Using a Target Product Profile (TPP) to guide innovation for future In Vitro Diagnostic (IVD) developments in the United States

Figures & data

Figure 1. IVD Development Competing Attributes. IVD device development can be viewed as a balance between meeting a clinical need, the technological innovation, and potential overlap with current offerings. Through this perspective, a developer can know where the product sits relative to competitors and in terms of prioritising the need. The green shaded region indicates the ideal goal of IVD development and where the innovation opportunity can be most impactful.

Table 1. Questions (and sample responses) that guide developers in scoping their product development.

Guiding Question	Example
What are the important unmet end-user needs?	Early screening test is needed for disease X
What is your proposed solution in simple, non-jargon terms?	The proposed device will identify the presence of a marker that is diagnostic for disease X
How is it done today and what are the limits of current practice?	Current methods rely on costly, invasive sampling that can lead to false results
What is unique in your approach and why will it be successful?	Method Y will be non-invasive and reduce costs by 10×, etc.
Who cares? If successful, what difference will it make?	Method Y will be accessible due to unit costs that are 10× less than what is on the market and will provide more diagnostic information, etc.
What are the risks?	Development process can have long lead times due to procurement of materials and testing
How much will it cost?	See above on unique approach and difference, etc.
How long will it take?	Use planning tools such as gantt charts to define milestones, etc.
What are mid-term and final milestones to measure success?	Define phase gates with entry and exit criteria to guide project development, etc.

Figure 2. A notional TPP development and review cycle. Relevant participant groups are listed at the key stages for the TPP development process who may help in properly defining an IVD product roadmap.

Table 2. IVD development criteria. List of key criteria, corresponding description, and examples for framing a target product profile.

Development Criteria	Rationale	Examples
Indication	The medical need such as the targeted disease affects how the device should be configured and when and on whom it should be used.	Qualitative vs Quantitative, Targeted disease and symptoms, syndromic panel (grouped analytes based on common syndromes).
Sample Type	IVD must target the proper sample type appropriate for capturing aetiological agent or for disease diagnosis.	Saliva, Swab, Blood, Urine, Fecal.
Regulatory Pathway	Legally marketed IVD must receive appropriate regulatory approvals and development time/costs will depend on the pathway.	US FDA pre-market clearances, authorisations, and approvals (e.g. 510(k), EUA, PMA).
Technical Principal	The working principal of the device dictates many development factors such as regulatory requirements, work flow, etc.	NAAT, antigen, ELISA.
User Type	The intended user influences stringency in validation testing needed.	Health care provider, lay user, lab technician.
Intended Use Environment	Where a test is used affects type of validation required and how device should be configured.	Lab, point-of-care, at-home.
Assay Configuration	Depending on disease or intended use the number and type of targets may vary.	Single-plex, multi-plex; pathogen, biomarkers.
Analytical Performance	Depending on the assay design/format basic performance parameters of the device itself may be required.	Time-to-result, Sample throughput, Sample processing/concentration, LOD, Inclusivity/Exclusivity, Controls, Reproducibility, Interference.
Clinical Performance	Requires evaluating the device in real world setting preferably in prospective studies but sometimes can be supplemented with retrospective archived samples.	PPV, NPV, PPA, NPA, Sensitivity/Specificity.
Quality Control	Having internal checks such as controls or standards ensures device reliability and assurance of test results.	Endogenous positive control, process control, negative control, external controls.
Human Factors	Depending on the intended user, validation may also involve additional studies to ensure usability.	Usability testing, Training, Flex studies, Result interpretation, Workflow.
Life Cycle Management	Product life cycle phases from conception to disposal of device helps drive how the device should be made and updated. Risk analysis for safety.	Post market service/support, maintenance/repair, replacement, raw material/supply chain, disposal-waste, biohazard.
Stability	The device should be evaluated under realistic, foreseeable conditions to ensure robustness of the device and its constituents.	Temperature and humidity testing, calibration, storage/shipping conditions, reagent stability.
Cost-effectiveness	Market success of a device will depend on device cost relative to factors that can reduce adoption barrier such as health benefits, insurance coverage, and consumer expectations.	Unit cost, Manufacturing scale, Recurring (test cartridges) vs fixed costs (Instrument), Insurance reimbursement, Provider/Consumer price acceptance.
Clinical Utility	The device should be closely linked to an expected health outcome and guide treatment or public health decision, not just subsist as a stand alone measurement tool (e.g. active infection diagnosis).	Decision support (triaging), companion diagnostic (guide therapeutics), wellness maintenance, pre-symptomatic illness prediction for public health measures (epi-surveillance).

Figure 3. IVD attributes and corresponding configuration options that are commonly considered in the development process. The attributes along the critical development path (i.e. Analyte, Intended Use, etc.) relate to each other and define the development focus areas of an IVD product. The four elements under the Technical attribute outline the common, IVD operational workflow..

Figure 4. Graphical representation showing generalised natural history of infection and notional patient condition during respiratory disease course. The illustration helps visualise how current diagnostic algorithms involving Nucleic Acid Amplification Tests (NAATs) and serological IVDs are implemented. Actual levels of analyte (i.e. pathogen nucleic acids or antibodies) could vary depending on disease.

Figure 5. Holistic diagnostic approach in future IVD developments is needed to classify patients and thus focus treatments and care management on individuals susceptible to developing severe disease. This can be considered part of a future precision medicine approach to addressing infectious diseases through novel IVDs that for instance can accomplish multi-omics testing.