61
8.21 Careful Donor Selection and
Rigorous Screening of Donations
CSL Behring uses source plasma, which is collected by
plasmapheresis, and recovered plasma, which is derived
from whole blood donations. The first step of the Integ-
rated Safety System incorporates all the measures for the
selection of donors and donations.
Judicious Selection and Regular Inspections
of Donation Centers
These safety measures begin with rigorous selection of
donation centers and, once selected, regular inspection of
these centers by competent authorities and audits by CSL
Behring.
Careful Donor Selection
CSL Behring also strives for careful selection of healthy
donors as part of its Integrated Safety System. The medical
investigation of donors, inventory hold of source plasma
for at least 60 days after donation, and the quarantining
of all first-time plasmapheresis donations comprise this
step. Donors are subjected to a rigorous pre-donation
evaluation. This includes a physical examination and
detailed questioning to ascertain the potential donor’s
medical history and possible exposure to high-risk activi-
ties.
Serology
Another safety precaution in the first step of the Inte-
grated Safety System includes testing of the individual
donations. All donations are screened in accordance
with the requirements of the competent authority in the
country of collection with approved test kits for antibodies
to HIV-1 and HIV-2, HCV, and HBV surface antigen. Only
plasma units that are non-reactive in the above tests are
released for testing with nucleic acid amplification tech-
nique (NAT). Plasma units that are positive are rejected and
destroyed and the donor deferred.
Nucleid Acid Amplification Technique/
Polymerase Chain Reaction (NAT/PCR)
In addition, samples of plasma donations are pooled (mini-
pools) and subjected to NAT/PCR testing for HAV RNA, HBV
DNA, HCV RNA, HIV-1/2 RNA, and high titer B19V DNA.
A positive NAT/PCR signal in a mini-pool results in testing
sub-pools and in discarding the positive donation(s); do-
nors of reactive donations are deferred.
Testing Plasma Pools for Fractionation
As a further step, the fractionation pools are subjected to
serology and NAT/PCR testing. Only pools that test non-
reactive by the respective assays are used for further pro-
cessing.
All these measures lead to a progressive reduction of the-
se blood borne viruses that may have inadvertently been
present in the starting material.
8.22 Manufacturing Processes for Virus
Inactivation and Removal (Virus Reduction)
112
The second step of CSL Behring’s Integrated Safety System
concerns the commercial production of Berinert
®
, carrying
out product-specific purification procedures and effective
virus inactivation and removal steps. During the produc-
tion of Berinert
®
, the stabilized protein solution is heated
for 10 hours at 60°C as an aqueous solution to inactivate
viruses (pasteurization). HIC and virus filtration (also called
nanofiltration) are further important virus-reduction steps.
Validation of the Manufacturing Process
Virus validation studies are performed to evaluate the
capacity of the manufacturing process to remove or in-
activate various viruses.
Validation of the virus inactivation and removal capacity
of the manufacturing process is performed in a virological
laboratory, using a validated scaled-down model of the
manufacturing process that accurately mimics the production-
scale process.
Production
