Page 48 - Assurance of Sterility for Sensitive Combination Products and Materials

36 Assurance of sterility for sensitive combination products and materials

the sterilization of surfaces and components of the final package without
penetrating the pre-filled content. Another example is the sterilization of
bioabsorbable polymers which can be compromised when treated using
the established methods but has been demonstrated to have good compat-
ibility with alternative gases. Radiation sterilization of these polymers at
traditionally high doses causes degradation, while the high temperature and
high relative humidity of EO processing can lower the T g and plasticization
of the materials, which can result in the softening as well as the loss of the
secondary and tertiary structure [30]. The degradation or softening of the
material reduces structural integrity and the performance of devices such as
stents or bone screws.
Another opportunity might involve combining novel methods with
established methods to create an adjunct sterilization process. Consider
the scenario of a combination device composed of a drug-coated poly-
mer which has a limited sterilization dose range due to degradation from
a radiation process. The reduction of bioburden can be achieved through
improved controls in the manufacturing process which would enable vali-
dation of a lower sterilization dose. Typically in a combination product, only
certain components of the drug-device combination product are sensitive
to the sterilant. The application of novel gas sterilization treatment during
the manufacturing process just prior to the incorporation of the sensitive
component provides extra insurance against incidental spikes in bioburden
that could occur during earlier stages of the manufacturing process.
The final example is the rapidly expanding consumer wearable sector.
The merging of technology and health care has created the digital health
space which is transforming chronic care management between the patient
and the physician. The FDA is actively engaged in this sector as it brings
several benefits such as personalized medicine, increased compliance, and
reduced costs to the patients [31]. This next wave of innovation introduces
electronics to the already complex matrix of polymers, metals, and drugs in
the existing sensitive combination devices. New sterilization methods and
new validation approaches are a welcome addition providing an additional
toolset to the engineer to bring products to the market.

3.4 Conclusion

The early development of what is now the established sterilization modal-
ities occurred when devices were constructed with simpler materials and
designs. These devices are extremely tolerant to the assaults of radiation, EO