Citation: Welch B, “Optimising Clinical Trials with Autoinjectors: Strategies for Success”. ONdrugDelivery Online, January 15, 2025.
Bill Welch of PCI Pharma Services discusses the key considerations for integrating autoinjectors into clinical trial programmes, and the myriad benefits that doing so can bring for trial sponsors in terms of standardisation, data quality and patient-centricity.
“Making the most of autoinjectors in clinical studies requires a strategic approach to address various design, regulatory and user-centric challenges to ensure a successful implementation.”
As the drug delivery industry continually seeks innovative solutions to improve delivery, enhance patient compliance and optimise therapeutic outcomes, autoinjectors have emerged as a pivotal technology. The earlier adoption of autoinjectors into clinical trials is testament to their potential in revolutionising drug delivery systems. However, making the most of autoinjectors in clinical studies requires a strategic approach to address various design, regulatory and user-centric challenges to ensure a successful implementation.
UNDERSTANDING AUTOINJECTORS
Traditionally, single- or multi-use vials have been the primary container of choice for intravenous drug administration during preclinical and early-phase clinical trials. These vials offer significant flexibility in terms of fill volume and dosage, aligning with the primary objectives of early trials – establishing proof of concept, ensuring safety and determining tolerated doses.
“Prefilled syringes, needle safety devices and autoinjector delivery systems are becoming an integral part of product portfolios, catering to the demand for more convenient and patient-friendly options.”
However, with a growing emphasis on patient-centricity and the increasing prevalence of self-administration devices in treating chronic diseases, the industry is shifting towards subcutaneous dosage forms. Prefilled syringes, needle safety devices and autoinjector delivery systems are becoming an integral part of product portfolios, catering to the demand for more convenient and patient-friendly options.
The autoinjector market is experiencing rapid innovation, driven by its potential to improve patient compliance and satisfaction, as well as offer greater product differentiation. Biopharmaceutical companies are actively investing in research and development to enhance device functionality, ensure compatibility with a wide range of drug molecules and incorporate these devices into clinical trials earlier in the development process.
BENEFITS OF AUTOINJECTORS IN CLINICAL TRIALS
The key benefits of using autoinjectors in clinical trials are as follows:
- Improved Patient Compliance and Retention: Self-administration enabled by autoinjectors reduces dependency on healthcare professionals and empowers patients. This convenience can increase adherence to trial protocols, particularly in long-term studies where frequent clinic visits might otherwise lead to dropouts.
- Standardisation of Drug Delivery: Autoinjectors deliver precise and consistent doses, minimising the human error associated with traditional syringe-based methods. This standardisation is crucial for ensuring that the gathered pharmacokinetic and pharmacodynamic data are accurate.
- Enhanced Patient Experience: The user-friendly designs, minimal pain and reduced injection-related anxiety offered by autoinjectors contribute to a more positive patient experience, fostering greater engagement and retention throughout the trial.
- Real-World Insights: Autoinjectors mimic post-market use scenarios, providing valuable data on device performance and patient interaction in a controlled environment.
- Optional Connectivity: Autoinjectors may support add-on modules to capture dosing events, thereby providing confirmation of adherence.
KEY CONSIDERATIONS FOR THE SUCCESSFUL USE OF AUTOINJECTORS IN CLINICAL TRIALS
Despite their many advantages, incorporating autoinjectors into clinical trials requires meticulous planning and evaluation. The following are essential factors that trial sponsors and researchers should consider.
Device Design and Usability
The design of an autoinjector must prioritise ease of use, safety and reliability. During clinical trials, participants may have varying levels of dexterity and familiarity with medical devices. Ensuring that the device incorporates the following design attributes can enhance usability:
- Ergonomics: The autoinjector must be easy to handle and operate, accommodating diverse populations, including those with limited dexterity or vision impairments.
- Intuitive Operation: Clear instructions and simple operation – as few as two steps – are vital to ensure proper use. Features such as audible clicks, visual indicators and tactile feedback can provide reassurance to users and enhance usability.
- Safety Features: Incorporating needle shields, automatic needle retraction and lock mechanisms can prevent accidental activation and needle-stick injuries.
- Customisation: The device should align with the specific requirements of the drug product being tested, such as viscosity, dose volume and injection speed.
