Why syringe type matters for intravitreal injections

At the GERPAC congress 2024 (held in October 2024) Dr Chennell described a study that evaluated of two types of syringes for bevacizumab solutions for intravitreal administration.  The thinking behind the study was that bevacizumab, a monoclonal antibody, could be altered or destabilised by contact with silicone oil in the syringe.

How the syringe lubricant interacts with the drug inside it

Dr Chennell’s study compared the stability of bevacizumab injection in two different types of syringe – conventional polypropylene syringes, lubricated with silicone oil and syringes that had (non-extractable) cross-linked silicone on the internal surface of the barrel of the syringes. The results showed that fewer bevacizumab particles were formed and the drug appeared to retain its initial physical characteristics in the cross-linked silicone syringes compared with the polypropylene syringes.

Why ready-to-administer syringes improve clinical care

The provision of ready-to-administer bevacizumab in syringes reduces the risks of altering or destabilising the monoclonal antibody during the preparation process and saves time in the administration process.

Unfortunately, cross-linked silicone syringes of the type used in the study are not yet available to hospital pharmacists in France in suitable packs and Dr Chennell is trying to find alternative syringe manufacturers who might be able to provide suitable products.

About Philip Chennell

Philip Chennell is a pharmacist, at the University Hospital of Clermont-Ferrand. He is currently in charge of the Quality Control and Development Laboratory of the hospital’s pharmacy. He is also Assistant Professor at the University Clermont Auvergne and a member of the Materials for Health Research Team, focusing on medical devices and content/container Interactions.

Read and watch the full series on our website or on YouTube.

There are a number of advantages of providing bevacizumab as a ready-to-administer injection, preloaded into a syringe. First, even a brief contact with silicone oil (in polypropylene syringes) combined with the mechanical stresses of manipulating the syringe or, for example, flicking the syringe to remove air bubbles can be enough to trigger changes in the bevacizumab. Second, the clinical care process is smoothed. “By preparing these syringes directly in a pharmaceutical compounding unit it allows us to provide …… ready-to-administer syringes for the ophthalmologist or the end-user which means that they save time – they don’t have to perform the manipulation themselves. What they need to do is to just take the syringe, adjust the needle, [and] inject”, explains Dr Chennell.

Unfortunately, cross-linked silicon syringes are not yet available to hospital pharmacists in France in suitable packs. The packs that are available are designed for industrial use and are too large for use in hospital pharmacy compounding units.   “We can’t really purchase a big bag containing 1,200 syringes and expect to be able to do something with them when we see that in our clinical setting, we only use a couple of dozen every week. Okay, after a year it does add up but we don’t need 1,200 in one big go – and how would we store them? How would we keep them sterile?”, he says.

Since giving the presentation at the GERPAC congress Dr Chennell has been contacted by several colleagues in France who are also interested in this topic. He is also trying to find alternative syringe manufacturers who might be able to provide suitable products.

About Philip Chennell

Philip Chennell is a pharmacist, at the University Hospital of Clermont-Ferrand. He is currently in charge of the Quality Control and Development Laboratory of the hospital’s pharmacy. He is also Assistant Professor at the University Clermont Auvergne and a member of the Materials for Health Research Team, focusing on medical devices and content/container Interactions.

Read and watch the full series on our website or on YouTube.

Dr Chennell’s study set out to compare the stability of bevacizumab injection in two different types of syringes. One type was the conventional polypropylene syringe type, lubricated with silicone oil. The other had (non-extractable) cross-linked silicone on the internal surface of the barrel of the syringe. “Our main hypothesis was that these cross-linked silicone syringes would induce less aggregation, ….. of the antibody so that therefore it wouldn’t impact its stability compared to normal silicone-oil-lubricated syringes”, explains Dr Chennell. Syringes (1 ml) containing 0.2 ml of bevacizumab, 25mg/ml were prepared and stored at 5°C and 32°C for three months. The contents were investigated at three days, one month and three months. In addition to visual examination of the contents, aggregation index measurements, size exclusion chromatography, subvisible particulate counting and dynamic light scattering analysis were also carried out. “These assays allowed us to …..  gain insight into …. the number of particles [and] their size but also how the antibody behaved – did it fragment or did it aggregate into high-molecular-weight species which hadn’t, for example, quite yet formed particles”, he says.

The main finding was that physical stability seemed to be superior with the cross-linked silicone syringes compared to the classical, normal, silicone-oil-lubricated syringes. Fewer bevacizumab particles were formed and the drug appeared to retain its initial physical characteristics.  These differences were likely to be linked to the presence of the silicone oil in the polypropylene syringes, he says. “I think the main conclusion …… from a pharmaceutical point of view, is that it shows, yet again, that choosing the right primary container for monoclonal antibodies, or in fact any medication, really remains [paramount] if you want to maximize patient therapeutic safety”, he adds.

About Philip Chennell

Philip Chennell is a pharmacist, at the University Hospital of Clermont-Ferrand. He is currently in charge of the Quality Control and Development Laboratory of the hospital’s pharmacy. He is also Assistant Professor at the University Clermont Auvergne and a member of the Materials for Health Research Team, focusing on medical devices and content/container Interactions.

Read and watch the full series on our website or on YouTube.

At the GERPAC congress 2024 (held in October 2024) Dr Chennell presented the findings from a study concerned with the evaluation of two types of syringes for bevacizumab solutions for intravitreal administration. An intravitreal injection involves injecting medication directly into the vitreous humour at the back of the eye. It is used to treat retinal diseases such as age-related macular degeneration.

Although, at first sight, this might seem straightforward, there is a risk of interaction between the silicone oil that is used to lubricate the syringe and the medication solution inside the syringe. Specifically, there is a risk that the silicone oil can migrate into the drug solution and then be injected, in this case, into the eye. If the patient has multiple injections, then there is a risk that the oil will accumulate at the back of the eye. “It has been shown that it can cause reduced visual acuity, endophthalmitis, or for example, a reversible rise of intraocular pressure. It’s also been noted that certain patients have the impression that they have, like, floaters impacting their vision”, explains Dr Chennell.

About Philip Chennell

Philip Chennell is a pharmacist, at the University Hospital of Clermont-Ferrand. He is currently in charge of the Quality Control and Development Laboratory of the hospital’s pharmacy. He is also Assistant Professor at the University Clermont Auvergne and a member of the Materials for Health Research Team, focusing on medical devices and content/container Interactions.

Read and watch the full series on our website or on YouTube.