R&D1:

Undertake generic research methods and technology development

BM1:

Understand IP management and contract-related research disclosure agreements

R&D1:

Undertake generic methods and technology development of device components, following good lab practice (GLP) principles with accurate and detailed record keeping

R&D2:

Perform scientific literature review on applied methods and technology development based on available health & care data. For wearables and prosthetics this could include examining prior knowledge on toxicity, biocompatibility, and (bio)-degradability of materials.

HEST1:

Understand health & care need and identifying if there is a potential area for a healthcare application

R1:

Understand Ethical and governance (e.g. HTA, contracts (MTAs etc.), HRA) approvals required for testing of medical devices in pre-clinical and clinical investigations.

BM1:

Consider IP protection (e.g. patenting) freedom to operate and identify / record IP ownership and record funding and contracts for IP ownership

R&D2:

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

R&D3:

Refine technological development of component parts. Basic design and product specifications for prototype

R&D4:

Consider human factors in concept design

R&D5:

Consider responsible innovation in concept design to cover ethically sourced materials, sustainable materials and bias free

HEST1:

Understand current and foreseeable specific health & care need.

HEST2:

Understand the current and foreseeable clinical care pathway for the unmet clinical need and the related guidelines for care. This will be needed for the value proposition.

HEST3:

Understand the health and care workflow (i.e. how are the guidelines put into practice) and how the proposed device could fit in. Determine cost of current and foreseeable approach. This will be needed for the value proposition.

HEST4:

Initialise preparation for service transformation model which will be required for final business case (i.e. how will current and foreseeable practice need to be changed / be changed by for your device to be used).

HEST5:

Initialise value proposition and TPP – what is the expected benefit of the device in terms of costs, patient care. This will be needed for funding applications and the technical file. Consider competing solutions (existing or currently under development) which may impact the clinical need, guidance, workflows or pathways.

HEST6:

Consider current and upcoming competing solutions and initialise health economics “desk research” (literature review) and conceptualise a preliminary health economic model to inform concept development.

R1:

Arrange ethical approvals for suitable (pre-) clinical testing of concept to be done in D4 if required.

R2:

Formalise intended use (derived from outputs of HEST2/3) to inform concept development before initialising TPP in HEST5. Identify possible device and risk classification and regulatory steps involved for each potential market (see BM2 based on formalised intended use document.

R3:

Understand the requirements for accurate audit / traceability of prototype device development is in place.

P&D1:

Development of components of device and initial production process with view to scaling up and regulatory implications for clinical investigations. Consider end users requirements in design of full prototype. This may require industry partner engagement (including services providers, suppliers, manufacturers and distributors).

BM1:

Consider freedom to operate; record funding and contracts for IP ownership and consider if additional IP protection is needed based on concept development.

BM2:

Identify the market understanding of market size to determine if there is a viable market.

BM3:

Understand of market share including analysis of competitors.

HCE1:

Gather and analyse initial feedback from stakeholders on relevance of solution.

R&D3:

Undertake full prototype development and pre-clinical testing (including comparison to existing solutions - aiming to show improvement or equivalency) in laboratory models, including in-vivo models if required

R&D4:

Include human-centric design principles in prototype

R&D5:

Ensure the materials are suitable for use in humans. Ensure prototype design meets regulatory requirements, is sustainable in design, is sourced from ethically verified materials and its manufacture is can be audited. This can be done by an external test house.

R&D6:

Determine safety (bio-compatibility / bio-degradability / formulation / toxicity) of device is suitable for use in a clinical setting by testing in model systems. This can be done by an external test house.

R&D7:

Adapt prototype based on pre-clinical data and key stakeholder feedback to ensure health and care feasibility (design input) i.e. after performing HCE activities in D4

HEST4:

Refine and update preparation for service transformation model which will be required for final business case (i.e. how will current practice need to be changed / be changed by for your device to be used)

HEST5:

Refine Value proposition and TPP – what is the expected benefit of the device in terms of costs, patient care. This will be needed for funding applications and the technical file.

