CPHI Annual Report 2024: Drug Delivery Trends & Insights From a Device Perspective

By: Chris Hurlstone, Director of Drug Delivery, Team Consulting

INTRODUCTION

Significant growth in the drug delivery sector is predicted for many areas, with headliners including cell and gene therapies and the GLP-1 blockbusters. Small molecule-based formulations still dominate innovator pipelines, but advanced biologics are also growing significantly. In terms of therapy areas, many pharma companies are targeting oncology, immunology, cardio-vascular and cell and gene therapy.

GIVEN THESE PREDICTED ADVANCES IN DRUG FORMULATION, WHAT ARE THE IMPLICATIONS FOR DRUG DELIVERY DEVICES?

Oral presentations are simple, effective and currently account for as much as 90% of the global market share of all pharmaceutical formulations for human use. Where these are not suitable, companies will seek to deliver these drugs using established delivery systems. Injectables include pre-filled syringes, auto-injectors, pen injectors and infusion systems, while for respiratory drug products there are many existing device technologies including capsule, reservoir and blister-based inhalers, nasal delivery systems and nebulisers.

INJECTABLES

Nobody wants to develop a new device if they can avoid it. Hence in the injectables sector formulators will target 1ml subcutaneous delivery or similar where possible, as this is an area very well served by existing devices. But for some new formulations, including those driven by a desire to move treatment away from IV delivery in the hospital or clinic to the home, increased volumes and/or viscosity are often necessary. Such payloads are falling into the space between autoinjector and on body delivery systems, so new developments of both are in progress, with some devices now appearing on the market.

Figure 1. the recently approved Ypsomed 5ml autoinjector (Ypsomed)

SUSTAINABILITY AND COST

Two of the challenges that need to be addressed by new device technologies are cost and sustainability. In an increasingly competitive market, the need to minimise cost per dose delivered is more important than ever. Meanwhile, the sustainability of such devices, typically measured by carbon footprint analysed across the product lifecycle, is becoming a real – and high – priority for many pharma companies. Optimising device designs for the most effective use of materials and manufacture from highly efficient production systems can be one way to achieve both cost and carbon footprint savings. However, in some cases more sustainable solutions can be more expensive (e.g. the use of specialist bio-feedstock materials or multiple, more localised supply chains).

One other way to reduce the cost and sustainability impact of devices is to re-design them to include ‘retained’ or ‘durable’ elements as well as the disposable element, which usually contains the primary pack. This approach is not new – the UCB ava Connect was launched some years ago for biologic treatment of rheumatology and dermatology – but it is being pursued by a number of companies. This includes Phillips-Medisize (Aria), The Smartclic® device licensed by Pfizer in Australia for Enbrel, and the very recently announced Elexy™ from SHL, all of which include electro-mechanical and software elements.

BALANCING THE DIGITAL BENEFITS

Meeting cost and sustainability targets for these larger and more complex devices, including on body delivery systems such as patch pumps, is difficult without moving away from the entire device being single use. There is scope in such systems to provide additional value though, through the use of digital tools and device connectivity. However, the high levels of activity seen in this area in recent years seem to be abating to some extent. This is partly due to ‘cost and carbon constraints’, but also because the ways to realise or demonstrate true user benefit have proven difficult to establish. Challenges over data capture and handling also present a barrier. Efforts to resolve these challenges will continue but, in the meantime, opportunities to leverage other digital tools and approaches are being developed, e.g. through the use of smart labelling and packaging, sometimes linking to mobile apps and website support materials.

Other areas of activity in parenteral drug delivery include intradermal delivery, using patches and micro-needles, and also ocular delivery. The latter is of particular interest for new gene therapies, following on from FDA approval for Luxturna in 2017.

The October medical technology conferences are likely to feature announcements of new device developments in a number of these of these areas.

RESPIRATORY

The respiratory device sector has seen less innovation in recent years, with much of what has been happening focused on the development of generic devices for asthma and COPD. This is beginning to change, however, in both inhaled pulmonary and nasal drug delivery. Alternative therapies for conditions including lung cancer, idiopathic pulmonary fibrosis, Parkinson’s disease, and more advanced antibiotics appear to be getting closer and there are signs that device developments are progressing to match the particular requirements of these new therapy areas.

One example of device development in this area is in intra nasal drug delivery of both liquid and dry powder dose forms, targeting both CNS (via the blood brain barrier) and systemic delivery. Significantly, these have been extending to treatment areas which were previously the preserve of injectables only, including vaccines and emergency use devices. One example of the latter is the recently FDA-approved neffy® epinephrine nasal spray for the treatment of severe (Type 1) allergic reactions including anaphylaxis.

