Author: Cambridge Design Partnership

181_2025_Dec_CDP_header
By Karla Sanchez, Emily Chang and Jessica Alzamora
January 14th 2026
Find the authors
on LinkedIn:
Karla Sanchez

Karla Sanchez

Head of Biomedical Engineering
Emily Chang

Emily Chang

Biomechanical Engineer
Jessica Alzamora

Jessica Alzamora

Mechanical Engineer

Precision Delivery: The Missing Link In Cell & Gene Therapy

Featured in ONdrugDelivery News, Jessica Alzamora, Dr Karla Sanchez and Emily Chang discuss the necessity for precision when delivering cell and gene therapies, explore how this precision can be designed and demonstrated, then go on to describe how a minimum viable product approach to device development can act as a strong predictor of a successful drug delivery device.

Cell and gene therapies (CGTs) are at the forefront of precision medicine, with the potential to repair or replace faulty genes and cells to treat disease at its biological source. Despite this promise, the success of CGTs depends on one defining factor: precision. Every stage, from designing a vector to delivering it in the body, demands careful control to ensure that the treatment reaches the targeted region and/or cells, at the right dose and with minimal off-target effects (Figure 1).

 

181_2025_Dec_CDP_Fig1
Figure 1: Commonly targeted delivery sites for CGTs.

A clear example of this reliance on precision comes from a currently available gene therapy to help improve functional vision in patients with an inherited retinal disease due to a genetic mutation. The approved adeno-associated virus 2 (AAV2) gene therapy Luxturna® (voretigene neparvovec, Spark Therapeutics, Philadelphia, PA, US) must be delivered via a highly targeted subretinal injection to ensure that the therapy reaches and acts on the exact layer of cells needed for vision. Even small variations in injection depth or placement can change how effectively it restores function, and incorrect placement can increase the risk of inflammation.1 This shows that the success of a therapy depends as much on how it is delivered as what it delivers – the therapeutic effect is dependent on the accuracy of the delivery modality.

To unlock the full potential of CGTs, the industry must not only consider molecular innovation but also focus equally on the method of precision delivery to expand the pivotal link between discovery and patient benefit. Achieving reproducible precision will determine how effectively these breakthroughs translate from rare success stories into accessible, scalable therapies.

“This shows that the success of a therapy depends as much on how it is delivered as what it delivers – the therapeutic effect is dependent on the accuracy of the delivery modality.”

Where Precision Matters Most In CGTs

CGTs are not produced in the same way as small molecules or standard biologics. Many programmes are patient-specific or produced in small, labour-intensive batches, with customised biomanufacturing and strict cold chain to preserve vector integrity or cell viability. These constraints make products extremely costly: Luxturna®, for example, is priced at around US$850,000 (£650,000) per patient.2 Given the resource-intensive nature of producing usable material, development teams must prioritise process efficiency and precision from the earliest stages of production.

Potency and safety are also tightly linked. Small deviations in target delivery or poor biodistribution control can provoke serious immune-mediated toxicities,3 among other serious side effects, which is particularly true in gene therapies.4 For instance, intrathecal delivery (administration into the cerebrospinal fluid, e.g. via lumbar injection, allowing direct access to the central nervous system) can have a biodistribution-associated risk that results in dorsal root ganglion inflammation and neuronal degeneration, particularly with higher doses, where neither the therapy’s tropism (affinity with specific cells) nor cerebrospinal fluid dynamics have been fully characterised.4

“Precision in where and how therapies are delivered determines how safely it can be dosed, how consistently it can be scaled and how much product is needed to achieve a therapeutic effect.”

Some therapies may only succeed when they are placed with millimetre-scale accuracy. For a rare neurological disorder called aromatic L-amino acid decarboxylase deficiency, the AAV2-based therapy Upstaza™ (eladocagene exuparvovec, PTC Therapeutics, Warren, NJ, US), is delivered through stereotactic neurosurgery, which delivers four small infusions into the putamen in a single session (two per hemisphere).5 The product label specifies the route, infusion sites and dosing parameters, as the efficacy of the therapy depends on reaching the correct brain region while avoiding wider systemic exposure. This is precision delivery built directly into the treatment’s design. Furthermore, for one-off or single-administration gene therapies, re-delivery may not be possible (e.g. due to pre-existing antibodies to AAV) or may be considered too risky to conduct (e.g. direct-to-brain administration).

Precision in where and how therapies are delivered determines how safely it can be dosed, how consistently it can be scaled and how much product is needed to achieve a therapeutic effect.

When Precision Becomes A Moving Target

Precision is easy to define, in theory, but difficult to achieve in practice. For many CGTs, location, distribution and dose must be defined long before clinical trials begin, yet each is influenced by complex and patient-specific variables (Figure 2). Precision is less critical for ex vivo approaches, such as chimeric antigen receptor T-cell therapies, where cells are modified outside of the body prior to intravenous administration. These treatments have demonstrated success, as seen with Kymriah® (tisagenlecleucel, Novartis) and Yescarta® (axicabtagene ciloleucel, Kite Pharma, Santa Monica, CA, US) in haematological malignancies. In contrast, precision becomes far more consequential for in vivo gene and stem cell therapies. What seems simple – such as targeting a specific organ for a rare disease – quickly becomes challenging when teams must decide what level of precision is sufficient in terms of which part of the organ and its diverse cell populations to target for the therapy to be effective.

181_2025_Dec_CDP_Fig2
Figure 2: Achieving the correct location, dose and distribution.

Location

This challenge is clearly visible in liver-directed AAV therapies, where defining location goes beyond reaching the organ itself. The liver’s intricate vasculature and cell diversity means that vector access and expression vary widely, while efficacy depends on transducing enough hepatocytes without excessive uptake by other cells that may trigger immune responses or reduce potency.6 Achieving this balance relies on optimising the route of administration, delivery site and dose flow control.

Distribution

Parameters such as vector concentration, infusion rate and device (e.g. cannula) geometry determine how the therapy is distributed through the tissue and how reliably it reaches target cells. To manage these interdependencies, computational and experimental modelling are integral throughout development of the therapy and delivery device. By modelling vector flow, convection and uptake in patient-specific anatomy, device developers can predict how a formulation or delivery approach will behave before starting animal studies, or they can refine it alongside these studies. These models enable the integrated team (composed of formulation/modality specialists, device developers and more) to optimise distribution patterns, reduce experimental uncertainty and accelerate iteration, allowing precise delivery to be engineered rather than inferred.

Dose

A clearer understanding of anatomical location and distribution also improves how the team defines and manages dose precision, which ultimately determines efficacy and safety. Dosing CGTs is about far more than volume; it reflects how much active vector or number/type of cells are needed to ensure the desired effect within the target tissue. Achieving precise dosages means controlling both potency and delivery conditions so that the administered quantity can translate into a safe and effective treatment. Advances in data analytics (e.g. vector analysis), flow-controlled infusion and real-time delivery monitoring are helping to define this relationship more accurately, enabling teams to move from empirical dose escalation to evidence-based dose design.

