PDA Universe of Pre-Filled Syringes and Injection Devices Conference 2024 Posters

The MediPhorum Drug Delivery community represents eleven global organizations from the BioPharma industry coming together to collaborate and share knowledge on combination products for drug delivery.

The MediPhorum Drug Delivery community collaborates on a number of key topics that are vital for combination product development: Risk Management, Biocompatibility, Essential Performance Requirements, Human Factors and Regulatory considerations.
The objective of this poster presentation is to convene subject matter experts and thought leaders from various collaborative groups to exchange insights and tackle challenges pertinent to drug-device co-development. The ultimate goal is to refine an optimized model for Drug/device co-development.

The development of combination products demands a synergistic approach that spans pharmaceutical sciences, engineering, regulatory insights, and clinical research. Initiating device development at the Discovery/pre-clinical development stage (IND) is critical, with effective communication between drug and device teams being fundamental to success.

In February 2023 a restriction proposal to the European Chemicals Agency (ECHA) was submitted by five member countries of the European Union proposing a substantial restriction under the Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) regulation Annex XV for the use of all PFAS variants, thereby potentialy listing all PFASs as Substances of Very High Concern (SVHC).

The poster will address the development of the proposal to restrict and the corresponding proposal options defining the transition and derogation periods if the restriction is approved by the EU commisions, how it may affect parenteral primary packaging and what options are there.

PFS development requires a comprehensive understanding of the forces involved in drug administration that affect dose accuracy, injection safety, and patient adherence. To better predict injection dynamics, we refined the mathematical model for injection force by integrating both hydrodynamic and frictional forces.

In the improved model, we included drug viscosity properties (both Newtonian and Shear-thinning) and the syringe shape constant in the hydrodynamic force analysis, following the Hagen-Poiseuille law, and derived the friction force from empty barrels. The model also took into account the actual environmental temperatures during administration. Results highlighted the critical roles of the syringe shape constant and the rheological behavior of protein solutions in governing injection force dynamics.
We considered the counter pressure generated by the tissue during actual administration to address the inaccuracies in current injection force evaluations conducted in air, especially when the viscosity of the injected drug solution is below 9.0 cP (injecting with 1 mL L PFS staked with 29G ½ inch needle).

Finally, a simplified human factor study on injectability against viscosity was conducted, indicating that healthy adults were comfortable injecting medication with a viscosity of approximately 20 cP (1.0 mL in a 1 mL long PFS) within 15 seconds.

The regulatory landscape requires the identification and assignment of several control elements when developing a drug device combination product (DDCP).

Next to CQAs that are well established for drug products, primary functions (PFs) are required per ISO 11608-1, essential design outputs (EDOs) are required per ISO 13485:2016 and by 21 CFR 820.30, and essential performance requirements (EPRs) are used and required by the FDA. All these control elements aim for safety and efficacy and shall be declared for DDCPs.

At Boehringer Ingelheim, we have established a process that allows us to derive these control elements based on risk management according to ISO 14971, in a systematic and traceable approach. The definition of Critical Functions during the identification of Hazards allows to identify Primary Functions in a very early project stage supporting a control element-directed development.

Furthermore, we created the document “Device Control Plan” that gives an overview on critical design-related aspects. It documents which control elements are relevant for the product-specific CSS, keeping the CSS lean.

An engaging infographic format identifying sustainable design principles, theories, practices and technologies applicable to medical and pharmaceutical devices, that can be deployed to make significant reductions in device or system footprints, down to net zero. Circularity will be identified as the primary objective for sustainable design. The poster will highlight design opportunities in materials, manufacturing, transport, use, and end-of-life phases that facilitate emissions reduction and enable steps to be taken toward full or partial circularity. This will include the following categories:

• Sustainable design principles, including resource reduction, behavioural change, and system opportunities such as product-as-a-service business models.
• Technical considerations, such as manufacturing, packaging, electronics, and transport.
• Opportunities for component or module re-use, in preference to recycling or other waste streams.
• Materials, looking at conventional and alternative materials, and highlighting key meanings in sustainability claims such as mass-balance or recycled content.
• Tools and future technologies such as Life Cycle Analysis and lifecycle tracking through Digital Product Passports or Unique Device Identifiers.

