Interpretation of the national standard: <i>In Vitro Diagnostic Medical Devices-Requirements for Establishing Metrological Traceability of Values Assigned to Calibrators, Trueness Control Materials and Human Samples</i>_West China Medical Journal

Authors：

CUI Zinuo ¹ , KANG Juan ² , ZOU Yingshu ² , CHEN Wenxiang ¹ , ZHANG Chuanbao ¹ , MA Jie ¹ ,  ZHOU Weiyan ¹

1. National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Clinical Laboratory Engineering Technology Research Center, Beijing 100730, P. R. China;
2. Beijing Institute for Medical Device Testing (Beijing Research Center for Medical Biological Protection Equipment Testing), Beijing 101100, P. R. China;

Corresponding?author：

ZHOU Weiyan, Email: wyzhou@nccl.org.cn

Keywords：

In vitro diagnosis; metrological traceability; trueness control material; standardization; national standard

DOI：

10.7507/1002-0179.202607088

Video：

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GB/T 21415－2025 is identical to ISO 17511: 2020 and replaces GB/T 21415－2008. It extends metrological traceability requirements from calibrators and control materials to values assigned to human samples, and introduces enhanced elements such as maximum allowable expanded measurement uncertainty, validation of metrological traceability, commutability assessment, and international harmonization protocols. This article systematically reviews the scope, general requirements, and the six calibration hierarchy structures of the standard. It focuses on key implementation aspects including the definition of the measurand, selection of reference systems, uncertainty budget allocation, and commutability. In addition, it clarifies the responsibilities and requirements for in vitro diagnostic medical device manufacturers, reference material producers, reference measurement laboratories, and medical laboratories, aiming to help relevant institutions establish applicable and verifiable value-transfer chains and to promote accuracy, comparability and mutual recognition of test results.

Citation： CUI Zinuo, KANG Juan, ZOU Yingshu, CHEN Wenxiang, ZHANG Chuanbao, MA Jie, ZHOU Weiyan. Interpretation of the national standard: In Vitro Diagnostic Medical Devices-Requirements for Establishing Metrological Traceability of Values Assigned to Calibrators, Trueness Control Materials and Human Samples. West China Medical Journal, 2026, 41(8): 1235-1241. doi: 10.7507/1002-0179.202607088 Copy

