Some Federal agencies have defined their own set of TRLs to better meet their specific mission requirements. Agency-specific TRLs have been defined for the Biomedical Advanced Research & Development Authority (BARDA), Department of Defense (DoD), Department of Energy (DoE), National Aeronautics and Space Administration (NASA), and National Institutes of Health (NIH).

Biomedical Advanced Research and Development Authority (BARDA)

Diagnostics and Medical Devices TRLs

TRL 1
Review of Scientific Knowledge

Active monitoring of scientific knowledge base to identify clinical pathological markers for diagnostic countermeasure candidates. Scientific findings are reviewed and assessed as a foundation for characterizing approaches to intervene in disease. Basic research needs identified.

TRL 2
Concept Generation and Development of Experimental Designs

Develop research plans to answer specific questions and experimental designs for addressing the related scientific issues and to establish feasibility. Focus on practical applications based on basic principles.

TRL 3
Characterization of Preliminary Candidate(s) and Feasibility Demonstration

Begin R&D, data collection, and analysis in order to verify feasibility. Explore alternative concepts, identify and evaluate critical technologies and components, and begin characterizing specifications required. Demonstrate the performance of candidate diagnostic targets and high risk components. Develop a business case for the proposed product.

TRL 4
Optimization and Preparation for Assay, Component, and Instrument Development

Prepare for test system development. Finalize diagnostic target(s) and methods for detecting or quantitating target(s). Develop detailed plans and finalize critical design requirements. Execute commercial agreements with key external development partners. Identify manufacturing resources, vendor sourcing, and experimental designs.

TRL 5
Product Development – Reagents, Components, Subsystems and Modules

Develop reagents and buffers. Build and test non-GLP prototypes of components and subsystems. Code and unit test software. Begin pilot scale manufacturing preparations. Develop protocols for assay and integration testing. Initiate reagent stability testing. Hold pre-IDE meeting with FDA. Initiate Design History file.

TRL 6
System Integration & Testing

Integrate and test alpha and beta instruments/devices, software and assays, evaluating performance and updating specifications. Implement design improvements to address defects discovered during testing. Produce and evaluate pilot lots of reagents and beta (pilot) instruments. Increase the maturity of software. Prepare for clinical testing. Complete short term stability testing of reagents.

TRL 7
Analytical Verification and Preparation for Clinical Studies

Evaluate assay and integrated diagnostic system performance utilizing contrived, retrospective human and animal samples. Make preparations for clinical evaluation. Begin preparation for full scale production of instruments and assays.

TRL 8
Clinical Studies and/or Evaluation with Animal Studies, FDA Clearance or Approval, Finalize GMP Manufacturing Preparations

Complete clinical evaluations. Prepare and submit FDA filing.

End of TRL8: Acquire FDA approval, or clearance.

Department of Defense (DoD)

Acquisition Guidebook TRLs

TRL 1
Basic Principles Observed and Reported

Lowest level of technology readiness. Scientific research begins to be translated into applied research and development. Examples might include paper studies of a technology’s basic properties.

TRL 2
Technology Concept and/or Application Formulated

Invention begins. Once basic principles are observed, practical applications can be invented. Applications are speculative and there may be no proof or detailed analysis to support the assumptions. Examples are limited to analytic studies.

TRL 3
Analytical and Experimental Critical Function and/or Characteristic Proof of Concept

Active research and development is initiated. This includes analytical studies and laboratory studies to physically validate analytical predictions of separate elements of the technology. Examples include components that are not yet integrated or representative.

TRL 4
Component and/or Breadboard Validation in Laboratory Environment

Basic technological components are integrated to establish that they will work together. This is relatively “low fidelity” compared to the eventual system. Examples include integration of “ad hoc” hardware in the laboratory.

TRL 5
Component and/or Breadboard Validation in Relevant Environment

Fidelity of breadboard technology increases significantly. The basic technological components are integrated with reasonably realistic supporting elements so it can be tested in a simulated environment. Examples include “high fidelity” laboratory integration of components.

