The Clinic is asking for novel biomaterials and nanotechnologies to introduce new innovative medical devices and invitro diagnostics devices (IVD) into the hospital to address unanswered clinical needs. The introduction of these new nano-technologies, however, requires time and other factors are at play such as qualification, regulation, cost, biocompatibility and the need to be applicable worldwide. Nano-enabled Medical Technologies (MT) can be applied in nearly every medical field, with a major presence and increasing importance in cancer, regenerative medicine, advanced therapies, diagnostics, neurology, cardiology, orthopedics, and dentistry. Introducing such new nano-technology devices in the clinic needs to be carefully assessed in terms of risk/benefit ratio. Such careful regulatory, technical and medical assessment of nano-technology based medical devices and IVDs is delivered by the Open Innovation Test Bed (OITB) of the SAFE-N-MEDTECH consortium (www.safenmt.eu). The OITB of SAFE-N-MEDTECH offers companies, laboratories, notified bodies and authorities, the capabilities, knowhow, networks and services required for the development, testing, assessment, upscaling and registration of nanotechnology-based Medical and Diagnostic Devices. Let’s review the design and development process of such medical devices.
Why applying Design Control to product development?
FDA required for years that medical and invitro diagnostic devices are developed under design control. Their guidance on design control for medical device manufacturers (www.fda.gov/media/116573/download) is still very relevant for US product registrations but should also be applied to products developed in Europe and other territories.
Design controls are an interrelated set of practices and procedures that are incorporated into the design and development process, i.e., a system of checks and balances. Design controls make systematic assessment of the design an integral part of development. As a result, deficiencies in design input requirements, and discrepancies between the proposed designs and requirements, are made evident and corrected earlier in the development process. Design controls increase the likelihood that the design transferred to production will translate into a device that is appropriate for its intended use.
In practice, design controls provide managers and designers with improved visibility of the design process. That is, to recognize problems earlier, make corrections, and adjust resource allocations. Designers benefit both by enhanced understanding of the degree of conformance of a design to user and patient needs, and by improved communications and coordination among all participants in the process.
The medical device industry encompasses a wide range of technologies and applications, ranging from simple hand tools to complex nano-technologies, from implantable screws to artificial organs, from test strips to diagnostic imaging systems. These devices are manufactured by companies varying in size and structure, methods of design and development, and methods of management. These factors significantly influence how design controls are actually applied. Given this diversity, the FDA guidance does not suggest particular methods of implementation. But rather, expands upon the language of the quality system requirements with practical explanations and examples of design control principles. Armed with this basic knowledge, manufacturers can and should seek out technology-specific guidance on applying design controls to their particular situation.
Overview of the design control process
Manufacturers could have the tendency to focus only on the time and effort required in developing and incorporating the milestone controls into the design process. However, one should keep in mind the intrinsic value of design controls as well. It is a well-established fact that the cost to correct design errors is lower when errors are detected early in the design and development process. Large and small companies that have achieved quality systems certification under ISO 9001 or ISO 13485 cite improvements in productivity, product quality, customer satisfaction, and company competitiveness. Additional benefits are described in comments received from quality assurance managers of medical device firms regarding the value of a properly documented design control system. Here is an example:
“…there are benefits to an organization and the quality improvement of an organization by having a written design control system. By defining this system on paper, a corporation allows all its employees to understand the requirements, the process, and expectations of design and how the quality of design is assured and perceived by the system. It also provides a baseline to review the system periodically for further improvements based on history, problems, and failures of the system (not the product).”
MARACA International regulatory and medical partner of SAFE-N-MEDTECH consortium
MARACA International (https://maracainternational.com/services/) is the regulatory and medical consulting partner of the SAFE-N-MEDTECH consortium (www.safenmt.com).
MARACA has over 20 years of experience with designing medical and invitro diagnostic devices. Depending on the customer, MARACA can guide the team from a medical perspective or from a regulatory or quality perspective.
Medical Affairs service (https://maracainternational.com/home/medical-affairs/)
The unique part of the MARACA services is the medical review during the different development phases of the nano-technology based medical device or IVD (see milestone points in Fig 1 Design Control). The MARACA physician is capable to guide a multifunctional development team, consisting out of researchers, engineers, quality, clinical and regulatory representatives, across stuck points and focus them on the final objective. This kind of support is unique and highly appreciated by our clients.
Intended Purpose statement
MARACA found that developing a first draft Intended Use/ Intended Purpose statement early in the feasibility phase (see Fig 1) helps the team to stay focused on the key design elements of the device. Otherwise the team could meander and lose costly time and resources. Nearly every time, MARACA found that the initially proposed Intended Purpose to be incomplete and insufficiently defined. With a poorly defined intended purpose, the device cannot be classified by regulatory affairs.
A well-defined Intended Purpose statement for an IVD needs to have six key elements, Table 1.
The same applies to medical devices (MD): which is the intended use population; In what disease stage is the MD applied; Where will the medical device be located (skin, blood system); How is the MD being used (treatment, monitoring); How long is the MD in contact with the patient; Is the MD implanted; Who uses the MD: physician, nurse.
Risk Management during product development
The other development element where the MARACA physician provides a unique service is with the risk management documentation of the device. Risk management is a core element of the European medical device and the IVD regulations and spans the complete lifecycle of the device. MARACA had lots of experience with the development of the risk documents and the assessment of patient risks. Moreover, be aware that currently notified bodies require a physician, such as our MARACA physician, to develop and approve the device risk-benefit summary document.
Clinical Evaluation Report and Performance Evaluation Report
MARACA developed and assessed the clinical evidence for many Clinical Evaluation Reports (CERs) for medical devices and Performance Evaluation Reports (PERs) for invitro diagnostic devices. For these reports systematic literature searches were performed. A PER report typically includes sections on the scientific validity of the biomarker, the analytical validity of the verification and validation data and a section on the clinical validity of the new test. These CERs and PERs need to be reviewed and approved by a physician experienced in the clinical field of interest. The MARACA physician is uniquely positioned to review and approve all PERs and many CERs as the Clinical Evaluator.
Clinical investigations, Clinical Performance studies and Post-Market Follow-up studies
The physician of MARACA is used to develop the study synopses for clinical studies of medical devices and invitro diagnostic devices. The synopsis includes all the key elements of a clinical study and allows then to be further developed into the clinical plan and study protocol by the clinical team. Lately, the MARACA physician was heavily involved in the development of post-market clinical follow-up (PMCF) studies for medical devices and post-market performance follow-up (PMPF) studies for IVDs.
It should be clear also that MARACA excels in the representation of a company with the notified bodies, the FDA and the European competent authorities to defend the clinical evidence of the device under review.
Regulatory Affairs support to SAFE-N-MEDTECH (https://maracainternational.com/home/regulatory-affairs/)
MARACA provides also regulatory and quality support to the SAFE-N-Medtech consortium.
Early in the feasibility phase (see Fig 1) MARACA can develop the project regulatory strategy plan and list the guidance documents which the design team should follow.
MARACA can acts as regulatory representative in the design reviews (see Fig. 1).
Late in the development phase, after the clinical studies (see Fig. 1), MARACA can develop the General Safety and Performance Requirements (GSPR) checklist and develop the technical documentation for the device. Where after MARACA can represented the company with the Notified Body and or the Competent Authority. When agreement is reached, the manufacturer and the device can be registered by MARACA in the EUDAMED Database. MARACA can also develop the device Unique Device Identification (UDI) and load them into EUDAMED. Further details can be found on the MARACA International website and any remaining questions MARACA is happy to address.
FDA Design Control Guidance for Medical Device Manufacturers, 1997.