Page 24 - Assurance of Sterility for Sensitive Combination Products and Materials

Sensitive combination products 13

both changed. This product has not yet been commercialized, however, a
first-in-man clinical evaluation of a DEB preloaded with the multi-tyrosine
kinase inhibitor vandetanib [13] has been approved by the Medicines and
Healthcare Products Regulatory Agency (MHRA) in early 2017.

2.2.2 Drug delivery systems: Traditional and novel
Combination products that are classified as drug delivery systems are those
in which the PMOA is that of the drug and the device is designed to im-
prove the convenience and comfort of administration and improving effi-
cacy by targeting or localizing delivery. Traditional systems include drugs
combined or packaged together with injection devices to improve conve-
nience, such as prefilled syringes, pen-based systems, and drug pumps. The
novel drug delivery systems would normally enable drug to be delivered via
a nonclassical route of delivery [other than oral or parenteral (subcutaneous
or intravenous)]. Examples of this specific class of combination product are
as follows:
• transdermal or intradermal injection systems;
• transdermal patches;
• metered dose inhalers;
• implantable drug-eluting polymer disks for tumor treatments;
• implantable drug-eluting polymer rods releasing contraceptives;
• varicose vein sclerosing foam generating device
Where the drug and the delivery system are packaged separately, ster-
ilization is possible using the traditional approaches used for the individual
components. If the drug and delivery system are combined as one during
manufacturing and sold as a unit, then that combined product will need
to be sterilized by a method suitable to ensure the appropriate SAL and
without adverse effects on either component that would alter their safety
profile or performance. Indeed, the finished product may be sterilized by
multiple different sterilization processes throughout its manufacturing cycle
in order to provide sterility to each of the separate components. For ex-
ample, a drug-delivery device consisting of a vial of drug, water for injec-
tion (WFI), and a syringe requires that the device component is sterilized
without contamination of the drug or water. One approach to achieving
this could be to obtain the syringe components presterilized by gamma
irradiation and the WFI may then be sterilized by steam once contained in
the closed barrel of the syringe. The drug vial will be sterilized by filtration
during manufacture and then combined with the syringe in a kit which will