Diagnostic Reagent Biotechnology: Key Points of Quality Management System and Registration Review

I. Basic Requirements for the Quality Management System of In Vitro Diagnostic Reagents

As an important category of medical devices, in vitro diagnostic reagents require their manufacturers to establish a quality management system covering the entire product lifecycle. The quality management system generally includes institutions and personnel, premises and facilities, equipment, document management, design and development, procurement, production management, quality control, sales and after-sales service, and adverse event monitoring. The core objective of the system is to ensure that each batch of products maintains stable performance under the specified storage, transportation, and use conditions. Biotechnology-based diagnostic reagents are relatively sensitive to raw materials, environment, and process parameters; therefore, change management, supplier audits, and stability studies during production are particularly important.

In terms of personnel allocation, enterprises need to be staffed with production, testing, and quality management personnel who have the corresponding professional background and training experience. The verification and validation of critical processes and special processes should be supported by records, such as lyophilization processes, coating processes, and contamination control for nucleic acid amplification reagents. Document records should be authentic, complete, and traceable, ensuring that every step from raw material procurement to finished product release is documented. In cases of contract manufacturing or contract testing, the principal still bears responsibility for the quality of the final product and should sign a quality agreement with the contractor to clarify the responsibilities of both parties.

II. Technical Focus Points of Registration Testing and Performance Evaluation

Before applying for registration, diagnostic reagent products usually need to undergo registration testing in accordance with the product technical requirements. The product technical requirements are the basis for product performance verification and quality control, generally including indicators such as appearance, fill volume, accuracy, repeatability, inter-batch variation, linear range, minimum detection limit, and stability. The setting of performance indicators should be based on sufficient research and development data and risk analysis, and cannot be arbitrarily relaxed or tightened. Registration testing samples should be tested by qualified testing institutions in accordance with relevant standards or technical requirements, and the testing conclusions are an important reference for review and evaluation.

Biotechnology-based diagnostic reagents also need to focus on the comprehensiveness of analytical performance evaluation. For example, molecular diagnostic reagents need to evaluate cross-reactivity, interfering substances, nucleic acid extraction efficiency, amplification inhibition, etc.; immunoassay diagnostic reagents need to evaluate the hook effect, endogenous antibody interference, the effects of different anticoagulants, etc. Stability studies generally include real-time stability, transport stability, open-vial stability, freeze-thaw stability, etc., and the study conditions and duration should simulate the environments that may be encountered in actual use. All performance evaluation data should be able to support the intended use and applicable sample types claimed in the instructions for use, avoiding excessive claims.

III. Basic Logic of Clinical Evaluation and Trial Design

Clinical evaluation of in vitro diagnostic reagents is a key step in demonstrating the safety and effectiveness of a product. Depending on the product risk level and intended use, clinical evaluation may choose pathways such as clinical trials, methodological comparison with marketed products of the same type, or performance confirmation using clinical samples. For new biomarkers, new methodologies, or high-risk products, standardized clinical trials are usually required. The trial design should clearly define inclusion and exclusion criteria, sample size justification, selection of the reference method, statistical analysis plan, etc., to ensure that the results are scientific and reliable.

Common biases in clinical trials include sample selection bias, disease spectrum bias, and evaluator bias. To reduce bias, measures such as randomization, blinding, and independent evaluation may be adopted. The sample types tested should be consistent with the intended use of the product, such as serum, plasma, whole blood, throat swabs, urine, etc. For quantitative detection items, the correlation and consistency with the reference method need to be evaluated; for qualitative detection items, indicators such as sensitivity, specificity, positive predictive value, and negative predictive value need to be calculated, and confidence intervals should be reported. Clinical trial results cannot be simply publicized with absolute language such as "accuracy as high as"; the scope of the study and limitations should be objectively described.

IV. Standardized Expression of Instructions for Use and Labels

The instructions for use of diagnostic reagents are important legal documents guiding users to correctly use the product, and their content should be authentic, accurate, complete, and consistent with the content approved in registration. The instructions for use generally include product name, intended use, test principle, main components, storage conditions and shelf life, applicable instruments, sample requirements, test method, reference interval, interpretation of test results, limitations of the test method, precautions, symbols, etc. For self-testing products, easy-to-understand operation diagrams and result interpretation instructions should also be provided, and users should be reminded to consult professionals when necessary.

In publicity and promotion, absolute terms such as "" "most advanced" "" "" shall not be used, nor shall inappropriate promises be made regarding test results. The results of diagnostic reagents are affected by multiple factors such as sample quality, operating standards, environmental conditions, and individual patient differences, and the instructions for use should clearly state known interference and limitations.For example, some molecular tests may carry a risk of missing viral mutations, and some immunoassays may yield false-negative results during the window period in early infection. Clear statements of limitations not only comply with regulatory requirements but also help reduce misuse and disputes.

V. Post-Market Surveillance and Continuous Improvement

After a product is approved for marketing, the company still bears primary responsibility for quality and safety. Post-market surveillance includes adverse event monitoring, recall management, complaint handling, quality tracking, and periodic risk evaluation. Companies should establish an adverse event monitoring system, collect quality issues reported by medical institutions and users, promptly conduct cause analysis, and take corrective and preventive actions when necessary. In cases involving product defects or potential harm to human health, active recalls should be initiated and reported to regulatory authorities in accordance with regulatory requirements.

Biotechnology is developing rapidly, and diagnostic reagent products may face new scientific understanding and updated standards. Companies should continuously monitor changes in regulations, standards, and guidelines, as well as the real-world performance of marketed products. Through post-market research and data accumulation, product design can be further optimized, instructions for use improved, and quality management enhanced. Compliance is not a one-time task but a systematic project that runs through the entire product lifecycle. Only by internalizing quality management and regulatory requirements as part of daily operations can diagnostic reagent biotechnology companies ensure public health while achieving sustainable development.