Automated Actuation Ensures High Quality Reproducible Data
Orally inhaled and nasal drug products (OINDPs) are notoriously complex and difficult to develop and manufacture. Proper performance of these devices is sensitive to many variables, which must all be properly controlled. A lack of sufficient control can adversely affect data quality and reproducibility, which can in turn cause developmental delays or production quality issues. The formulation itself often becomes the primary focus of drug developers early on and less attention is devoted to understanding the device usage. By employing automated actuation from the earliest stages of development, you can eliminate variables introduced by manual actuation, greatly improve your testing throughput while minimizing any physical burden on lab technicians, and finally; you can gain full control over the important parameters affecting device performance. Some of these key factors include stroke length, velocity, acceleration, and shaking to ensure proper mixing (in the case of pMDIs). Proveris offers a whole family of Vereo Automated Actuators so that you can select the right one for your specific device type. Automated actuation is recommended by the US FDA as well as other regulatory agencies around the world and Proveris’ system are currently being used by many of the top pharmaceutical, biotech, CROs, and device manufacturers in order to accelerate development projects.
Actuation Platforms for Commonly Performed Tests
Pressurized Metered Dose Inhalers (pMDIs)
- Spray Pattern
- Plume Geometry
- Plume Velocity
- Evaporation Fraction
- Priming/Re-priming
- Aerodynamic particle size distribution (APSD)
- Valve delivery
- Delivered dose uniformity (DDU), through life
- Delivered mass uniformity
- Number of deliveries per inhaler
Nasal Sprays, Oral Sprays, Soft Mist Inhalers (SMIs)
- Spray Pattern
- Plume Geometry
- Priming/Re-priming
- Droplet size distribution (DSD)
- Pump delivery
- Single actuation content (SAC), through life
- Delivered dose uniformity
- Delivered mass uniformity
- Number of deliveries per inhaler
Data Captured using Viota® Software Illustrates the Importance of Automated Actuation
Automated versus Manual Actuation
The range of variation in hand actuation can be seen in Figure 1. The data is derived from an Ergo™, a Proveris Scientific device which measures and records human-usage parameters. The figure shows the high variability in stroke length, actuation velocity, and hold time as recorded from a human actuation (right) compared with the option of controlling parameters consistently with automated actuation (left) for a pressurized metered dose inhaler (pMDI) device.
Dose Delivery Variability Due to Lack of Shaking
Figure 2 shows the importance of shaking a pMDI product. Without adequate shaking, a high amount of drug will be delivered in the initial shots, followed by little to no drug at the end of device life. Proveris’ SFMDx Actuator design for pMDI devices allows the user to control the shaking of the device with the ability to modify parameters such as shake angle, frequency as well as shake to fire delay. Performing a shaking study in combination with dose content uniformity measurements is essential to optimizing the shaking protocol for a device and eliminating the variable of dose fluctuations in your in vitro testing.
Reference Listed Drug and Three Generic Candidates
Figure 3 shows how three candidate valves for a generic product perform differently with the same actuation profile (stroke length, velocity, acceleration, and hold time). Each valve has a different actuation force, end-of-stroke force, and force profile. In this case, Valve #1 has the closest performance to the reference listed drug (RLD) product. Besides metering valve selection, the time-sequenced force feedback can be applied to ensure consistent valve performance across both the product’s lifecycle and different lots and batches (release testing). Additionally, it can be used to identify whether the root cause for an OOS measurement is valve failure.
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Vereo® Automated Actuators Family
Kinareo™ pMDI High-Throughput Fire-Down System
Reducing variability in test results for OINDPS with automated actuation