TRL 6
System/Subsystem Model or Prototype Demonstration in a Relevant Environment

Representative model or prototype system, which is well beyond that of TRL 5, is tested in a relevant environment. Represents a major step up in a technology’s demonstrated readiness. Examples include testing a prototype in a high-fidelity laboratory environment or in simulated operational environment.

TRL 7
System Prototype Demonstration in an Operational Environment

Prototype near, or at, planned operational system. Represents a major step up from TRL 6, requiring demonstration of an actual system prototype in an operational environment such as an aircraft, vehicle, or space. Examples include testing the prototype in a test bed aircraft.

TRL 8
Actual System Completed and Qualified Through Test and Demonstration

Technology has been proven to work in its final form and under expected conditions. In almost all cases, this TRL represents the end of true system development. Examples include developmental test and evaluation of the system in its intended weapon system to determine if it meets design specifications.

TRL 9
Actual System Proven Through Successful Mission Operations

Actual application of the technology in its final form and under mission conditions, such as those encountered in operational test and evaluation. Examples include using the system under operational mission conditions.

Medical TRLs

TRL 1
Review of Scientific Knowledge Base

Active monitoring of scientific knowledge base. Scientific findings are reviewed and assessed as a foundation for characterizing new technologies.

TRL 1
Review of Scientific Knowledge Base

Active monitoring of scientific knowledge base. Scientific findings are reviewed and assessed as a foundation for characterizing new technologies.

TRL 2
Development of Hypotheses and Experimental Designs

Scientific “paper studies” to generate research ideas, hypothesis, and experimental designs for addressing the related scientific issues. Focus on practical applications based on basic principles observed. Use of computer simulation or other virtual platforms to test hypotheses.

TRL 3
Target/Candidate Identification and Characterization of Preliminary Candidate(s)

Begin research, data collection, and analysis in order to test hypothesis. Explore alternative concepts, identify and evaluate critical technologies and components, and begin characterization of candidate(s). Preliminary efficacy demonstrated in vivo.

3a. Identify target and/or candidate.

3b. Demonstrate in vitro activity of candidate(s) to counteract the effects of the threat agent.

3c. Generate preliminary in vivo proof-of-concept efficacy data (non-GLP).

TRL 4
Candidate Optimization and Non-GLP In Vivo Demonstration of Activity and Efficacy

Integration of critical technologies for candidate development. Initiation of animal model development. Initiation of animal model development. Non-GLP in vivo toxicity and efficacy demonstration in accordance with the product’s intended use. Initiation of experiments to identify markers, correlates of protection, assays, and endpoints for further non-clinical and clinical studies.

Animal Models: Initiate development of appropriate and relevant animal model(s) for the desired indications.

Assays: Initiate development of appropriate and relevant assays and associated reagents for the desired indications.

Manufacturing: Manufacture laboratory-scale (i.e., non-GMP) quantities of bulk product and proposed formulated product.

4a. Demonstrate non-GLP in vivo activity and potential for efficacy consistent with the product’s intended use (i.e., dose, schedule, duration, route of administration, and route of threat agent challenge).

4b. Conduct initial non-GLP toxicity studies and determine pharmacodynamics and pharmacokinetics and/or immune response in appropriate animal models (as applicable).

4c. Initiate experiments to determine assays, parameters, surrogate markers, correlates of protection, and endpoints to be used during non-clinical and clinical studies to further evaluate and characterize candidate(s).

TRL 5
Advanced Characterization of Candidate and Initiation of GMP Process Development

Continue non-GLP in vivo studies, and animal model and assay development. Establish draft Target Product Profiles. Develop a scalable and reproducible manufacturing process amenable to GMP.

Animal Models: Continue development of animal models for efficacy and dose-ranging studies.

Assays: Initiate development of in-process assays and analytical methods for product characterization and release, including assessments of potency, purity, identity, strength, sterility, and quality as appropriate.

Manufacturing: Initiate process development for small-scale manufacturing amenable to GMP.

