China CMDE Releases New Review Documents for Oncology NGS & HLA-B*58:01 Reagents

On June 15, 2026, the Center for Medical Device Evaluation (CMDE) released two new guidance documents:

• "Technical Review Guidelines for Tumor Gene Variant Detection Reagents (Trial)" (Announcement No. 18 of 2026)
• "Registration Review Guidelines for HLA-B*58:01 Gene Detection Reagents" (Announcement No. 17 of 2026)

Together, the documents provide manufacturers with more specific direction on product design, analytical validation, clinical evaluation, and registration strategy. While the oncology technical review key points have been issued on a trial basis and may be refined over time, both documents signal CMDE's current regulatory expectations.

The core takeaway is that CMDE is creating more flexible pathways for complex molecular diagnostics, but these are accompanied by clearer boundaries around product claims, supporting evidence, and registration scope.

Oncology NGS: More Flexibility, but Stricter Boundaries

Issued on a trial basis, the oncology technical review key points outline CMDE's current review expectations for high-throughput sequencing reagents used to detect tumor-related gene variants in FFPE tissue and/or plasma samples from patients with solid tumors.

It addresses three issues that are particularly important for developers: Tier III variants, non-originator companion diagnostics, and tissue-versus-plasma registration strategy.

Tier III Variants May Stay in the Panel, but Not in Clinical Claims

CMDE allows large NGS panels to include Tier III variants to preserve the potential for future expansion. However, this flexibility comes with conditions.

Relevant companion-diagnostic and Tier II variants should first be sufficiently included, and the overall panel design must be scientifically justified. Because Tier III variants do not yet have established clinical significance, they should not appear in the intended use or in clinical reports provided to physicians or patients.

Instead, the product technical requirements should document the relevant genes, covered regions, probe or primer information, and variant types.

Tier III variants do not require clinical trials, but representative analytical-performance studies are still expected for each variant type.

Takeaway: Manufacturers can build broader panels for future use, but they must separate technically detectable content from clinically reportable content.

Originator Comparison Can Simplify CDx Clinical Evaluation

For eligible non-originator companion diagnostics, CMDE permits clinical significance to be evaluated through a consistency-comparison study with an originator companion diagnostic.

This route is available when the test product and the originator product have good consistency in the variant sites and variant types they cover.

The comparator should generally be an originator companion diagnostic already marketed in China. A clinical trial assay used during drug development is not acceptable for this comparison pathway.

A limited exception may apply to certain older oncology drugs where no qualifying originator companion diagnostic is marketed in China. In those cases, an overseas-marketed originator product may be considered.

Where the comparison shows a high level of agreement and all applicable conditions are met, further evaluation of the relationship between the test result and drug efficacy may not be required.

Takeaway: The pathway may reduce the clinical-evaluation burden, but eligibility depends on close technical alignment with the originator assay and a compliant comparator strategy.

Tissue and Plasma Assays Should Usually Be Separate Registration Units

CMDE generally recommends separate registration units for tissue-based assays and plasma ctDNA assays.

The rationale is technical: the two sample types may differ substantially in gene-variant composition, sequencing depth, nucleic-acid input, and bioinformatics workflows.

Combined registration may be possible in limited cases, such as where a plasma-detected variant has direct drug-efficacy evidence from a drug clinical trial or from bridging to a tissue clinical trial assay, and the product is technically designed to support both sample types.

Even then, manufacturers should not extend plasma claims to additional variants without supporting evidence.

Takeaway: Multi-specimen platforms should not assume that one product design or one evidence package will support both tissue and plasma claims.

HLA-B*58:01 Guidance: Elevated Analytical Standards

The HLA-B58:01 document primarily applies to fluorescence PCR reagents that qualitatively detect HLA-B58:01 in human venous whole blood to support allopurinol prescribing.

Products using other molecular methods or sample types may refer to the guidance, but some provisions may not be fully applicable.

Cross-Reactivity Must Be Evaluated Broadly

CMDE recommends both bioinformatic analysis and wet-laboratory testing.