In the intricate landscape of pharmaceutical packaging, elastomeric closures emerge as indispensable keystones, playing a pivotal role in fortifying the integrity and efficacy of injectable drug products. Beyond mere containment, these closures exert influence over critical aspects such as administration precision, maintenance of sterility, and the formidable prevention of product contamination.

For decades, the U.S. Pharmacopeia (USP) has been the guiding beacon, offering insights into the evaluation of sterile product packaging integrity through USP 1207 Package Integrity Evaluation – Sterile Products. Recently, however, the pharmaceutical landscape has witnessed a significant paradigm shift with the revisions encapsulated in USP 382, a focused directive set to reshape industry standards, particularly with respect to products employing elastomeric closures.

Understanding proper CCI method selection for PFS, risk assessment, and component compatibility lead to packaging success.

Manufacturers are increasingly challenged to meet the demand for high-speed and large scale production and the need for containers that can be filled quickly and efficiently, while reducing costs without compromising on quality or regulatory compliance. In addition, with increasing regulatory pressure, companies need to find ways to reduce CO2 emissions and minimize waste management cost. Therefore Bausch+Ströbel SE+Co. KG partnered with SCHOTT Pharma for gamechanging transformations to achieve operational excellence and sustainability, while maintaining the production of high quality drugs. 

With the new 10 x 16 TOPPAC® Nest 160 our customers operational efficiency and sustainability is unlocked by increasing efficiency as much as 60%. Thanks to the optimized packing density 67% more syringes per nest can be processed in comparison to the conventional 10 x 10 Nest 100. This makes the Nest 160 in combination with the SFM5072 filling and closing machine from Bausch+Ströbel ideal for high-speed production of vaccines, diluents or dermal fillers, without compromising on quality or sterility and with 100% identical inspection.

Manufacturers can retrofit their existing and proven processing B+S nest filler SFM5072 and benefit from a 60% increase in output, higher machine availability, a reduction in waste and all with the same machine footprint.

Large-volume auto-injectors and wearable devices exceeding 2.25ml play a crucial role in the transition from hospital-based intravenous (IV) treatments to self-administration via subcutaneous (SC) injection.

These devices are pivotal across various medical fields such as oncology, immunology, and neurodegenerative diseases, where they are often tasked with delivering high-viscosity and delicate biologics.

Ensuring the highest standards of quality and purity in elastomers, along with flawless functional performances, is imperative to guarantee the reliability of administration and patient safety.

In this presentation, we will delve into the technical hurdles encountered in designing and manufacturing larger coated plungers for pre-filled syringe (PFS) and cartridge containers intended for device integration.

We will showcase our journey in conceptualizing and refining these new plungers, as well as evaluating their performance throughout the entire value chain to the patient.

Additionally, we will underscore the significance of fostering an open collaboration with the container manufacturer and among the additional stakeholders involved in the development of the final combination product.

Transitioning from concept to production design in drug delivery devices requires meticulous planning and execution. This poster explores strategies crucial for this transition for implementation during the innovation phases. Before moving to production design, critical-to-function parameters must be thoroughly explored for feasibility and optimization. Collaboration with critical suppliers is essential to identify component performance and reliability boundaries, particularly in the context of modern electromechanical devices in drug delivery.

Beyond force specifications and injection stroke lengths, understanding the usability features of device presentation is vital during the innovation phase. Secondary packaging solutions, instructions for use, and quick reference guides undergo design/build/test cycles to define successful product presentation aligning with clinical setting, strategic vision, and user expectations. Clarifying these characteristics before the transfer-to-production phase facilitates efficient and informed decision-making. Micro case studies from a host of customer programs are included to illustrate the critical scaffolding needed to navigate this transition.

