Medical Device Development
Medical device development is a comprehensive series of well-coordinated activities and events from the moment of product concept and ideation, to risk assessment and feasibility analysis, to design development verification and validation, leading to activities for the pre-launch preparation, and ultimately the product launch, market commercialization, and post-market surveillance.
Medical device development is a difficult process, and each stage takes a long time depending on how intricate the device is. The whole medical device development cycle might take months, if not years, to complete. The time taken on each step, from idea conception through development procedures leading to product launch, will differ depending on a range of elements unique to that product. While a lot of companies are aware of the general requirements, they often lack clarity on the specific requirements that apply to their product and the clinical application for which they plan to launch the product.
It’s crucial to have a competent staff with a lot of real-world expertise in regulatory, quality, and relevant standards. Medical devices are impacted due to legislative changes, as well as modifications to international standards, over time. For example,
⦿ The MDD has transitioned into MDR in Europe
⦿ ISO 14971 has been revised with new criteria as of 2019
⦿ IVDD 98/79/EC transition into IVDR 2017/746 in May 2022
⦿ TGA guidance update on implantable devices
⦿ FDA guidance on regulating SaMD utilizing AI / ML.
Medical device manufacturers are also held accountable for continuing compliance, regardless of regulatory or international standard updates. There are numerous problems that arise because of not involving the right team of Advisors and Executors. Some of these issues include but are not limited to:
⦿ Increased product development time
⦿ Additional hours to retest if test results are not as expected
⦿ The regulatory bodies asking for additional testing based on ill-defined criteria
⦿ Issuing letters requesting additional information or clarification, or, worst of all,
⦿ Being cited by regulatory authorities
These are all consequences of not having a strong team that clearly understands and can successfully execute these types of projects.
A partner like ELEXES, with robust expertise in regulatory, quality, clinical, and project management has successfully brought many medical devices, IVDs, and combination products to the market, and maintained regulatory compliance, efficiently and cost-effectively for the life of the product.
Let’s explore the processes involved in medical device development in greater detail:
Ideation & Product Concept
During the medical device ideation phase, a significant amount of time and effort is invested in research and development. The feedback from a variety of sources, including research, consumers, and internal teams needs to be assessed thoroughly.
Even at this early stage, documentation is crucial, especially to document the user’s needs and to safeguard any protected intellectual property (IP) or if the idea or technology would necessitate filing for a patent.
It also necessitates assessing if the product is an enhancement of the predicate device, or if the product concept is entirely novel, in which case additional testing will be required to confirm its safety and efficacy. It is necessary to determine the criteria for pre-clinical and clinical testing.
It’s also crucial to establish and document a QMS that complies with legal requirements and is implemented early on. The QMS serves as the framework for addressing product design, production, risk management, clinical data, and product complaint handling, among other things.
Establishing the processes immediately will guarantee that the firm and the product comply with regulatory requirements from the start. Concurrently ensuring the product will have the highest levels of quality and safety once launched.
Risk Assessment and Product Feasibility
This requires fine-tuning the concept or idea to make it a viable product. It also requires a regulatory strategy, and having an understanding of whether the regulatory pathway follows a 510(k), PMA, or is deemed to be a De Novo classification.
Financial analysis needs to be performed during this feasibility phase. Documentation at this stage is valuable as the documentation here for concept development will lay the groundwork for DHF (Design History File), a regulatory requirement for design controls.
The development of risk control processes that are intended to reduce potential future risks associated with the product is another regulatory requirement for medical device manufacturers. These processes must be developed and documented.
Risk assessments also identify risks or hazards associated with the product concept or design. The de facto worldwide standard for risk management that medical device manufacturers must adhere to is ISO 14971.
Design and development documentation meets regulatory requirements to demonstrate the presence of comprehensive and complete design records, and that the medical device product development was conducted per an approved product design plan.
This is accomplished with a Design History File (DHF). A DHF must be established for each medical device intended to be marketed by the medical device manufacturer, and the DHF must contain the appropriate records that show the product design was designed to the approved design plan and requirement for design controls.
Detailed design and development plans that outline design tasks and specific deliverables; approved design input and approved design output documents; activities related to the phases of the product design process, such as product revisions; verification and validation protocol, as well as a device risk management plan (RMP) are some examples of DHF file content.
The DHR is compiled in tandem with the device master record (DMR), which contains all device information required to produce the medical device.
Suggested records as part of the DMR would include product identification (for example, product Model Numbers, or Product family); production specifications (like assembly drawings, and production processes); quality assurance procedures, and their related specifications to ensure the highest product quality levels (via control documents that detail control measures for quality, contracts, purchasing, supplier controls, corrective actions, and operating procedures).
This is distinctly different compared to the device history file (DHF), which serves as the record of production for a specific medical device, confirming the device was produced per the device master record.
Product Design and Development, Verification, and Validation
The next phase involves establishing many processes and good planning to ensure product compliance. Verification is the process of confirming the product ‘output’ mirrors the design ‘input’. Validation is assessing the user’s needs and confirming that the product is being designed to meet those user needs.
Clinical plans should be well-defined, and trials should be conducted before the product launch. Testing is a demanding, drawn-out process. It is paramount to have well-defined testing criteria, as well as understanding the appropriate standards that must be followed.
Proper clinical plans and knowing what is required by the appropriate regulatory body will help ensure that submitted test results will be sufficient, the outcomes are in compliance (like good clinical practice, ISO 14155), and therefore regulatory clearance.
