R&D1:

Develop generic methods and technology including assessments of biological relevance and indications of biocompatibility

BM1:

Understand IP management and contract-related research disclosure agreements

R&D1:

Develop generic methods and technology of device components, following good laboratory practice (GLP) principles and accurate / detailed record keeping

R&D2:

Perform scientific literature review; applied methods and technology development based on available health & care data to identify potential application areas within biological environment, understand biocompatibility, toxicity issues, and biodegradability (if applicable)

HEST1:

Identify potential areas for current and foreseeable healthcare applications

R1:

Consider regulatory approval and other governance issues (e.g. MTAs, HTA) for in vitro and in vivo testing of the material and understanding ethical approvals for testing of medical devices in clinical investigations (including contracts and sponsorship).

BM1:

Consider IP protection (e.g. patenting), record funding and contracts for IP ownership

R&D2:

Record device requirements, prior knowledge, and evidence of a valid clinical association to inform device specification

R&D3:

Prototype design and development (not for human use). Assess efficacy in preclinical models (in vitro, ex vivo, and in vivo – small and large animal models)

R&D4:

Consider human factors that can influence concept design and development (e.g. will the device need removing? what are the consequences if not?)

R&D5:

Consider responsible innovation, including potential effects on the environment, that can influence concept design and development

HEST1:

Understand current and foreseeable specific health & care need

HEST2:

Understand current and foreseeable clinical care pathway and guidelines of care for the specific clinical need

HEST3:

Understand current and foreseeable clinical care workflow and current gold standard of care for the specific clinical need

HEST4:

Draft plans describing how the device will affect and integrate with current and foreseeable service/clinical practice

HEST5:

Prepare initial target product profile to define an outline of the value proposition – what is the expected benefit of the device in terms of costs, patient care. Consider competing solutions (existing or currently under development) which might impact the clinical need, guidance, workflows or pathways. This will be needed for funding applications and the technical file.

HEST6:

Conceptualise health economics evaluation and cost benefit analyses (“desk research”, literature review) and conceptualise a preliminary health economic model which will inform concept development (considering current and upcoming competing solutions).

R1:

Arrange ethical approvals (including sponsorship) for suitable (pre)clinical testing of concept

R2:

Formalise intended use (based on HEST2/3); Understanding of device regulations and risk classification to inform concept development (including identification of regulatory steps needed for future clinical testing)

R3:

Understand the requirements for accurate audit trail / traceability of prototype device development is in place through a quality management system.

P&D1:

Development of prototype and design initial production process (not for human use) with view to adapt (for human use) and scaling up considering regulatory implications for clinical investigations.

BM1:

Consider additional IP protection based on concept development (could include design and manufacturing processes), consider freedom to operate; record funding and contracts for IP ownership.

BM2:

Understand the market and its size to determine commercial opportunities and potential economic impact

BM3:

Understand of potential market share based on competing solutions and analysis of competitors

BM4:

Understand on the nature of the intervention within the clinical landscape and consider plans for delivering device to market

BM5:

Understand potential exit strategies such as commercialisation venues (e.g. spin-out vs license vs not-for-profit (e.g. via community interest company))

HCE1:

Collect patient and end user feedback of concept

R&D3:

Full prototype (human use) development, manufacture at good manufacturing practice (GMP) level, and complete pre-clinical testing

R&D4:

Include human centric design principles in prototype

R&D5:

Ensure prototype design meets regulatory and GMP manufacturing requirements, is sustainable in design, is sourced from ethically verified materials and its manufacture is auditable. This can be performed by external industry partner/ test house

R&D6:

Determine if biocompatibility / toxicity / biodegradability and formulation of prototype device with methods and materials that are suitable for (human) use in a clinical setting and compare to current clinical solutions. This can be performed by external industry partner/ test house

R&D7:

Adapt prototype based on pre-clinical data and key stakeholder feedback to ensure health and care feasibility will be achieved (design input)

HEST4:

Review how the device will affect current and foreseeable service/clinical practice

HEST5:

Review the value proposition for the developed prototype highlighting benefits compared to current gold standard of care and existing competing solutions.

HEST6:

Review the conceptualised health economics model and cost benefit analyses which will inform on what data needs to be collected.

R1:

Prepare ethics and research governance applications (including sponsorship) for clinical investigations / feasibility studies in T1 – T4 stages

R2:

Determine device categorisation and necessary regulatory approvals required.

