111To date, there are no complete GMP guidelines for cell-based products, although
some main principles should be noted during the manufacturing process (Fig. 6.3 ).
- Materials: According to GMP guidelines, all raw materials must be controlled
for quality. Popular materials produced under GMP should be chosen for further
development. Otherwise, they should have documented quality with a certifi cate
of analysis for each batch. For cell-based products, materials such as culture
medium and kits for isolation should be clinical or in vitro diagnostics (IVD)
grade. However, in some cases, there are no commercial products that satisfy
these requirements, and non-clinical-grade materials are used. When using non-
clinical- grade raw materials, it is important to note the endotoxin concentration. - Manufacturing processes: all steps in the manufacturing process must be orga-
nized as standard operational procedures (SOPs). All batches should be docu-
mented from beginning the preparation of raw materials to storage of the fi nal
product. Any deviations from SOPs must be documented. - Validation: National legislation usually has sets of recommended procedures for
certain parts of the manufacturing process (e.g., required tests for bacterial con-
tamination are described in pharmacopoeia). Validation is the comparison of
alternative procedures to customary procedures and proof that these deviations
from standard procedures bring desired outcomes. - Standardization: Good management of internal quality controls is necessary. At
present, there are many programs for external quality controls, which are per-
formed by national authorities or commercial organizations. A set of standards
has to be adopted for the release of product batches.
Requirements for cellular products are also mentioned in the International
Standards for Cellular Therapy Product Collection, Processing and Administration
(Fourth Edition, Version 4.1, April 2011) established by FACT-JACIE.
Fig. 6.3 Five principles of
GMP. There are fi ve
principles for GMP
including (1) hygiene in
production, (2) quality
management, (3) suitable
facilities and qualifi ed
personnel, (4) complaints
and recall, and (5)
traceability
6 Production of Clinical-Grade Mesenchymal Stem Cells