Target Product Profile: Draft preliminary Target Product Profile. Questions of shelf life, storage conditions, and packaging should be considered to ensure that anticipated use of the product is consistent with the intended use for which approval will be sought from FDA.

5a. Demonstrate acceptable Absorption, Distribution, Metabolism and Elimination characteristics and/or immune responses in non-GLP animal studies as necessary for IND filing.

5b. Continue establishing correlates of protection and/or surrogate markers for efficacy for use in future GLP studies in animal models. Identify minimally effective dose to facilitate determination of “humanized” dose once clinical data are obtained.

TRL 6
GMP Pilot Lot Production, IND Submission, and Phase 1 Clinical Trial(s)

Manufacture GMP pilot lots. Prepare and submit Investigational New Drug (IND) package to FDA and conduct Phase 1 clinical trial(s) to determine the safety and pharmacokinetics of the clinical test article.

Animal Models: Continue animal model development via toxicology, pharmacology, and immunogenicity studies.

Assays: Qualify assays for manufacturing quality control and immunogenicity, if applicable.

Manufacturing: Manufacture, release and conduct stability testing of GMP bulk and formulated product in support of the IND and clinical trial(s).

Target Product Profile: Update Target Product Profile as appropriate.

6a. Conduct GLP animal studies for toxicology, pharmacology, and immunogenicity as appropriate.

6b. Prepare and submit full IND package to FDA to support initial clinical trial(s).

6c. Complete Phase 1 clinical trial(s) that establish an initial safety and pharmacokinetics assessment.

TRL 7
Scale-Up, Initiation of GMP Process Validation, and Phase 2 Clinical Trial(s)

Scale-up and initiate validation of GMP manufacturing process. Conduct animal efficacy studies as appropriate. Conduct Phase 2 clinical trial(s).

Animal Models: Refine animal model development in preparation for pivotal GLP animal efficacy studies.

Assays: Validate assays for manufacturing quality control and immunogenicity if applicable.

Manufacturing: Scale-up and validate GMP manufacturing process at a scale compatible with USG requirements. Begin stability studies of the GMP product in a formulation, dosage form, and container consistent with Target Product Profile. Initiate manufacturing process validation and consistency lot production.

Target Product Profile: Update Target Product Profile as appropriate.

7a. Conduct GLP animal efficacy studies as appropriate for the product at this stage.

7b. Complete expanded clinical safety trials as appropriate for the product (e.g., Phase 2).

TRL 8
Completion of GMP Validation and Consistency Lot Manufacturing, Pivotal Animal Efficacy Studies or Clinical Trials, and FDA Approval or Licensure

Finalize GMP manufacturing process. Complete pivotal animal efficacy studies or clinical trials (e.g., Phase 3), and/or expanded clinical safety trials as appropriate. Prepare and submit NDA/BLA.

Manufacturing: Complete validation and manufacturing of consistency lots at a scale compatible with USG requirements. Complete stability studies in support of label expiry dating.

Target Product Profile: Finalize Target Product Profile in preparation for FDA approval.

8a. Complete final pivotal GLP animal efficacy studies or pivotal clinical trials (e.g., Phase 3), and any additional expanded clinical safety trials as appropriate for the product.

8b. Prepare and submit New Drug Application (NDA) or Biologics Licensing Application (BLA) to the FDA.

8c. Obtain FDA approval or licensure.

TRL 9
Post-Licensure and Post-Approval Activities

9a. Commence post-licensure/post-approval and Phase 4 study commitments, such as safety surveillance, data to support use in special populations, and clinical trials to confirm safety and efficacy as feasible and appropriate.

9b. Maintain manufacturing capability as appropriate.

Software TRLs

TRL 1
Basic Principles Observed and Reported

Lowest level of software technology readiness. A new domain is being investigated by the basic research community. This level extends to the development of basic use, basic properties of software architecture, mathematical formulations, and general algorithms.

TRL 2
Technology Concept and/or Application Formulated

Once basic principles are observed, practical applications can be invented. Applications are speculative, and there may be no proof or detailed analysis to support the assumptions. Examples are limited to analytic studies using synthetic data.

