Information on Coagulation Factors and Prions

On 10th Januarv 2005, ZLB Behring informed the Paul-Ehrlich-Institut (PEI) in Langen, Germany that the plasma of a French woman donor, who later developed vCJD, was used in an intermediate product in 1996. The intermediate product was used to manufacture Haemate HS/P 1000 (Batch No 5676641). Haemate is used in the prophylaxis and therapy of bleeding relating to Haemophilia A and acquired factor VIII deficiency, in the therapy of patients with antibodies against factor VIII, and the prophylaxis and therapy of bleeding relating to Willebrand syndrome.

The batch referenced was introduced into the German market by the then license holder, Centeon, in 1997. However, the PEI had withdrawn the batch release in November 1997 after detecting non-conformities in the donor selection in the French blood donor centre that had become known in retrospect. Following this, Centeon recalled the batches at its own responsibility. 1269 of 1494 packages marketed in Germany had apparently already been consumed, 225 were sent back.

The risk of infection of patients with vCJD by using the batch in question is to be considered as extremely low. In addition, no confirmed or suspected case of transmission of vCJD by plasma derivatives has occurred. The Paul-Ehrlich-Institut has carried out a risk calculation for the batch concerned on the basis of the following parameters:

• the amount of the donor's plasma used
  
• the size of the plasma pool in which the plasma donation was used
  
• the amount of plasma processed for a single dose (package)
  
• an assumed pathogen concentration based on data from animal experiments
  
• the experimentally examined capacity of the purification steps to remove prions during the manufacturing procedure of factor VIII products

According to this calculation, the possibly remaining residual amount of infectivity in a single dose of the Haemate HS/P 1000 batch in question is considered as very low (4.1 x 10-4 IU₅₀/ package to 4.1 x -5 IU₅₀/ package).

In other words, one out of 2,500 to 25,000 packages could contain one theoretical infective unit of prions. Since these considerations indicate that only every 2,500th to 25,000th package may be contaminated, there is a high probability that none - or at least only a small percentage - of the 1269 packages contain residual amounts of infected material. Therefore, the risk is still small even for patients who received several packages from this batch.

At a European level, extensive discussions have been underway concerning the safety of plasma-derived products for several years. A position paper of the Committee for Medicinal Products for Human Use (CHMP (formerly CPMP)) at the European Agency for the Evaluation of Medicinal Products (EMEA) dated June 2004 states that in using French plasma, too, the safety margin regarding prion infection is sufficient. These evaluations are being continuously adapted to the state of the art.

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