Core Role and Selection Key Points of Recombinant Proteins in the Research and Development of In Vitro Diagnostic Reagents

Positioning of Recombinant Proteins in In Vitro Diagnostics

In in vitro diagnostic reagent systems, recombinant proteins are commonly used to prepare specific antigens, detection antibodies, calibrators, and quality controls. Compared with native extracted proteins, recombinant proteins generally offer greater batch-to-batch controllability and supply stability, and can reduce inter-batch variability and biosafety risks associated with animal tissue or human-derived samples. For test items such as infectious diseases, tumor markers, and autoimmune diseases, the design of recombinant antigens should focus on whether immunoreactive epitopes are intact and whether the conformation is close to the native state, rather than merely pursuing expression yield.

Common Forms of Recombinant Antigens and Antibody Fragments

Recombinant protein forms commonly used in diagnostic reagents include full-length antigens, truncated antigens, fusion-tagged antigens, and recombinant antibody fragments. Full-length antigens are suitable for preserving a relatively complete conformation, but expression and purification may become more difficult; truncated antigens can improve solubility by removing signal peptides or hydrophobic regions; fusion tags such as histidine tags facilitate affinity purification, but the impact of the tag on immunoreactivity must be evaluated. For sandwich assays, recombinant antibodies or single-chain antibody fragments have also begun to be used to replace traditional monoclonal antibodies, with key validation needed for affinity, specificity, and thermal stability.

Key Points for Raw Material Screening and Quality Control

When screening recombinant protein raw materials, attention generally needs to be paid to indicators such as purity, activity, endotoxin level, residual host cell nucleic acid, and residual host protein. High purity does not necessarily mean ideal activity; it is also necessary to simulate the actual detection environment through platforms such as enzyme-linked immunosorbent assay, chemiluminescence, or lateral flow. Batch-to-batch consistency is a core requirement for in vitro diagnostic reagent companies. It is recommended to specify the acceptance ranges of critical quality attributes in supply agreements and to conduct functional retention sample testing on each batch of raw materials. Common specifications are usually provided in the form of lyophilized powder or solution containing protective agents, and storage and reconstitution conditions should be determined based on stability studies.

Compliance and Supply Risk Management

For recombinant protein raw materials used in in vitro diagnostic reagents, the manufacturing site and quality management system should preferably refer to the relevant regulatory requirements for medical devices or in vitro diagnostic reagents, and establish supplier audits, change notification, and traceability mechanisms. When key processes, host systems, or purification methods of raw materials change, the possible impact on the analytical performance of diagnostic products needs to be evaluated. Companies should retain complete records of procurement, inspection, and use to meet the general requirements of medical device quality system audits and post-market surveillance. Through scientific raw material selection and stable supply chain management, recombinant proteins can help diagnostic products achieve more controllable analytical performance and long-term supply consistency.