Page 27 - Assurance of Sterility for Sensitive Combination Products and Materials

16 Assurance of sterility for sensitive combination products and materials

2.2.3 Regenerative medical devices with biologics
Biologics (sometimes also referred to as biological drugs or agents) may be
diagnostic, preventive, or therapeutic in nature. These products are gener-
ally developed and manufactured through biological processes using, for
instance, bacterial, animal, or human sources, and include entities of vary-
ing degrees of complexity from sugars, proteins and nucleic acids, through
to cells, blood, and other tissues. The major classes of these products in-
clude vaccines grown in cell culture, products obtained through viral gene
therapy, those extracted from living systems or produced by recombinant
DNA methods. Drug-biologic combination products include regenera-
tive medicinal products that combine devices with biologically active sub-
stances to facilitate healing and regenerate damaged tissues. The device
often serves as a scaffolding for the growth of the biologic component and
the product is often an implant; this type of product may also be classified
for use in tissue engineering. Examples of device-biologic combinations
as follows:
• human fibroblast-derived dermal substitute (e.g., dermagraft);
• spinal fusion cages with recombinant human bone morphogenetic
proteins;

Case study 5: Novel method for protein stabilization
A German biotech company, Leukocare AG, has developed technologies
that enable the stabilization of proteins during production, sterilization by
irradiation, and subsequently during storage. The technologies are known
as stabilizing and protecting solutions (SPS), which can be applied to medi-
cal devices, biopharmaceuticals, vaccines, and diagnostic products (Fig. 2.6)
[15]. SPS technology is a combination of 5–8 different excipients that form
a thin protective amorphous coating around proteins during the drying
process, increasing stability during storage and protecting the sensitive pro-
tein conformation during gamma, E-beam or EtO sterilization processes.
The protective SPS layer is washed away when it comes in contact with
water or body fluids prior to the application of the product, the origi-
nal functionality of the proteins being restored. Proof of concept has been
demonstrated with small peptide, oligonucleotides, enzymes, growth fac-
tors, and even antibodies such as IgM. This technology could therefore be
of particular interest in the development of sensitive combination products
in which a biologic is combined with a device and may offer a route to ter-
minal sterilization that would not normally be possible due to deactivation
of the biologic.