Phases and Milestones
Concept Definition phase and milestone 1
Concept phase activities:
- Describe project and project goals; propose partners, timelines and budget
- Prepare milestone 1 (Concept) with documents for Concept review and Feasibility planning to initiate next project phase (Feasibility).
Milestone 1 (Concept defined) deliverables:
Documents to be prepared for this milestone.
| Concept review | Feasibility planning |
| - Concept Definition (CD) - Customer Requirement Document (CRD) - Project Description (PD) |
- Feasibility Target Specification (FTS) - Feasibility Plan - Milestone On-Track Assessment Table - Risk Assessment and Mitigation Table - Milestone 1 Checklist |
Example of documents:
Concept DefinitionFeasibility phase and milestone 2
Feasibility phase activities:
- Sign agreements with Feasibility partner(s)
- Develop with partner(s) reagents or prototype-like products and prove feasibility of product concept in Feasibility study(ies)
- Specify product design and select appropriate industrial partners for development and manufacturing of IVD
- Prepare milestone 2 (Feasibility completed) with documents for Feasibility review and Development planning to initiate next project phase (Development)
The Feasibility phase is based on documents completed during Concept Definition (Customer Requirement Definition, Feasibility Plan, and Feasibility Target Specification).
Milestone 2 (Feasibility completed) deliverables:
Documents to be prepared for this milestone.
| Feasibility review | Development planning |
| - Performance Report Feasibility - Feasibility study protocol - Feasibility Study Report - Contractual agreements - Update trial site list (if applies) - Technical Due Diligence Inspection Report(s) |
- Product Specification (PS) - Development Plan - Milestone On-track Assessment Table - Risk Assessment and Mitigation Table - Milestone 2 Checklist |
Examples of documents:
Product SpecificationDevelopment Plan
Development phase and milestone 3
Development phase activities:
- Prepare quality assessment of manufacturing partner’s processes and conduct financial and GMP-IVD due diligence inspection Part A
- Sign agreement with development partner
- Develop with selected partner(s) the final IVD within projected timelines and budget
- Provide evidence that IVD prototype meets Product Specification to lock design and scale-up manufacturing
- Prepare milestone 3 (Development completed) with documents for Development review and Evaluation planning to initiate next project phase (Evaluation)
The Development phase is based on the Product Specification, Customer Requirement Document and Development Plan.
The Development phase is not necessary if a product was developed by the partner without FIND involvement and/or is ready for distribution in partner-target markets. FIND may subcontract such partners for performance evaluation of their product in FIND-target markets. Such projects can enter directly into the Evaluation phase once the approved MS 3 checklist and related document deliverables have been completed.
Development studies for performance testing of final prototype (“Alpha” trial) must be planned and conducted to prove Product Specification, lock product design and scale-up manufacturing for Evaluation study (“Beta” trial). Prototype studies can be conducted at one or more trial sites and can be initiated if:
- FIND-supported product development is assumed to be completed and final prototype can be manufactured
- Contractual agreements for the purchase and dispatch of clinical trial materials have been signed off (or were already included in the binding agreement with the manufacturer)
- Clinical trial materials, such as test kits, reagents or instruments, can be shipped to the trial site. Shipment of materials is only possible once an agreement with the trial site or trial partner has been signed off or is under negotiation
- Trial sites have been inspected and certified to conduct Development studies for specific IVDs according to FIND’s Clinical Trial Standard
Milestone 3 (Development completed) deliverables
Documents to be prepared for this milestone.
