The CCQM Organic Analysis Working Group (OAWG) agreed on a Track A comparison for the measurement of polar organic in biological matrix as part of its 10-year strategic plan. As a model for this comparison, two polar clinical biomarkers: urea and uric acid, in human serum were chosen. This comparison was designed to enable participating National Metrology Institutes (NMIs) or Designated Institutes (DIs) to demonstrate their measurement capabilities in the determination of analytes with molecular mass of 50 to 500 g/mol, having the polarity pK(OW) > 2 in the range of 10 to 2,000 mg/kg in a biological matrix such as human serum, blood and urine. Two pools of human serum materials with different concentration levels of urea and uric acid were used as the comparison materials. Fifteen NMIs/DIs participated in this Track A comparison. All of them submitted the results for urea and 14 NMIs/DIs submitted the results for uric acid. With the exception of one NMI, all participating institutes employed isotope dilution mass spectrometry (IDMS) for the measurement of both urea and uric acid. Protein precipitation, liquid-liquid extraction and/or clean-up were applied, followed by instrumental analyses using GC-HRMS, GC-MS/MS, GC-MS, LC-HRMS, LC-MS/MS, LC-MS or HPLC-DAD. The Laplacian weighted medians were used as the Key Comparison Reference Values (KCRVs). The assigned KCRVs were the weighted medians of 13 results for urea (both serum pools), 10 results for uric acid (Serum I) and 11 results for uric acid (Serum II). Urea (Serum I) was assigned a KCRV of 1,486.0 mg/kg with a standard uncertainty of 9.0 mg/kg, urea (Serum II) was assigned a KCRV of 334.7 mg/kg with a standard uncertainty of 1.8 mg/kg, uric acid (Serum I) was assigned a KCRV of 136.50 mg/kg with a standard uncertainty of 0.98 mg/kg, and uric acid (Serum II) was assigned a KCRV of 39.39 mg/kg with a standard uncertainty of 0.11 mg/kg. The degree of equivalence (with the KCRV) and its uncertainty were calculated for each result. The majority of the participating institutes in CCQM-K109 demonstrated their capabilities in the measurement of the clinical markers in the biological matrix using IDMS.