The prefillable solution — how packaging solutions can help in an innovative drug landscape

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The field of prefillable syringes is constantly changing, driven by the innovations in active ingredients and patient safety at affordable costs. Here Bernd Zeiss, manager technical support medical systems, business development at Gerresheimer reveals the challenges and how packaging solutions can help.

Prefilled syringes have been around for several years and has a reasonably mature market within Europe, being worth around $300 million and growing between eight and 10% each year.1 However, the field of prefillable syringes is constantly turning up new trends and developments, largely driven by the innovations in active ingredients available and a desire for patient safety at affordable costs.

There are many uses for prefillable syringes within various sectors and the delivery devices are increasing in popularity due to the advantages they hold over the more traditional delivery device.2

Within pharma, customers are interested in syringe systems that fulfil extremely strict requirements in terms of quality and can be filled without any problem. An important advantage of prefillable syringes for a pharmaceutical company is the reduction in drug waste — if using vials it is common for manufacturers to overfill by 25% to ensure the end user gets the correct dose. In the advent of biotech drugs, which can be more expensive, this will be truly beneficial to the manufacturer.

However, with these advantages a drug manufacturer must also consider the challenges they will face when trying to incorporate a drug product into a prefillable syringe and what packaging solutions are available to overcome these.

The modern combination

Modern injectables in prefilled syringes are classed as ‘combination products’ — most of which are relatively expensive and produced using complex biotechnological processes.

Current approaches being adopted include ways of adapting syringe systems to the requirements of new formulations. The additional therapeutic value for this process is closely linked in order to ensure the injectable and the syringe system work together smoothly. Development is focusing on facilitating higher dosage volumes per injection, dealing with higher viscosities and overcoming the sensitivity that the liquid formulation has to some of the syringe’s individual components.

Additionally, the requirements placed on the syringe as an ‘interface’ between the medication and the patient are becoming increasingly demanding. The effective dosage needs to be injected safely.

With all these combined factors to consider it is vital to ensure the syringe itself is of consistently high quality — after all, it needs to be able to store the medication safely (primary packaging) and make the injection itself safe, patient-friendly and as painless as possible (injection device).

Bearing this in mind, we at Gerresheimer have extensively investigated the functionality — the break-off and slipping forces — with a number of stoppers to help pharmaceutical customers choose the appropriate injection system. Functionality of the syringe is also essential to its integration in automatic injection systems, a factor which is becoming increasingly important.

Properties and production

Patient safety when using the syringe system is always at the forefront of all research: Properties of the medications such as viscosity and technical properties such as break resistance and reliable force regulation when emptying the syringe are deal-breakers, especially when it comes to integration in automatic injection systems.

Highly viscous medications

Increasing numbers of biotechnologically produced medications are highly viscous. When the syringe is emptied into the tissue through the cannula, this leads to high backflow forces, making injection more difficult.

The aim of making injections quick and painless can be achieved using needles with a larger inside diameter: ‘thin-walled’ cannulas allow a higher flow rate per unit of time, at a lower pressure. They also reduce shearing forces, which can sometimes impair the often-sensitive liquid formulations.

To cater to the requirements of modern injectables, we have developed a range of thin-walled cannulas. In addition to the traditional 27G cannulas, we also have 29G, 26G and 25G and we offer a 23G thin-walled cannula for extremely viscous medications.

Minimising interactions with active ingredients

One of the challenges that developers need to consider is the potential interaction of the material the prefilled syringe is made from and the drug.

Two components of the syringe are of particular significance when it comes to interaction with sensitive medication: silicone oil, which is used as a lubricant in prefillable syringes and residual traces of tungsten, which can remain in the syringe from the manufacturing process for the glass body.

Silicone oil can be kept to a minimum using baked-on siliconisation, a process that Gerresheimer has offered for many years with its Baked-on RTF syringes. Traces of tungsten can be significantly reduced using a special washing process, or avoided completely by using a special ceramic as an alternative pin material.

Break resistance

After performing extensive studies on the break resistance of glass syringes we have found that it is possible to improve the break resistance of the finger flange and also to significantly improve the stability of the shoulder area and the cone. Our newly developed Valor glass offers further improvements in terms of break resistance. High break tolerance and compact dimensions are important parameters for a prefilled syringe, especially when using automatic injection systems.

High-volume syringes

In certain applications, a higher-volume syringe is becoming a more established product, with a move away from the ‘traditional’ 1 mm syringe and to a 2.25 mL syringe being witnessed.

Not only can this increased volume lead to fewer required injections but can also allow patients to be injected with medication that acts as a deposit for a long-term effect, or based on a number of reasons, for which higher concentrations are unfeasible or impossible. In all these cases, high-volume syringes represent a significant expansion in the therapies that can be offered by a physician.

Among other products, Gerresheimer offers a 2.25 mL syringe that allows subcutaneous injection for such applications.

Production technology

Modern production technology for glass forming, needle mounting and the ‘ready-to-fill’ (RTF) process is important in ensuring product quality. Using camera technology (G3 camera system) and transporting syringes individually during the RTF process to avoid glass-to-glass contact are just two examples of the measures we take in order to improve quality for our customers and minimise rejection rates.

Looking to the future

Close collaboration with pharmaceutical customers is imperative in the further development and improvement of existing injection systems. Highly viscous and high-volume injections are just two examples of the developments in the administration of modern medication, and the solutions a packaging manufacturer can offer in this field.

Gerresheimer continually works with customers in its own labs to is constantly working in close collaboration with its pharmaceutical customers in its own labs to respond to the changing trends and demands of the pharmaceutical industry, doctors and nursing staff, and the patients themselves.

References:

  1. https://www.medica-tradefair.com/cgi-bin/md_medica/lib/pub/tt.cgi/Future_of_Prefilled_Syringes_Manufacturer_s_Perspective_–_Challenges_and_Opportunities.html?oid=16672&lang=2&ticket=g_u_e_s_t
  2. Makwana, S., et al., Int. J. Pham. Investig., 2011;1(4):200–206. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465144/