TRL 3
Analytical and Experimental Critical Function and/or Characteristic Proof of Concept

Active R&D is initiated. The level at which scientific feasibility is demonstrated through analytical and laboratory studies. This level extends to the development of limited functionality environments to validate critical properties and analytical predictions using non-integrated software components and partially representative data.

TRL 4
Module and/or Subsystem Validation in a Laboratory Environment (i.e., Software Prototype Development Environment)

Basic software components are integrated to establish that they will work together. They are relatively primitive with regard to efficiency and robustness compared with the eventual system. Architecture development initiated to include interoperability, reliability, maintainability, extensibility, scalability, and security issues. Emulation with current/legacy element as appropriate. Prototypes developed to demonstrate different aspects of eventual system.

TRL 5
Module and/or Subsystem Validation in a Relevant Environment

Level at which software technology is ready to start integration with existing systems. The prototype implementations conform to target environment/interfaces. Experiments with realistic problems. Simulated interfaces to existing systems. System software architecture established. Algorithms run on a processor(s) with characteristics expected in the operational environment.

TRL 6
Module and/or Subsystem Validation in a Relevant End-to-End Environment

Level at which the engineering feasibility of a software technology is demonstrated. This level extends to laboratory prototype implementations on full-scale realistic problems in which the software technology is partially integrated with existing hardware/software systems.

TRL 7
System Prototype Demonstration in an Operational, High-Fidelity Environment

Level at which the program feasibility of a software technology is demonstrated. This level extends to operational environment prototype implementations, where critical technical risk functionality is available for demonstration and a test in which the software technology is well integrated with operational hardware/software systems.

TRL 8
Actual System Completed and Mission Qualified Through Test and Demonstration in an Operational Environment

Level at which a software technology is fully integrated with operational hardware and software systems. Software development documentation is complete. All functionality tested in simulated and operational scenarios.

TRL 9
Actual System Proven Through Successful Mission-Proven Operational Capabilities

Level at which a software technology is readily repeatable and reusable. The software based on the technology is fully integrated with operational hardware/software systems. All software documentation verified. Successful operational experience. Sustaining software engineering support in place. Actual system.

Department of Energy (DoE)

TRL 1
Basic Principles Observed and Reported

This is the lowest level of technology readiness. Scientific research begins to be translated into applied R&D. Examples might include paper studies of a technology’s basic properties or experimental work that consists mainly of observations of the physical world. Supporting Information includes published research or other references that identify the principles that underlie the technology.

TRL 2
Technology Concept and/or Applications Formulated

Once basic principles are observed, practical applications can be invented. Applications are speculative, and there may be no proof or detailed analysis to support the assumptions. Examples are still limited to analytic studies. Supporting information includes publications or other references that outline the application being considered and that provide analysis to support the concept. The step up from TRL 1 to TRL 2 moves the ideas from pure to applied research. Most of the work is analytical or paper studies with the emphasis on understanding the science better. Experimental work is designed to corroborate the basic scientific observations made during TRL 1 work.

TRL 3
Analytical and Experimental Critical Function and/or Characteristic Proof of Concept

Active research and development is initiated. This includes analytical studies and laboratory-scale studies to physically validate the analytical predictions of separate elements of the technology. Examples include components that are not yet integrated or representative tested with simulants. Supporting information includes results of laboratory tests performed to measure parameters of interest and comparison to analytical predictions for critical subsystems. At TRL 3 the work has moved beyond the paper phase to experimental work that verifies that the concept works as expected on simulants. Components of the technology are validated, but there is no attempt to integrate the components into a complete system. Modeling and simulation may be used to complement physical experiments.

