| Phase 1: research and development |
| Typically consists of upstream research and development to define and validate a prototype, followed by laboratory validation under international standards that culminate in a design-locked product |
| WHO interacts with developers if requested to discuss end-user requirements such as biosafety, assay robustness and intended setting of use |
| Phase 2: evaluation and demonstration |
| The performance of the new diagnostic product should be evaluated in controlled trials at three to five trial sites in high-burden TB and HIV countries, ideally using pre-specified and-user product specifications. These data are often used for product registration with global and/or regulatory authorities such as FDA and/or CE marking. |
| Product specifications and performance should subsequently be validated in uncontrolled trials under field conditions in five to 10 trial sites in high-burden TB and HIV countries, and include cost-effectiveness studies. |
| Phase 3: WHO evidence assessment using GRADE |
| For new technologies or new indications for use of technologies already approved by WHO |
| Submission of dossier with phase 1 and 2 data to WHO |
| Structured evidence assessment process (described in figure 3) |
| For fast-follower or generic versions of technologies already approved by WHO |
| Manufacture of the technology under ISO 13:485 standards; equivalent performance demonstrated in two to three independent supranational TB reference laboratories, to the reference technology already approved by WHO |
| Structured evidence assessment process (described in figure 3) |
| WHO is not a regulatory authority and does not recommend technologies for individual country use |
| Phase 4: phased uptake and collection of evidence for scale-up |
| New diagnostic successfully implemented in routine diagnostic services by early implementers in high-burden TB and HIV countries; systemic assessment of proposed algorithms, laboratory workload, operational constraints, country by cost-effectiveness. Lessons learnt by early implementers used for country adaptation. |
| Phase 5: scale-up and policy refinement |
| Scale-up of the new diagnostic, with subsequent data used to inform and refine WHO policy guidance in a dynamic and ongoing process |
FDA: Food and Drug Administration; CE: Communauté Européenne (European Community); GRADE: Grades of Recommendations Assessment, Development and Evaluation; ISO: International Organization for Standardization.