R3:

Ensure accurate audit trail / traceability of prototype device development (inc. device materials, design iterations and equipment uses) is in place for example by working through a quality management system (ISO 13485)

R4:

Initialise a technical file (incl. risk assessment), determine the documentation required for MHRA notification for clinical investigation approval

R5:

Understand the requirements for Regulatory Approvals (e.g. CE/UKCA/FDA/other). Ensure requirements for clinical investigation standards are met.

P&D1:

Optimise the full prototype (if applicable) for human use and refine production methods for preclinical testing. Seek industry partners (including service providers, suppliers, manufacturers and distributors - also considering start-up formation)

P&D2:

Develop testing protocols for the full prototype in pre-clinical models and understanding of protocols for the final product required for clinical investigations.

P&D3:

Test compliance with technical file requirements (safety, compliance, interoperability and usability)

P&D4:

Conduct quality control of the prototype according to product specifications

BM2:

Identify market (i.e. target payer vs user), finalise market size analysis to determine if there is a viable market

BM3:

Refine market share analysis including analysis of competitors and opportunities, and finalise market share assumptions to feed into HEST4

BM4:

Start defining the nature of the intervention within the clinical landscape and initialize plans for delivering device to market

BM5:

Start Exploring potential exit strategies such as commercialisation venues (e.g. spin-out vs license vs not-for-profit (e.g. via community interest company))

BM6:

Draft an outline of the business model (considering future requirements/steps, plan to seek for investors/funding for larger / pivotal / multisite clinical studies)

HCE1:

Evaluate prototype in the competitive landscape based on pre-clinical studies (i.e. how does the prototype compare to gold standard). Create a clinical evaluation plan (CEP) to define the scope and outline the systematic approach of the planned clinical investigation to demonstrate scientific, analytical and clinical validity

R&D6:

Refine the final prototype for use in a small scale, first in man, feasibility study on small patient groups for usability, safety testing and considerations of efficacy

R&D7:

Adapt prototype based on preliminary clinical data and key stakeholder feedback to ensure health and care feasibility and efficacy will be achieved (design input)

R&D8:

Refine the prototype to ensure health and care effectiveness will be achieved

R&D9:

Completion of R&D activities including the creation of the Device Master List (DML, detailing all processes required to create the device; to include in the technical file) and freeze of the design of the refined product.

HEST4:

Refine how the device will affect current and foreseeable service/clinical practice

HEST5:

Refine a value proposition for the developed prototype highlighting benefits compared to current gold standard of care and existing competing solutions

HEST6:

Refine the conceptualisation of the health economics model and cost benefit analyses which will inform health economics data collection needs

R1:

Gain ethical and research governance clearance (including sponsorship) for current and subsequent clinical studies

R3:

Obtain ISO 13485 Certification, and any other required ISO certificates (e.g. 27001). Relevant ISO standard include (but are not limited to) ISO 10993 (biological testing requirements), ISO 14644 (GMP manufacturing), ISO 14155 (GCP – good clinical practice), ISO 11137-2 ISO 11737 (sterilisation and validation of sterilisation), and ISO 14971 (risk management), ISO 20417 (information to be supplied by manufacturer), ISO 14630 (non-active surgical implants), ISO 15223 (labelling), ISO 11607 (packaging), and ISO 20416 (post market surveillance.) Involve industry partners (e.g. manufacturer) as needed to obtain ISO certification.

R4:

Refine and submit the technical file (e.g. design decisions, regulatory risk assessments, test methods) for MHRA approval for clinical investigation

R5:

Start collecting clinical evidence on efficacy and safety for regulatory compliance (e.g. CE/UKCA/FDA/Other), and if affecting clinical outcomes run the study to accepted good clinical practice (GCP) standards (e.g. ISO 14155)

P&D1:

Work with industry partners (including service providers, suppliers, manufacturers and distributors- also considering start-up formation) to produce the final quality assured product, based on the final prototype, to be used in clinical setting

P&D2:

Develop testing protocols for the final quality assured product in a clinical setting

P&D3:

Test compliance with technical file requirements (safety, compliance, interoperability and usability)

P&D4:

Conduct quality control of the product according to product specifications

P&D5:

Scale up production and batch release (GMP compliant) for first in man clinical investigation

BM4:

Finalise the nature of the intervention within the clinical landscape and initialize plans for delivering device to market

BM5:

Finalise plans for potential academic exit strategies such as commercialisation venues (e.g. spin-out vs license vs not-for-profit (e.g. via community interest company)) to position the proposed intervention within the clinical landscape

BM6:

Refine the business model (considering future requirements/steps, plan to seek for investors/funding for larger / pivotal / multisite clinical studies)

HCE1:

Position of the concept within the competitive landscape and perform health & care risk assessment

HCE2:

Perform clinical evaluation of prototype in first in man, Phase I, clinical investigation study to assess feasibility and safety

HCE3:

Perform clinical evaluation of prototype clinical investigation study to assess feasibility, safety, and efficacy. This can be, but does not need to be, the same clinical investigation undertaken in HCE2.