| Development review | Evaluation planning |
| - Performance Report Development - Financial Due Diligence Report - GMP-IVD Due Diligence Inspection Part A Report - Regulatory Control Level Questionnaire - Development study protocol - Development Study Report - Intellectual property - Contractual agreements - Trial Site Certification Reports - Update trial site list |
- Evaluation Plan - Access Plan - Update Product Specification - Milestone On-track Assessment Table - Risk Assessment and Mitigation Table - Milestone 3 Checklist |
Examples of documents:
Performance Report DevelopmentEvaluation Plan
Access Plan
Evaluation phase and milestone 4
Evaluation phase activities:
- Prove clinical performance criteria of IVDs with Evaluation trials in controlled settings
- Make final quality assessment of manufacturing partner and conduct GMP-IVD due diligence inspection Part B
- Prepare milestone 4 (Evaluation completed) with documents for Evaluation review and Demonstration planning to initiate next project phase (Demonstration)
The Evaluation phase can only be started once MS 3 checklist and related documents have been signed off and milestone 3 has either been approved or an exemption from this rule has been granted by the CEO.
The Evaluation phase anticipates the availability of design locked IVDs manufactured in compliance with GMP-IVD standards or quality controlled manufacturing conditions. Products can be either FIND-supported IVDs (proving achievement of product specification) or IVDs developed by partners without FIND support (proving design locked IVD performance criteria).
Evaluation studies can be planned and conducted for already commercially available IVDs.
The Evaluation phase is based on documents prepared in previous project phases (e.g. Customer Requirement Definition, Product Specification and Evaluation Plan), and one of its major activities is planning and conducting an Evaluation study to prove performance of design locked IVD (e.g. zero series of production or already commercial IVD), and compare results with product specification.
The Evaluation study can be initiated if:
- Contractual agreements for the purchase and dispatch of clinical trial materials have been signed off
- Incoming Quality Control (IQC) SOP has been prepared and validated by the manufacturer
- Clinical trial materials such as test kits, reagents or instruments can be shipped to the trial site. Shipment of material is only possible once agreement with trial site or partner has been signed off or is under negotiation
- Trial sites have been inspected and certified to conduct Evaluation trials for specific IVDs according to FIND standards, or waiver of trial site certification has been prepared
The process of Outgoing Quality Control (OQC) of the IVD at the manufacturing site and IQC at the clinical trial site following shipment of the IVD must be developed and implemented by the manufacturer. Results must be recorded at the trial site. The project leader must approve lot release for the study.
GMP-IVD due diligence inspection Part B has to be scheduled with the manufacturer at the time when production of subcontracted IVD has been started.
Evaluation studies must take into consideration country regulatory requirements. Data can be used for diagnostic product registration if studies have been conducted in compliance with country-specific regulatory demands.
Milestone 4 (Evaluation completed) deliverables:
Documents to be prepared for this milestone.
| Evaluation review | Demonstration planning |
| - Performance Report Evaluation - Evaluation study protocol - Evaluation Study Report - IQC Report - Contractual agreements - Trial Site Certification Reports - Update trial site list - GMP-IVD Due Diligence Inspection Part B Report - Intellectual property |
- Senior Management Meeting Record - Demonstration Plan - WHO Endorsement Schedule - Global and National Policy Endorsement Schedule - Customer Support Plan - Update Access Plan - Milestone On-track Assessment Table - Risk Assessment and Mitigation Table - Milestone 4 Checklist |
Examples of documents:
GMP-IVD Due Diligence Inspection Part B Report
Customer Support Plan
Demonstration phase and milestone 5
Demonstration phase activities:
- Prepare and conduct large scale Demonstration studies to prove feasibility, performance of IVD and utility under field conditions (actual diagnostic routine conditions prevailing in target settings of the IVD)
- Demonstrate clinical utility and health economic impact for defined intended use (effectiveness) of FIND-supported IVD
- Prepare document with sufficient data for submission to global and national health organizations and institutions for endorsement of IVD or IVD-based technology (e.g. WHO endorsement)
- Start implementing laboratory support projects
- Prepare milestone 5 (Demonstration completed) with documents for Demonstration review and Access planning to initiate next project phase (Access)
The Demonstration phase is scheduled for commercially available and registered (if necessary) diagnostic products that may or may not have been manufactured with FIND support. Demonstration studies are interventional studies in which results of the new IVD are used to manage patients in the study group. Results from the study group will be compared with control group results.
