| BioMRL1:Basic manufacturing implications identified | Prior to physical research and development efforts, a study of manufacturing capacity is performed. Criteria include identification and investigation of global trends in the industrial base, manufacturing science, material availability, supply chain, and metrology. | 
| BioMRL2:Manufacturing concepts identified | Key manufacturing concepts have been identified, including broad-based studies that address analysis of material and process approaches, material effects and availability, potential supply chains, needed workforce skillsets, potential future investments, etc. Manufacturing scale and quality requirements for potential markets are identified and analyzed. An understanding of manufacturing feasibility and risk is emerging. | 
| BioMRL3:Manufacturing subsystems or components | Components of the biomanufacturing process have been proven in a laboratory environment. This includes genetic engineering efforts needed to create strains capable of producing the desired products in titers that support the transition to pilot-scale production (typically in excess of 1 g/L). Methods for the purification and analysis of the product of interest are also required but can rely on lab-scale equipment that is not suitable for larger-scale DSP. | 
| BioMRL4: Independent validation and verification of proof-of-concept | The proof-of-concept system has been demonstrated in a strain suitable for commercial-scale manufacturing and has been independently reproduced/validated/verified. Additionally, an initial assessment of the manufacturability is complete, including preliminary techno-economic analysis (TEA) and life-cycle analysis (LCA). This assessment should include plans for the scale-up production (SUP) and downstream processing (DSP) needed to produce sufficient quantities to allow testing and evaluation by downstream stakeholders. These plans incorporate production-relevant environments. Product quality risks and mitigation plans are documented. | 
| BioMRL5: Demonstration of prototype unit operations in a production relevant environment | Identification of enabling/critical unit operations is complete. Prototype materials, tooling, and test equipment, as well as personnel skills, have been demonstrated empirically for unit operations in a production-relevant environment. Scale-up production and downstream processing have been performed at suitable scales to deliver sufficient quantities of end-product to downstream stakeholders for testing and evaluation. The TEA has been further refined to assess projected manufacturing costs. A risk management plan to mitigate technical and economic risks is integrated with the manufacturing strategy. | 
| BioMRL6: Demonstration of a prototype system or subsystem in a production relevant environment | Manufacturing processes have been selected for the end-to-end manufacturing pipeline, even if engineering and/or design variables still need to be optimized. Prototype manufacturing processes and technologies, materials, tooling, and test equipment, as well as personnel skills, have been demonstrated on systems and/or subsystems in a production-relevant environment. The TEA is refined based on system performance and is expanded to include inventory control, production scheduling, plant maintenance, and production quality attributes (PQAs). Long-lead and key supply chain elements have been identified, and supply chain risk mitigation strategies exist. | 
| BioMRL7: Demonstration of systems or subsystems in a production representative environment | Detailed system design is complete. Manufacturing processes and procedures have been demonstrated in a production representative environment. Sufficient quantities of product have been made to test packaging and distribution systems. Unit cost reduction strategies, such as statistical process controls (SPCs), are underway in a production representative environment. Quality assurance of supply chains is in place, and procurement schedules for long-lead elements are established. The manufacturing process is sufficient to support low-level commercial manufacturing. | 
| BioMRL8:Manufacturing line demonstrated, ready for low-rate initial production (LRIP) | This maturity level is associated with manufacturing readiness for entry into LRIP. The detailed system design is complete and sufficiently stable to enter LRIP. All materials, manpower, tooling, test equipment, and facilities are proven on the manufacturing line and are available to meet the planned low-rate production schedule. STE/SIE has been validated in accordance with plans. Manufacturing and quality processes and procedures have been proven and are ready for LRIP. Known technical and business risks pose no significant challenges for LRIP. The cost model and yield and rate analyses have been updated with manufacturing line results. Supplier qualification testing and first article inspections have been completed. The industrial base has been assessed and shows that industrial capability is established to support LRIP. | 
| BioMRL9:Low rate production demonstrated; Capability in place to begin full rate production (FRP) | Manufacturing has successfully achieved LRIP and is ready to enter FRP. All systems engineering/design requirements have been met such that there are minimal system changes. Major system design features are stable and have been proven in operational tests and evaluations. Materials, parts, manpower, tooling, test equipment, and facilities are available to meet planned rate production schedules. STE/SIE validation is maintained and re-validated as necessary. Manufacturing process capability is at an appropriate quality level to meet customer tolerances. LRIP cost targets have been met. The cost model has been updated for FRP and reflects the impact of continuous improvement. | 
| BioMRL10:FRP demonstrated and lean production practices in place | Engineering/design changes are few and generally limited to continuous improvement changes or obsolescence issues. System, components, and items are in FRP and meet all engineering, performance, quality, and reliability requirements. Manufacturing process capability is at the appropriate quality level. All materials, tooling, inspection and test equipment, facilities, and manpower are in place and have met FRP requirements. Process infrastructure and analytical equipment validation are maintained and re-validated as necessary. Rate production unit costs meet goals, and funding is sufficient for production at the required rates. Continuous process improvements based on risks identified during FRP are ongoing. |