1.	White GH. Metrological traceability in clinical biochemistry[J]. Ann Clin Biochem, 2011, 48(5): 393-409.
2.	Armbruster D. Metrological traceability of assays and comparability of patient test results[J]. Clin Lab Med, 2017, 37(1): 119-135.
3.	Panteghini M. Traceability as a unique tool to improve standardization in laboratory medicine[J]. Clin Biochem, 2009, 42(4/5): 236-240.
4.	GB/T 21415-2008 體外診斷醫療器械生物樣品中量的測量校準品和控制物質賦值的計量學溯源性[S].
5.	GB/T 21415-2025 體外診斷醫療器械建立校準品、正確度控制物質和人體樣品賦值的計量溯源性要求[S].
6.	ISO 17511: 2020 In vitro diagnostic medical devices - requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples[S].
7.	van Schrojenstein Lantman M, van Berkel M, Kuijper P, et al. Clinical decision-making suffers from inequivalent measurement results and inadequate reference intervals[J]. Clin Chem, 2024, 70(11): 1383-1392.
8.	Kavsak PA, Lam CSP, Saenger AK, et al. Educational recommendations on selected analytical and clinical aspects of natriuretic peptides with a focus on heart failure: a report from the IFCC Committee on Clinical Applications of Cardiac Bio-Markers[J]. Clin Chem, 2019, 65(10): 1221-1227.
9.	WS/T 403-2024 臨床化學檢驗常用項目分析質量標準[S].
10.	GB/T 19703-2020 體外診斷醫療器械生物源性樣品中量的測量有證參考物質及支持文件內容的要求[S].
11.	JJF 2155-2024 檢驗醫學標準物質互換性評估要求[S].
12.	CLSI EP09c-2018 Measurement procedure comparison and bias estimation using patient samples[S].
13.	CLSI EP14-2022 Evaluation of commutability of processed samples[S].
14.	CLSI EP30-2024 Characterization and qualification of commutable reference materials for laboratory medicine[S].
15.	WS/T 356-2024 參考物質互換性評估指南[S].
16.	Budd JR, Weykamp C, Rej R, et al. IFCC Working Group recommendations for assessing commutability part 3: using the calibration effectiveness of a reference material[J]. Clin Chem, 2018, 64(3): 465-474.
17.	Miller WG, Schimmel H, Rej R, et al. IFCC Working Group recommendations for assessing commutability part 1: general experimental design[J]. Clin Chem, 2018, 64(3): 447-454.
18.	Nilsson G, Budd JR, Greenberg N, et al. IFCC Working Group recommendations for assessing commutability part 2: using the difference in bias between a reference material and clinical samples[J]. Clin Chem, 2018, 64(3): 455-464.
19.	Miller WG, Greenberg N, Panteghini M, et al. Guidance on which calibrators in a metrologically traceable calibration hierarchy must be commutable with clinical samples[J]. Clin Chem, 2023, 69(3): 228-238.
20.	Miller WG, Budd J, Greenberg N, et al. IFCC Working Group recommendations for correction of bias caused by noncommutability of a certified reference material used in the calibration hierarchy of an end-user measurement procedure[J]. Clin Chem, 2020, 66(6): 769-778.
21.	Braga F, Pasqualetti S, Frusciante E, et al. Harmonization status of serum ferritin measurements and implications for use as marker of iron-related disorders[J]. Clin Chem, 2022, 68(9): 1202-1210.
22.	Ribeiro de Oliveira Longo Schweizer J, Ribeiro-Oliveira A Jr, Bidlingmaier M. Growth hormone: isoforms, clinical aspects and assays interference[J]. Clin Diabetes Endocrinol, 2018, 4: 18.
23.	Panteghini M, Camara JE, Delatour V, et al. Feasibility of metrological traceability implementation using the Joint Committee on Traceability in Laboratory Medicine database entries including the fulfillment of “fit-for-purpose” maximum allowable measurement uncertainty[J]. Clin Chem, 2024, 70(11): 1321-1333.
24.	Panteghini M. Traceability, reference systems and result comparability[J]. Clin Biochem Rev, 2007, 28(3): 97-104.
25.	Bunk DM. Reference materials and reference measurement procedures: an overview from a national metrology institute[J]. Clin Biochem Rev, 2007, 28(4): 131-137.
26.	Schumann G, Bonora R, Ceriotti F, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 5. Reference procedure for the measurement of catalytic concentration of aspartate aminotransferase[J]. Clin Chem Lab Med, 2002, 40(7): 725-733.
27.	Jeppsson JO, Kobold U, Barr J, et al. Approved IFCC reference method for the measurement of HbA1c in human blood[J]. Clin Chem Lab Med, 2002, 40(1): 78-89.
28.	Hoelzel W, Weykamp C, Jeppsson JO, et al. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study[J]. Clin Chem, 2004, 50(1): 166-174.
29.	Schulster D, Gaines Das RE, Jeffcoate SL. International standards for human prolactin: calibration by international collaborative study[J]. J Endocrinol, 1989, 121(1): 157-166.
30.	Sturgeon CM, Berger P, Bidart JM, et al. Differences in recognition of the 1st WHO international reference reagents for hCG-related isoforms by diagnostic immunoassays for human chorionic gonadotropin[J]. Clin Chem, 2009, 55(8): 1484-1491.
31.	Zhang R, Xu Z, Zhao R, et al. Accurate method for value assignment of carcinoembryonic antigen reference materials[J]. J Clin Lab Anal, 2023, 37(11/12): e24936.
32.	GB/T 44672-2024 體外診斷醫療器械建立校準品和人體樣品賦值計量溯源性的國際一致化方案的要求[S].
33.	孫運苗, 鄒迎曙, 張傳寶, 等. GB/T 44672-2024/ISO 21151: 2020《體外診斷醫療器械建立校準品和人體樣品賦值計量溯源性的國際一致化方案的要求》國家標準解讀[J]. 中華臨床實驗室管理電子雜志, 2026, 14(1): 29-35.
34.	Myers GL, Miller WG. The roadmap for harmonization: status of the international consortium for harmonization of clinical laboratory results[J]. Clin Chem Lab Med, 2018, 56(10): 1667-1672.
35.	Thienpont LM, Van Uytfanghe K, De Grande LAC, et al. Harmonization of serum thyroid-stimulating hormone measurements paves the way for the adoption of a more uniform reference interval[J]. Clin Chem, 2017, 63(7): 1248-1260.
36.	ISO 21151: 2020 In vitro diagnostic medical devices-requirements for international harmonisation protocols establishing metrological traceability of values assigned to calibrators and human samples[S].