TRL 4
Component and/or System Validation in Laboratory Environment

The basic technological components are integrated to establish that the pieces will work together. This is relatively “low fidelity” compared with the eventual system. Examples include integration of ad hoc hardware in a laboratory and testing with a range of simulants and small scale tests on actual waste. Supporting information includes the results of the integrated experiments and estimates of how the experimental components and experimental test results differ from the expected system performance goals. TRL 4-6 represent the bridge from scientific research to engineering. TRL 4 is the first step in determining whether the individual components will work together as a system. The laboratory system will probably be a mix of on hand equipment and a few special purpose components that may require special handling, calibration, or alignment to get them to function.

TRL 5
Laboratory Scale, Similar System Validation in Relevant Environment

The basic technological components are integrated so that the system configuration is similar to (matches) the final application in almost all respects. Examples include testing a high-fidelity, laboratory scale system in a simulated environment with a range of simulants and actual waste. Supporting information includes results from the laboratory scale testing, analysis of the differences between the laboratory and eventual operating system/environment, and analysis of what the experimental results mean for the eventual operating system/environment. The major difference between TRL 4 and 5 is the increase in the fidelity of the system and environment to the actual application. The system tested is almost prototypical.

TRL 6
Engineering/Pilot-Scale, Similar (Prototypical) System Validation in Relevant Environment

Engineering-scale models or prototypes are tested in a relevant environment. This represents a major step up in a technology’s demonstrated readiness. Examples include testing an engineering scale prototypical system with a range of simulants. Supporting information includes results from the engineering scale testing and analysis of the differences between the engineering scale, prototypical system/environment, and analysis of what the experimental results mean for the eventual operating system/environment. TRL 6 begins true engineering development of the technology as an operational system. The major difference between TRL 5 and 6 is the step up from laboratory scale to engineering scale and the determination of scaling factors that will enable design of the operating system. The prototype should be capable of performing all the functions that will be required of the operational system. The operating environment for the testing should closely represent the actual operating environment.

TRL 7
Full-Scale, Similar (Prototypical) System Demonstrated in Relevant Environment

This represents a major step up from TRL 6, requiring demonstration of an actual system prototype in a relevant environment. Examples include testing full-scale prototype in the field with a range of simulants in cold commissioning. Supporting information includes results from the full-scale testing and analysis of the differences between the test environment, and analysis of what the experimental results mean for the eventual operating system/environment. Final design is virtually complete.

TRL 8
Actual System Completed and Qualified Through Test and Demonstration

The technology has been proven to work in its final form and under expected conditions. In almost all cases, this TRL represents the end of true system development. Examples include developmental testing and evaluation of the system with actual waste in hot commissioning. Supporting information includes operational procedures that are virtually complete. An Operational Readiness Review (ORR) has been successfully completed prior to the start of hot testing.

TRL 9
Actual System Operated Over the Full Range of Expected Conditions

The technology is in its final form and operated under the full range of operating mission conditions. Examples include using the actual system with the full range of wastes in hot operations.

National Aeronautics and Space Administration (NASA)

Hardware TRLs

TRL 1
Basic Principles Observed and Reported

Scientific knowledge generated underpinning hardware technology concepts/applications.

TRL 2
Technology Concept and/or Application Formulated

Invention begins, practical application is identified but is speculative, no experimental proof or detailed analysis is available to support the conjecture.

TRL 3
Analytical and Experimental Critical Function and/or Characteristic Proof of Concept

Analytical studies place the technology in an appropriate context and laboratory demonstrations, modeling and simulation validate analytical prediction.

TRL 4
Component and/or Breadboard Validation in Laboratory Environment

A low fidelity system/component breadboard is built and operated to demonstrate basic functionality and critical test environments, and associated performance predictions are defined relative to the final operating environment.

TRL 5
Component and/or Breadboard Validation in Relevant Environment

A medium fidelity system/component brassboard is built and operated to demonstrate overall performance in a simulated operational environment with realistic support elements that demonstrates overall performance in critical areas. Performance predictions are made for subsequent development phases.

TRL 6
System/Sub-System Model or Prototype Demonstration in an Operational Environment

A high fidelity system/component prototype that adequately addresses all critical scaling issues is built and operated in a relevant environment to demonstrate operations under critical environmental conditions.

