Design and Development Management of a MD / IVDMD according to Standard EN ISO 13485:2016 + A11:2021

For manufacturers of medical devices (MD) and in vitro diagnostic medical devices (IVDMD), the design and production of their products represent a significant challenge. How can they ensure that each device meets the intended performance? How can manufacturers ensure that each device is suitable for its intended use under normal conditions? How can they ensure that every step of the development process is controlled and documented?

To address these questions, devices must meet the General Safety and Performance Requirements (GSPR), outlined in Annex I of the Medical Devices Regulation (MDR) 2017/745 and the In Vitro Diagnostic Medical Devices Regulation (IVDR) 2017/746. Chapter II of these annexes emphasizes specific requirements related to design and manufacturing, stages where manufacturers may encounter significant challenges.

The standard EN ISO 13485:2016, particularly section 7.3, defines the requirements for controlling the various stages of MD/IVDMD design. Thus, the manufacturer must establish, implement and comply with a procedure for the design and development of their MD/IVDMD, which is divided into several phases, each subject to review and documentation.

These design phases must be documented through a design file (also known as a Design History File (DHF)) to trace the design history and demonstrate compliance with design and development requirements. Each document created during the various design phases contributes to a chapter of this file and the file must be maintained and updated throughout the various stages of the product lifecycle.

How can these development phases be effectively structured to meet the requirements of the standard and regulations? What tools and best practices can help manufacturers overcome these challenges? This article will guide you through the different stages of MD/IVD design and development according to the EN ISO 13485:2016 standard.

1. Prerequisite: Feasibility

Before initiating a design and development project for a MD/IVDMD, a multidisciplinary team, led by a project manager, is appointed.

Feasibility activities can cover various tasks and are based on several project inputs, such as the expression of a need or a design idea arising from a business opportunity and/or a market context and/or a clinical need. These activities enable the project to be launched following management approval.

This leads to the drafting of the design request, which outlines the main objectives of the project and serves as the foundation for the first design phase: planning.

2. Phase 1: Planning

Planning plays a key role in enabling management to better control the design process. It relies on clear communication of policies, procedures, and objectives to the design team members while providing a solid foundation for measuring compliance with quality system objectives.

Design activities must be specified with sufficient precision to ensure the proper execution of the design process. The extent of planning depends on several factors, such as the size of the organization responsible for development and the complexity of the device to be developed.

During this first phase, potential critical paths of the project, as well as the roles and responsibilities of each stakeholder, are identified.

The development and design plan drafting begins with the definition of product requirements (read our article on this topic here). These requirements are derived from the design request document, as well as any feasibility studies or state-of-the-art analyses conducted previously.

This planning phase is a central element that must also include a clear definition of the project objectives, an assessment of necessary resources (human and material), and an estimation of costs associated with MD/IVDMD development. The division of organizational responsibilities must be explicitly defined, particularly when contributions come from diverse sources, such as multidisciplinary teams, subcontractors, or external consultants.

It is also necessary to plan the various stages and strategies of development, the different activities associated with each phase, as well as phase reviews by establishing a schedule.

The design and development plan should be considered as an evolving document, maintained and regularly updated as the project progresses.

3. Phase 2: Design Inputs

Design inputs represent the starting point for product design. They establish a foundation for carrying out subsequent design tasks and validating the design. Therefore, developing a solid set of requirements is the most important design control activity.

ABased on the previously defined requirements (marketing, user needs, etc.), this phase aims to specify the design inputs for the device design. To do so, the following requirements must be formulated:

• Normative and regulatory requirements, including those applicable in the countries where the device will be marketed (e.g., compliance with ISO standards or local regulations),
• Functional requirements,
• Performance requirements,
• Usability requirements (concerning ease of use and ergonomics for users),
• Safety requirements (including aspects related to risk management for patients and users; Read our article on this topic here),
• Any other requirements (commercial, market, …).

These requirements must be translated into design inputs, ensuring that they are complete, unambiguous, can be verified or validated, non-contradictory, and representative of the use environment.

They must be reviewed, approved, and finalized for subsequent phases by the relevant project members (e.g., Regulatory Affairs, Clinical Affairs, Research & Development, etc.).

Regardless of the origin of the initial product concept, developers play a key role in formulating the design inputs. When provided with a set of essential characteristics, they identify associated challenges and determine the level of detail required to design the product.

4. Phase 3: Design Outputs

Activities carried out during this phase aim to convert design inputs into design outputs.

Design outputs represent the results of the design effort (typically cycles of prototyping and associated testing to refine the resulting product) at each design phase and at the end of the design effort. In general, the final design outputs include the device itself, its packaging and labeling, as well as the Device Master Record (DMR). In practice, the DMR is finalized during the design transfer phase (phase 6).

Design outputs include all deliverables resulting from a design task identified in the design and development plan.

These include the R&D product specifications as well as the descriptive documentation that define and characterize the design. Among this information are notably:

• The raw material specifications,
• The bill of materials,
• The manufacturing flow diagrams,
• The plans.

Thus, design outputs form an essential basis for ensuring that the device and its components meet the defined requirements. This is the objective of verification.