Although device design cannot completely negate biological variability, it can stabilise the physical conditions of delivery in terms of location flow and distribution, reducing the influence of external factors on therapeutic performance. In this sense, delivery systems are an integral and essential part of the therapy’s design; the therapeutic without the device is useless. A minimum viable product (MVP) delivery device is essential even in early-stage therapy development, as it underpins both the predictability and scalability of clinical outcomes, as well as reducing risk to both the patient and therapy programme.

How To Demonstrate Precision

If defining precision is difficult, demonstrating it under clinical conditions is even harder. Many CGTs show encouraging results in modelling and in vitro studies, only to encounter unexpected variability once tested in animals or humans. Translating a theoretical understanding of location, dose and delivery pattern into reproducible, in vivo performance remains one of the toughest challenges in the field.

The difficulty often emerges during the transition from therapeutic discovery to device-specific preclinical testing. Early studies may demonstrate vector bioavailability or device function separately, focusing on establishing foundational performance characteristics; however, this separation can limit understanding of how the two interact under physiological conditions. As a result, the first time the full system is tested, typically in animal models, teams may struggle to interpret poor outcomes. The question being: is the issue with the therapy itself or with how it was delivered?

If the delivery device or route is not well characterised before entering in vivo preclinical work, study design, surgical procedures and even success criteria can become ambiguous or have a lack of reproducibility.

Study Design

Preclinical study design therefore becomes the first true test of precision. The chosen route of administration determines not only how the therapy will be delivered, but also which model is appropriate for advancing an MVP approach to device design that supports overall therapy development. For example, a device that matches the therapy development stage and its requirements allows for evidence gathering on the control of delivery – isolating results for therapeutic effectiveness.

Anatomical and physiological differences, particularly in vascular structure, tissue density or organ size, mean that delivery parameters optimised in animals may not translate directly to humans. Building these constraints into the study design early on can help teams interpret results with greater confidence.

Procedural Control

Demonstrating precision also depends on procedural control. Every step, from therapy preparation and handling to administration and post-delivery care, can influence efficacy. For cell therapies, cell sedimentation during preparation or delays between thawing and delivery can alter dose consistency and viability. For gene therapies, infusion rate, device placement and user variability can all shift distribution patterns. Integrating human factors engineering into device and protocol design using procedural expertise helps to standardise these steps, thus improving reproducibility and safety.

Regulatory Scrutiny

Ultimately, preclinical and clinical studies are where precision delivery meets regulatory scrutiny. Demonstrating that a therapy and its delivery system consistently achieve targeted exposure is essential for proving both safety and efficacy. Without an early integrated approach to development of the device, formulation and route of administration, teams risk employing complex and expensive animal models or clinical studies only to discover that the delivery method itself limits their ability to assess therapeutic potential.

Incorporating delivery design and evaluation early in development is therefore not just good engineering – it is a strategic safeguard. Precision that is defined, engineered and tested in parallel with the therapy dramatically increases the chances of reproducible success in the clinic.

Conclusion: Precision Delivery Is The Next Frontier

The future of CGTs will not be defined solely by novel vectors or manufacturing breakthroughs, but by the industry’s ability to deliver these therapies with accuracy and consistency at scale. As CGTs move towards broader indications, the need for predictable, accessible delivery will only intensify. Achieving precision demands earlier integration of biological, engineering and human factors design, alongside continued investment in modelling and device innovation. Precision delivery bridges the gap between discovery and patient impact, turning theoretical efficacy into real-world benefit.

The lesson is clear: precision delivery is not a supporting technology, but the missing link that will connect scientific ingenuity with clinical and commercial success. Those who master it will define the next era of CGTs.

“The future of CGTs will not be defined solely by novel vectors or manufacturing breakthroughs, but by the industry’s ability to deliver these therapies with accuracy and consistency at scale.”

References
  1. Patel MJ et al, “Surgical Approaches to Retinal Gene Therapy: 2025 Update”. Bioengineering, 2025, Vol 12(10), art 1122.
  2. “Spark’s gene therapy price tag: $850,000”. News Article, Nature Biotech, Feb 6, 2018.
  3. Morris EC, Neelapu SS, Giavridis T & Sadelain M, “Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy”. Nature Rev Immunol, 2022, Vol 22(2), pp 85–96.
  4. Perez BA et al, “Management of Neuroinflammatory Responses to AAV-Mediated Gene Therapies for Neurodegenerative Diseases”. Brain Sci, 2020, Vol 10(2), art 119.
  5. “Upstaza (eladocagene exuparvovec)”. Web Page, EU EMA, accessed November 2025.
  6. Cao D et al, “Innate Immune Sensing of Adeno-Associated Virus Vectors”. Hum Gene Ther, 2024, Vol 35(13–14), pp 451–463.

Get in touch

This article highlights how the right device can turn complex two-component injectables into simple, safe, and accessible treatments. If you’re exploring delivery challenges or want to design patient-friendly solutions for advanced formulations, we’d love to talk.

Contact Us
|||||
By María FM Balson
October 8th 2025
Find the authors
on LinkedIn:
María FM Balson

María FM Balson

Consultant Biomedical Engineer

Delivering complexity: device considerations for two-component injectable formulations

Featured in ONdrugDelivery, María FM Balson shares her expertise in device selection for two-component injectable formulations, and why this product area is becoming increasingly important.

Since the 1980s, when modern-day prefilled syringes (PFSs) and intravenous (IV) bags became prevalent, injectable drug delivery has steadily moved towards ready-to-use formats and integrated devices – as evidenced by the widespread adoption of self-injection devices such as autoinjectors and pen injectors.

Human factors considerations, now recognised as integral to safe and effective use of such drug-device combination products, have driven a clear trend towards simpler, more automated solutions with fewer use steps. This shift has enabled at-home care for more therapies than ever before – a key development given the growing strain on healthcare systems.

Nevertheless, the delivery of certain drugs, such as lyophilised injectables, often remains burdensome and dependent on administration by specially trained professionals. As injectable therapies evolve and become more complex, unique challenges and opportunities emerge.

Two-Component Injectables on the Rise

Let’s define two-component formulations as those consisting of two parts that, for stability or other reasons, must be kept separate throughout the product’s shelf-life, and are delivered together at the point of administration. The two constituent parts may be a solid drug and a liquid solvent or diluent (e.g. sterile water for injection) that must be mixed thoroughly before use. Alternatively, both constituents may be liquid, in which case they may either require mixing prior to delivery or be delivered sequentially (Figure 1).

web_body_ONDD-dual-chamber-issue_Figure-1
Figure 1: A simplified model of two-component injectables, classified according to the state of matter of constituent parts.

The Archetype: Solid/Liquid Reconstitution

Reconstitution is the process of adding a liquid solvent to a solid medication to dissolve it and form a solution. This may be required, at point of use, when a drug is unstable in liquid form and must therefore be stored dry. In such cases, the formulation is often filled as a liquid and then lyophilised (freeze dried) in situ. Alternatively, it may be manufactured and handled as a powder.

Freeze drying is an effective way to increase formulation stability. For small molecules, it can eliminate the need for cold-chain storage. For biologics (especially those that are large, complex or prone to aggregation) it can be a necessity in order to achieve an acceptable shelf-life.

