Biomedical Engineering Reference
In-Depth Information
Material risk
Low
Medium
High
Audit every five years
Vendor certified for CofA
acceptance
Audit every five years
Vendor certified for CofA
acceptance
Audit every three years
Vendor certified for
minimal testing
Audit every two years
Vendor certified for
minimal testing
Audit every two years
Skip-lot testing of
incoming lots
Annual Audit
Skip-lot testing of
incoming lots
Annual audit
Test all lots received
Review all vendor non-
conformances
Annual audit
Test all lots received
Annual audit
Figure 12.3
Example of a 9-block assessment tool.
Several risks are associated with raw materials. Chief among these for bio-
pharmaceuticals is the use of animal-derived materials. This risk is addressed
through adherence to sound animal husbandry and procedural controls, as well
as, through the use of screening tests to assess material quality before use. The
use of animal-derived materials may be linked to microbiological contamina-
tion, by bacteria, fungi, mycoplasmas, viruses, and/or prions. This risk is also
addressed through procedural controls and then verified through testing. Manu-
facturers should also be concerned with lot-to-lot variation in incoming materials.
The effects of lot-to-lot variation were discussed earlier. They can be assessed
by using multiple lots during material qualification and through supplier qualifi-
cation, as well as through the use of monitoring programs that periodically test
and assess the quality of incoming materials.
12.3.2 Cell Banking
12.3.2.1 Process Overview
Cell banking assures an adequate supply of homo-
geneous and well-characterized cells for manufacturing over the expected lifetime
of a biopharmaceutical product. Cell substrates that are banked must be stable,
reproducible, and available in sufficient quantities. Specifically, cell substrate
stability is important in terms of safety and quality because it ensures that only
the desired and specific biopharmaceutical product is manufactured without the
introduction of any mutations and with minimal likelihood of contamination by
infectious agents. Cell substrate reproducibility is important over time because
the biopharmaceutical product manufactured during the first manufacturing cam-
paign has to match the product that is produced in subsequent campaigns. Finally,
cell substrate availability is important to ensure that there is adequate long-term
inventory for commercial production. Typically, manufacturers prepare a mas-
ter and a working cell bank to ensure supply of stable and reproducible genetic
source materials [10].
A cell bank construction strategy is usually in two stages. The first stage is the
construction of a master cell bank (MCB). The MCB is produced directly from
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