Drug overdose is a critical, life-threatening emergency that can happen suddenly and escalate quickly due to ingesting excessive amounts of opioids or other substances. Overdoses may result from both prescription medications and illegal narcotics and can affect individuals of any age, background, or medical history. Without timely and appropriate first-line treatment, overdoses can cause respiratory depression, unconsciousness, and even death. Because drug overdose emergencies usually occur outside of clinical settings, they often rely on non-healthcare practitioners (HCP) to rapidly administer life-saving interventions.

One widely used approach to treating drug overdose is the prompt administration of an emergency antidote that reverses the harmful effects and helps restore normal breathing and alertness. This critical medication is often given through an intramuscular auto-injector—a device engineered to deliver a fast, accurate, and automated dose, even through clothing, which is especially useful in urgent scenarios. Although nasal sprays have gained popularity as a needle-free, easy-to-use alternative, auto-injectors continue to be highly regarded for their consistent effectiveness, precise delivery, and speed. For cases requiring quick, controlled intervention, auto-injectors remain a vital tool in saving lives.

The reliability of the auto-injector device is of utmost importance when considering a scenario where a person in need of immediate drug overdose intervention experiences an auto-injector failure due to a design, manufacturing, or usability issue. This forbidding reality highlights the immense challenges faced in designing reliable emergency auto-injectors. According to FDA Guidance, auto-injectors intended for use in such life-threatening situations must meet strict design specifications to ensure greater than 99.999% reliability of injection success, with a 95% level of confidence, meaning that device-related failure should occur in only 1 out of 100,000 attempted injections. In this article, we will explore some of the design challenges involved in achieving this level of reliability for such life-saving devices.

Reliable Design: The Heart of Auto-Injector Functionality

Reliable design for emergency auto-injectors refers to the engineering processes that ensure consistent performance, accuracy and effectiveness during emergency situations. This includes incorporating features and quality measures to minimize risks of failure, guided by the “5 Rights” concept, which is fundamental for medication administration and patient safety:

1. Right Patient: Ensuring that the device is used on the appropriate individual who is experiencing an overdose.
2. Right Route/Place: The correct injection site must be identified for optimal drug absorption into the intramuscular tissue, improving the chances of survival.
3. Right Drug/Medication: Verifying that the device contains the correct antidote medication in a reliable format, that remains effective despite its required use in a wide range of environmental conditions.
4. Right Dose: The emergency auto-injector must deliver the appropriate amount of medication to effectively counteract the overdose.
5. Right Time: The device must be capable of immediate and rapid deployment, since timing is critical in overdose situations.

The challenge in achieving a successful injection will depend on multiple factors, including:

• Body Size and Composition: Fat tissue, muscle mass, and clothing can influence needle penetration and systemic absorption of medication.
• Injection Site Variability: Anatomical differences between areas of the body affect how the medication is delivered and absorbed.
• Patient Positioning: The effectiveness of the injection may vary based on how the patient is positioned.
• User Training and Administration: In most overdose situations, a bystander or non-HCP caregiver must be able to use the device correctly, whilst under stress.

The Challenge to Get It Right

Emergency-use auto-injectors are designed for use by patients, caregivers or first responders outside of healthcare settings. In critical situations, such as opioid overdose, there may be only one opportunity to correctly use the device, which makes it essential to achieve a successful first-time injection. Since these single-use injectors cannot be test-fired before use, thus creating an inherent risk of failure. Consequently, in order to enable safe and effective operation, FDA recommends the use reliability engineering methodologies.