5. Phase 4: Verification

This phase ensures the adequacy of design outputs in relation to design inputs. In other words, it verifies that each phase of the design process produces results that comply with the established target specifications. The manufacturer must establish and document, in accordance with the state of the art, the verification plans and protocols, methods used, acceptance criteria, as well as justification for the sample size. Verification activities are carried out on prototypes that are representative of the final version of the MD.

In the case of IVDMDs, this stage evaluates analytical performance in accordance with the requirements specified in the design inputs. Currently, methodologies described by the Clinical and Laboratory Standards Institute (CLSI*) are recognized as representing the state of the art in this domain.

If a design verification activity fails, it may be necessary to perform a design iteration by modifying the design inputs and/or the design outputs.

* An international organization that develops standards and guidelines to improve healthcare quality by standardizing practices in medical and clinical laboratories.

6. Phase 5: Validation

Design validation is a comprehensive evaluation aimed at ensuring that the device meets user needs and intended uses. Unlike verification, which focuses on specific aspects of the design, validation assesses the device as a whole.

During this phase, the manufacturer carries out clinical activities (clinical investigations for MDs, if applicable, and/or performance evaluations for IVDMDs). The manufacturer must establish and document the following:

• Validation plans and protocols for MD/IVDMD in relation to user needs and the intended use of the device,
• Methods used,
• Acceptance criteria,
• Justification for the sample size.

Validation must be performed on initial production units or their equivalents, rather than on prototypes manufactured in a laboratory. This ensures that the validation results accurately reflect the performance of devices produced under normal manufacturing conditions.

• The Traceability Matrix

The traceability matrix is a commonly used tool for documenting the relationship between design inputs, design outputs, and the associated verification and validation activities. It establishes a link between each design input requirement and its corresponding output, ensuring that no design requirement has been overlooked. The matrix is completed throughout the design process, as indicated by the different areas in the matrix model below.

7. Phase 6: Design transfer

The design transfer phase ensures that all essential design elements are communicated and applied to production/industrialization for the manufacturing of the MD/IVDMD. This phase is critical to ensuring that production specifications enable the consistent and reliable manufacturing of devices in accordance with design requirements.During this final phase, the development team:

• Finalizes and compiles the DHF,
• Completes the DMR, which contains all the information necessary to produce the device. The DMR is based on the “Design Output Specifications” from R&D, defined in Phase 3 (e.g., raw material specifications, finished product release specifications, bill of materials, process flow diagrams, drawings, manufacturing procedures and instructions, equipment qualification, manufacturing process FMEA, process validation, etc.).

8. Design reviews

Design reviews are essential in the development process of a MD/IVDMD. These reviews, conducted at appropriate stages, aim to:

• Ensure a systematic evaluation of design outcomes, including the device design and associated production process and support,
• Assess the progress of the project,
• Identify blocking points and necessary actions, if applicable,
• Confirm that the phase deliverables are ready, reviewed, and approved, thereby ensuring the project is ready to proceed to the next development phase.

The presence of all stakeholders involved in the  phase under review is necessary. Participants in a design review should be selected based on their qualifications and expertise. It is customary for at least one participant to take on the role of an independent reviewer during the design phase, to provide an objective perspective.

Each phase review is concluded with a formal record that includes a list of participants, a list of phase deliverables with their version and date, the points discussed, and the actions to be taken.

9. Design changes

In cases where  an existing product needs to be modified (e.g., function, performance, specification, etc.), the change management process must be applied.

The primary objectives are to ensure that:

• Corrective actions are tracked until completion,
• Modifications are implemented in such a way that the initial issue is resolved without creating new problems; if new issues arise, they are also tracked until resolved,
• The impact of the modification on the associated documentation is taken into account, and the design documentation is updated to accurately reflect the revised design. The EN ISO 13485 : 2016 standard requires a systematic and documented approach to change control to ensure that any modification is properly assessed, implemented, and integrated into the DHF, while maintaining traceability and product quality.

Conclusion

Mastering the design and development of a MD or IVDMD in accordance with the EN ISO 13485:2016 standard is a critical step to guarantee the product’s safety, performance, and regulatory compliance. This structured process, based on clearly defined phases and systematic reviews, ensures complete traceability and efficient management of requirements throughout the device’s lifecycle. By integrating tools such as the traceability matrix and applying rigorous change control, manufacturers can meet user needs while complying with the requirements of the MDR 2017/745 and IVDR 2017/746 regulations. Thus, the EN ISO 13485:2016 standard provides a robust framework for developing reliable devices that are suited to their intended use and compliant with international standards.

Need help?

Our R&D teams can assist you in ensuring compliance with the design dossier in accordance with EN ISO 13485:2016 as well as Chapter II of Annex I of the MDR and IVDR by providing regulatory and methodological support:

• Assessment of existing documentation,
• Training on design and development following EN ISO 13485:2016 (1 or 2 days depending on the need), offered virtually or in-person,
• Drafting deliverables and documentation in compliance with regulatory and normative requirements,
• Operational support by one or more consultant(s), overseen by a Technical Manager from Efor’s Technical Division, including a posteriori design control for legacy products if needed,
• Drafting state-of-the-art reports during the development phase to determine intended uses, indications, and product claims,

Our Technical Division teams are available for your projects and can be reached at TechnicalDivision@efor-group.com.