TRL 7
System Prototype Demonstration in an Operational Environment

A high fidelity engineering unit that adequately addresses all critical scaling issues is built and operated in a relevant environment to demonstrate performance in the actual operational environment and platform (ground, airborne, or space).

TRL 8
Actual System Completed and “Flight Qualified” Through Test and Demonstration

The final product in its final configuration is successfully demonstrated through test and analysis for its intended operational environment and platform (ground, airborne, or space).

TRL 9
Actual System Flight Proven Through Successful Mission Operations

The final product is successfully operated in an actual mission.

Software TRLs

TRL 1
Basic Principles Observed and Reported

Scientific knowledge generated underpinning basic properties of software architecture and mathematical formulation.

TRL 2
Technology Concept and/or Application Formulated

Practical application is identified but is speculative, no experimental proof or detailed analysis is available to support the conjecture. Basic properties of algorithms, representations and concepts defined. Basic principles coded. Experiments performed with synthetic data.

TRL 3
Analytical and Experimental Critical Function and/or Characteristic Proof of Concept

Development of limited functionality to validate critical properties and predictions using non-integrated software components.

TRL 4
Component and/or Breadboard Validation in Laboratory Environment

Key, functionally critical, software components are integrated, and functionally validated, to establish interoperability and begin architecture development. Relevant environments defined and performance in this environment predicted.

TRL 5
Component and/or Breadboard Validation in Relevant Environment

End-to-end software elements implemented and interfaced with existing systems/simulations conforming to target environment. End-to-end software system, tested in relevant environment, meeting predicted performance. Operational environment performance predicted. Prototype implementations developed.

TRL 6
System/Sub-System Model or Prototype Demonstration in an Operational Environment

Prototype implementations of the software demonstrated on full-scale realistic problems. Partially integrate with existing hardware/software systems. Limited documentation available. Engineering feasibility fully demonstrated.

TRL 7
System Prototype Demonstration in an Operational Environment

Prototype software exists having all key functionality available for demonstration and test. Well integrated with operational hardware/software systems demonstrating operational feasibility. Most software bugs removed. Limited documentation available.

TRL 8
Actual System Completed and “Flight Qualified” Through Test and Demonstration

All software has been thoroughly debugged and fully integrated with all operational hardware and software systems. All user documentation, training documentation, and maintenance documentation completed. All functionality successfully demonstrated in simulated operational scenarios. Verification and Validation (V&V) completed.

TRL 9
Actual System Flight Proven Through Successful Mission Operations

All software has been thoroughly debugged and fully integrated with all operational hardware/software systems. All documentation has been completed. Sustaining software engineering support is in place. System has been successfully operated in the operational environment.

NIH Centers for Accelerated Innovations (NCAI)

Therapeutics

TRL 1
Review of Scientific Knowledge Base

Scientific findings are reviewed and assessed as a foundation for characterizing new technologies.

TRL 2
Development of Hypotheses and Experimental Designs

Activities: Scientific studies to identify and validate disease target. Screen potential compounds (HTS, antibody, etc.) to develop preliminary hits. Develop assays to test activities of candidate compounds in vitro. Initial intellectual property search for patentability.

Milestone: Identify compound series.

TRL 3
Identification and Characterization of Preliminary Product

Activities: Decision on which compounds to advance in development. Synthesize novel series of compounds; test efficacy and toxicities in vitro. Test PK/tox of selected compounds in relevant in vivo models on a non-GLP level. Survey relevant patent literature to identify white space and assess patentability of compound series. File a provisional patent on the pharmacophore. Synthesize and assess several potential lead compounds.

Milestones: Demonstrate in vitro efficacy. Preliminary efficacy demonstrated in vivo in appropriate small animal model. Identify lead series. File patent.

TRL 4
Optimization and Demonstration of Activity and Efficacy

Activities: Initiate experiments to identify markers, assays, and endpoints for further non-clinical and clinical studies. Conduct in vivo distribution and elimination studies. Non-GLP in vivo toxicity and efficacy of lead compound; pharmacokinetic studies.

