— Natural pathogen · Dual calibration · Flexible configuration · Full-spectrum coverage · Batch-to-batch stability —

A new standard, an “upgrade of the benchmark” for the industry.

On March 9, 2026, the National Medical Products Administration officially released YY/T 2001-2026, “In Vitro Diagnostic Testing Systems—Qualitative Test Reagents—Requirements for the Establishment of Enterprise Reference Materials,” which will take effect on March 1, 2027. This is the first domestic industry standard specifically addressing the establishment of enterprise reference materials for qualitative test reagents, marking a transition from ad hoc, self‑initiated practices to a unified, standardized framework.

Although YY/T standards are voluntary, in the registration and review of IVD products, they are generally regarded as an important reference for technical evaluation. When a product fails to meet the standard requirements, the reviewing authority may require the applicant to provide justification or submit additional validation data. Therefore, a pragmatic approach is to treat these standards as de facto technical minimums.

This standard applies to Positive reference material, negative reference material, limit-of-detection reference material, precision reference material The design specifies clear technical requirements for each case. For enterprises, understanding the standard requirements is one thing; finding a reference material supplier that can directly meet those requirements is quite another.

Ningpu Quality Control has developed a reference material solution centered on “natural raw materials + dual certification + flexible configuration + full‑range coverage + stable supply,” in alignment with the requirements of all chapters of YY/T 2001‑2026. Below, we will break this down step by step across five key dimensions.

Ningpu Quality Control: A Quick Overview of Five Key Competencies

① Complete natural pathogen (non-plasmid/non‑pseudovirus) → Meets the criteria of Chapter 4: “Consistent with real clinical samples”

② Dual quantification using digital PCR and TCID50, with traceability → in compliance with Chapter 4, “Validation of the Gold-Standard Method”

③ Freely dilute the high-concentration stock solution as needed → Complies with Chapters 5, 7, and 8 on “Multiple Concentration Levels/Series Dilutions.”

④ Coverage of over 1,000 bacterial strains and more than 200 viral types → Complies with Chapters 5, 7, and 8’s requirements for “full coverage of serotypes” and “independent quantification by serotype.”

⑤ Batch validation of the head IVD with the clinical testing center demonstrates that inter-batch variability is controllable → Meets the requirement of Clause 4.1: “Uniformity and stability are satisfactory.”

I. Authenticity of the Raw Material: A complete, natural pathogen—not a plasmid, not a pseudovirus.

Chapter 4 of the standard—General Requirements: The matrix and nucleic acid type of enterprise reference materials should, where feasible, be consistent with those of the intended real clinical samples.

Ningpu Protocol: All pathogens are used in their fully intact, naturally cultivated form.

• Bacteria/fungi, etc.: standard strains + standardized cultivation + inactivation process, preserving the microorganisms’ intact structure.

• Virus: Live virus cultivation followed by physical/chemical inactivation, preserving intact viral particles and native conformational epitopes.

It is neither a plasmid, nor a pseudovirus, nor a recombinant protein. The native pathogen ensures that the matrix of the Ningpu reference material is naturally equivalent to that of real clinical samples.

II. Assay Accuracy: Dual quantification using digital PCR and TCID50, with traceability to the gold standard.

Chapter 4 of the standard: Genotypes, genotypic subtypes, serotypes, concentrations/titers, and other parameters shall be validated using diagnostic accuracy reference methods (i.e., “gold standard” methods) or other appropriate methods.

In the course of actual review, the credibility of the reference material’s concentration value is a frequent concern that triggers supplementary requests. If the reference material is labeled with only a single concentration—without any description of the assignment method or a traceability pathway—the reviewing experts will very likely require additional information, and may even return the submission for resubmission.

Ningpu Scheme: Certified Value of the Gold-Standard Combined Process

• Digital PCR (dPCR): Absolute quantification in copies/mL

• TCID50 (Tissue Culture Infectious Dose 50): A measure of biological potency, traceable to internationally standardized protocols for cell culture systems.

Dual‑coordinate assignment enables a single reference material to simultaneously meet the assignment requirements for both molecular diagnostics (copy number) and immunological diagnostics (infectious titer). The concentration calibration of weakly positive reference materials is critical—whether the signal is truly weak or falsely so directly determines the validity of the limit of detection verification.

