Drugdu.com expert's response:

For IVD reagents with different sampling methods, their registration inspection and clinical evaluation need to follow certain procedures and standards to ensure product safety and effectiveness. Below is a detailed breakdown of this process:

I. Registration Inspection

1.Selection of Representative Specifications for Inspection: According to the Measures for the Registration of In Vitro Diagnostic Reagents, if a registration application includes different packaging specifications (such as different sampling methods), one representative specification can be selected for inspection. The selected specification should cover the key performance parameters of all sampling methods, such as the limit of detection (LoD) and precision.

2. Performance Verification Items:

Key Parameter Verification: This includes accuracy, precision (repeatability/reproducibility), LoD, limit of quantitation (LoQ), linear range, matrix effect, cross-reactivity, etc.

Sampling Method Specificity Verification: Testing should be conducted separately for different sampling methods (e.g., manual/automatic, different sampling volumes) to ensure consistency in results.

Communication with Inspection Agencies: Prior communication with inspection agencies is necessary to confirm the testing scheme and clarify whether additional verification data on sampling method differences are required. A complete analytical performance research plan, including sample types, interfering substance assessments, statistical methods, etc., should be provided, with reference to international standards such as those from CLSI.

II. Clinical Evaluation

1. Choice of Evaluation Pathway:

Conditions for Exemption from Clinical Trials: If comparable products have demonstrated through comparison that different sampling methods do not affect safety and effectiveness, clinical evaluation can be completed through literature review or comparison with similar products.

Scenarios Requiring Clinical Trials: If the sampling method significantly alters detection performance (e.g., increased sensitivity or changes in applicable scenarios), clinical trials are required.

2.Key Points in Clinical Trial Design:

Comparative Trial Design: Multi-center, randomized, blinded trials should be adopted to compare different sampling methods with already marketed similar products or gold standards to verify equivalence.

Sample Size Allocation: It should cover the application scenarios of different sampling methods, with balanced sample sizes for manual sampling and automated instruments, and consideration of interfering substance samples.

Statistical Indicators: For qualitative reagents, attention should be paid to positive/negative concordance rates and Kappa values; for quantitative reagents, correlation coefficients (r) and regression equations should be analyzed to verify the consistency of results from different sampling methods.

Data Submission Requirements: Detailed analytical performance data (e.g., LoD comparisons under different sampling methods) and clinical performance data (e.g., sensitivity, specificity) should be provided.

III. Compliance with Regulations and Standards

Domestic Regulations: In accordance with the Technical Guidance Principles for Clinical Evaluation of In Vitro Diagnostic Reagents (No. 74 of 2021), the evaluation pathway should be clarified. Registration inspection should comply with standards such as GB/T 21415.

FDA Requirements: If applying for FDA 510(k), it is necessary to demonstrate substantial equivalence between different sampling methods and the predicate device, and submit analytical performance verification data (e.g., LoD, precision) and clinical performance comparison results.

Ethics and Quality Systems: Ensure that clinical trials pass ethical review and that production complies with GMP requirements.

In summary, for IVD reagents with different sampling methods, their registration inspection and clinical evaluation need to comprehensively consider product performance parameters, sampling method specificity, regulatory compliance, and clinical trial design. Through systematic performance verification and difference analysis, registration and clinical evaluation can be efficiently completed, accelerating the product launch process.