Milestones: Finalize formulation appropriate for route of administration. Draft Product Profile. Determine Regulatory strategy. Identified preclinical candidate compound and animal models for GLP tox studies.

TRL 5
Advanced Characterization of Product and Initiation of Manufacturing

Activities: Develop a scalable and reproducible manufacturing process amenable to GMP. Develop assays/analytical methods for product characterization and release (potency, purity, ID, sterility, etc.). Perform IND-enabling toxicology studies. Identify KOL’s that can help design a clinical trial. Identify clinical sites and begin contract negotiations. Begin stability testing on drug substance (i.e., API).

Milestones: Identify candidate. Demonstrate acceptable ADME characteristics and/or immune responses in GLP animal studies as necessary for regulatory filing. Identify manufacturing partners. Pre-IND meeting with FDA.

TRL 6
Regulated Production, Regulatory Submission, and Clinical Data

Activities: Prepare and submit IND. Initiate Phase 1 study.

Milestones: Manufacture GMP-compliant pilot lots. Prepare and submit regulatory package to FDA and conduct Phase 0 and/or 1 clinical trial(s) to determine the safety and pharmacokinetics of the clinical test article.

TRL 7
Scale-Up, Initiation of GMP Process Validation, and Phase 2 Clinical Trial(s)

Activities: Post Phase 2 meeting with FDA. Determine dosing and treatment population for Phase 3 study.

Milestones: Scale-up and validate GMP manufacturing process at a scale compatible with USG requirements. Complete stability studies of the GMP drug product in a formulation, dosage form, and container consistent with Target Product Profile. Complete Phase 2 clinical trials.

TRL 8
Completion of GMP Validation and Consistency Lot Manufacturing, Clinical Trials Phase 3, and FDA Approval or Licensure

Milestones: Finalize GMP manufacturing process. Complete clinical efficacy trials (e.g., Phase 3), and/or expanded clinical safety trials as appropriate. Prepare and submit New Drug Application or Biologics Licensing Application NDA/BLA.

Devices (Diagnostic and Therapeutic)

TRL 1
Review of Scientific Knowledge Base

Scientific findings are reviewed and assessed as a foundation for characterizing new technologies.

TRL 2
Development of Hypotheses and Experimental Designs

Activities: Scientific “paper studies” to generate research ideas, hypotheses, and experimental designs for addressing the related scientific issues. Use of computer simulation or other virtual platforms to test hypotheses where possible. Initial intellectual property search for patentability and to refine prototype configuration options.

TRL 3
Identification and Characterization of Preliminary Product

Activities: Explore prototypes, identify and evaluate critical technologies, critical design features needed, and components. Initiate user feedback on prototypes.

Milestones: Demonstrate in vitro efficacy. Preliminary efficacy and safety demonstrated ex vivo or in vivo. Identification of reimbursement and regulatory classification (pathway identification). File a provisional patent.

TRL 4
Optimization and Demonstration of Activity and Efficacy

Activities: Collection of user feedback on prototypes utilized to refine design inputs and identify new ones as needed. Iteration and elimination of prototype designs based user feedback, bench testing, ex vivo and non-GLP in vivo testing. Integration of critical technologies. Initiation of animal model development for desired indication (if necessary). Initiation of experiments to identify endpoints for further non-clinical and clinical studies.

Milestones: Initiate Design Control activities, establish Design and Development Plan, capture Design Inputs. Determine IFU, Regulatory & clinical strategy. Preliminary FDA meeting. Non-GLP in vivo efficacy demonstration in accordance with the product’s intended use.

TRL 5
Advanced Characterization of Product and Initiation of Manufacturing

Activities: Develop test methods for device characterization, performance testing, and product release if relevant. Explore potential manufacturing options as well as manufacturability and sustainability of device design, including third-party partners. Develop a scalable and reproducible manufacturing process amenable to GMP.