Artificial Intelligence (AI) is increasingly playing a pivotal role in research and development (R&D). BD is focused on applying AI to de-risk combination product development for our pharma partners. Two examples using AI in BD are highlighted:

• Deep learning for Sub Visible Particulate (SVP) analysis:
  Characterization of SVP in pharmaceutical containers is difficult due to their diverse origins.  Their morphology and size vary significantly and are assessed by flow imaging techniques. The accurate identification of SVP is challenging yet essential to derisk combination product development of biologics. Through a partnership with IBISC and SATT, we are using AI to develop a new model that combines existing methods to identify subvisible particles. The goal is to increase confidence in distinguishing between protein aggregation and other subvisible particles.
• Knowledge Capitalization:
  Knowledge is an invaluable asset, particularly in the realm of innovation in R&D.  The capitalization of tacit knowledge, powered by AI, not only fuels our innovation engine but could also provide benefits in terms of reduced innovation lead time and effective risk mitigation. Our commitment to knowledge capitalization and rapid innovation aims to translate into high customer satisfaction.

mRNA technology represents a significant breakthrough in drug development. Several mRNA- based vaccines candidates are in the pipeline for the prevention of influenza, respiratory syncytial virus, cancer, and other diseases.

When glass pre-fillable syringes have been developed, typically tests have not been carried out at temperature below 0°C. Rapid temperature changes can cause glass to expand or contract suddenly, leading to potential breakage. Additionally, cold temperatures can affect the flexibility and movement of the plunger, potentially causing functionality concerns and impact container closure integrity. Consideration must be taken by using rubber materials designed to maintain flexibility at low temperatures.
With this poster, we provide new data on low temperature storage and demonstrate that the key attributes for functionality of glass pre-fillable syringes have been met. Focus is on the behaviour of the glass barrel and the sealing interfaces.

Authors:

Luca Durante, Technical Support Engineer, Nipro PharmaPackaging International
Charlotte Leconte-Ostrowski, Product Portfolio Manager PFS, Nipro PharmaPackaging International

RFID technology is mainstream in retail where apparel is tracked and inventory is managed with digital reader systems. All items at e.g. Walmart, Nordstrom and H&M are equipped with an RFID tag. Thus, warehouse managers and sales staff have full visibility on the movement and availability of items. The pharma industry is starting to follow this trend.

Pre-filled syringes equipped with RFID are gaining importance in US hospitals. Administration of drugs for use in the operating room is enormously facilitated with RFID. Inventory, recall and lot/expiry management are digitized, easy and accurate. Smart cabinets can read and document every step in the supply chain and keep track of drugs on item level. Another advantage is the efficient return process of unused drugs to inventory.

But how to prove that a syringe has not been opened while being removed from inventory? There is obviously a critical gap in the automated process as manual intervention is required to check PFS integrity. This gap can now be closed with a digital seal assuring that a life-saving data point is tracked though the whole chain of use. This is not only crucial for patient safety but also to monitor diversion and misuse of drugs.

The patient’s voice is often missing in medicine and device development processes. This poster presents our methodology for developing a deeper understanding the capabilities of patients across different disease areas.  We aim to listen and ensure the patients’ voices are at the forefront of the decisions we make—from early research through to marketed products.

An important component in the development of the voice of the patient is our User Capabilities methodology and tools which were developed by GSK’s Inclusive Design team in collaboration with the University of Cambridge and an external research consultancy. Through direct engagement with patients, our survey tool presents a suite of questions that yield the data building blocks for analysis and development of patient capability profiles. This provides a clear picture of the capability loss patients experience due to their health conditions, and highlights aspects that will require particular attention in research and development processes to ensure that exclusion from the use of our products is minimized.

Design verification is often thought about far too late in device development, leading to a compressed timeline to achieve a successful outcome, as well as the potential for costly late-stage design iterations. It is all too easy during pre-verification activities to underestimate the time and costs that go into test method development and validation, as well as the number of samples that are needed and the implications in terms of manufacturing capabilities.

Since 1997, the FDA ‘Design Control Guidance for Medical Device Manufacturers’ has offered a waterfall diagram which shows how design controls can be applied to any product development. This arguably over-simplified representation of design controls has since been adapted by device manufacturers to meet their specific requirements, resulting in a variety of “out of the box” approaches to design verification thinking.

This paper will highlight some of the most effective “out of the box” thinking for design verification, discussing how early influence and pre-verification planning can help to de-risk the verification phase and help to save time and costs in the long run.

