63
8.23 Risk Reduction for Other Pathogens
Creutzfeldt-Jakob disease (CJD) is caused by the patho-
logical isoform of the prion protein. In humans, it occurs
in different forms: the sporadic (sCJD) and genetic forms
and the variant form (vCJD), the latter being low in terms
of the total number of cases. The probable transmission
of vCJD by blood components was reported in the United
Kingdom.
CSL Behring carries out the following specific measures in
regard to plasma donations to minimize the theoretical
risk of vCJD transmission:
•
Because of the geographical risk, donors who spent
a short cumulative time in the United Kingdom between
1980 and 1996 are excluded in line with the stipulations
of the various state authorities relevant to the donation
centers.
•
Donors who received blood after 1980 in the
United Kingdom or who underwent surgery in the
United Kingdom after 1980 are excluded.
•
Donors who have received a dura mater or cornea
transplant or human growth hormone are excluded.
•
Donors with CJD or a familial history of CJD are
likewise excluded.
•
Donors injected with products of bovine origin
(eg, insulin) from countries where bovine spongiform
encephalopathy is endemic are likewise excluded.
•
Batches with processed plasma from persons
potentially infected with vCJD will be recalled in
close cooperation with authorities.
On the basis of CSL Behring investigations and published
data for comparable manufacturing steps, a high total
prion-reduction factor has been demonstrated for the
Berinert
®
manufacturing process (Table 19) resulting in an
extremely remote risk of vCJD transmission by the appli-
cation of vCJD.
112
8.24 Strict Adherence to Current
Good Manufacturing Practices and
Quality Assurance Measures
Strict adherence to state-of-the-art Good Manufacturing
Practices and Quality Assurance measures help ensure that
all previously described procedures are followed, so that
the described high product safety is applied to every batch
of Berinert
®
produced.
8.25 Postmarketing Surveillance
Since 1985, in more than half a million treatments world-
wide, no proven cases of infection due to HIV-1, HIV-2,
HAV, HBV, HCV, or B19V have been reported with the use
of Berinert
®
.
1
Production
Table 19 – Mean Prion Reduction Capacity of the Manufacturing Process of Berinert
® 112
Manufacturing Stages
Prion Evaluation Studies
Microsomes
Purified Pathological Isoform of the Prion Protein
Prion Load Spiked
Starting Material
Prion Load
Final Sample
Prion Reduction
Factor
Prion Load Spiked
Starting Material
Prion Load
Final Sample
Prion Reduction
Factor
Ammonium sulfate precipitation
5.8
2.8
3.0
4.4
≤
1.2
≤
3.2
HIC
4.1
≤
0.7
≥
3.4
4.5
≤
0.7
≥
3.8
20N/15N virus filtration
4.0
a
4.0
a
Overall prion reduction factor
≥
10.4
≥
11.0
HIC=Hydrophobic interaction chromatography.
a
Prion reduction capacity of the 20N/15N virus filtration step was assumed based on evaluation studies for other plasma proteins (and published data).
