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Table 6 Stability-Indicating Tests to Consider for Drug-Eluting Stent (DES)

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

  1. Table modified from (Liu et al. 2018)