Biomedical Engineering Reference
In-Depth Information
be provided of controlled access, air locks, biosafety cabinets where no work is allowed on
open benches; all surfaces must be sealed, all penetrations—telephone, lights, gas, vacuum,
electrical line, water—are to be caulked, collared or sealed to prevent leaks, and negative
airflow pressure, doublebacked ventilation system and absolute filtration units must be
available, working and properly maintained);
• rooms where cell cultures are performed for clinical use must be used for that purpose only;
in the case of research institutions performing a few tissue engineering cultures in a limited
period of time, dedication of the same cell culturing rooms to other activities can be ac-
cepted by the competent authority upon validation of the cleaning and sterilization proce-
dures prior to cell culturing for clinical applications;
• rooms must be scheduled for routine cleaning procedures and sterilization; additionally
BL3 rooms must have independent accesses; operational procedures in the cell culture rooms
must avoid cross contaminations between cells derived from different donors/patients (spa-
tial of temporal separation are strongly suggested);
• all the hardware used in cell culturing for clinical applications should be provided of spe-
cific sensors and visual/acoustic malfunction alarms (i.e., freezers, incubators, laminar flow
hoods, cryogenic hardware); backup apparatuses must be available, working and properly
maintained);
• certified procedures must ensure sterility of the outgoing products, either from viruses,
mycoplasma or bacteria;
• certified procedures must ensure the tracking down of any used material in any produced
lot of final products;
• for each manufacturing location a floor diagram should be included that indicates facilities
layout. The diagram does not need to be a detailed engineering blueprint, but rather a
simple schematic that depicts the relationships between the different rooms of the manu-
facturing areas and that indicates the use of adjacent ones. The diagram must report the
flow of production of the biological substance and any other specific activity in dedicated
rooms (for example storage of raw materials, quarantine, etc.)
• in the absence of any specific regulation, Good Laboratory Practices (GLPs), GMPs and
ISO 9002 certifications must be considered as the normal working standard.
For clear economical and technical reasons, controlled areas and rooms are normally in-
cluded and surrounded by lower-requirement areas (i.e., where the control parameters, such as
air purity, sterility, safety containment are less strict). This disposition reduces costs to maintain
elevated safety levels. The interfaces between areas of different levels are critical: while planning
the production process, fluxes of materials/operations from the interior to the exterior of the
different areas must be considered. Segregation of the different areas can be obtained by dislo-
cation (low pressure, high flux) or differential (high pressure, low flux) air pressure between the
areas. This concept applies to both sterile and nonsterile productions and is summarized in
Figure 1.
Personnel Requirements
a legal representative, distinct from the scientific/clinic responsible officer, must be identi-
fied in each structure;
the scientific/clinic responsible officer must have a proven expertise in the biomedical field
of interest;
a quality control responsible officer must also be identified, distinct from the scientific
officer. Only in the case the structure performs a few cell cultures in a limited amount of
time the scientific/clinic responsible officer can serve also as quality control responsible;
personnel must be aware of the standard working operational procedures as well as of the
safety and emergency procedures; in this respect the European Countries are also commit-
ted to follow international guidance on the safety issue, as indicated by the european direc-
tives on safety measures. 14
 
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