III. Flexible Compatibility: One vial of stock solution can be diluted to produce all concentration gradients.

The standard repeatedly emphasizes “multiple concentration levels” in the positive reference material (Chapter 5), the limit of detection reference material (Chapter 7), and the precision reference material (Chapter 8):

• Positive reference materials should include multiple concentration levels and, at a minimum, contain weakly positive samples.

• The limit of detection reference material should be prepared as samples with different concentrations or a series of serial dilutions.

• The precision reference material shall contain at least two distinct concentration levels, including a concentration near the limit of detection.

If a separate batch of finished reference material were procured for each concentration, not only would costs be high, but matrix differences between batches could also render the validation data incomparable. Ideally, a single batch of high‑concentration stock solution should be diluted as needed to generate multiple gradient levels—ensuring a consistent matrix, controllable concentrations, and comparable results.

Ningpu Solution: High-concentration stock solution—just one vial is enough to dilute into…

→ Concentrations near the limit of detection (LoD) (used for LoD verification in Chapter 7)

→ Weakly positive / Moderately positive / Strongly positive (used for the positive reference materials in Chapter 5)

→ Three levels—high, medium, and low (for the precision reference material in Chapter 8)

4. Strain Diversity: Over 1,000 bacterial strains and more than 200 viral strains—leaving no claimed strain unaccounted for.

The standard’s requirements for type overriding are addressed throughout multiple sections:

• Genotyping assay reagents: Positive reference materials shall cover all genotypes/subtypes/serotypes claimed to be detectable (Chapter 5a).

• Universal diagnostic reagents: shall include at least the major serotypes and clinically common serotypes (Chapter 5b)

• Limit of detection reference material: When the limits of detection vary across different genotypes or subtypes, separate settings shall be established for each (Chapter 7c).

• Precision reference materials: Common genotypes/subtypes/serotypes should be included (Chapter 8a).

A typical issue in practical applications is that the reagent claims to detect more than a dozen genotypes, yet the reference panel covers only two or three. An even more subtle problem is that the limit of detection may vary across different genotypes; using the LOD data for a single genotype to represent all genotypes is logically untenable.

Ningpu Solution: Comprehensive Coverage of the Microbial (Pathogen) Strain Resource Library

• Bacterial strains: over 1,000, covering common and rare pathogens across multiple systems, including the respiratory, gastrointestinal, urogenital, and bloodstream infection pathways.

• Viral strains: over 200, covering respiratory viruses, enteric viruses, arboviruses, hepatitis viruses, herpesviruses, and more.

Regardless of the pathogens and serotypes that a reagent claims to detect, Ningpu can provide corresponding reference materials for each serotype independently, thereby meeting multiple regulatory requirements: “full coverage” for typing reagents, “major plus common serotypes” for universal reagents, and “independent quantification by serotype” for limit-of-detection assays.

5. Stability and Reliability: Verified by head‑level IVD assays and the Clinical Testing Center, with inter‑batch variability kept under control.

Clause 4.1 of the standard: The homogeneity and stability of enterprise reference materials shall meet the requirements for evaluating the measurement procedure.

Ningpu Solution: Rigorously validated by multiple parties, it stands up to market scrutiny.

• The choice of numerous leading IVD companies

• Real-world clinical scenario testing conducted at multiple on-site testing centers

Based on long-term monitoring data, the inter-batch coefficient of variation (CV) is controllable. The product demonstrates clear stability under various storage conditions, including 2–8°C, –20°C, and –80°C.

New standard requirements × Ningpu’s corresponding capabilities

Allow ample lead time: from now until March 2027.

The new standard will be officially implemented in less than eight months. For new product registration and registration amendments, now is the optimal window to reassess reference material preparation in light of the new standard. The key lies in three matters:

1. Conduct a clause-by-clause review of existing product reference materials against the relevant standards, and prepare a gap analysis report.

2. Evaluate and supplement any missing reference material types (e.g., weakly positive, type-specific detection limits, etc.).

3. If an alternative is used, complete the equivalence verification and prepare a verification report to support the registration application.

Ningpu Quality Control can provide corresponding products and technical support at every stage.

YY/T 2001‑2026 has standardized the establishment of enterprise reference materials, with clearer requirements, a more systematic framework, and more rigorous validation. For IVD companies, this represents an opportunity to upgrade their reference material systems; for Ningpu Quality Control, our response to this standard is “natural raw materials + dual-value assignment + flexible configuration + comprehensive coverage + stable supply.”

Business Inquiries: Please contact the Ningpu Quality Control Team to obtain a customized enterprise reference material solution compliant with YY/T 2001–2026.