1. White GH. Metrological traceability in clinical biochemistry[J]. Ann Clin Biochem, 2011, 48(5): 393-409.
2. Armbruster D. Metrological traceability of assays and comparability of patient test results[J]. Clin Lab Med, 2017, 37(1): 119-135.
3. Panteghini M. Traceability as a unique tool to improve standardization in laboratory medicine[J]. Clin Biochem, 2009, 42(4/5): 236-240.
4. GB/T 21415-2008 體外診斷醫療器械生物樣品中量的測量校準品和控制物質賦值的計量學溯源性[S].
5. GB/T 21415-2025 體外診斷醫療器械建立校準品、正確度控制物質和人體樣品賦值的計量溯源性要求[S].
6. ISO 17511: 2020 In vitro diagnostic medical devices - requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples[S].
7. van Schrojenstein Lantman M, van Berkel M, Kuijper P, et al. Clinical decision-making suffers from inequivalent measurement results and inadequate reference intervals[J]. Clin Chem, 2024, 70(11): 1383-1392.
8. Kavsak PA, Lam CSP, Saenger AK, et al. Educational recommendations on selected analytical and clinical aspects of natriuretic peptides with a focus on heart failure: a report from the IFCC Committee on Clinical Applications of Cardiac Bio-Markers[J]. Clin Chem, 2019, 65(10): 1221-1227.
9. WS/T 403-2024 臨床化學檢驗常用項目分析質量標準[S].
10. GB/T 19703-2020 體外診斷醫療器械生物源性樣品中量的測量有證參考物質及支持文件內容的要求[S].
11. JJF 2155-2024 檢驗醫學標準物質互換性評估要求[S].
12. CLSI EP09c-2018 Measurement procedure comparison and bias estimation using patient samples[S].
13. CLSI EP14-2022 Evaluation of commutability of processed samples[S].
14. CLSI EP30-2024 Characterization and qualification of commutable reference materials for laboratory medicine[S].
15. WS/T 356-2024 參考物質互換性評估指南[S].
16. Budd JR, Weykamp C, Rej R, et al. IFCC Working Group recommendations for assessing commutability part 3: using the calibration effectiveness of a reference material[J]. Clin Chem, 2018, 64(3): 465-474.
17. Miller WG, Schimmel H, Rej R, et al. IFCC Working Group recommendations for assessing commutability part 1: general experimental design[J]. Clin Chem, 2018, 64(3): 447-454.
18. Nilsson G, Budd JR, Greenberg N, et al. IFCC Working Group recommendations for assessing commutability part 2: using the difference in bias between a reference material and clinical samples[J]. Clin Chem, 2018, 64(3): 455-464.
19. Miller WG, Greenberg N, Panteghini M, et al. Guidance on which calibrators in a metrologically traceable calibration hierarchy must be commutable with clinical samples[J]. Clin Chem, 2023, 69(3): 228-238.
20. Miller WG, Budd J, Greenberg N, et al. IFCC Working Group recommendations for correction of bias caused by noncommutability of a certified reference material used in the calibration hierarchy of an end-user measurement procedure[J]. Clin Chem, 2020, 66(6): 769-778.
21. Braga F, Pasqualetti S, Frusciante E, et al. Harmonization status of serum ferritin measurements and implications for use as marker of iron-related disorders[J]. Clin Chem, 2022, 68(9): 1202-1210.