“Lyophilised formulations now represent over 30% of all FDA-approved parenteral medications – and demand for lyophilised parenteral products is increasing.”

Lyophilised formulations now represent over 30% of all US FDA-approved parenteral medications1 – and demand for lyophilised parenteral products is increasing, as evidenced by past drug approvals (~35 such drugs were approved by the FDA each year over the past decade, compared to ~12 per year in the decade prior2). Considering lyophilised parenterals approved in 2023, oncology and infectious disease indications represented the largest share, together accounting for ~75% of total approvals.2

As lyophilisation is on the rise, so too are devices to simplify reconstitution. A wide range of solutions are available beyond the well-established vial-and-syringe method – from primary container adaptors to dual-chamber systems.

Solid/Liquid Suspensions

Suspensions are a dosage form in which insoluble solid particles are mixed into a liquid medium. They enable delivery of insoluble drugs and can be used to formulate long-acting injections. Suspensions may be supplied as separate wet and dry components (in which case the liquid phase is added to the solid phase and mixed prior to administration) or in a single primary container that is shaken to resuspend.

While solutions can readily be reconstituted with gentle swirling, suspensions usually need a greater energy input to achieve even mixing – the required amount varies greatly depending on the chemical and physical properties of the formulation. In some cases, vigorous shaking is insufficient and benchtop equipment, such as a vortex mixer, must be used.

Given sufficient energy input, the particles will be uniformly dispersed within the liquid, however the resulting mixture will be heterogenous and unstable; it will eventually settle. Therefore, suspensions must be thoroughly mixed immediately before use. Inconsistent dispersion can lead to inaccurate dosing or needle clogging – persistent challenges for device integration.

Injectable suspensions are becoming more prevalent, particularly for severe chronic conditions such as schizophrenia and HIV,3,4 where extended-release formulations are of particular value and which are often reliant on a suspension format to produce a long-acting depot. When formulated as separate wet and dry components, these products largely rely on vial-and-syringe or vial-adaptor workflows, with the occasional exception, such as Eligard’s reciprocating syringes, or the Abilify Maintena dual-chamber syringe.3,4

Liquid/Liquid Mixtures

Injection of two-liquid mixtures is rarer but not unheard of. Two liquids may be mixed and delivered together out of:

  1. Necessity: when a formulation consisting of two fluid phases is unstable in mixed form, but must be mixed prior to injection in order to achieve the intended therapeutic effect (e.g. API and polymer solutions that mix to form a long-acting depot).
  2. Convenience: if two liquid formulations are frequently administered together, such as in combination vaccines, pharma companies may choose a dual-chamber presentation over developing a coformulation, such as with Vivaxim.6 In this case, mixing isn’t necessary but rather a side effect of leveraging mature dual-chamber systems (which mix the two liquids prior to administration) rather than betting on more niche sequential delivery technology.

Sequential Delivery of Two Liquids

Sequential delivery of two different liquids through a single needle or injection port has been proposed for combination therapies, as well as for IV drug administration through a vascular access device (with the drug preceded, or followed, by a catheter flush).7

While there are several delivery technologies in development that might enable these use cases, only one combination product in this category is on the market at the time of writing, according to data from PharmaCircle. The DuoDote emergency-use autoinjector, based on a custom primary container, sequentially injects atropine and pralidoxime chloride. It is approved for treatment of nerve agent or insecticide poisoning.

Choosing the Right Device

Choosing the right device for a two-component injectable is often an exercise in trade-offs, highly dependent on the properties of the formulation itself, indications for use and the stage of development. Hereafter, this article will assume that a two-component injectable consists of separate wet and dry constituents that are reconstituted prior to injection, unless otherwise stated. This section will briefly cover the range of available technologies, and factors to consider when it comes to device selection.

“Choosing the right device for a two-component injectable is often an exercise in trade-offs, highly dependent on the properties of the formulation itself, indications for use and the stage of development.”

Vial and Syringe: Trusty but Burdensome

Two-component injectables are often supplied in vials, with off-the-shelf (OTS) needles and syringes used for fluid transfer and subsequent injection (Figure 2). By leveraging mature primary containers and fill-finish technologies, this approach benefits from low unit cost and a robust supply chain. It is also extremely versatile, with fewer restrictions on formulation volume and viscosity compared with alternatives, the ability to accommodate different doses in a single stock keeping unit, and no need for device-specific training.

On the other hand, the process is onerous and a high degree of technical expertise is required to perform all steps correctly. Dose accuracy is highly dependent on the user, and there is a greater risk of contamination and sharps injury compared with other methods, meaning that this type of system is typically limited to trained staff in clinical settings. Moreover, some drug wastage is inevitable, with vials often overfilled by 10–20% to ensure that a full dose can always be drawn.

web_body_ONDD-dual-chamber-issue_Figure-2
Figure 2: A summary of steps required for manual reconstitution using vials and syringes.

Devices to Simplify the Reconstitution Process

Given the growing prevalence of two-component injectables and the limitations of the established vial-and-syringe method, it is no surprise that a wide range of specialist devices have been developed to aid reconstitution. Figure 3 illustrates some of the solutions available.

  1. Primary Container Adaptors: Co-packaged with standard prefilled primary containers, these allow for drug components to be accurately pre-dosed during manufacturing, while maintaining low device and fill-finish costs.
  2. Integrated Manual and Automated Systems: Some of these leverage standard OTS containers, while others are designed around bespoke primary containers (e.g. dual-chamber cartridges).
    • Integration of device components reduces the number (and sometimes complexity) of use steps, reducing the burden of use and the likelihood of errors.
    • Automated devices take this further by incorporating mechanisms in the design (such as springs or electronics) to enable reconstitution and/or delivery with minimal user input.

 

web_body_ONDD-dual-chamber-issue_Figure-3
Figure 3: Examples of reconstitution devices for intravenous, intramuscular and subcutaneous administration. Devices marked with an asterisk are in development at the time of writing; the others are on the market. Note that prefilled dual-chamber systems can fall within the “integrated manual” or the “automated” categories, depending on device function.

Horses for Courses: Different Drugs Have Different Needs

When choosing a device, key trade-offs include cost, time to market, dose accuracy and ease of use. Consider:

  • Properties of the Formulation: All reconstitution devices have their strengths and limitations; the choice of device must be compatible with the needs of the formulation. For example, dual-chamber PFSs are limited to products with relatively low volumes that reconstitute readily.
  • Use Case and Dose Accuracy: The choice should be made with the final user in mind; integrated and automated systems greatly simplify usage, making accurate reconstitution accessible to users with less technical expertise (e.g. patients in the home setting).
  • Supply Chain Implications: The choice of primary container is the single most important factor influencing development timeline and manufacturing cost of the device. Dual-chamber fill-finish is highly complex; expertise is rare and CMO capacity limited.
  • Stage of Drug Development: Priorities differ depending on the stage of development. For example, a novel drug in clinical trials may benefit from the use of vials, since they offer flexible dosing and use only OTS components, whereas more integrated systems may be introduced post-launch to encourage wider adoption.

