en Pharmaceutical Biotechnology Pharmaceutical Biotechnology مقاله کامل Full Length/Original Article <div style="text-align: justify;"><span style="font-family:Times New Roman;"><span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:10.5pt"><span style="color:black">Background: </span></span></b><span style="font-size:10.5pt"><span style="color:black">Injectable products, particularly human vaccines, must be free from fever-inducing agents and thoroughly tested for pyrogens as part of a quality control. Consequently, manufacturing facilities are required to conduct appropriate pyrogen tests per pharmacopoeial standards. This study aimed to evaluate the reliability of the monocyte activation test (MAT) in quantifying pyrogenic content in the recombinant hepatitis B vaccine. </span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:10.5pt"><span style="color:black">Methods: </span></span></b><span style="font-size:10.5pt"><span style="color:black">We assessed pyrogen activity in the active pharmaceutical ingredient (API), formulated vaccine, and aluminum hydroxide by comparing the limulus amebocyte lysate (LAL), rabbit pyrogen test (RPT), and MAT, measuring activity in </span></span><span style="font-size:10.5pt"><span style="color:black">relative pyrogen unit (RPU) as per the European Pharmacopoeia. Monocytes from healthy donors were isolated and identified via flow cytometry to measure the CD14⁺ marker frequency. </span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:10.5pt"><span style="color:black">Results: </span></span></b><span style="font-size:10.5pt"><span style="color:black">The study found that the pyrogenic concentration of lipoteichoic acid (LTA) in the MAT was 50,000 ng/mL (5.19 EEU/mL). In contrast, the same concentration in the rabbit pyrogen test (RPT) was deemed non-pyrogenic based on rectal temperature assessments. The MAT showed sensitivity to the API and adjuvant, with a detection limit of 2.5 EU/mL for IL-6, outperforming the RPT, which had a detection limit of 5 EU/mL. </span></span></span></span><br> <b><span style="font-size:10.5pt"><span style="line-height:115%"><span style="color:black">Conclusion: </span></span></span></b><span style="font-size:10.5pt"><span style="line-height:115%"><span style="color:black">A strong IL-6 response to both lipopolysaccharide (LPS) and LTA stimulation was observed, indicating that IL-6 could serve as a valuable marker for pyrogen testing. The MAT appears to be an effective alternative to the RPT for assessing pyrogenicity, demonstrating commendable consistency and accuracy across various testing systems allowed by the Ph. Eur. General MAT Chapter, especially given the RPT&#39;s limitations in controlling pyrogenicity in injectable products.</span></span></span></span></div> Hepatitis B, Interleukin-6, Pyrogens 273 281 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-5636-1&slc_lang=en&sid=1 Delaram Doroud 0000-0003-4167-9921 No Pasteur Institute of Iran, Tehran, Iran Zohre Eftekhari z_eftekhari@pasteur.ac.ir 0000-0001-9705-5179 Yes Biotechnology Department, Pasteur Institute of Iran, Tehran, Iran Mojtaba Daneshi 0000-0003-4980-7502 No Department of Animal Science, North Dakota State University, Fargo, North Dakota, USA Parisa Gheibi 0000-0002-0645-317X No Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Nazanin Jabbari 0000-0002-2926-9631 No Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Maryam Khatami 0000-0002-0059-7156 No Quality Control Department, Research & Production Complex, Pasteur Institute of Iran, Tehran, Iran Marzieh Hosseini 0000-0002-7998-2208 No Pasteur Institute of Iran, Tehran, Iran