It also mitigates any potential questions on validation endpoints that could necessitate additional testing. Finally, the outputs of the study should be well accepted or better. One way is to have study criteria reviewed by the FDA, for example at the pre-submission phase.
Finally, Quality Systems must be completely established and comprehensive to define, document, and implement a quality system that is appropriate for the degree of device risk as well as the specified procedures by the company’s real-world operations (processes defined for in-house versus third-party contract manufacturing, as an example).
A strong quality management system includes product design, production, customer complaints, clinical data, product handling and storage, product distribution, and labeling.
The internationally accepted standard for quality management systems for manufacturers of medical devices is ISO 13485.
Manufacturing
To ensure rapid, quality, and regulatory-compliant product production, one should assess the capabilities, and regulatory compliance of the processes, and the manufacturer’s Quality Management System.
Pre-Launch Product Preparation
The activities are focused on creating a high level of curiosity and interest about the new medical device with the healthcare provider community so the healthcare provider community will be receptive to embracing the new product when it is commercialized.
A scientific publication plan creates an execution strategy of when, where, and how to publish clinical data. A scientific publication dashboard can assess the impact of reach on a particular publication where the clinical data has been released.
By educating users, customers, KOLs, and members of the medical community at large on the need for the product and what the technology is; what all health-related problems the medical device intends to solve, this education and messaging helps ease issues surrounding healthcare provider acceptance and elevates brand prominence.
Concurrent training activities should also take place with sales and customer services teams. In addition to brand-building activities, all regulatory requirements must be met by the device manufacturer before the product launch.
The specific regulatory activities include product registration once regulatory clearance has been obtained, as well as establishing a facility listing for where the device is to be manufactured.
Product Launch and Post Market Surveillance
Regulatory obligations do not end with the medical device product launch; rather, a product launch triggers new regulatory requirements that come into play once the product is commercialized for continued efficacy, safety, and quality.
Given the fact that clinical testing was performed with a limited pool of participants, it is the process of real-world use and documentation, via post-market surveillance that helps to ensure continued compliance.
The Post Market Surveillance activities address specific regulatory requirements as dictated by the governing regulatory body; second, information is acquired via ‘real-world’ use amongst the general population compared to a limited population conducted via clinical trials, which helps to confirm continued product safety and efficacy.
It affords manufacturers the power to mine the data for continued risk assessment, and identify both adverse events and positive outcomes not previously exhibited during clinical trials with a limited population to demonstrate continued safety and efficacy once in the market.
The continued feedback and collection of data, analysis, and reporting of useful information about a medical device helps establish a baseline and maintains the highest levels of safety and quality over the lifetime of an approved medical device.
By developing an all-inclusive data collection and analysis system, a medical device manufacturer can identify, document, and take action, if warranted and as appropriate, for continued safety and product performance.
It is at this phase where post-market surveillance begins, and regulated activities, like medical device reporting, or MDR, commence. Required reporting by regulatory bodies determines what must be reported, such as Adverse Events, where either death or serious injury has occurred in conjunction with the use of the medical device, as well as product problems, such as a device malfunction, or a customer complaint, needs to be documented.
There are specific reporting requirements regarding the timing to submit once a medical device manufacturer is made aware of a problem, and in some instances, the regulatory body has specific reporting tools/templates that must be used as part of the submission.
Corrective and Preventative Actions (CAPA)
CAPA is also mandated, to question and verify the existing quality systems to identify gaps with root causes once a product has been launched.
As stated in another way, CAPA is a gap assessment exercise, and it is the process of identifying the gaps where CAPA redefines and documents where corrective actions may be necessary based on field use reporting, and documenting ways to improve.
The proper utilization of CAPA techniques enhances the overall effectiveness of a quality management system.
Examples of leveraging CAPA may be obtaining customer feedback about a product currently in use, as a way to improve the quality of a medical device.
Based on the feedback, a manufacturer may elect to make design changes based on the evaluation of the information received, or it might require documentation updates, for example, on a User Manual, or other product documentation.
It can also emanate from collecting information, such as customer complaints, which could lead to identifying a root cause issue and documenting an outcome for improvement going forward.
In the post-market phase, the regulatory requirements are intertwined and complex – there are regulatory requirements at the product level to ensure the safety and efficacy of the medical device for its full lifecycle.
On the product side, post-market surveillance ensures a formalized, systematic, and continual process of evaluating, analyzing, documenting, and reporting activities specific to that medical device after initial regulatory clearance and subsequent market introduction.
There is concurrent compliance that must be followed for sustenance. Shifts, or amendments, to regulatory compliance, require a ‘watch’ system, to be aware and to identify when there are pending or actual changes issued by an international regulatory body.
Further, the responsibility falls to the medical device manufacturer to ensure their continued due diligence and adherence to any regulatory updates in the markets where the device is marketed to remain compliant with regulations.
Elexes Regulatory and Quality Compliance Consulting has successfully carried out numerous client projects in the areas of regulatory, quality, clinical, and project management document controls, not only in providing the required regulatory documentation for initial compliance but also in providing the insight and content for their clients for their respective continued post-market and regulatory compliance.
With their breadth, depth, and extensive insight related to regulatory compliance, Elexes’ strengths in understanding the shifts in regulatory requirements and documentation ensure their clients remain fully compliant for the life of their medical devices.
If you are a medical device firm wanting assistance in bringing your device to the various markets, and if you are confused with the path to be taken, ELEXES is your answer! Elexes is a well-known name in regulatory and quality compliance for medical device, software, and IVD manufacturers.
If you have any concerns about the clinical studies and the accompanying requirements, please contact us at jennifer@elexes.com.
