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Renchi Yang,1 Yongqiang Zhao,2 Xuefeng Wang,3 Jing Sun,4 Runhui Wu,5 Chenghao Jin,6 Jie Jin,7 Depei Wu,8 Pablo Rendo,9 Feifei Sun,10 Jeremy Rupon,9 Francois Huard11,†, Joan M Korth-Bradley,12 Lihong Xu,10 Binyu Luo,10 Yingxue Cathy Liu13 1Thrombosis and Hemostasis Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People’s Republic of China; 2Department of Hematology, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Department of Clinical Blood Transfusion, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Hematology, Beijing Children’s Hospital and Capital Medical University, Beijing, People’s Republic of China; 6Department of Hematology, Jiangxi Provincial People’s Hospital, Jiangxi, People’s Republic of China; 7Department of Hematology, The First Affiliated Hospital – Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 8Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 9Rare Disease, Pfizer Inc, Collegeville, PA, USA; 10 Pfizer (China) Research & Development Co, Ltd, Shanghai, People’s Republic of China; 11Clinical Pharmacology, Pfizer PIO, Paris, France; 12Pfizer Inc, Collegeville, PA, USA; 13Statistics, Pfizer (China) Research & Development Co, Ltd, Shanghai, People’s Republic of China†Dr. Francois Huard passed away on July 20, 2017.Correspondence: Renchi Yang Email rcyang65@163.comIntroduction: Moroctocog alfa albumin-free cell culture (AF-CC) increases plasma levels of factor VIII (FVIII) activity and, in China, is indicated for the control and prevention of bleeding episodes in patients with hemophilia A. This study aimed to evaluate the efficacy, safety, and recovery data of moroctocog alfa (AF-CC) in patients with hemophilia participating in two open-label studies, both conducted in China.Methods: The authorization study (clinicaltrials.gov identifier NCT00868530) enrolled patients aged ≥ 6 years, previously treated with ≥ 1 exposure day of FVIII replacement therapy. The real-world study (clinicaltrials.gov identifier NCT02492984) enrolled patients of any age who were previously untreated or requiring surgical prophylaxis. In both studies, on-demand treatment was administered over 6 months. Key assessments included response to treatment, FVIII inhibitor development, and recovery.Results: In the authorization study (N = 53; mean age, 23.2 years; severe hemophilia, 23%), response was excellent/good for 90% of infusions at 24 hours. Seven patients developed inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.77 (0.50) and 1.67 (0.45) (IU/dL)/(IU/kg), respectively. In the real-world study (N = 85; mean age, 9.5 years; severe hemophilia, 58%), response was rated as excellent or good for most (87%) on-demand infusions and for all surgical prophylaxis patients (n = 14). Seven patients developed FVIII inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.71 (0.50) and 1.68 (0.31) (IU/dL)/(IU/kg), respectively. No new safety signals were observed in either study.Conclusion: On-demand treatment and surgical prophylaxis with moroctocog alfa (AF-CC) is safe and effective for both previously treated and previously untreated Chinese patients with hemophilia A.Keywords: Asian, blood coagulation factor VIII, deficiency, factor VIII, ReFacto, Xyntha

Objective: This study compared the safety and efficacy of Safacto® versus xyntha® in patients with severe hemophilia A. Methods: Thirty-three male patients with severe hemophilia A were randomly divided into two groups. Seventeen patients received Safacto® and 16 patients received Xyntha® for four consecutive times. The dosage of FVIII was 40-50 IU/kg for each injection. Plasma level of FVIII activity was evaluated before every injection, 15 minutes after the injection and one month after the start of the trial. The rate of factor VIII activity, pain and joint motion were also assessed before and after the treatment. Results: Plasma level of FVIII clotting activity in Safacto® and Xyntha® were 1.96±0.5 IU/dl and 1.63±0.5 IU/dl and increased to 88.84±25.2 IU/dl and 100.09±17.8 IU/ dl, respectively (P

Recombinant clotting factors are important biotherapeutics that Pfizer has produced and marketed for over fifteen years. Owing to the complexity of the structure and function of these blood factors, it can be challenging to achieve the required product quality and manufacturing productivity. The article highlights the semi-continuous and continuous cell culture processes employed by Pfizer for the production of BeneFIX and ReFacto AF. The benefits of such processes, the challenges of maintaining an aseptic production culture for extended periods, and batch definition are discussed in this article. [ABSTRACT FROM AUTHOR]

ReFacto® Antihemophilic Factor is a second-generation antihaemophilia A product manufactured using a process that includes therapeutic grade human serum albumin (HSA) in the cell culture medium, but is formulated without HSA as a stabilizer. Even though this second-generation antihaemophilia product has a good safety profile, a programme was implemented to eliminate all animal- and human-derived raw materials from the production process, thus producing a third-generation product. To that end, HSA has been removed from the master and working cell banks and from the culture medium. The hybridoma-derived monoclonal antibody formerly used in the purification process has been replaced by a chemically synthesized affinity peptide, and a virus-retaining filtration step has been added to enhance the clearance of large viruses, such as retroviruses. The purification process has been validated for the removal of a panel of model viruses and provides significant clearance of all viruses tested. Host cell- and process-derived impurity removal validations also were conducted, including host cell DNA and protein, in addition to the affinity peptide. Compared with the product manufactured according to the original process, these changes had no detectable effect on the structural integrity, stability or clinical efficacy of this antihaemophilia A product. The product produced by the improved manufacturing process is named Xyntha™/ReFacto AF. [ABSTRACT FROM AUTHOR]

Objective: This study compared the safety and efficacy of Safacto ® versus xyntha ® in patients with severe hemophilia A., Methods: Thirty-three male patients with severe hemophilia A were randomly divided into two groups. Seventeen patients received Safacto ® and 16 patients received Xyntha ® for four consecutive times. The dosage of FVIII was 40-50 IU/kg for each injection. Plasma level of FVIII activity was evaluated before every injection, 15 minutes after the injection and one month after the start of the trial. The rate of factor VIII activity, pain and joint motion were also assessed before and after the treatment., Results: Plasma level of FVIII clotting activity in Safacto ® and Xyntha ® were 1.96±0.5 IU/dl and 1.63±0.5 IU/dl and increased to 88.84±25.2 IU/dl and 100.09±17.8 IU/dl, respectively (P<0.001). Pain score and range of motion improvement were 9.3±0.9 and 8.7±0.1 in Safacto ® (P=0.17); and 9.4±0.8 and 8.8±0.3 in Xyntha ® (P=0.35), respectively. No allergic or other unfavorable reactions was observed with either of the preparations., Conclusion: This study showed that Safacto ® has a favorable efficacy and safety profile., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.