Several factors influence the design and manufacturing of these auto-injectors, such as:

• Packaging and Safety Mechanisms: Ensuring easy preparation for use and deactivation of any device safety features.
• Use Environments and Transportation of Device: Emergencies are unplanned events and take place in many situations. It is that a device can be kept close to the at-risk individual, requiring that it is designed to be conveniently carried and available for immediate use during everyday situations and environments.
• Injection Activation: Determining the appropriate force required to initiate the device’s injection mechanism.
• Material Selection: Choosing the appropriate materials for the construction of the device.
• Injector Needle Specifications: Addressing needle aspects such as force, depth, insertion, bevel shape, resistance to bending – and assurance of needle patency.
• Needle Penetration Factors: Considering elements such as thickness of clothing, patient skin type, and tissue characteristics.
• Injection Depth and Target Tissue: Ensuring the required depth of needle penetration to effectively deliver the medication.
• Medication Properties: Accounting for factors like the viscosity of the antidote formulation.
• User Information and Feedback: Providing clear, audible, visual, and/or tactile signals to guide correct use of the auto-injector and to confirm successful injection.

Achieving the required needle penetration depth is critical for the reliability of the auto-injector. The injector must reach the intended target tissue within the patient’s body in order to effectively deliver the medication, taking consideration of factors such as variations in patient body size, weight, body composition and other anatomical differences.

To address these challenges, the design team at E3D Elcam Drug Delivery Devices has collaborated closely with manufacturing experts to develop our Flexi-Q EEAI, an emergency auto-injector device platform that accommodates the inherent variability among patients. The design of Flexi-Q EEAI enables a long, needle extension, combined with sufficient power to ensure adequate needle penetration, across a wide range of the patients’ body composition and layers of clothing to be penetrated. The design can be optimized for different patient populations, ranging from small children to large adults, taking into account factors such as skin type, adipose tissue layers, and muscle tissue.

Flexi-Q EEAI’s reliable performance is enhanced by a robust spring-based energy source, enabling the device to deliver a full dose of medication in just 0.2 seconds. With the capability to administer full or partial antidote dose volumes – ranging from 0.15 mL to 1 mL, to tissue depths between 13 mm and 16 mm, its design minimizes the effects of patient variability, in order to achieve consistent and successful injections.

Designing an emergency auto-injector involves several critical steps:

1. Identify Critical Performance Requirements: Define the device’s key performance criteria based on the “5 Rights” framework, as outlined above. Consider device attributes such as size, usability, weight, and design.
2. Learn from Others: Study existing auto-injector designs to identify best practices and opportunities for improvement and optimization.
3. Conceptualization: Collaborate between designers and engineers to create a conceptual design that balances form factor, the need for convenient and immediate use, and mechanical functionality. Prototypes and mock-ups help inform and visualize the design.
4. Feasibility Testing: Engage industrial designers and experts to test the feasibility of all elements of the design. Incorporate feedback loops to refine the design.
5. Analyze and Evaluate: Assess the design’s ability to meet the performance requirements, ensuring reliability, manufacturability and cost-effectiveness. Regular evaluation and feedback throughout the design process ensures that the final product meets the required standards for performance and reliability.
6. Relate Critical Performance to Specific Actions: Ensure that each performance requirement is met by incorporating specific actions into the design, such as precise dosage mechanisms and safety features.

By following such steps, E3D has systematically developed a reliable, cost-effective, and optimized emergency auto-injector that meets the needs of the widest range of patients and potential users.

While the design and manufacturing processes for emergency auto-injectors are well understood, device developers may apply various approaches based on their proprietary technologies and operational expertise. At E3D, challenges and setbacks during the development process for Flexi-Q EEAI have provided valuable learning opportunities, leading to continuous improvement in functionality, reliability, and performance.

Conclusion

The design and development of emergency auto-injectors is a complex and challenging process – and one that requires careful consideration of numerous factors. From achieving optimal needle penetration depth to ensuring delivery of accurate doses of medication, every aspect of the design must be optimized to guarantee successful operation in life-threatening situations. Through a rigorous design process, E3D has created Flexi-Q EAI as a solution that meets the needs of overdose patients and emergency responders, ensuring that these life-preserving products perform reliably in the most critical and stressful scenarios.