Viral safety

Q5A(R1) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin... 

Quality of biotechnological products. Viral safety evaluation of biotechnology products derived from cell lines of human or animal origin... 

Several documents describe the requirements for viral clearance studies. The ICH guidance on viral safety evaluation provides information on the design of viral clearance studies and their interpretation [37], Unlike most other aspects of process validation, viral clearance cannot be performed at full scale. There are several reasons for this. Direct testing methods may not detect low concentrations of virus, which requires that viruses be spiked into the feedstream. Assays may detect only known viruses, and they may also fail to detect variants. Worker safety is another issue that necessitates the need to perform the validation at a small scale. Scaling down is addressed in the ICH guidelines and in the literature [38,39]. 

Q5 Quality of Q5A Viral safety evaluation of biotechnology prod-... 

ICH (1997), CPMP. Viral safety evaluation of biotechnology products derived from cell lines of human or animal origin, Geneva. Available at http //www.ich.org/ LOB/media/MEDIA425.pdf (accessed October 2006). 

Q4 Q5A Pharmacopoeial Harmonisation Quality of Biotechnological Products Viral safety Evaluation of Biotech- CPMP/ICH/295/95 Step 5... 

Reid, K.G. Cuthbertson, B. Jones, A.D.L. McIntosh, R.V. Potential contribution of mild pepsin treatment at pH 4 to the viral safety of human immunoglobulin products. Vox Sang. 1988, 55, 75-80. 

The Viral Safety Group, created in 1994 by decision of 17 May 1994 (official 8 June 1994) of the Director General of the Agency, is responsible for advice on the safety of viruses and other transmittable products, medicines containing biological products or during the method manufacture constitute a product for which MA is applied. 

These are beyond the scope of this chapter but include guidances on viral safety, genetic stability, cell substrate characterization, and the stability of biotechnological products. 

For intentionally introduced, endogenous, and adventitious viruses, the ability of the manufacturing process to remove and/or inactivate viruses should be demonstrated as described in ICH guidance Q5A Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin. 

The production process for protein prepared by fractionation/ purification includes a heat inactivation step to ensure viral safety of the product. The heat inactivation step is followed by a precipitation step that further purifies the product. The purpose of our study was to determine whether the process steps are robust within the parameter ranges routinely used in manufacturing. 

Bouzidi A, Majewski W, Hober D, Perrut M. Supercritical fluids improve tolerance and viral safety of fresh frozen plaza. Nice International Society for the Advancement of Supercritical Fluids, 1998 717-721. 

Fages J, Mathon D, Poirier B, Autefage A, Larzul D, Jean E, Frayssinet P. Supercritical processing enhances viral safety and functionality of bone alografts. Proceedings of 4th International Symposium on Supercritical Fluids, 1997 383-386. 

First marketed in the United States in 1996,recombinant factor IX is produced in Chinese hamster ovary cells transfected with the factor IX gene. Blood and plasma products are not used to produce recombinant factor IX nor to stabilize the final product thus recombinant factor IX has an excellent viral safety profile. Clinical trials have shown the product to be safe and efficacious in the treatment of acute bleeding episodes and in the management of bleeding associated with surgical procedures. Although the half-life of recombinant factor IX is similar to that of the plasma-derived products, recovery is approximately 28% lower. As a result, doses of recombinant factor IX concentrate must be higher than those of plasma-derived products to achieve equivalent plasma levels. Because individual pharmacokinetics may vary, recovery and survival studies should be performed to determine optimal treatment. Recombinant factor IX is often considered the treatment of choice for hemophilia B. 

As noted earlier, the optimal management of von Willebrand disease starts with adequate identification of the patient s disease type. Desmopressin is considerably less expensive than plasma-derived factor VIII concentrates. It should be the treatment of choice for all patients responsive to the test dose because of its viral safety, reduced cost, and ease of administration. 

Adamson S, Charlebois T, O Connell B, et al. Viral safety of recombinant factor IX. Semin Hematol 1998 35 22-27. 

Ludlam CA. Viral safety of plasma-derived factor VIII and IX concentrates. Blood Coagul Fibrinolysis 1997 8(Suppl 1) S19-S23. 

The characterization and safety testing of the cell banks has been described extensively elsewhere [16]. In brief, the identity, sterility, viral safety, absence of PrPsc protein, tumorigenicity and genetic characterization, including chromosome analysis, has been performed. 

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