Appendix 3 - Technology Readiness Level (TRL) for Hardware/Systems (HW/S) and Pharmaceutical, Medical Devices, Lab Capabilities & Human Countermeasures (PMLH)* TRL 1. Basic principles of technology observed and reported HW/S • Scientific research begins to be translated into applied R&D activity • Examples include paper studies of a technology's basic properties PMLH • Maintenance of scientific awareness, and generation of scientific and technological knowledge base • Scientific findings reviewed and assessed as a foundation for characterising new technologies 2. Technology concept and/or application formulated • Invention of practical applications begins • Applications are speculative; may not have proof or detailed analysis to support the assumptions • Examples are limited to analytic studies • Intense intellectual focus on the problem, with generation of scientific "paper studies" that review and generate research ideas, hypotheses and experimental designs • Develop new/improved concept/platform/method for approaching problem • Hypothesis formed, preliminary studies to define parameters. Demonstrate feasibility 3. Analytical and laboratory studies to validate analytical predictions • Active R&D activity initiated • 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 • Proof of concept • Research, data collection and analysis begin in order to test hypothesis, explore alternative concepts, and identify and evaluate critical technologies and components • Initial proof-of-concept demonstrated in a limited number of in vitro and in vivo research models; device candidates may be demonstrated in laboratory models including animal studies • Validated hypothesis. Understanding of scientific processes underlying problem 4. Component and/or basic sub-system technology validation in laboratory environment • Basic technological components integrated to establish that they will work together • Relatively "low fidelity" compared to the eventual system • Examples include integration of ad hoc hardware in the laboratory • Non-GLP (Good Laboratory Practice) lab to refine hypothesis and identify relevant parametric data required for technological assessment in a worst case experimental design • Proof of concept demonstrated in defined laboratory/animal models • Safety and toxicity problems, adverse effects and side effects identified and assessed • Proof of concept for method/platform for analysing specific targets to understand potential and limitations 5. Component and/or basic sub-system technology validation in relevant environment • Basic technological components integrated with reasonably realistic supporting elements for testing in a simulated environment • Examples include "high fidelity" laboratory integration of components Pharmaceutical • Intense period of non-clinical and pre-clinical research studies involving parametric data collection and analysis in well-defined systems, with pilot lots of candidate pharmaceutical produced and further development of selected candidates • Determined that sufficient data on the candidate pharmaceutical exist in the draft technical data package to justify proceeding with preparing Investigational New Drug (IND) application Medical Devices • Further development of selected candidates • Devices compared to existing modalities and indications for use and equivalency demonstrated in model systems • Product Development Plan drafted • Investigational Device Exemption (IDE) prepared and submitted Lab Capabilities • Test critical analytical components and protocols for performance, sensitivity and specificity with simulated specimens Human Countermeasures • Lab testing of potential countermeasure in subjects; initial demonstration of feasibility and efficacy 6. System/ subsystem model or prototype demonstration in a relevant environment • Representative model or prototype system is tested in a relevant environment • Examples include testing a prototype in a high-fidelity laboratory environment or in a simulated operational environment • Phase I clinical trials conducted to demonstrate safety of candidates in small number of subjects under carefully controlled and intensely monitored clinical conditions • For pharmaceutical, IND application is prepared and submitted • For lab capabilities, retrospective study on real (clinical or operational) samples in lab; interpretation and correlation of results for accuracy, validity with results aggregately reported • For human countermeasures, lab/clinical testing of potential countermeasure in subjects to demonstrate efficacy of concept * Taken from Ministry of Defence Singapore: http://www.mindef.gov.sg/imindef/mindef_websites/atozlistings/drtech/trl/trl_descriptors.html