Dual-Chamber Delivery Systems

Prefilled dual-chamber systems (DCSs) are “all-in-one” devices built around bespoke primary containers, designed to simplify the reconstitution and delivery of two-component injectables. This final section delves deeper into this device category – strengths, limitations and key design considerations.

Anatomy of a Dual-Chamber System

In a DCS, the primary container consists of a barrel (typically made of glass) divided into two chambers by a central stopper. This barrier keeps the drug components separate from each other throughout storage. Once the DCS is activated, a bypass mechanism allows fluid to flow from the back (wet) chamber into the front (typically dry) chamber (Figure 4).

web_body_ONDD-dual-chamber-issue_Figure-4
Figure 4: Use steps and function of a typical DCS embodiment. Note that the linear application of force causes the bypass mechanism to activate, opening a fluid path that connects the two chambers.

DCSs vary in type of closure and bypass:

  • The closure can be PFS-style or cartridge-style (Figure 5).
  • The bypass is usually external (a blister bypass), but can also be internal (such as the multi-groove design of the Genotropin MiniQuick – Figure 5, Device 5). Note that an internal bypass allows the use of standard syringe or cartridge tubs, which is advantageous for manufacturing. Emerging designs, such as Credence MedSystems’ fenestrated needle bypass, also have the additional benefit of being compatible with OTS syringes.
web_body_ONDD-dual-chamber-issue_Figure-5
Figure 5: Approved DCS products (all marketed, bar Tanzeum, which has been discontinued). Left: dual-chamber prefilled syringes. Right: integrated injection devices built around dual-chamber cartridges. Device 1 contains a lyophilised suspension; Devices 2, 4, 5 and 6 contain lyophilised solutions; and Device 3 contains two liquids for co-administration.

Bespoke Primary Containers: A Double-Edged Sword

Like other specialist reconstitution devices, DCSs make administration of two-component injectables accessible to a wider range of users and care settings. They require less technical expertise to use accurately and consistently, with fewer and simpler handling steps, pre-measured drug components and reduced sharps exposure.

“Thanks to this design, DCSs can readily be integrated into devices with enhanced usability and/or advanced features.”

However, their unique strength lies in their form factor – the single barrel with a bypass that can be activated with a co-linear application of force (so both mixing and delivery are done by pushing on the rear plunger in a straight motion). Thanks to this design, DCSs can readily be integrated into devices with enhanced usability and/or advanced features. For example:

  • Xyntha Solofuse, an easy-to-use device with a simple finger flange (Figure 5 Device 2).
  • Caverject Impulse, an integrated manual system with dose selection capability (Figure 5 Device 4).
  • The reusable Skytrofa Autoinjector, pictured in Figure 3 with the green needle guard.

The flip side of the form-factor coin is that complexity is pushed into the manufacturing and filling process. Fill-finish for these devices requires specialist equipment and know-how (as noted above, expertise is rare and capacity is limited) and lyophilisation is inherently less efficient in the dual-chamber geometry compared with vials (smaller batches, poorer energy transfer, longer cycle times6). It all adds up to greater up-front investment and time-to-market, higher unit cost and a restricted supply chain.

For this reason, DCSs have so far been limited to premium value products, such as those used to treat rare diseases (e.g. haemophilia, growth hormone deficiency) or those that solve complex or critical clinical challenges (e.g. unmet needs, home care).6

Design Considerations

Current marketed DCSs have inherent technical limitations that impact formulation compatibility and device design. For example:

  • Capacity is limited to ~4 mL total reconstituted volume: Headspace in the front chamber must be sufficient to accommodate the initial plunger stroke required to open the bypass, both drug components, and additional room for swirling and mixing. Therefore, there is a limit to how much can be delivered with these devices before they become too large to be practical.
  • Venting and orientation are important: There usually needs to be a path to atmosphere during mixing to avoid pressure build-up in the front chamber (if there is a large amount of headspace in the powder chamber, this may not be required). In all cases, excess air must be vented prior to injection, which can be challenging and requires careful handling, as the device must be kept upright whenever there is a path to atmosphere to avoid drug spilling through the needle.
  • Plunger motion must be well controlled: When the bypass opens, the pressure in the system drops sharply. Unless the plunger’s forward motion is well controlled, there is a risk of prematurely locking out the fluid path, which would prevent the liquid in the back chamber from being fully incorporated into the mixture. To prevent this, many devices incorporate a screw mechanism that enforces a slower twist-to-mix action.
  • They are best suited to lyophilised formulations that are readily reconstituted with gentle swirling: Suspensions can only be delivered if the energy required to suspend is low. In addition, sequential delivery is not possible without specialised valve design (some mixing will always take place with the currently marketed DCSs). Finally, very particular considerations apply to the delivery of liquid/liquid mixtures – space is at an even greater premium, venting becomes critical and mixing performance varies widely depending on the specific device and formulation.

Looking Ahead

Meeting the next generation of injectable delivery challenges will demand the best of device innovation, alongside advances in formulation and process development. As therapies grow more complex, the need for close cross-functional collaboration becomes increasingly critical.

Developers of combination products will continue to face trade-offs between usability, flexibility, cost and manufacturability. To navigate these successfully, device and formulation experts must work hand-in-hand with clinical, regulatory, commercial and access stakeholders. Working together, we can deliver medicines that are fit for purpose today, and ready to meet the needs of tomorrow.

References
  1. Kumar S et al, “Application of lyophilization in pharmaceutical injectable formulations: An industry and regulatory perspective”. J. Drug Deliv. Sci. Technol., 2024, Vol 100, article 106089.
  2. Gray J, “LyoHUB 2024 Annual Report”. 2024. Available from: https://pharmahub.org/resources/1112
  3. “Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations”. Web Page, US FDA, accessed Jul 2025.
  4. “Purple Book: Database of Licensed Biological Products”. Web Page, US FDA, accessed Jul 2025.
  5. “DailyMed: Prescription drug labeling and information.” US National Library of Medicine, accessed Jul 2025.
  6. Werk T et al, “Technology, Applications, and Process Challenges of Dual Chamber Systems”. J Pharm Sci, 2016, Vol 105, pp 4–9.
  7. Sousa et al, “Brief Report on Double-Chamber Syringes Patents and Implications for Infusion Therapy Safety and Efficiency”. Int J Environ Res. Public Health, 2020, Vol 17(21), art 8209.

Get in touch

This article highlights how the right device can turn complex two-component injectables into simple, safe, and accessible treatments. If you’re exploring delivery challenges or want to design patient-friendly solutions for advanced formulations, we’d love to talk.

Contact Us
||||||
By Cambridge Design Partnership
July 16th 2025

Designed to deliver: How collaboration created an award-winning device that puts patients first

When Credence MedSystems set out to build on the capabilities of their Dual Chamber Syringe System (DCSS), they weren’t just looking to adapt it – they wanted to expand its potential. Together, we set out to create a new platform for at-home, sequential-drug delivery: one that combined human-centered design, deep technical know-how, and the power of partnership. Over the course of the project, our teams worked together to bring that vision to life. The result? A Red Dot 2025 award-winning demonstration autoinjector that not only showcases the functionality of the DCSS, but also reimagines how two drugs can be delivered at home in one simple injection.