The SKAN ebeam is designed to transfer pre-sterilised tubs with RTU components like syringes, vials, and cartridges into an isolator filling line. It is a safe surface sterilisation and transfer system for high-speed sterile pharma production, but also for C(D)MOs who seek a flexible and efficient transfer solution for different products and container sizes. 2”, 3”, and 4” tubs can be processed with only minor adjustments.

The ebeam tunnel is not only available as part of new installations but can be integrated into existing isolator filling lines. This does not only offer you state-of-the-art technology with a small footprint, but also decreases your operational expenditure (OPEX) in the long run.

Designing combination devices for individuals with hand impairments requires designers to give great care to the accessibility and user experience of the product; dexterity, precision, control, and comfort — without them, no combination device design is a success. Ergonomic design is a strategy whereby all decisions made throughout the development process are considered through the lens of the user.

Five key human factors to consider when designing a combination device that delivers a drug for people with hand impairments are as follows:

1. The varying sizes, shapes, and capabilities among people’s hands.
2. The design of combination devices and their relation to prevalent diseases.
3. The transition from a dexterous multilateral grip to a clamping pincer grip.
4. The hands’ pruning, with skin becoming translucent and prone to tearing.
5. The discrepancies between patient-reported behaviors and observed actions.

Hand impairments significantly alter grasping strategies and underscores the urgency of user-centric design. Understanding nuances between people with hand impairments is key to creating world-class ergonomic designs; by prioritizing user experience and observing real behaviors, designers can create ergonomic solutions tailored to the unique needs of patients with hand impairments.

Extended injection durations and a fear of needles are common hurdles encountered by patients with needle-based injection therapies. The use of highly viscous formulations further exacerbates these challenges. To address these issues, we present an alternative method: a needle-free drug delivery system called PRIME. Here, we showcase a series of comprehensive studies assessing PRIME’s capabilities in terms of viscous ejection and injection durations in comparison to an autoinjector and a needle & syringe. We demonstrate the performance and translatability of jet injector technology from benchtop air ejections to ex-vivo porcine tissue injections.

Using various concentrations of polyethylene glycol, we were able to simulate the patient experience of injecting medications with a range of viscosities from cold storage to room temperature. 1 mL ejection durations in air and injection performance into porcine ex-vivo tissue were assessed. Results demonstrated the ability of PRIME to consistently eject and inject low to high viscosity fluids with a 0.3 s duration. This injection performance was compared to an autoinjector with ejection durations of 1-2 min and needle & syringe injection durations up to ~25 s. An analysis of injection deposition in tissue revealed no significant differences between PRIME and the needle & syringe.

Every New Drug Application must include an extractables and leachables study to demonstrate the drug is safe. Several guidance and recommendations documents provide insight on how to perform these analyses and which methods to use, but as each drug combination product is unique, Pharma manufacturers must adapt to the requirements of their drug.

In this poster, we dwell into the techniques that are most appropriate to perform a robust extractables study, the adaptation required for addressing specific drug storage conditions, choice of solvent and the definition of the Analytical Evaluation Threshold (AET) for subsequent leachables analysis. We describe how to perform semi-quantitative and quantitative studies while allowing for identification of the leached compounds, to provide pharma partners with a complete dataset that demonstrates the drug’s safety while supporting regulatory filing.

We also present a case demonstrating how extractables studies can be designed by components suppliers without having prior information on the final drug products while ensuring it is appropriate for regulatory filing. When combined with simulated leachables studies, such approaches can greatly support pharma partners in anticipating the result of their actual leachable studies and support them in choosing the most appropriate closure solution for their drug.

When submitting a generic drug-device combination product in the US, pharmaceutical companies must follow the FDA guidance “Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA: Draft Guidance for Industry”. As part of this guidance, a threshold analysis is performed to assess the differences between the Reference Listed Drug (RLD) and the generic drug-device combination product. If “other” differences are identified, a comparative use human factors (CUHF) study may be needed to prove the non-inferiority between the two products. 

During this presentation, a case study will show how a device constituent developer performed a comparative analysis and formative CUHF study to help inform pharmaceutical companies’ final CUHF parameters and de-risk their combination product ANDA submission.

