NMPA CMDE Releases Two IVD Registration Review Guidelines (2026 Revisions)

On October 13, 2026, the NMPA CMDE issued two in vitro diagnostic reagent registration review guidelines: the Guideline for Registration Review of Human Epidermal Growth Factor Receptor 2 Gene Amplification Detection Reagents (Fluorescence In Situ Hybridization) (2026 Revision) and the Guideline for Registration Review of Hepatitis C Virus Genotyping Detection Reagents (2026 Revision), under Announcement No. 28 of 2026. The revision aims to strengthen regulatory guidance for IVD product registration and technical review, providing updated references for applicants and technical review departments. The full announcement and attachments are available on the CMDE website.

For the HER2 guideline, the revision applies to reagents using fluorescence in situ hybridization to detect HER2 gene amplification in tissue sections from surgical resection and/or biopsy samples. It covers both single-signal detection of average HER2 gene copy number and dual-signal detection of the ratio between average HER2 gene copy number and average CEP17 sequence copy number, with a primary focus on breast cancer and gastric cancer. Such products are managed as Class III IVD reagents with classification code 6840. The revised guideline further emphasizes that analytical performance studies should cover tissue sections from all intended cancer types, sensitivity evaluation should use representative samples such as breast invasive carcinoma or gastric cancer and adjacent normal tissues to assess hybridization efficiency, and positive cut-off value studies should refer to the latest clinical guidelines and include borderline samples with HER2/CEP17 ratios around 2 or average HER2 copy numbers around 4 to 6. For clinical evaluation, at least three registered medical device clinical trial institutions are required, and the original companion diagnostic reagent of the claimed anti-tumor drug should be prioritized as the comparator to ensure good consistency in test results related to therapy guidance.

For the HCV guideline, the revision applies to hepatitis C virus genotyping detection reagents based on real-time fluorescent PCR methods, intended for in vitro qualitative detection of different HCV genotypes in human serum, plasma, and other samples. Combined with clinical manifestations and other laboratory indicators, the test can serve as one of the auxiliary indicators for clinical diagnosis and treatment of HCV-infected individuals. In China, HCV genotypes 1b and 2a are relatively common, followed by genotypes 2 and 3; genotypes 4 and 5 are very rare, genotype 6 is relatively uncommon, and a small number of mixed-genotype patients exist. The revised guideline requires systematic studies on sample stability, accuracy, precision, limit of detection, mixed genotypes, cross-reactivity, microbial interference, competitive interference, interfering substances, nucleic acid extraction and purification performance, and reaction systems. Clinical trials should select no fewer than three registered clinical trial institutions. For common genotypes or subtypes, no fewer than 120 cases each are recommended; for rare types or subtypes, no fewer than 30 cases each are recommended; when genotypes 3a and 3b are not distinguished, the total number of cases is recommended to be no fewer than 70; for genotypes 4 and 5, scientifically validated serum panels may be considered. The instructions should also clearly state that the product is only for clinical sample testing from HCV nucleic acid-positive patients, is not suitable for quantitative detection, and should note the limitations of mixed-genotype detection.

In terms of industry impact, these two guideline revisions reflect the NMPA’s continuous refinement of quality requirements across the IVD lifecycle. HER2 FISH reagent companies need to pay closer attention to tumor heterogeneity handling, borderline sample validation, and the completeness of companion diagnostic evidence, while HCV genotyping reagent companies need to strengthen capabilities for mixed infections, competitive interference, and coverage of different genotypes. Companies are advised to review their existing registration documentation against the new requirements as early as possible to improve submission efficiency.