Milestones: Demonstrate intended device design addresses. Design inputs to support regulatory filing (Design freeze). Preliminary FDA meeting (depending on device type and classification). Reimbursement strategy.

TRL 6
Regulated Production, Regulatory Submission, and Clinical Data

Activities: Initiate manufacturing using scalable and reproducible process. Integrate Quality. Complete testing, bench, in vitro and in vivo GLP study, if necessary, intended to verify and validate the product design (per Design Controls) to support Regulatory submission at design freeze. Initiate Shelf Life/Product Stability studies. Finalize packaging of the device and sterilization validation.

Milestones: Manufacture GMP-compliant devices. Complete Design Verification and Validation testing. Prepare and submit regulatory package to FDA (510k, IDE, as needed).

TRL 7
Scale-Up, Initiation of GMP Process Validation, and Phase 2 Clinical Trial(s)

Activities: Validate manufacturing processes at scale intended to support production. Implement CAPA and other Quality requirements. Support activities needed to complete clinical trials (for de novo or PMA pathway, if needed).

Milestones: Design Transfer activities such as scale-up and validate GMP manufacturing process. Complete clinical trials (as needed for IDE or EFS). Regulatory submission of results.

TRL 8
Completion of GMP Validation and Consistency Lot Manufacturing, Clinical Trials Phase 3, and FDA Approval or Licensure

Milestones: Complete Design Transfer into finalized GMP manufacturing process. Prepare and submit for market approval: Premarket Approval (PMA), Premarket Notification (510(k)), HUD or Humanitarian Device Exemption (HDE). Prepare postmarket clinical strategy/surveillance plan.

Diagnostics (Assay/Test)

TRL 1
Review of Scientific Knowledge Base

Active monitoring of scientific knowledge base. Identify links between disease in humans and animals.

TRL 2
Development of Hypotheses and Experimental Designs

Activities: Scientific “paper studies” to generate research ideas, hypotheses, and experimental designs for addressing the related scientific issues. Initial intellectual property search for patentability.

TRL 3
Identification and Characterization of Preliminary Product

Activities: Explore assay components via prototypes and screening; identify and evaluate critical technologies and components, and begin characterization of lead design. Initiate user feedback.

Milestones: Demonstrate preliminary assay with simplified sample/artificial matrices. Demonstrate sensitivity and specificity with spike/recovery studies in the appropriate matrices.

TRL 4
Optimization and Demonstration of Activity and Efficacy

Activities: Integration of critical technologies and components (including hardware and software). Select appropriate candidate reference and QC (quality control) reagents.

Milestones: Assay/test method validation in accordance with the product’s intended use (sample type, volume, assay components). Establish Draft Product Profile. Determine Regulatory and reimbursement strategy.

TRL 5
Advanced Characterization of Product and Initiation of Manufacturing

Activities: Design freeze. Develop a scalable and reproducible manufacturing process aligned with regulatory guidelines (as needed). Finalize QC criteria.

Milestones: Identify supply chain and/or manufacturing partners. Demonstrate acceptable performance as necessary for regulatory filing. Preliminary FDA meeting.

TRL 6
Regulated Production, Regulatory Submission, and Clinical Data

Milestones: Manufacture product compliant with quality protocols. Based on regulatory classification (e.g., CLIA vs IVD route), submit regulatory package.

TRL 7
Scale-Up, Initiation of GMP Process Validation, and Phase 2 Clinical Trial(s)

Milestones: Assays used to assess product quality are validated. Assays used to assess critical outcomes in clinical trials and in animal efficacy studies are validated.

Sources
  1. U.S. Government Accountability Office (GAO) (August 2016). Technology Readiness Assessment Guide: Best Practices for Evaluating the Readiness of Technology for Use in Acquisition Programs and Projects. GAO-16-410G. Available at: https://www.gao.gov/products/GAO-16-410G.
  2. NIH Centers for Accelerated Innovations (NCAI) (May 2016). Technology Readiness Guidelines [Excel file]. Available at: https://ncai.nhlbi.nih.gov/ncai/resources/techreadylevels.