Verification of the EDA Concept Through an Assessment of Theoretical Failure Modes, Failure Mode Analysis, and Case Studies with Real Data - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 259

API concentration
Suspension stability
Cosolvent levels
Surfactants

Impurities
Moisture

Leachables/Extractables

Propellant

Drug
deposition
Moisture ingress
Head space
Leak rate

Particle size/morphology
New Impurity
Water content
Residual solvents

Formulation

Device-Formulation
interactions

API

Amorphous content
Physical stability
Synthetic route

Age of API
Stirring speed
Stirring time
Recirculation time
Suspension temperature
Crimping
Heat stress
Batch size
Vessel headspace
Quarantine time
Damage to valve (pressure fill)
Errors in composition
Fill volumes
Filling interruptions
Leakage
Packaging integrity

Can size

Seals, crimps, etc.
Surface features
Actuator deposition
Spray orifice diameter
Stem block angles
Flashing in stem
Spray orifice eccentricity
Materials of construction
Electrostatics
Airflow geometry
Metering volume
Spring tension
Spring sticktion
Stem friction
Process residues
Geometric dimensions
Materials of construction

Can

APSD Change

Manufacturing Processes

Actuator

Device

Temperature

Value

Orientation
Humidity

Storage

Spacer electrostatics

Accessories

Fig. 9.9 Potential causes for APSD changes related to MDIs ( From [ 9 ] —used with permission )

Fig. 9.10 Control strategies
in OIP development and
manufacture ( From [ 9 ] —used
with permission )