Page 86 - Assurance of Sterility for Sensitive Combination Products and Materials

72 Assurance of sterility for sensitive combination products and materials

Any growth should be investigated. The goal of the investigation is to iden-
tify the root cause or probable cause of the sources of the contamination.
This investigation should include microbiological identification in the pos-
itive units and compare them with potential areas where that organism
might be found, environmental monitoring results both historical as well as
during the fill.
Each possible contamination source should be evaluated to determine
if controls and evidence would eliminate that source from aseptic process
simulation contamination. Those possible sources that cannot be eliminated
should be considered as though they are the source of aseptic process sim-
ulation contamination.
CAPAs (corrective actions and preventive actions) should be taken to
eliminate each of the remaining causes. After the actions are completed,
aseptic process simulation studies should be repeated to confirm both the
effectiveness of the CAPAs and that the changes did not have any unin-
tended consequences. Although in general, the number of aseptic process
simulation runs may be risk-based, three additional aseptic processing runs
should be the default number in response to a CAPA [4, 7].

4.29 The future of aseptic processing

The most innovative new therapies will likely be heat sensitive sterile bio-
pharmaceutical products. It is likely that more of those biopharmaceuticals
will be delivered using innovative container and system designs. Therefore,
many of the more innovative products will be combination products re-
quiring aseptically processing to manufacture. The cost and availability of
these therapies will require and depend on the efficiency, effectiveness, and
control of the manufacturing process. The use of advanced technology to
achieve the requirements of these products will be essential.
Despite advances in technology in other industries, aseptic processing
of sterile medicinal products has struggled to keep up. The reason for this
lack of innovation is ultimately due to “keeping the status quo” philosophy
because of the perceived risk due to regulatory, change notification, and
additional work and time required to support the change.
However, conditions in this industry may be changing and this may
be the right time for a technology revolution. This is based in part on the
following points:
• Regulators are ready: Global health authorities and regulators are en-
couraging new approaches. An example is the recent release of the