Three Ingredients for Award-Winning Device Design

1. End-to-End Expertise

This project brought together two areas of specialist knowledge. Credence brought the core technology: a dual-chamber syringe system with automatic needle retraction that uses standard glass components, designed for sequential delivery of two formulations. Our team contributed deep experience in autoinjector design, usability, and manufacturing engineering. We translated complex drug delivery requirements into devices that are safe, manufacturable, and easy to use.

2. Close Collaboration

This was a shared, iterative development process built on close collaboration. From the outset, the teams worked together to define key requirements and align on a shared vision. By combining Credence’s knowledge of their container system with our insight into autoinjector mechanisms and user experience, This allowed us to accelerate from concept to working demonstration.

We shaped the engineering and design direction through regular feedback loops. Both teams were actively involved in decision-making throughout. When the Credence team visited our site in Cambridge, UK, we held a hands-on working session to evaluate both functional prototypes and industrial design handling models. Together, we assessed the feel of device activation, form factor, and visual cues. We blended technical and aesthetic considerations to arrive at the perfect overall experience.

The feedback was immediate. One mechanism was described as “smooth as butter”. This was a clear signal that we were on the right path.

3. Built-in User-Centered Thinking

While the request was to develop a reloadable, robust model for demonstration purposes. The long-term goal was always to support at-home use. We designed the experience to closely emulate the familiar, two-step workflow of a single-chamber autoinjector, while delivering the additional benefit of dual-drug administration. In addition, we made the demo unit reusable and resettable for hands-on use. We developed it with a clear development pathway towards a single-use, commercial device.

We also considered communication and clarity from the outset. Exploring iconography, leaving space for regulatory labeling, and ensuring the device visually conveyed key aspects of the user benefits.

web_body_reddot-dual-chamber-syringe_2-2
From initial sketches…
web_body_reddot-dual-chamber-syringe_3-3
…through concept renders…
web_body_reddot-dual-chamber-syringe_4
…to the real thing

Platform Flexibility

What makes this device stand out isn’t just the sequential delivery of two formulations. It’s the fact that the same primary container can be used across both prefilled syringe and autoinjector formats without changing any drug-contacting components. This flexibility helps reduce development burden. It simplifies supply chains and makes it easier for pharmaceutical partners to scale and adapt their delivery format over time. There’s also a clear benefit for patients. Fewer injections, simpler instructions, and added confidence that both parts of the treatment are delivered, every time. Beneath it all lies a sustainability advantage. With a sequential delivery device, there’s only one autoinjector to manufacture, ship and dispose of. This can make a meaningful difference at scale.

As a result, this wasn’t just a concept exercise. It was a real-time demonstration of what’s possible when two expert teams bring their strengths to the table. We developed a fully-functioning demo platform and in doing so, also laid the groundwork for future commercial evolution, including a clear view of what it would take to move from demo model to single-use device.

Our shared focus, technical excellence, and momentum powered this collaboration. We’re proud to see this work recognized with an industry award.

web_body_reddot-dual-chamber-syringe_1-1

Connect with CDP

For more on how to turn patient-centred thinking and collaborative engineering into award-winning drug delivery devices, contact Cambridge Design Partnership.

GET IN TOUCH
feature_insights-from-ECSMID25-2
By Dan Haworth, James Blakemore and Leigh Shelford
May 23rd 2025
Find the authors
on LinkedIn:
Dan Haworth

Dan Haworth

Head of Diagnostics
James Blakemore

James Blakemore

Senior Insight and Strategy Consultant
Leigh Shelford

Leigh Shelford

Consultant Physicist

Insights from ESCMID 2025: trends and future in diagnostic testing

SUMMARY

This year’s ESCMID event reinforced that access to effective diagnostic tests must increase, and that long-promised technologies are finally close to delivering clinical value.

What makes your platform different?
One recurring message: speed, accuracy, and cost effectiveness are now expected. Differentiation lies in how well a platform fits real-world clinical settings, from training and workflow to data interpretation and system integration.

Takeaway for developers: Think beyond technical specs. Differentiation increasingly depends on usability, trust at scale, and measurable impact on care delivery and operational efficiency.

ESCMID 2025 marked a shift from technology-led innovation to outcome-led development. The key question is no longer “Can it be done?” but “Does it solve the right problem, in the right way, at the right scale?”

Headline Trends

  • Antimicrobial resistance (AMR) and antibiotics use – increasing access to and uptake of diagnostic testing is key for effective interventions
    AMR remains a major global health challenge. Antibiotic use continues to rise, especially in primary care, where most prescriptions are issued without diagnostic support. Addressing this requires a broader range of diagnostic systems. These must balance performance with affordability and usability, enabling appropriate treatment decisions in both hospital and community settings.
  • The role of syndromic testing is still being debated
    While useful in hospital and acute care, syndromic panels have seen limited uptake in primary care due to cost and complexity. They support antimicrobial stewardship. But they must become more accessible and cost-effective to broaden adoption.
  • Genetic sequencing may bring a step change in clinical utility in diagnostics
    Sequencing is moving closer to clinical use. It has the potential to reshape diagnostics. Developers must build workflows and systems that integrate sequencing seamlessly. They must interpret results clearly and deliver clinical value at scale.
  • ML, AI, and automation are maturing
    AI tools are expanding from imaging to in-vitro diagnostics. They offer clinical augmentation value to tedious manual workflows, image interpretation, and data integration. The focus is shifting from innovation to implementation, embedding tools into workflows with trust, reproducibility, and regulatory alignment.

The annual congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) brings together clinicians, researchers, and industry leaders to explore the evolving landscape of diagnostics. This year’s event highlighted some key themes shaping the future of diagnostic impact and delivery.

AMR and Antibiotic Use: Access to Testing Is Critical

Antimicrobial resistance remains a central challenge. With an estimated 40–50 billion antibiotic doses taken daily and use projected to rise 50% by 2030, intervention is urgent. The vast majority of prescriptions occur in primary care. They are often without diagnostic support.

Improved access to diagnostics is key. Many current platforms focus on performance where demand already exists, but the biggest opportunity lies in reaching settings where no testing is currently available. Systems must support appropriate treatment decisions. They must balance speed, accuracy, and pathogen identification with usability, affordability, and integration into clinical workflows.

Syndromic Testing: Performance vs Cost

Multiplexed syndromic panels are established in hospitals and acute care, but uptake in primary care remains low. Their value in guiding antibiotic use is clear yet cost and complexity are barriers to broader use.
Developers must reduce system cost and complexity to reach more healthcare environments and fit into reimbursement frameworks. Technical capability alone is no longer enough. Integration, ease of use, and clinical decision support are now central to adoption.

Sequencing-based diagnostics are also beginning to compete with syndromic approaches, raising the bar for accessibility and performance in multiplexed testing.

Sequencing: Moving Toward Clinical Routine

Genetic sequencing is rapidly approaching routine use in clinical diagnostics. With falling costs and expanding platform availability, it holds the potential to reshape infectious disease diagnostics, particularly in syndromic or multiplexed contexts.
At ESCMID, multiple case studies demonstrated the use of same-day metagenomic sequencing for pathogen identification in respiratory and bloodstream infections. Amplicon-based approaches were also discussed, particularly for rapid variant detection and resistance gene profiling. Broader sequencing methods, including microbiome analysis, may also play a role in future clinical applications.

