The author explores the major trends in the prefilled syringe (PFS) and injection sphere — aside from patient-centricity.

The injection market has been evolving rapidly over the past decade, with a number of crucial developments and trends shaping the sector.

These trends have a myriad of implications for manufacturers, particularly when it comes to overcoming packaging challenges to keep up with market demand for PFSs and other more complex injectable presentations. Failure to respond to these developments could mean manufacturers fall behind the competition.

Here are the key developments to be aware of:

• Injectable devices of every type are rapidly increasing their market share. For example, the demand for PFSs, as opposed to traditional syringes, has been steadily increasing for a number of years. The global PFS market expanded from $6.39 billion in 2022 to $7.29 billion in 2023 at a compound annual growth rate (CAGR) of 14.0%, and is forecast to reach $12.19 billion by 2027 at a CAGR of 13.7%^[1].

In addition to PFSs, other injectable devices that improve the patient experience of injectable medicine administration have been developed simultaneously. Autoinjectors, injection pens and infusion pumps have all been actively increasing their share in the sterile manufacturing market. The global autoinjectors market, for example, was valued at $46.8 billion in 2021 and is expected to reach $247.3 billion by 2030, with a CAGR of 20.32% over the forecast period².

Syringe components have also evolved significantly. Engineers have been actively exploring integrated safety systems that can be applied to PFSs to enhance needle safety and useability, and to enable multi-barrel options. Syringe portfolio ranges are being expanded with respect to volume options and needle sizes.

• Developments in biologics and new regulations are driving PFS growth in particular. When it comes to biologics and biosimilars, PFSs have become the primary alternative to multi-vial solutions. In the current market, PFSs are widely used for antithrombotics, vaccines and biologics, as well as small molecules. Harnessing PFSs in these areas has helped to boost the efficiency of the manufacturing process and minimise waste while also ensuring that the correct dose is administered.

There has also been a significant shift towards using PFSs in therapeutic segments such as immunology, oncology and gene therapy. As such, biologics are now being given a higher priority in the pharmaceutical industry’s pipeline. The administration of biologics is mostly performed via injection, as alternative routes of administration often drastically lower their effectiveness. As both the biologics and the biosimilars markets expand, the industry is seeing greater demand for new packaging solutions for injectables – hence the increasing popularity of PFSs.

Supportive government regulations, such as the European Union (EU) Directive 2010/32/EU –  prevention from sharp injuries in the hospital and healthcare sector – are also providing a boost to the PFS market growth³. PFSs with added safety features offer an ideal approach to reducing the rate of needlestick injuries in line with this legislation.

Additionally, the recent Institute for Safe Medication Practices (ISMP) guidelines heavily support an increased use of ready-to-administer (RTA) syringes⁴. The ISMP guidelines have increased awareness and guidance regarding the use and manufacture of RTA syringes. In its guidelines published in 2020, the ISMP again addressed the main downsides of admixing faced by clinicians during emergency situations, introducing new safe practices that include the use of RTA products. Similar guidelines are also being released by regulatory bodies and serve as an additional driver for the PFS market.

• Increasing sophistication of PFSs is driving demand for more complex packaging. When it comes to packaging, the current challenges faced by pharmaceutical companies include securing key components for format parts and/or equipment and key packaging materials for secondary and tertiary packaging, as well as having the agility to ensure that new products are launched to new markets on time and with the flexibility to adapt to different regulatory, market, equipment and process requirements.

As PFSs and other devices become more complex, achieving these goals has become more complicated and challenging. For instance, their packaging needs have shifted from solely carton-based packaging to a more stable and durable packaging solution. Carton-based packaging does offer some form of structural stability with the inclusion of paper-based custom inlays to keep the devices in place, but alternative approaches are becoming more widespread. For example, companies can place devices in an unsealed blister with a clamp-in option or in a sealed blister with or without a clamp-in option.

These trends are leading companies to adopt various non-standardised solutions, driving demand for flexible secondary packaging capabilities to meet increasingly diverse packaging requirements. Due to the challenge of investing in in-house capacity, manufacturers are turning to contract packaging organisations (CPOs) for support, particularly to those that can offer automated packaging of PFSs into blisters.

Advanced blistering lines can automate the secondary packing of injectables – including vials, ampules and PFSs – into rigid PVC with high thermoformability. These PVC blisters are then sealed, ensuring that all components remain intact. The blister, along with a patient information leaflet, is then placed inside a carton that can be serialised later or aggregated based on market-specific requirements.

• New serialisation legislation is making packaging of PFSs more complex. Although serialisation has been high on the pharmaceutical agenda for a decade now, new legislation is still appearing in key markets, changing the landscape.

In particular, Title II of the US Drug Quality and Security Act (DQSA) is due to come into force at the end of 2023. A key requirement of the new legislation will be to use product identifiers to verify products at the package level. With that, it will further enhance secure tracing of each pack of medication across the US, boosting response to counterfeit drugs and optimising the efficiency of recalls.