HEST4:

Refine how the device will affect current and foreseeable service/clinical practice based on your own data acquired in the clinical investigation

HEST5:

Refine the value proposition for the developed prototype by integrating your own data to highlight benefits compared to current gold standard of care and existing competing solutions

HEST6:

Refine health economics evaluation by integrating your own data to inform the cost benefit analyses

R1:

Gain ethical and research governance clearance (including sponsorship) for current and subsequent clinical studies

R4:

Seek approval for subsequent clinical studies. Notify Regulatory Authority (e.g. MHRA in the UK) of any design changes that might have occurred since the first clinical investigation approval

R5:

Refine the technical file for Regulatory Compliance (e.g. CE/UKCA/FDA/Other) (e.g. design decisions, risk assessments, test methods) (engaging notified body)

P&D3:

Test compliance with technical file requirements (safety, compliance, interoperability and usability)

P&D4:

Conduct quality control of the product according to product specifications

P&D5:

Increase manufacturing (if needed) for the larger clinical investigation studies

BM4:

Review commercial strategy to deliver the device to market (consider refinements of the product/service)

BM5:

Review commercial strategy including the academic exit strategy (e.g. spinout vs license)

BM6:

Refine business model to implement future steps

BM7:

Assess the commercial viability of the product to confirm that the manufacturing, distribution and marketing of the device is financially sustainable (including return-on-investment analysis); seek company or venture capitalist funding

HCE3:

Conduct large scale clinical investigation study in relevant patient groups to validate safety and efficacy of the device

HCE4:

Larger scale / pivotal / multisite clinical investigation study in relevant patient groups to validate safety, efficacy and effectiveness of the device. Write a clinical evaluation report (CER) summarising the clinical outcomes of the clinical investigations for inclusion in technical file to notified body.

HCE5:

Initialise plans for post-market surveillance to include in technical plan and clinical follow up

HEST4:

Finalise how the device will affect current and foreseeable service/clinical practice (health & care pathway based on your own data acquired in the clinical investigation

HEST5:

Finalise the value proposition for the developed prototype by integrating your own data to highlight benefits compared to current gold standard of care and existing competing solutions

HEST6:

Finalising full Health economics evaluation and cost benefit analyses

HEST7:

Define the end user-business model / procurement case

HEST8:

Consider adoption of the product into policy and/or guidelines as a routine method or approach; NICE Health Technology Evaluation (Early Evaluation Assessment)

R5:

Finalise and submit technical file (e.g. design decisions, risk assessments, clinical evaluation report) for Regulatory Approval (e.g. CE/UKCA/FDA/Other)

P&D5:

Increase manufacturing for future commercialisation / industry adoption following quality assurance processes to ensure safety and compliance with product specifications. If changes in manufacturing are needed, further regulatory approvals might be required.

BM6:

Finalise and implement the chosen full business model

BM7:

Confirm commercial viability of the product; seek company or venture capitalist funding

BM8:

Refine sales and marketing strategy based on business model

HCE5:

Refine and finalise plans for post-market surveillance to include in technical plan and clinical follow up

HEST7:

Monitor the end user-business model / procurement case (e.g. product adoption and effect on service post market); ongoing health economic analysis

HEST8:

Obtaining NICE Health Technology Evaluation recommendation

R6:

Collate post market post-market clinical evidence; update clinical evaluation report annually and maintain quality management system

P&D5:

Ensure that manufacturing is performed at a scale which meets with market demand, or further increase manufacturing output if required. If changes in manufacturing are needed, further regulatory approvals might be required.

P&D6:

Product launch and distribution (including strategies for communication and training processes to increase acceptability by end users)

BM8:

Market and promote of device on new markets

HCE5:

Real world evidence post launch (Phase 4); Post-market surveillance and post-market clinical follow-up of the product to collect data on long-term effectiveness, potential adverse effects, and usage of the device