However, sequencing workflows are not yet plug-and-play. Upstream processes, such as sample collection, DNA extraction, host depletion, and library preparation, remain technically demanding. Downstream, interpretation, bioinformatics pipelines, and clinically actionable reporting are major hurdles. While sequencing speed and cost are improving, the challenge now lies in integrating these steps into streamlined, automated, and interpretable systems that deliver value at the point of care.

Developers must ask strategic questions. Should initial diagnostic applications focus on relatively simple, targeted sequencing? For example, amplicon sequencing for variant detection, or on broader, hypothesis-free metagenomic approaches? Will sequencing be decentralized or remain concentrated in specialized hubs? How can systems present complex data in ways that support decision-making by non-specialist clinicians? The opportunity is significant. But realizing it will require systems that balance performance, usability, and clinical relevance.

ML, AI, and Automation: From Hype to Implementation

Artificial intelligence has already made an impact in diagnostic imaging, including MRI, CT, and ultrasound. At ESCMID, attention turned to the broader use of AI and machine learning in in-vitro diagnostics, with exciting potential across three main areas:

  • Image analysis: AI is enabling rapid interpretation of high-resolution optical data in fields like digital pathology, haematology, and spectral imaging. These tools can increase diagnostic accuracy while reducing the burden on human reviewers.
  • Multi-marker data interpretation: AI models are increasingly used to integrate complex biomarker datasets, where the combined signal across markers yields diagnostic insight. Some platforms already use deterministic models; the shift toward machine learning promises greater flexibility and performance, particularly as training datasets grow.
  • Workflow optimization and automation: AI is being applied to streamline laboratory operations, reducing hands-on time, standardizing results, and minimizing error rates. This is especially valuable in high-throughput or resource-constrained settings.

Several ESCMID sessions showed AI being used to support antimicrobial resistance prediction, improve taxonomic resolution, and aid diagnostic decision-making. Importantly, the field is moving from exploratory development to real-world deployment. The emphasis is now on clinical validation, regulatory clarity, reproducibility, and integration with existing systems.

For developers, success will depend on more than accuracy. Trust, interpretability, and usability are emerging as key differentiators. Tools that embed smoothly into clinical workflows, minimize training requirements, and deliver repeatable, high-confidence outputs will define the next wave of AI in diagnostics.

Receive further news from Diagnostics at CDP

Connect with CDP

Wondering what these trends mean for your next diagnostic system? A quick conversation could help you shape a clearer path from concept to clinical impact. Get in touch with one of our team:

Dan Haworth, Head of Diagnostics
dan.haworth@cambridge-design.com

James Blakemore, Senior Insight and Strategy Consultant
james.blakemore@cambridge-design.com

Leigh Shelford, Consultant Physicist
leigh.shelford@cambridge-design.com

GET IN TOUCH
Advancing Injectable Drug Delivery Systems
By Cambridge Design Partnership
May 8th 2025

Advancing Injectable Drug Delivery Systems

EXCLUSIVE INSIGHTS

Advancing Injectable
Drug Delivery Systems

Unlock expert opinions and insights with four in-depth interviews on the challenges of parenteral innovation.

By Clare Beddoes • Head of Drug Delivery

Featuring exclusive interviews from industry leaders and pharma innovators

Get insider insights

Tell us a bit about yourself and we’ll email the guide directly to you.

Each article provides exclusive insights on different aspects of injectable drug delivery, offering valuable perspectives on design, usability, and market trends.

Expert Perspectives and Innovations

  • As more complex injectable drugs move from clinic to home, are devices keeping pace with patient expectations and healthcare system expectations?
  • What does it take to make drug delivery safer, simpler, and more effective, especially when every second counts?
  • What role does user-centered design play in making advanced therapies more accessible and effective?
  • Looking ahead, how can delivery technology help unlock access to life-changing treatments?

To answer these questions, this downloadable PDF explores the future of injectable drug delivery, spotlighting innovations that are transforming patient care. Furthermore, through real-world examples, we dive into how device design, patient-centricity, and pharma-device collaboration are reshaping the landscape.

Download the guide to access the full interviews and explore these insights in detail:

Epinephrine injectors for pediatric use
Improving usability for effective emergency treatment

Ocular drug delivery
Advancing sustained release to ease the burden of acute therapies

User-centered infusion pumps
Enhancing patient comfort and convenience

Advanced Parkinson’s Disease treatments
Strategies to overcome regulatory challenges

 

surgical robotics development
April 18th 2025
Find the authors
on LinkedIn:
Tom Brittain

Tom Brittain

Head of RAS
James Boonzaier

James Boonzaier

Deputy Head of RAS
James Boonzaier

James Boonzaier

Deputy Head of RAS

How fast can you bring new Surgical Robotics tech to market? Know the 3Cs to rapid development.

SUMMARY
  • Speed to market has essential benefits for all top Robotic Assisted Surgery (RAS) companies – from maintaining and driving investor confidence to realising the commercial value as quickly as possible. But speed is often associated with risk.
  • Bringing new surgical robotics development tech to market quickly and confidently requires the 3Cs: Capability, Capacity and Culture.
  • A skunkworks approach provides R&D teams with all 3Cs, allowing them to focus on working without interference or interruption.
  • Our RAS leadership team will be speaking at DeviceTalks Boston on April 30, on the 3Cs and showcasing an example of a successful robotic assisted surgery device design and product development for one of our clients.

Companies that build technologies for robotic-assisted surgery (RAS) are under growing pressure to deliver new products quickly. Whether you’re a global corporation or a small startup, you need to show executives and investors that you can rapidly innovate and go to market, and you need to realize the value of investment as quickly as possible. The keys to moving fast, avoiding risks and maximizing the odds of market success? Capability, Capacity and Culture.

If you’re a longtime leader in MedTech, you undoubtedly have capabilities with a large in-house talent pool of experienced engineers, design experts and other specialists. But your development efforts can stumble if teams are stretched thin across multiple projects or are delayed by bureaucratic red tape – which are problems of capacity and culture.

If you’re a startup, on the other hand, you might have launched with a promising concept but lack the breadth and depth of capabilities, and the maturity in all three Cs. Without a broad and deep field of experts – capability and capacity – and a proven culture built on the experience of delivering many other previous projects quickly, you might struggle to meet investors’ expectations of fast results.

What’s the solution to bringing all 3Cs together? A skunkworks approach.

“A skunkworks approach enables R&D teams to focus on projects in a way that’s protected from distraction, such as internal politics,” says James Boonzaier, Deputy Head of RAS and part of Cambridge Design Partnership’s new RAS leadership team. “Too often, what we see is that key people are constantly being pulled onto other projects, or they’re spread too thin, or there are political agendas getting in the way of things. In order to get these programs running fast, you need capability, capacity and culture. Capability means, ‘Do you have the required skills across your individual engineers’ brains?’ Capacity means, ‘Are they available right now?’ And culture is, ‘Are they able to work in the right kind of context for fast, deliberate progress?’”