HEST6:

Refine the health economic model and identify data to collect

R1:

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

R2:

Determine device categorisation and necessary regulatory approvals required. This will determine if a clinical investigation is required for CE marking.

R3:

Ensure accurate audit trail / traceability of prototype device development is in place (inc. device materials, design iterations and equipment uses) for example by working towards the ISO13485 standard for quality management systems

R4:

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

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. This may require industry partner engagement (including services providers, suppliers, manufacturers and distributors).

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 prototype components to determine material safety, electric safety and bio-compatibility.

BM2:

Finalise Market UK, EU, US or worldwide and the relevant regulatory pathways required for each market to feed into HEST4.

BM3:

Finalise market share assumptions to feed into HEST4.

BM4:

Initialise plans for delivering the device to market - will it be a product or service.

BM5:

Initialise a commercial strategy for delivering the device to market (set up spin-out or license out innovation or develop as not-for-profit (e.g. via community interest company) as academic exit strategy).

BM6:

Initialise business model based on decisions from BM4 and BM5

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 clinical data from first in man study and key stakeholder feedback to ensure health and care feasibility (design input) i.e. after the HCE activities in this stage

R&D8:

Adapt prototype based on clinical efficacy data and key stakeholder feedback to ensure health and care efficacy (design input) i.e. after the HCE activities in this stage

R&D9:

Complete R&D activities including the creation of the Device Master List (detailing all processes required to create the device) to include with technical file and freezing the design of the refined product.

HEST4:

Refine service transformation model which will be required for final business case (i.e. how will current practice need to be changed / be changed by for your device to be used).

HEST5:

Update Value proposition based on HEST4/6 – what is the expected benefit of the device in terms of costs, patient care. This will be needed for funding applications and the technical file.

HEST6:

Refine the health economic model and identify data to collect.

R1:

Gain ethical and research governance clearance for clinical studies.

R3:

Obtain ISO 13485 (QMS certification) certification or ensure using and working to ISO certified QMS system. Obtain any other ISO certifications. This may involve engagement with industry partners (e.g. manufacturers and test houses) to obtain ISO certification. Relevant ISO standard include (but are not limited to) ISO 10993 (biocompatibility testing), ISO 14155 (GCP – good clinical practice), IEC 60601 (electrical medical equipment) and ISO 14971 (risk management), ISO 20417 (information to be supplied by manufacturer), and ISO 20416 (post market surveillance.) ISO certifications will also need to be worked to for the type of sterilisation procedure your device will undergo.

R4:

Refine technical file based on pre-clinical data (e.g. design decisions, regulatory risk assessments (evidence working at ISO 14971 standards), test methods). For any clinical investigations that may affect the outcome of a patient, submit the technical file for MHRA approval for clinical investigations of final product (as you require exemption for use of a non-CE/UKCA marked device in humans to undertake the clinical investigation in HCE2/3) including CEP.

R5:

Initialise documentation for CE/UKCA marking application and start to collect clinical evidence on efficacy and safety for CE/UKCA marking 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

P&D2:

Work with industry partners (including service providers, suppliers, manufacturers and distributors - also considering start-up formation) to undertake quality assurance of final product.

P&D3:

Determine the safety, compliance, interoperability and usability of device of scaled up prototype from the in man studies in HCE3.

P&D4:

Conduct Quality control of scaled up device to ensure meeting quality control specifications

P&D5:

Scale up production to good manufacturing practice (GMP) standards for use of device in pilot clinical investigations

BM4:

Refine plans for delivering the device to market -will it be a product or service

BM5:

Refine plans for delivering the device to market - set up spin out or licence out innovation. Define the academic exit strategy

BM6:

Refine business model based on decisions from BM4 and BM5

HCE2:

Perform Feasibility and safety in early-stage clinical investigation (phase 1 – on healthy patients) / first-in-man studies / clinical investigation

HCE3:

Undertake Pilot in man study to determine validation of device efficacy done as part of feasibility and safety testing in HCE2

HEST4:

Refine preparation for service transformation model which will be required for final business case (i.e. how will current practice need to be changed / be changed by for your device to be used)

HEST5:

Update value proposition – what is the expected benefit of the device in terms of costs, patient care. This will be needed for funding applications and the technical file.