Figure 2. Neffy® epinephrine nasal spray[1]

A new challenge for drug delivery devices arises from advances in formulation techniques for larger molecules such as peptides and nucleic acids, which require devices capable of handling higher dose sizes of often delicate formulations. This has led to a shift in the design landscape for inhaled pulmonary drug delivery systems, many of which have been developed to deliver no more than 10–15mg of powder per use. The emerging need for effective aerosol drug delivery devices which can deliver higher masses of formulations, often in excess of 25mg, cannot be easily accommodated by simply re-engineering currently available products.

TARGETED DRUG DELIVERY

One significant area of device innovation, driven to a large extent by developments in both oncology and cell and gene therapies, is that of drug delivery direct to target sites in the body such as organs, tissues and tumours. The need for innovation in this area is due to a number of key factors.

Firstly, many of the target sites are difficult to get to, both in terms of physical access but also due the need for accurate targeting in an environment which is highly variable and personalised. The use of surgical robots is becoming more commonplace and, in some cases, can be utilised for such delivery techniques. However, the fact that there are often differences between such systems, and how they are implemented, means that standalone delivery devices may present a flexible approach that can be deployed more broadly, such as through the use of standard laparoscopic methods. Guidance systems of various types, forming part of or used in conjunction with the delivery system, are often also required and will make use of a range of imaging and navigation tools.

Figure 3. DaVinci robot system (Intuitive Surgical)

Another reason why it is highly unlikely there will be many (or any) one-size-fits-all device solutions is the huge variation in payload that such devices will need to deliver. This is both in terms of delivered dose volumes but also the drug’s physical characteristics, including viscosity, single/multi-phase, sensitivity (e.g. to temperature, to shear) and stability.

Once the drug has been delivered, there is then the need to control distribution and retention within the target site. This is partly to ensure the necessary amount of drug is delivered but also in some cases to ensure neighbouring non-target tissue is not at risk of damage or contamination. Given the huge range of tumour and organ types this again points to a need for bespoke solutions, and also the need to fully understand tissue characteristics. This can be very challenging and is best approached through a combination of experimental and analytical methods.

These and other challenges, such as the need to ensure that delivery technology can be deployed across a wide range of varying healthcare settings, mean it is critical to begin device developments very early, alongside the development of the formulation. This is frequently the case but not always appreciated.

DRUG MANUFACTURE

Historically, and in most current cases, drug manufacture can be considered separately to the drug delivery device. Most of the challenges relate to selection, design, manufacture and filling of the appropriate primary packaging (e.g. syringes, cartridges, vials, capsules, powder reservoirs, blisters), and how these are then incorporated into the device technology.

PERSONALISED MRNA & RADIOPHARMACEUTICALS

New types of drug formulation are shifting some of these barriers, bringing production methods and delivery devices closer together. Two examples are personalised mRNA and radiopharmaceuticals, both of which bring with them specific challenges.

mRNA is extremely sensitive to contamination and needs to be produced to cGMP, but may at the same time be highly personalised and hence must be handled and tracked carefully.

Manufacture, packaging, transportation and handling of radiopharmaceuticals also needs to be handled extremely rigorously, for different reasons. In addition, the time sensitive nature of the drug preparation due to the half-life of the radioisotopes within them means that the effective shelf-life can be extremely short – sometimes just a few hours. This has major implications for the location of the manufacturing site, and the supply logistics.

REGULATORY DRIVERS & HURDLES

Perhaps the main regulatory factor impacting the development of new drug delivery devices is the continued adjustment to the introduction of the Medical Device Regulation (MDR). Whilst the introduction of the MDR did increase the focus on the medical device aspects of drug delivery systems and combination products, which we believe is a good thing, it has led to challenges in a number of areas.

The need both for full notified body review of any new Class 2 and 3 devices, alongside re-certification of existing devices, is putting excessive pressure on an insufficient number of approved notified bodies. Coupled with this, companies are new to the process and hence submissions are frequently incomplete and need further work (75% according to a European Commission survey).

Both of these factors are leading to long delays in device approval which will have major implications. The pain is felt particularly by start-up companies looking to commercialise their first product, and one result is that many such organisations are looking to the US or other non-EU markets for their first launch.

Companies entering the US market need to bear in mind new guidance from the FDA. New draft guidance documents covering Essential Drug Delivery Outputs and Use Related Risk Analysis were published in June and July 2024 respectively, with the industry given 60 days to submit comments. Meanwhile, the interpretation and application of the “five nines” draft guidance for demonstrating reliability of emergency use injectors, published in April 2020, is still a source of discussion and debate within the industry.

Despite all the challenges faced, the pharma industry continues to make huge progress in helping more people live healthier lives. It will be interesting to see how many of this year’s trends will still be impacting the industry in years to come.

REFERENCES

[1] ARS Pharmaceuticals Receives FDA Approval for Neffy™ (Epinephrine), ARS Pharmaceuticals, September 2023, https://ir.ars-pharma.com/news-releases/news-release-details/ars-pharmaceuticals-receives-fda-approval-neffyr-epinephrine/.