Page 233 - Assurance of Sterility for Sensitive Combination Products and Materials

212 Assurance of sterility for sensitive combination products and materials

The difference in approach reflects the evolution as aseptic processing was
often associated with pharmaceuticals and the alternative SAL approach
was developed for medical devices. Aseptic processing has demonstrated
a long history of delivering safe products to the patient, while alternative
SAL has inherent benefits in the statistical rigor. This is covered extensively
in Chapter 7.

8.3 Aseptic processing

The first biologic, a recombinant insulin Humilin developed, approved, and
sold by Genentech/Lilly in the United States in 1982 [3], is still on the
market today. ISO 13408-1:2008 [4] was developed to help provide guid-
ance for these aseptic processed products. A similar approach was used by
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the European Medicines Agency (EMA) [5]. The demonstration that a 10
SAL is unattainable is a prerequisite for aseptic processing. One strategy is
to follow the EMA approach [5] to document this. The product is system-
atically assessed as summarized in Figs. 8.1 and 8.2, which have been repro-
duced from the EMA guidelines [5]. For some materials, such as biologics,
that are known to be incompatible with terminal sterilization, a literature
review may suffice. For other products, the strategy will depend on whether
the product is aqueous or nonaqueous based.
For aqueous-based products, steam sterilization should be explored. If
this sterilization modality is not successful, alternative methods for biobur-
den reduction such as sterile filtration and terminal microbial reduction
processes should be used whenever possible in conjunction with aseptic
manufacturing (Fig. 8.1).
Nonaqueous-based products should explore different terminal
sterilization modalities. The flowchart in Fig. 8.2 does not explicitly
identify EO as a modality because the EMA guidance document [5]
assumes that most powders will not be compatible. Assessment of other
sterilization modalities such as lower radiation doses using Method 1,
Method 2, or Method VD max should be completed. If these methods are
demonstrated not to be successful, sterile filtration and other bioburden
reduction processes should be considered in conjunction with aseptic
manufacturing.
With this information in hand, an assessment can be made to iden-
tify both the risks and benefits for an aseptic processed product knowing
that the due diligence was first performed to have a terminally sterilized
product.