Primer, probe, and target-region sequences should be compared with all non-HLA-B*58:01 alleles at the HLA-B locus in the IPD-IMGT/HLA database.

Wet-laboratory studies should include closely related alleles that could cause cross-reactivity, including relevant HLA-B58 alleles such as HLA-B58:12.

The assay should not cross-react with other HLA-B serotypes or with common HLA-B58 alleles other than HLA-B58:01.

Inclusivity Requires More Than a Database Check

Manufacturers should compare the selected target, primer, and probe sequences against all HLA-B*58:01 alleles in the database.

Where relevant nucleotide differences are identified, those alleles should be included in inclusivity studies.

CMDE recommends using genuine samples or extracted DNA where feasible, followed by cell lines and plasmids when necessary.

Takeaway: A general claim of allele coverage will not be enough. Manufacturers should be able to show how sequence diversity was assessed and how potentially affected alleles were tested.

Clinical Study Design Is More Clearly Defined

For sample-size estimation, CMDE recommends a single-group target-value method based on positive and negative agreement.

The clinical acceptance standards used in the calculation should generally be no lower than 95%.

Clinical trials should use original venous whole-blood specimens from the intended patient population. Extracted genomic DNA should not be used directly as the clinical-study specimen.

Takeaway: Existing studies based primarily on banked DNA may not align with the guidance’s preferred clinical design.

Intended Use Remains Narrow

The product is intended to support prescribing decisions for patients planning to receive allopurinol for gout, hyperuricemia, or similar indicated conditions, with the aim of reducing the risk of severe cutaneous adverse reactions.

The result is intended as clinical reference information and should be interpreted together with the patient’s condition, treatment response, and other laboratory findings.

Strategic Recommendations for Overseas Manufacturers

Together, the two guidance documents provide greater clarity for developers of molecular diagnostic products while setting more explicit technical expectations.

For NGS Developers

Review:

• Whether Tier III variants are appropriately justified and controlled
• Whether analytical validation covers each relevant variant type
• Whether tissue and plasma claims belong in separate registration units
• Whether a non-originator CDx qualifies for the originator-comparison pathway

For HLA-B*58:01 Developers

Assess whether the existing evidence package adequately covers:

• Cross-reactivity with closely related HLA-B alleles
• Inclusivity across relevant HLA-B*58:01 variants
• Whole-blood specimen requirements
• Nucleic-acid extraction performance
• The recommended clinical study design and acceptance thresholds

Partnering with an experienced regulatory partner early in the process allows for a comprehensive gap assessment. Identifying potential hurdles before dossier preparation is the most effective way to minimize the risk of costly delays during the technical review.

Final Thoughts

The two CMDE documents create clearer pathways for molecular diagnostic registration in China, but they also draw firmer boundaries around what manufacturers may claim, report, and combine within a registration unit.

For oncology NGS products, the biggest opportunities are broader panel design and a potentially simplified pathway for eligible non-originator companion diagnostics.

For HLA-B*58:01 reagents, the key challenge is a more detailed and traceable demonstration of specificity, inclusivity, and clinical performance.

Identifying these technical hurdles early is critical to avoiding registration delays, yet the interpretation of trial guidance often requires localized regulatory expertise. With more than two decades of on-the-ground experience, Cisema supports manufacturers throughout the product lifecycle — from interpreting evolving CMDE requirements and developing effective registration strategies to preparing submission dossiers and managing post-registration regulatory activities in China.

If your company is developing oncology NGS assays or HLA-B*58:01 genetic testing reagents for China, contact Cisema to evaluate how these new CMDE guidelines affect your registration strategy.

Further Information

• Explore Cisema’s services for IVD registration in China.

References

• Announcement from the Organ Review Center of the National Medical Products Administration on the Release of the "Key Points for Technical Review of Tumor Gene Mutation Detection Reagents (Trial)" and Its Interpretation (2026 No. 18) 
• Announcement from the Instrumental Review Center of the National Medical Products Administration on Issuing the "Guidelines for Registration Review of HLA-B*58:01 Genetic Testing Reagents" (2026 No. 17)