HEST6:

Re-engage with health economist for full cost benefit analysis after clinical investigations in HCE3/4.

R1:

Gain any additional ethical and research governance clearance for clinical studies required for larger clinical investigations.

R4:

Seek approval for subsequent larger clinical investigations and include refined technical file based on clinical data and any design changes (e.g. design decisions, regulatory risk assessments, test methods). For any clinical investigations that may affect the outcome of a patient, submit the updated technical file for approval with the relevant regulatory Authority (e.g. MHRA in the UK) for clinical investigations of final product (as you require exemption for use of a non-CE/UKCA marked device in humans to undertake the clinical investigations).

R5:

Refine Regulatory Compliance (e.g. CE/UKCA/FDA/Other marking) technical documentation (which includes risk assessment) based on early phase clinical data.

P&D3:

Determine the safety, compliance, interoperability and usability of device of scaled up prototype from the in man studies in HCE3.

P&D4:

Confirm specifications for larger scale manufacture ahead of larger clinical investigations.

P&D5:

Scale up production for use of device in larger scale clinical investigations.

BM4:

Refine plans for delivering the device to market - will it be a product or service.

BM5:

Refine plans for delivering the device to market - set up spin-out or licence out innovation. Define the academic exit strategy.

BM6:

Refine business model based on decisions from BM4 and BM5 to apply for funding

BM7:

Assess commercial viability to confirm manufacturing, distribution and marketing of the device is financially sustainable (including return on investment study).

HCE3:

Perform larger scale clinical investigation (phase 2) in relevant patient.

HCE4:

Undertake larger scale clinical investigation (phase 3/ pivotal) in relevant patient group to confirm patient effectiveness.

HCE5:

Initialise plans for post-market evaluation to include in technical plan.

HEST4:

Finalise service transformation model.

HEST5:

Finalise value proposition – what is the expected benefit of the device in terms of costs, patient care. This will be needed for funding applications and the technical file. Include information from HEST4/6.

HEST6:

Finalise health economics modelling.

HEST7:

Refine end user business model.

HEST8:

Submit to NICE if required.

R5:

Finalise Regulatory Assessment (e.g. CE/UKCA/FDA/Other) based on clinical data and submit technical file to notified body (determined by MHRA) in order to obtain conformity mark (CE marking / UKCA) or self-declare product (risk class dependent).

P&D5:

Determine how to increase manufacturing output to meet demand following quality assurance processes to ensure compliance with product specifications and safety p for productisation and distribution. If changes to the manufacturing process are required then new regulatory approvals maybe required.

BM4:

Refine and finalise plans for delivering the device to market - will it be a product or service.

BM5:

Refine and finalise plans for delivering the device to market - set up spin-out or licence out innovation. Determine the academic exit strategy.

BM6:

Refine and finalise business model based on decisions from BM4 and BM5.

BM7:

Implement business plan (i.e. approach funders).

HCE4:

Prepare a clinical evaluation report (CER) summarising the clinical outcomes of the clinical investigations for inclusion in technical file to notified body.

HCE5:

Refine and finalise plans for post-market evaluation to include in technical plan.

HEST7:

Monitor end user business model

R5:

Ensure CE/UKCA approval and device registered with MHRA or appropriate approval body.

R6:

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

P&D5:

Increase manufacturing output to meet demand and if this requires a change in manufacturing processes then gain new regulatory approval.

P&D6:

Productisation and distribution (i.e. launch the product)

BM7:

Approach funders, investment capitalists for funds to upscale manufacturing process

BM8:

Refine sales and marketing strategy.

HCE5:

Post-market surveillance and clinical follow-up of the product to collect data on long-term effectiveness, potential adverse effects, and usage of the device.