A pressing challenge facing designers of medical devices today is the goal to develop robust products while striving towards net-zero carbon emissions. Delrin® acetal can contribute to this journey.

This presentation considers the whole life cycle of a device, considering material selection, component design, energy in manufacture and end of life considerations, including handling of returned post-consumer devices.

Using the example of an autoinjector device, the discussion begins with material selection, comparing global warming potential (GWP) of the various plastics in use today. Here we describe how Delrin Renewable Attributed, produced from renewable feedstock, shows potential to reduce GWP significantly while maintaining the properties and regulatory compliance.

Next the focus is design, considering how harnessing a material’s superior mechanical properties and long-term performance, enables the design of products with less material and greater longevity.

With low GWP materials the need to accurately model the energy of injection molding becomes increasingly important.  This section provides insight into how alternative models can better match the reality.

Finally, we will consider practical end-of-life considerations of devices including opportunities for mechanical recycling by exploring mixed plastic separation through processes such as density, electrostatic and NIR separation – assessing their yield and efficiency.

The growing demand for subcutaneous (SC) drug administration, especially for high-dose indications, has driven the development of high concentration formulations. While chemical issues like deamidation and isomerization are typically independent of drug delivery, physical challenges such as aggregation, viscosity, and volume are closely tied to device selection. High concentration formulations also face reduced yields due to potential equipment adsorption and blockages, further linking formulation and device teams in SC combination product development. Despite this interconnectedness, cross-functional team members without a background in formulation science often fail to appreciate the time, costs, and risks involved in creating high concentration SC formulations. This misunderstanding can lead to project timeline delays, ultimately affecting clinical trial entry and product launch.

This survey study delves into expert opinions and insights from formulation science experts regarding challenges with high-concentration formulations, their preferred ways of working with device teams, and their preferences in SC combination product development. The goal is to understand the trade-offs between high and low concentration formulations in SC combination product development. Additionally, it examines the utility of on-body delivery systems with large volume capacities (5-25 mL) as an alternative to developing high-concentration formulations, which may reduce formulation complexity and associated risks.

There is an increasing recognition that health care and its supply chains are important contributors to greenhouse gas emissions (GHG). Today they collectively represent 8.5% of US GHG emissions, and approximately 5% of global emissions. This presentation will review a Life Cycle Assessment (LCA) performed per ISO 14040 and 14044 that quantifies the environmental impact of five different sterile drug injection solutions:

1. Single-Dose Glass Vials and Syringes
2. Multi-Dose Glass Vials with Syringes
3. Luer Prefilled Syringes
4. Staked-type Prefilled Syringes
5. ApiJect Platform (blow-fill-seal container and needle assembly)

The LCA includes comprehensive life cycle stages from cradle-to-grave, encompassing all upstream materials production, manufacturing, inspection, packaging, transportation, use, and waste management. The study finds a substantial difference in the environmental impact comparing the injection platforms, favoring the ApiJect Platform across all categories of resource use and environmental impact. The carbon footprint impact is especially noteworthy.

Disclaimer: the ISO 14040 and ISO 14044 critical review is in process and will be completed prior to the conference in October.

Smart devices and the digital health applications that support the training and use of injection devices can be powerful tools to enhance patient engagement and promote better health outcomes. Effectively leveraging these digital technologies relies on a robust understanding of the patient, their care journey, and the behaviors and mentalities that have the greatest impact on device use.

In this talk, the presenter will highlight a behavior design framework that demonstrates how device manufacturers can embed an understanding of the patient in the design of digital health applications, to effectively target engagement and adherence. The framework will illustrate how to:

1. Conduct exploratory research and experience mapping activities to contextualize injection device use, errors, and anxieties within broader care journeys.
2. Translate this research to prioritize pain-points and behaviors that have the greatest impact on clinical outcomes, and thus are the most relevant to specifically target in the product design.
3. Apply behavior science methods to identify techniques from the literature that have shown success in analogous use cases, ensuring concept designs (e.g. educational tools, adherence tracking) are rooted in evidence.
4. Iteratively conduct UX design activities informed by risk-benefit analysis, behavior science, and user insights.