From: Stability considerations for drug-device combination products-21 CFR part 4 update
Stability-Indicating Test | Combination Product Portion | Technique(s) | Purpose |
---|---|---|---|
Appearance | Drug, Device & Sterile Barrier System (SBS) | Optical Inspection Microscopy Machine Vision Systems | Drug—Color change, foreign debris Device – Cracks, color change SBS- Voids, tears color change |
Assay (Total Drug Content) | Drug Only | HPLC | Changes in concentration |
Impurities or Degradation Products | Drug Only | HPLC GC–MS ICP-MS (elemental impurities) | Formation of inactive or toxic byproducts over time. May be completed as part of the Assay method |
In Vitro Drug Release (Drug Elution) | Drug Only | Dissolution (USP apparatus 4) | Confirmation that API is released from the device in a controlled, consistent, and reproducible manner |
Particulates | Drug & Device | USP < 788 >  | Detect shedding from drug coating/surface or device delivery system |
Packaging Integrity | SBS Only | Bubble Leak Dye Penetration Vacuum Decay | Confirmation that sterility will be maintained |
Package Seal Strength | SBS Only | Peel Strength Burst Strength | Confirmation that contents and sterile barrier will be maintained |
Polymer Molecular Weight | Drug & Device | Size Exclusion Chromatography (SEC) | Evidence for the polymeric coating on the device degrading over time. Molecular Weight (Mn, Mw) and Polydispersity Index (PDI) measurements at time points can be compared to T0 |
Antioxidant/Drug Stabilizer | Drug Only | HPLC GC–MS | Determine low-level additives to stabilize drug substance. May be challenging to analyze due to the low concentration and interference from excipients in the product matrix |
Tensile Strength | Device Only | Instron | Confirmation of linear elongation and break strength |
Compression Strength | Device Only | Instron | Confirmation of resistance to externally applied forces |
Burst Strength | Device Only | Instron | Confirmation of resistance to internally exerted forces |
In-Vitro Strength (Tensile, Compression, and/or Burst) | Device Only | Instron | Confirmation of resistance to forces in the clinically relevant modality after exposure to physiological buffered solution for a clinically relevant period of time |