- Sustainability: Early in the design process, whilst maintaining product safety and efficacy, eco-friendly device components, packaging and distribution solutions should be considered to identify those that will have the greatest environmental impact.
Drug Compatibility
Autoinjectors must be compatible with the specific drug product formulation being tested. This includes:
- Viscosity and Stability: High-viscosity biologics require autoinjectors with sufficient force to deliver the drug effectively. Additionally, the device must not interact with the formulation and must prevent drug degradation to maintain its stability throughout its shelf life.
- Volume Constraints: It is important to ensure that the autoinjector can accommodate the required dose volume without compromising usability.
- Delivery Speed: Injection speed should be optimised to balance patient comfort and effective drug delivery.
- Dose Accuracy: The device must consistently deliver the intended dose, especially for biologics where precise dosing is critical.
- Shelf-Life Synchronisation: The autoinjector and drug must have aligned shelf lives to ensure usability throughout the trial.
Patient-Centric Considerations
Understanding and addressing the needs of trial participants are fundamental to the success of autoinjector integration. Key considerations include:
- Demographic Diversity: Design and testing should account for variations in age, physical ability and cultural preference.
- Psychological Barriers: Fears related to self-injection should be addressed through features such as hidden needles or automatic retraction mechanisms. This can alleviate anxiety and hesitation, particularly for needle-phobic participants.
- Feedback Mechanisms: Participant feedback should be collected during the trial to identify potential issues and guide future device improvements to enhance overall patient satisfaction.
- Training and Support: Providing comprehensive training materials, including videos and hands-on demonstrations, is critical to ensure that patients understand how to use the device correctly.
Regulatory Compliance
Autoinjectors must meet stringent regulatory requirements to ensure patient safety and device efficacy. Clinical trial sponsors must address the following regulatory considerations:
- Device Classification: It is crucial to understand the classification of the autoinjector in the trial’s regulatory jurisdiction based on its principal mode of action, as it will influence submission requirements and clinical evaluation.
- Combination Product Approval: Autoinjectors are often considered combination products, requiring integrated regulatory submissions for both the drug and device components.
- Human Factors Studies: Conducting usability testing to demonstrate that the product can be used safely and effectively by the intended user population under real world conditions is often a regulatory requirement. Incorporating human factors studies early in the design process can streamline approval processes.
- Material Safety: A vital aspect of design is to ensure that the materials used in the autoinjector are biocompatible and do not interact negatively with the drug formulation.
“Effective autoinjector development requires reliable sourcing, balancing cost and quality and taking strategic decisions between exclusivity, customisation and standardisation.”
Manufacturing and Scalability
Ensuring a robust and scalable supply chain is necessary for the clinical, and ultimately commercial, success of an autoinjector. Effective autoinjector development requires reliable sourcing, balancing cost and quality and taking strategic decisions between exclusivity, customisation and standardisation. The interconnected nature of the drug and device components, each with their own set of manufacturing and sourcing considerations have their own significance.
- Supply Chain Considerations: Reliable sourcing of autoinjector components is vital to avoid delays in trial timelines. Sponsors should establish strong relationships with suppliers, partner contract design and manufacturing organisations, implement risk-mitigation strategies and have contingency plans in place to address potential disruptions.
- Cost-Effectiveness: Balancing device quality with cost is critical, particularly for large-scale trials or when the autoinjector is intended for commercial use post-approval.
- Customisation Versus Standardisation: Deciding between bespoke autoinjectors tailored to the trial drug or off-the-shelf devices, often with a limited set of available options, can impact both cost and speed of development (Table 1).
- Manufacturing Strategy: Defining a low-volume starting point and expected commercial-volume end-point enables the development of a cost-effective scaling strategy, eliminating excess costs for equipment, tooling and validations.
| Advantages | Disadvantages | |
| Established (off-the-shelf) platform |
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| Proprietary (bespoke) platform |
|
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Table 1: Comparison of bespoke and off-the-shelf autoinjectors.
Cultural and Geographic Considerations
Often driven by cost and reimbursement when supplying commercial markets, companies increasingly need to bring different injectable formats to different geographical locations. For clinical studies, the following should be considered:
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- Regional Preferences: Preferences for device design, operation and language may vary across geographies, necessitating region-specific adaptations. For example, the preference in eastern Europe may be vials for with syringes with western Europe and the US looking to more advanced prefilled syringes with safety devices and autoinjectors, or even on-body injectors.
