where no mitigation is possible, residual risks are usually unavoidable risks which are highlighted to the user via warnings on the labelling and/or the instructions for use.
Mitigation controls can include the use of standards. For example, a device which has patient contact and has been sterilised using ethylene oxide. The risk would be that ethylene oxide residuals maybe left on the device post sterilisation and packaging, which could come into contact with the user. Ethylene Oxide is known to cause irritation, organ damage, mutagenicity and carcinogenicity in human and animals, and reproductive effects in animals.
The risk control measure would be to ensure that the ethylene oxide sterilisation process has been followed in accordance with ISO 11135 – Sterilization of health care products, and that testing has been carried out on the final finished post sterilised device in accordance with ISO 10993-7 – Biological evaluation of medical devices – Ethylene oxide sterilization residuals, and the test results evaluated as part of the Biological Evaluation Report by an expert toxicologist inline with the requirements of ISO 10993-1 Biological evaluation of medical devices – Evaluation and testing within a risk management process.
The risk should then be scored again based on the control measure.
Risk Evaluation
All of the risks then be evaluated to ensure that the risk control measure has reduced the risk to an acceptable level or an acceptable residual risk.
Risk-benefit
Once all risks have been evaluated, they should be reviewed overall to establish if the benefit of using the medical device outweighs the consequences of the risks that the device could cause.
Proof of concept
Proof of concept testing or feasibility testing is used to demonstrate that critical design features of a developed concept will function as intended. This is early design testing or testing of prototype models. This is not part of clinical evaluation or clinical studies.
Design History
A full and detailed record of Medical Device Design and Development must be kept as part of the design history. This should be kept with the device technical documentation and sit within the QMS.