Based on recommendations from FIND senior management and customer feedback, a protocol for the Demonstration study will be prepared and sites and settings selected.
Data from the Demonstration study will be presented to the relevant WHO group for endorsement, facilitating purchase of the new diagnostic and uptake in national health programs. At the same time, strategies to engage managers from national disease control programs, senior policy makers in Ministries of Health of endemic countries, civil society, and donors have to take effect in order for the FIND-supported IVD to be adopted and included in national health policies and guidelines.
As evidence begins to accumulate from laboratory preparedness studies, market adoption and scale-up will be accelerated.
Milestone 5 (Demonstration completed) deliverables
Documents to be prepared for this milestone.
| Demonstration review | Access planning |
| - Performance Report Demonstration - Demonstration study protocol - Demonstration Study Report - Dossier for WHO - Update Global and National Policy Endorsement Schedule - Update trial site list - Intellectual property |
- Update Access Plan - Laboratory support projects - Update Customer Support Plan - Milestone On-track Assessment Table - Risk Assessment and Mitigation Table - Milestone 5 Checklist |
Example of document:
Global and National Policy Endorsement ScheduleAccess phase and milestone 6
Access phase activities:
- Make IVD available in first target (pilot) country at agreed upon price (product is on shelf and can be procured)
- Implement Customer Support Plan with distribution partner
- Prepare availability of IVD in other developing countries
- Reinforce laboratory strengthening by laboratory support projects
- Prepare milestone 6 (Access in one country) with documents for Access review and Impact planning to initiate next project phase (Impact phase)
Milestone 6 (Access in one country) deliverables:
Documents to be prepared for this milestone.
| Access review | Impact planning |
| - Access Report - Update Customer Support Plan - Update Access Plan |
- Impact Plan - Milestone On-track Assessment Table - Risk Assessment and Mitigation Table - Milestone 6 Checklist |
Impact phase and milestone 7
Impact phase activities:
- From customers, collect and evaluate data of FIND-supported IVD according to Impact Plan
- Analyze collected data and prove significant impact of IVD on health care. Use data to demonstrate clinical utility, health economics, cost benefit and efficiency of the IVD
- Continue to implement Access Plan and facilitate scaling up in pilot countries with laboratory support projects
- Implement Customer Support Plan and prove efficiency of customer support
- Prepare milestone 7 (Impact monitored) with documents for Impact review
Milestone 7 (Impact monitored) deliverables:
Documents to be prepared for this milestone.
| Impact review | |
| - Impact Report - Timeline (Gantt chart) - Milestone On-track Assessment Table |
End of project |
Concept Definition (CD)
The Concept Definition contains the following:- Current status of available diagnostics in target market segment
- Diagnostic needs and rationale for the project
- Intended use of product and diagnostic product positioning
- Scientific and technological background of project
- Steps and related activities to achieve project targets
- Risks and potential hurdles to overcome
- Potential partners and duties
- Potential co-sponsors
- Required time period to achieve goal
Product Specification (PS)
The Product Specification describes the target performance characteristics of the final IVD product such as reagent, assay, instrument, and/or software. The PS is based on the Customer Requirement Document and regulatory requirements, and includes:
- Intended use:
- Patient characteristics
- Type of specimens to be used
- Diagnostic purpose of IVD
- Whether IVD can be used as stand alone product or in combination with other gold standard tests
- Whether the IVD can be used for self-testing
- Product positioning:
- At which health care level in which countries IVD can be used with described intended use
- Current gold standard for this product
- Minimum and optimum performance characteristics of the final product under consideration
The Product Specification reflects the compromise between the desired product features documented in the Customer Requirement Document and those that can be realistically achieved given technology, timeframe and budget constraints.