James-Boonzaier-e1744806299774

“In order to get these programs running fast, you need capability, capacity and culture.”

James Boonzaier | Deputy Head of RAS at Cambridge Design Partnership

A Better Approach to Rapid Surgical Robotics Development & Design

Cambridge Design Partnership’s (CDP) new RAS leadership team is headed up by Tom Brittain, James Boonzaier and Jack Hornsby. Their focus on fast delivery reflects CDP’s ongoing investment and long record of success in surgical robotics

CDP strengthens its clients’ RAS programs by enhancing capability, capacity, and culture. The company’s specialists work closely with client development teams to accelerate innovation and delivery.

“Key to working this way is being able to match highly skilled and technically capable people with the right expertise, experience, personalities, and a passion for RAS, and providing them with the right tools, conditions and working environment within which to do the best possible job,” says Tom Brittain, Head of RAS. “By collaborating closely with our clients’ teams, we’re able to operate as an extension of their own pool of people. And since we’ve been active in this sector, having worked with a number of the big players in surgical robotics, we know this approach works time and time again.”

This way of working, Tom says, enables quick development by providing organizations with turnkey access to deep technical expertise, system-level thinking and user-focused design capabilities. He notes that CDP’s success in the sector relies on a team dedicated and often exclusive to surgical robotics, with bespoke teams of experts often embedding with clients according to the unique requirements of each project.

“We’re passionate about our mission and committed to helping our clients’ RAS projects succeed,” says Tom. “And our approach works, as our track record shows. Since 2019, we’ve built four complete systems, along with multiple subsystems, for clients from the ground up. These have included both blue-sky development and remedial redesign with total system architecture development. Each of these systems has been designed and manufactured in under a year, which represents extraordinary speed in this industry. We have supported several single port trans-umbilical NPD programs, with detailed engineering of capital equipment, disposables and reposables, draping systems and more. This was made possible only by having the right capabilities on site, with the right capacity available as needed, all supported by a culture of innovation.”

Tom-Brittain-e1744807155147

“Since 2019, CDP has played a substantial role in four notable product development programs in robotic-assisted surgery, delivering system-level prototypes from the ground up. Each of these has been designed and manufactured in under a year, which represents extraordinary speed in this industry.”

Tom Brittain | Head of RAS at Cambridge Design Partnership

You need a strong foundation from which to build any RAS system

The development of any RAS system requires a strong foundation of strategy and system architecture between hardware and software, all aligned to the clinical user’s needs.

James states, “To ensure strong system architecture for our clients, we really focus on conducting structured clinical needs gathering to generate solid initial hypotheses on key requirements and constraints. Once a strong foundation for the platform architecture is created, we shift our focus to the high-risk areas.”

Risk management is vital throughout the entire process. Jack calls the approach CDP takes “targeted derisking,” adding, “we know from experience what the concept killers are and what we need to do to gain confidence that we’ve solved or avoided them. That is a key element of moving quickly. Not only that, the way in which we derisk is targeted in such a way that we’re not adding more complexity or unknowns. This enables us to iterate designs quickly, learn from each step what works and what doesn’t, and develop working prototypes at speed.”

Putting this approach into practice, CDP developed a single-port RAS prototype platform, moving from an early-stage concept to an alpha system prototype for pre-clinical trials in just seven months. Jack makes the further point that “In addition to speed, the client gets to retain all knowledge and intellectual property rights for any technologies developed for them.”

Jack-Hornsby-JH1-1

“The way in which we derisk is targeted in such a way that we’re not adding more complexity or unknowns. This enables us to iterate designs quickly, learn from each step what works and what doesn’t, and develop working prototypes at speed.”

Jack Hornsby | Deputy Head of RAS at Cambridge Design Partnership

Meet the RAS Team at DeviceTalks Boston

Building a surgical robot takes true teamwork. Success demands rapid development while meeting strict clinical and regulatory requirements. Cambridge Design Partnership continues to invest in the expertise and processes that help clients bring advanced surgical robotics to market.

The result is a comprehensive offering with unmatched expertise. Clients gain immediate access to deep knowledge in kinematics, human factors, cart design, optics, systems engineering, and disposables development. And our 26,000-square-foot Pilot Production Center quickly takes a client’s project from concept to prototype build to transfer to manufacturing.

Tom, James and Jack will be speaking at DeviceTalks Boston on April 30 about the importance of the 3Cs (“How Fast Are You? Accelerating Next-Generation Surgical Robotics”). They’ll also be showcasing a platform we developed that demonstrates our approach, going from early concept to Alpha prototype for preclinical studies in under seven months. They will be on hand at stand 735 to talk about CDP’s approach to rapid development in RAS. You can also reach out in advance and chat, or book in some time to meet them in Boston.

Connect with CDP

If you would like to discuss the content of this article, please get in touch with our RAS leadership team; Tom Brittain,  James Boonzaier and Jack Hornsby

Tom Brittain, Head of RAS
tom.brittain@cambridge-design.com

James Boonzaier, Deputy Head of RAS
james.boonzaier@cambridge-design.com

Jack Hornsby, Deputy Head of RAS
jack.hornsby@cambridge-design.com

GET IN TOUCH
|||
By Krai Chatamra and Steve Augustyn
February 6th 2025
Find the authors
on LinkedIn:
Krai Chatamra

Krai Chatamra

Vice President of Clinical Development at Intrance Medical
Steve Augustyn

Steve Augustyn

Deputy Head of Drug Delivery

Navigating new frontiers: Bringing Parkinson’s treatments to new markets

Advances in drug delivery and strategies to overcome regulatory challenges for global patient access

Patients with Advanced Parkinson’s Disease (APD) face significant challenges in managing their symptoms and maintaining their quality of life. Effective, continuous dopaminergic stimulation treatment options are critical, as conventional oral therapies no longer offer adequate relief with advancing disease state. Advanced device-aided therapies that provide consistent symptom control are essential for improving patient outcomes and enabling a more independent lifestyle.

However, bringing these innovative treatments to market is challenging. Adequate control of APD via continuous treatment can require a combination of drug products, delivered with an infusion pump that is flexible enough to meet the needs of different patient groups yet simple enough for home use.

When deciding on a pump solution, companies must choose whether to adapt existing technologies or develop new solutions from scratch; each path requiring different developmental strategies and involving differing levels of investment and risk. They must then navigate an often-changing regulatory landscape with distinct requirements across regions, adding complexity to the development and approval process.

This article, authored by Steve Augustyn, Deputy Head of Drug Delivery at Cambridge Design Partnership, featuring insights from Krai Chatamra, Vice President of Clinical Development at Intrance Medical Systems Inc (Intrance), explores the necessity of advanced therapies that provide consistent symptom control to improve patient outcomes and enable a more independent lifestyle.

Krai Chatamra has decades of experience in the pathology and treatment of APD. In this article, Steve Augustyn spoke to Krai about the process of bringing a new treatment for APD to the market.