- Healthcare Infrastructure: Trials conducted in areas with limited healthcare access may benefit from autoinjectors designed for robust performance in diverse settings.
Cost Implications
The inclusion of autoinjectors in clinical trials involves significant financial considerations. Sponsors should evaluate:
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- Device Manufacturing Costs: It is important to ensure scalability and cost-efficiency in producing trial-specific devices while also keeping an eye on the future and costs associated with larger scale commercial volumes.
- Training and Support Expenses: Resources should be allocated for comprehensive training and ongoing participant support.
- Long-Term Value: Although developing autoinjectors for clinical use brings significant upfront costs, long-term value should be assessed to review the potential cost savings through improved adherence and reduced reliance on healthcare facilities.
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Post-Trial Transition
The ultimate goal of incorporating autoinjectors in clinical trials is to prepare for real-world implementation. Key strategies for a seamless transition include:
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- Feedback Integration: It is wise to use trial findings to refine the device’s design and functionality.
- Regulatory Documentation: Comprehensive data should be compiled to support regulatory submissions for commercial use.
- Market Preparation: During development, patient education materials and training programmes should be prepared for broader deployment.
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BOX 1: PCI SUPPORTING THE SUCCESSFUL INTRODUCTION OF AUTOINJECTORS INTO CLINICAL TRIALS
- Scalable Sterile Fill-Finish Solutions: With a global sterile manufacturing network, PCI can support all its partners’ injectable clinical trial needs from parallel container closure studies to vial, prefilled syringe or cartridge filling and full analytical development.
- Device and Manufacturing Strategy Advice: PCI leverages deep industry expertise to guide clients in creating patient-centric drug-device combinations. Advising on strategies from established platforms to innovative designs, PCI ensures regulatory alignment and a patient-centric focus. The company’s in-house packaging design team is integrated early in the design process, delivering cost-effective solutions through human-centric engineering for late-phase clinical trials and efficient, accelerated market entry.
- Device Agnostic Scalable Technology: PCI’s device-agnostic technologies provide true customer focus and flexibility. For example, the company’s small-to-mid scale autoinjector assembly lines provide multi-platform solutions, including YpsoMate (Ypsomed), Molly (SHL Medical), and Physioject (BD), alongside other platform devices. Additionally, the capability to assemble and label needle safety device platforms, such as BD Ultrasafe/Plus and Safe & Sound (Nemera), makes PCI ideal for development studies, clinical trials and niche orphan drugs.
- Comprehensive Tooling for Most Common Platforms: Supporting a quick-to-patient supply chain, PCI’s scalable, device-agnostic technologies, coupled with its extensive, readily available assembly and test tooling for the most common device platforms, removes the lengthy lead time of up to six months for new tool sets and provides significant validation time and asset cost savings
- Autoinjector Testing to Ensure Patient Safety: PCI’s in-house laboratories provide a range of packaging and analytical services to support its clients’ development, clinical and commercial supplies of medicines globally. From product ID testing, method transfer, release and stability testing to autoinjector system testing with ISO 11608 functional tests, such as cap removal force, activation force, extended needle length, dose accuracy, injection time and lockout force, PCI ensures that life-changing therapies meet regulatory guidelines and are safe for patient use.
CONCLUSION
Autoinjectors represent a transformative advancement in drug delivery, offering significant benefits for both clinical trials and real-world applications. Their ability to enhance patient compliance, ensure consistent dosing and improve the user experience makes them invaluable in modern healthcare. However, their successful integration into clinical trials requires careful consideration of design, regulatory and user-centric factors.
“By addressing these challenges early and proactively, trial sponsors can harness the full potential of autoinjectors, ensuring that they meaningfully contribute to the trial’s success and pave the way for innovative therapeutic solutions.”
By addressing these challenges early and proactively, trial sponsors can harness the full potential of autoinjectors, ensuring that they meaningfully contribute to the trial’s success and pave the way for innovative therapeutic solutions. As the healthcare landscape continues to evolve, autoinjectors will undoubtedly play an increasingly prominent role in shaping the future of patient care.
Find out more about PCI Pharma Services here: pci.com.