Development Plan
The Development Plan describes all required activities, deliverables, budgets and timelines for this phase (between milestone 2 and milestone 3), including:- Financial due diligence inspection of partner
- GMP-IVD due diligence inspection Part A
- Binding agreement with development/manufacturing partner
- Objectives and success criteria
- Product description, including:
- Technical solution
- Product pricing
- Partners and duties
- Development tasks
- Intellectual property
- IP expert analysis report and conclusions: approach and timelines
- IP access strategy for FIND target markets
- Manufacturing and forecasting
- Manufacturing technology
- Estimated product volume and rationale
- Available manufacturing capacity
- Required investment by partner
- Regulatory demands
- Budget Forecast
- Timelines (Gantt chart)
Performance Report Development (PRD)
This document summarizes activities and results around product development, compares achieved results with set targets from Product Specification and describes conclusions on project continuation. It contains:- Development Report, including development steps, resulting technology, design of IVD and diagnostic platform, cost of manufacturing and pricing of IVD
- Technical report and packet insert
- Achieved Product Specification of assay, instrument and/or software in the Development phase versus target described in the Product Specification
- Significant deviations and conclusions
- Assessment of trials during the Development phase (if any): study design, analyzed number of samples, timelines, critical appraisal of trial site(s), incidents during the study
- Lessons learned and recommendations
Evaluation Plan
The Evaluation Plan describes all required activities, deliverables, budget, and timelines for the Evaluation phase:- Objectives of Evaluation phase and success criteria
- Manufacturer
- Supply agreement
- GMP-IVD due diligence inspection Part B: date of scheduled inspection
- SOP for outgoing (OQC) and incoming quality control (IQC).
- Outline of Evaluation study
- Study objectives, study design and endpoints
- Negative control groups and number of controls
- Patients to be enrolled (number and enrolment criteria)
- Diagnostic methods to be compared
- Study timelines
- Trial sites/partners, planned agreements and trial site certifications
- Regulatory strategy: regulatory demands in target countries of FIND-supported IVD
- Budget Forecast
- Timelines (Gantt chart)
Access Plan
The Access Plan describes all required activities, deliverables, budget and timelines for the Access phase:- Objectives of Access phase and success criteria
- First target country with access to IVD, and date of access
- Other target priority countries and timeline
- Funding stream, marketing and distribution channels and required activities
- Steps to accelerate access
- Country-specific measures for adoption of IVD: scaling up strategy including laboratory support projects in pilot countries
- Distributor(s)
- Contractual agreements
- Special requirements of customer support in target priority countries
- Further required steps and activities for access
- Required budget
GMP-IVD Due Diligence Inspection Part B Report
The report describes whether skills, expertise, technical equipment and facility of the manufacturing partner are in compliance with GMP standards. Part A describes the facility and manufacturing processes in general, while Part B describes the specific manufacturing processes of the FIND-supported IVD and the partner’s ability to comply with IVD-GMP standards. Part B inspection should also indicate whether recommendations from Part A inspection have been included. Status of inclusion must be recorded in Part B Report.The cooperation partner is responsible for ISO and GMP-compliant manufacturing processes, release and distribution of IVD, customer service and market vigilance. The cooperation partner is legally accountable and responsible for the quality of the manufactured product and has to assign legally accountable person(s) for release of the product.
The FIND inspector makes recommendations on whether the agreement (e.g. Supply Agreement) with the manufacturing partner can be signed or whether improvements need to be included in the agreement.
Customer Support Plan
The Customer Support Plan describes:- Training of customers (training plan)
- Inquiry and claim handling
- Change notification procedure
- Installation, maintenance and repair service
- Measures for efficiency of customer support
- Budget, timelines
- Contractual agreements for customer support
Global and National Policy Endorsement Schedule
This document describes the strategy and timelines for achieving global and national policy endorsement for each target country. Strategy includes description of tools for engaging managers of national disease control programs, senior policy makers in Ministries of Health in high-burden countries, civil societies and donors.FIND will pursue effective communication and external relations strategies for engaging international and national policymakers, and additional stakeholders (i.e., advocates, the global health community) to function as allies in the process of adoption of new diagnostics.