Dr J. Löwer, Germany

In Europe, human plasma for fractionation must comply with:

• the European Pharmacopoeia Monograph on human plasma for fractionation, 1997;

• the Committee for Proprietary Medicinal Products (CPMP) Note for guidance on plasma-derived medicinal products (CPMP/BWP/269/95, rev.2); and

• Recommendation on the suitability of blood and plasma donors and the screening of donated blood in the European Community (EU Council Recommendation 98/463/EC).

The CPMP Note for guidance covers all aspects of sourcing, manufacture, quality control and virus safety including validation studies. It emphasizes the need for quality assurance systems, for information on the epidemiology in the donor population, and for the establishment of a post-collection information system. A new aspect is the requirement to test all- plasma pools using a procedure to detect the presence of Hepatitis C-Virus (HCV) RNA using a nucleic acid amplification technique. This is the consequence of the finding that many commercial pools contain HCV RNA despite testing donors for anti-HCV antibodies.

The basic EU strategy is stated as: “Three principal complementary approaches can be adopted to control potential viral contamination of biologicals: selecting and testing source material for the absence of viruses; testing the capacity of the production processes to remove or inactivate viruses; and testing the product at appropriate stages of production for freedom from contaminating viruses.”

It is important that the licensing authorities or official control laboratories are in a position to perform independent studies on the quality of screening tests. Hazards also arise when experimental controls are performed. In 1989, the requirement to test blood donors for anti-HCV antibodies was introduced. Immunoglobulin preparations from tested donations should consequently have been free of anti-HCV antibodies. The intention was to control complete introduction of donor testing by screening immunoglobulin preparations with commercial anti-HCV test kits. However, the results showed that some test kits regularly yielded false positive results, while others did not react at all. This was because test kits are optimized for their use with plasma or serum and not for immunoglobulin preparations. This “matrix effect” leads to unforeseeable reactions. Testing immunoglobulin preparations for anti-HCV antibodies, as a control measure in the final product, should be performed with very great caution. Such procedures require specific validation of each test for the product tested.