Attachment 1 TRL-BWI PT Barrier.docx

Technology Readiness levels

TRL 1 Decision Criterion: Scientific literature reviews and initial market surveys are initiated and assessed. Potential scientific application to defined problems is articulated.

Lowest level of technological readiness. Maintenance of scientific awareness and generation of scientific and bioengineering knowledge base. Scientific findings are reviewed and assessed as a foundation for characterizing new technologies.

TRL 1 Decision Criterion: Scientific literature reviews and initial market surveys are initiated and assessed. Potential scientific application to defined problems is articulated.

TRL 2 Decision Criterion: Hypothesis(es) is generated. Research plans and/or protocols are developed, peer reviewed, and approved.

Intense intellectual focus on the problem, with generation of scientific “paper studies” that review and generate research ideas, hypotheses, and experimental designs for addressing the related scientific issues.

TRL 2 Decision Criterion: Hypothesis(es) is generated. Research plans and/or protocols are developed, peer reviewed, and approved.

TRL 3 Decision Criterion: Initial proof-of concept for candidate drug constructs is demonstrated in a limited number of in vitro and in vivo research models.

Basic research, data collection, and analysis begin in order to test hypothesis, explore alternative concepts, and identify and evaluate component technologies. Initial tests of design concept and evaluation of candidate(s). Study endpoints defined. Animal models (if any) are proposed. Design verification, critical component specifications, and tests (if a system component or necessary for device test and evaluation (T&E)).

TRL 3 Decision Criterion: Initial proof-of concept for device candidates is demonstrated in a limited number of laboratory models (may include animal studies).

TRL 4 Decision Criterion: Proof-of-concept and safety of candidate drug formulation(s) are demonstrated in defined laboratory/animal model(s).

Non-GLP laboratory research to refine hypothesis and identify relevant parametric data required for technological assessment in a rigorous (worst case) experimental design. Exploratory study of candidate device(s)/systems (e.g., initial specification of device, system, and subsystems). Candidate devices/systems are evaluated in laboratory and/or animal models to identify and assess potential safety problems, adverse events, and side effects. Procedures and methods to be used during non-clinical and clinical studies in evaluating candidate devices/systems are identified. The design history file, design review, and, when required, a Device Master Record (DMR), are initiated to support either a 510(k)4 or Premarket Approval (PMA).

TRL 4 Decision Criterion: Proof-of-concept and safety of candidate devices/systems are demonstrated in defined laboratory/animal models.

TRL 5 Decision Criterion: A decision point is reached at which it is determined that sufficient data on the candidate drug exists in the draft technical data package to justify proceeding with preparation of an Investigational New Drug (IND) application.

Further development of selected candidate(s). Devices compared to existing modalities and indications for use and equivalency demonstrated in model systems. Examples include devices tested through simulation, in tissue or organ models, or animal models if required. All component suppliers/vendors are identified and qualified; vendors for critical components are audited for cGMP/Quality System Regulation (QSR) compliance. Component tests, component drawings, design history file, design review, and any DME are verified. Product Development Plan is drafted. Pre-Investigational Device Exemption (IDE) meeting is held with Center for Devices and Radiological Health (CDRH) for proposed Class III devices, and the IDE is prepared and submitted to CDRH. For a 510(k), determine substantially equivalent devices and their classification, validate functioning model, ensure initial testing is complete, and validate data and readiness for cGMP inspection.

TRL 5 Decision Criterion: IDE review by CDRH results to determine if the investigation can begin. For a 510(k), preliminary findings suggest the device will be substantially equivalent to a predicate device.

TRL 6 Decision Criterion: Data from Phase 1 trials meet clinical safety requirements and support proceeding to Phase 2 clinical studies.

Clinical trials are conducted to demonstrate safety of candidate Class III medical device in a small number of humans under carefully controlled and intensely monitored clinical conditions. Component tests, component drawings, design history file, design review, and any DMR are updated and verified. Production technology demonstrated through production-scale cGMP plant qualification.

For 510(k), component tests, component drawings, design history file, design review, and any DMR are updated and verified. Manufacturing facility is ready for cGMP inspection.

TRL 6 Decision Criterion: Data from the initial clinical investigation demonstrate that the Class III device meets safety requirements and support proceeding to clinical safety and effectiveness trials.

For a 510(k), information and data demonstrate substantial equivalency to predicate device and support production of the final prototype and final testing in a military operational environment.

TRL 7 Decision Criterion: Phase 3 clinical study plan or surrogate test plan has been approved.

Clinical safety and effectiveness trials are conducted with a fully integrated Class III medical device prototype in an operational environment. Continuation of closely controlled studies of effectiveness and determination of short-term adverse events and risks associated with the candidate product. Functional testing of candidate devices is completed and confirmed, resulting in final down-selection of prototype device. Clinical safety and effectiveness trials are completed. Final product design is validated, and final prototype and/or initial commercial scale device is produced. Data are collected, presented, and discussed with CDRH in support of continued device development.

For a 510(k), final prototype and/or initial commercial- scale device are produced and tested in a military operational environment.

TRL 7 Decision Criterion: Clinical endpoints and test plans are agreed to by CDRH.

For a 510(k), information and data demonstrate substantial equivalency to predicate device and use in a military operational environment and support preparation of 510(k).

TRL 8 Decision Criterion: Approval of the NDA for drug by CDER.

Implementation of clinical trials to gather information relative to the safety and effectiveness of the device. Trials are conducted to evaluate the overall risk-benefit of using the device and to provide an adequate basis for product labeling. Confirmation of QSR compliance, the design history file, design review, and any DMR are completed and validated, and device production is followed through lot consistency and/or reproducibility studies. Pre-PMA meeting held with CDRH. PMA prepared and submitted to CDRH. Facility PAI (cGMP/QSR/Quality System Inspection Technique (QSIT)) is completed.

For 510(k), prepare and submit application.

TRL 8 Decision Criterion: Approval of the PMA (or, as applicable, 510(k)) for device by CDRH.

TRL 9 Decision Criterion: None. Continue surveillance.

The medical device can be distributed/marketed. Post-marketing studies (non-clinical or clinical) may be required and are designed after agreement with the FDA. Post-marketing surveillance.

TRL 9 Decision Criterion: None. Continue surveillance.