Effect of Unintentional Storage and Handling Errors of Inhaled Medications: What Does This Mean for Therapeutic Equivalence Considerations?

Background: Currently, the equivalence and the substitutability of two inhaled medications are mainly driven by comparability of doses, in vitro performance, therapeutic equivalence and sameness, and handling of the inhalers. The packaging configuration is usually not considered as a factor. Methods: Two capsule-based inhaled tiotropium-containing products that differ by their primary packaging configurations (blister versus bottle) were compared in terms of potential handling and resulting storage errors due to unintentional misuse. Use error scenarios were identified and investigated for both the blister-packaged tiotropium and the bottled tiotropium capsules. The impact of the air exposure resulting from the packaging interaction errors was evaluated in vitro using fine particle dose (FPD) and delivered dose. Results: Numbers of potential errors and criticality in terms of the potential effect impact on the FPD were larger for the bottled product (between 40% and 90% loss on FPD related to initial dose). The loss of FPD could significantly impact the amount of medication that can actually reach the patient's lungs. Conclusion: When considering prescribing an inhaled medication, the specifics of the packaging and the patient's abilities and situation shall be taken into account to minimize possible handling and subsequent dosing errors.