To clarify some of the terminology used in this article;

  • a drug substance is the active pharmaceutical ingredient
  • a drug product is the final dosage form that includes the drug substance
  • a combination product (in this instance) is the drug product working with the specified infusion pump.
Intrance-Med-Sys-logo-Full-Color

Intrance Medical Systems, Inc. is developing a next-generation therapy for patients with APD. The lead product combines a proprietary gel formulation of carbidopa, levodopa and entacapone delivered by an ambulatory infusion pump. The pump delivers the medication directly to the jejunum via a percutaneous endoscopic gastrostomy (PEG) tube, enabling continuous treatment for patients with APD, removing the burden of managing complex oral dosing regimens and preventing the complications associated with the unpredictable motor fluctuations.

Cambridge Design Partnership (CDP) recently supported Intrance in the verification of its selected infusion device, clearing the way for a Phase III clinical trial as part of the company’s marketing application for the US. The verification required hundreds of delivery profile tests to meet the latest requirements in AAMI TIR 101:2021 (Fluid delivery performance testing for infusion pumps) to demonstrate the safety and accuracy of Intrance’s combination product.

Challenges and innovations in APD therapies

Complexity of APD

Krai: Parkinson’s Disease is a vast field. Currently, we are concentrating on the advanced stage of the disease, which is uniquely complex. As the disease progresses, it becomes increasingly multifaceted. Conventional oral therapies are ineffective at this advanced stage.
In APD, patients experience motor fluctuations between two highly disabling states: OFF, where they are unable to move, and hyperkinetic [dyskinetic], where they move uncontrollably. Patients typically spend at least 50% of their waking hours oscillating between these two states. Our goal is to thread the plasma level of L-dopa into the narrow therapeutic window, thereby avoiding patients experiencing such disabling OFF and dyskinetic states.

The challenge of maintaining levodopa levels

Krai: The plasma level of levodopa must be maintained within this very narrow therapeutic window, which continues to narrow as the disease progresses. Therefore, we need a drug delivery system that can precisely regulate the plasma levodopa levels within this narrow synaptic window. This is our biggest challenge.

Our current product, Lecigon, is an investigational drug in the US. However, it has already been approved in multiple European countries. So, the challenges we face are distinct from those encountered by other companies developing drugs or devices for different stages of PD.

Krai-Chatamra-Intrance-Medical

“We need a drug delivery system that can precisely regulate plasma levodopa levels within a narrow synaptic window.”

Krai Chatamra | Vice President of Clinical Development at Intrance Medical

Identifying a suitable device platform

Multifaceted challenges

Krai: The challenges are multifaceted. Firstly, there is a constantly changing regulatory landscape. Secondly, each regional governance has its own requirements, which are not necessarily aligned. Lastly, we had to weigh the availability of existing pumps versus the invention of a completely new device, both of which require different developmental pathways. Before deciding on the final infusion device, we had to go through numerous qualifying steps in great detail.

We initially targeted the European market. We are now moving to the US, and ultimately Japan.

“There is a constantly changing regulatory landscape, and each regional governance has its own requirements, which are not necessarily aligned.”

Krai Chatamra | Vice President of Clinical Development at Intrance Medical

Differences in verification and validation: drug products vs. medical infusion pumps

Distinct development pathways

Krai: The developmental pathways from a regulatory perspective for a drug product and a medical device are quite different. While there are some common themes, such as ensuring safety for patients, the requirements, especially in the US, differ significantly between the drug and the device.

We are dealing with different administrative arrangements, review procedures, and guidelines. Collectively, these differences mean that the paths to take a product – whether it be a drug, device, or combination of both – from development to market are distinct.

For those new to drug-device development, whether developing products independently or as combination products, it’s important to understand that the process, in the US, ultimately depends on which center (e.g. CDER, CBER or CDRH) your product is filed with.

“The requirements, especially in the US, differ significantly between the drug and the device.”

Krai Chatamra | Vice President of Clinical Development at Intrance Medical

Advice for developing a combination product for neurological conditions

Do your homework

Krai: The single most important piece of advice I would give [when developing a combination product] is to do your homework thoroughly. This may sound simplistic, but it involves several critical steps. First, understand the disease you are targeting.

Second, know the region [you plan to seek marketing approval in]: Understand the regulatory and market conditions. For example, if you are targeting the US, you need to be aware of the existing availability of infusion pumps, which can help you navigate the requirements for pump testing. (Using an infusion pump that is already approved for use in the US can substantially reduce the amount of testing and risk in the process.)

Third, decide on the product approach: Determine whether you want to use an existing device that is already in use elsewhere, or develop something new yourself.

These three elements are crucial prior to committing additional resources to your program.

Krai-Chatamra-Intrance-Medical

“Determine whether you want to use an existing device that is already in use elsewhere, or develop something new yourself.”

Krai Chatamra | Vice President of Clinical Development at Intrance Medical

Future trends and developments in APD therapies

Promising advances in drug administration

Krai: The future looks promising. Over the past ten years, many companies have recognized that different methods of drug administration are not only useful but are also safe and effective. There are now multiple ways to introduce drugs to patients. Oral treatment is now considered the least effective for APD due to the inability to completely overcome the issues associated with gastric complications of the stomach, e.g. erratic discharge, interaction with amino acids etc. The only way to overcome this is to bypass the biggest culprit, the stomach.

Several companies are exploring alternative methods of administration for PD therapies, such as enteral, subcutaneous, or sublingual routes. These methods, combined with advancements in drug formulation, have significantly improved treatment options. Levodopa, for example, is recognized as notoriously insoluble until recent advancements enabled it to be dissolved in a suitable medium.

Advancements in formulation, pump technology, and alternative methods of administration have contributed to the development of multiple new products. It is an exciting time to be involved in this field.

Opportunities for continuous blood serum monitoring

Krai: It would be remiss of us in PD therapeutic development not to recognize how other fields have successfully approached similar problems. For example, in diabetes management, continuous monitoring is crucial, and the ability to intervene as needed has been a significant success.

For PD, the challenges are similar. If we could monitor patients’ symptoms – both motor and non-motor – and adjust the treatment dosage accordingly, it would be highly advantageous. There are ongoing developments in this field, particularly with various wearables that are being developed rapidly and are becoming more prevalent.

The future I envision involves the combined use of infusion treatments and continuous monitoring. Imagine if we could detect when a patient’s plasma levodopa level is dropping, accompanied by certain symptoms, and then automatically adjust the drug delivery. That would be ideal.

“Imagine if we could detect when a patient’s plasma levodopa level is dropping, accompanied by certain symptoms, and then automatically adjust the drug delivery.”

Krai Chatamra | Vice President of Clinical Development at Intrance Medical

PD therapy is rapidly advancing, marked by significant advances in drug delivery technologies. These innovations are already providing significant improvements in patient outcomes and quality of life. Navigating the distinct regulatory environments across different markets is crucial. Understanding these differences is essential for successfully bringing new treatments to the market. CDP helps clients address this challenge by providing expert guidance on all aspects of drug delivery device design and verification.

Connect with CDP

If you would like to discuss the content of this article, please get in touch with Steve Augustyn, Deputy Head of Drug Delivery at Cambridge Design Partnership:

Steve Augustyn, Deputy Head of Drug Delivery
steve.augustyn@cambridge-design.com

GET IN TOUCH