22. Ribeiro de Oliveira Longo Schweizer J, Ribeiro-Oliveira A Jr, Bidlingmaier M. Growth hormone: isoforms, clinical aspects and assays interference[J]. Clin Diabetes Endocrinol, 2018, 4: 18.
23. Panteghini M, Camara JE, Delatour V, et al. Feasibility of metrological traceability implementation using the Joint Committee on Traceability in Laboratory Medicine database entries including the fulfillment of “fit-for-purpose” maximum allowable measurement uncertainty[J]. Clin Chem, 2024, 70(11): 1321-1333.
24. Panteghini M. Traceability, reference systems and result comparability[J]. Clin Biochem Rev, 2007, 28(3): 97-104.
25. Bunk DM. Reference materials and reference measurement procedures: an overview from a national metrology institute[J]. Clin Biochem Rev, 2007, 28(4): 131-137.
26. Schumann G, Bonora R, Ceriotti F, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 5. Reference procedure for the measurement of catalytic concentration of aspartate aminotransferase[J]. Clin Chem Lab Med, 2002, 40(7): 725-733.
27. Jeppsson JO, Kobold U, Barr J, et al. Approved IFCC reference method for the measurement of HbA1c in human blood[J]. Clin Chem Lab Med, 2002, 40(1): 78-89.
28. Hoelzel W, Weykamp C, Jeppsson JO, et al. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study[J]. Clin Chem, 2004, 50(1): 166-174.
29. Schulster D, Gaines Das RE, Jeffcoate SL. International standards for human prolactin: calibration by international collaborative study[J]. J Endocrinol, 1989, 121(1): 157-166.
30. Sturgeon CM, Berger P, Bidart JM, et al. Differences in recognition of the 1st WHO international reference reagents for hCG-related isoforms by diagnostic immunoassays for human chorionic gonadotropin[J]. Clin Chem, 2009, 55(8): 1484-1491.
31. Zhang R, Xu Z, Zhao R, et al. Accurate method for value assignment of carcinoembryonic antigen reference materials[J]. J Clin Lab Anal, 2023, 37(11/12): e24936.
32. GB/T 44672-2024 體外診斷醫療器械建立校準品和人體樣品賦值計量溯源性的國際一致化方案的要求[S].
33. 孫運苗, 鄒迎曙, 張傳寶, 等. GB/T 44672-2024/ISO 21151: 2020《體外診斷醫療器械建立校準品和人體樣品賦值計量溯源性的國際一致化方案的要求》國家標準解讀[J]. 中華臨床實驗室管理電子雜志, 2026, 14(1): 29-35.
34. Myers GL, Miller WG. The roadmap for harmonization: status of the international consortium for harmonization of clinical laboratory results[J]. Clin Chem Lab Med, 2018, 56(10): 1667-1672.
35. Thienpont LM, Van Uytfanghe K, De Grande LAC, et al. Harmonization of serum thyroid-stimulating hormone measurements paves the way for the adoption of a more uniform reference interval[J]. Clin Chem, 2017, 63(7): 1248-1260.
36. ISO 21151: 2020 In vitro diagnostic medical devices-requirements for international harmonisation protocols establishing metrological traceability of values assigned to calibrators and human samples[S].

West China Medical Journal

Interpretation of the national standard: In Vitro Diagnostic Medical Devices-Requirements for Establishing Metrological Traceability of Values Assigned to Calibrators, Trueness Control Materials and Human Samples

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