Other challenges still arise from the differences in serialisation requirements across different global markets. For example, although serialisation within Europe is uniform (except for Italy and Greece), many companies come across difficulties when they decide to go into international markets. The differences are concentrated around medicine verification systems, the extent of required ‘Track & Trace’, pick processes for different markets and mandatory aggregation.

• The globalisation of the pharma supply chain is causing labelling challenges. Different markets have different language requirements, which makes stock-keeping unit artwork management critical. Some markets, such as Switzerland and the Benelux countries, have multiple language requirements, which means more complex booklets and labels – something companies need to be aware of as they expand their market operations beyond their home countries.

Another challenge arising from the rapid globalisation of the pharmaceutical market is posed by varying storage temperature requirements – for biologics in particular. This can have significant implications for the choice of label and adhesive.

Standard labelling processes are often done under ambient conditions in the range of 15–25°C. However, for cold-chain products (2–8°C), it is prudent to follow the product guides of ‘Time Out of Range’ to ensure that the end-product temperature conditions are met.

Optimum label materials should be selected to ensure proper adhesiveness even under condensation. For ultra-cold environments (-20°C), it is a good idea to pack products for clinical trials in dry-ice trays.

Keeping up with the trends

The complexities of following these trends shouldn’t dissuade pharmaceutical companies from harnessing the benefits of new injectable forms or of PFSs in particular. One approach that is proving effective is to outsource the packaging part of the production process to packaging specialists.

For many years, packaging was considered a small, unimportant part of the manufacturing process for pharmaceutical products. This led companies to outsource it as part of a broader, end-to-end service to contract development and manufacturing organisations (CDMOs) and contract manufacturing organisations (CMOs).

However, there is a significant drawback to this approach. CDMOs do not always have dedicated expertise not just in packaging of PFSs, but in the technology transfer for a project. A number of factors have to be considered to ensure a successful technology transfer for packaging. These include:

• Analytical tests (performed by certified third parties at the client’s wish).
• Identification of key components (safety device and format parts for plunger rods, backstops or finger flanges).
• Identification of necessary packaging materials (such as foils and films), with subsequent stability studies executed by a certified third party.
• Quality validation to ensure that each step of the PFS assembly process is safe for the end-product and for patients to use.

The packaging of PFSs differs from the packaging of other dosage forms, such as oral solids and vials. Oral solids are primarily packed into blisters, bottles and similar, and therefore have different in-process controls to ensure that there is no contamination. Since oral solids come in different sizes and shapes, there is not always one standard solution that fits all. However, for PFS packaging, the key considerations are the type of PFS assembly (with or without a safety device) and format parts for plunger rods, backstops or finger flanges. Identifying the optimum foil with deep stretch properties to hold the PFS in its blister and a suitable lidding foil are some of the other key considerations.

Benefits of CPOs

To overcome the issues posed by outsourcing packaging to standard CDMOs and CMOs, a growing number of companies are turning to specialist CPOs instead.

CPOs are uniquely well-equipped to support the industry with the packaging of new – more patient-centric yet complex – dosage forms, such as prefilled syringes. They have comprehensive knowledge of the injectables market, the regulatory environment and the unique processing needs of injectables. Due to the nature of their role in the supply chain, they can offer the flexibility and the capacity to develop customised packaging services that can add real value to customers, benefiting their partners over the long term.

CPOs are becoming an integral component in the pharmaceutical ecosystem, supporting drug companies in meeting the needs of their customers while reducing cost and enhancing production efficiency. They offer much more than a simple transactional service; they are an integral strategic partner that can help pharma companies deliver an improved experience for patients.

Key to successful adaptation

The PFS and wider injectables market is in a constant state of flux. New segments are exploring the convenience and efficiency benefits of PFSs, and new legislation is appearing, which is not only driving further demand, but also shaping the design of future devices.

Navigating these complex and interlinked trends can be daunting, especially for manufacturers exploring injectable drug products and PFSs for the first time. By collaborating with expert partners, these companies can be confident that they have the insight, the guidance and the resources available to help them address challenges presented by a rapidly transforming market. In doing so, they can stay ahead of the competition and ensure that their drug innovations reach the patients that need them with minimal delay.

^[1] https://www.researchandmarkets.com/reports/5752075/pre-filled-syringes-global-market-report?utm_source=CI&utm_medium=PressRelease&utm_code=srxnsz&utm_campaign=1837125+-+Pre+Filled+Syringes+Global+Market+Report+2023%3a+Connected+Syringes+to+Reshape+Industry+Moving+Forward&utm_exec=como322prd

² https://www.precedenceresearch.com/autoinjectors-market

³ https://osha.europa.eu/en/legislation/directives/council-directive-2010-32-eu-prevention-from-sharp-injuries-in-the-hospital-and-healthcare-sector

⁴ https://www.ismp.org/sites/default/files/attachments/2022-11/RTA%20IV%20Meds_handout_2022.pdf

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