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Biosimilar anti-VEGF- is prefilled syringe (PFS) a challenge?

Eye volume 38, pages 244–245 (2024)Cite this article

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Biosimilar anti-VEGFs are emerging as a wave with a series of biosimilar ranibizumab approvals in the last 2 years across the globe by various regulatory agencies including the United States Food and Drug Administration (US-FDA) and European Medical Agency (EMA) [1]. Furthermore, multiple biosimilar aflibercept molecules are in the final stages of regulatory approval process [2]. Once the aflibercept patent expires, these molecules will be available for clinical use.

We have observed that many of these approved biosimilar anti-vascular endothelial growth factor (anti-VEGF) molecules and candidates in the pipeline have prefilled syringes (PFS) testing in their clinical trial protocol. However, to the best of our knowledge, no manufacturer has however yet started trials on patients using prefilled syringes. The US-FDA approved the reference molecule (Lucentis, Genentech, USA) in the year 2006 [3]. However, the PFS of Lucentis was approved by the US-FDA in the year 2016 (0.5 mg) and 2018 (0.3 mg) [4]. Furthermore Aflibercept (Eylea, Regeneron, USA) received US-FDA approval in 2011 [5]. However, PFS of Eylea was approved in 2019 [6]. Similarly, though brolucizumab (Beovu, Novartis, USA) received US-FDA approval in 2019 [7], it received PFS approval in June 2022 [8]. Faricimab (Vabysmo, Roche, USA) received FDA approval in Jan 2022 [9]. but PFS are not yet available for clinical use. PFS provides many advantages such as reduced injection time, possible reduced risk of endophthalmitis, possible reduction in intraocular air bubbles and silicone oil droplets, and possible improved precision in the volume and dose of the intravitreal medication administered. It was thought to be very simple to introduce prefilled syringes. However, prefilled syringes for intravitreal therapy pose a significant challenge when compared to prefilled syringes in any other field of medicine. The multiple challenges and complexities in developing PFS have led to the delay in their approval compared to vials for all anti-VEGF agents licenced so far for the therapy of retinal diseases. This manuscript will discuss the potential difficulties that biosimilar companies potentially face in developing prefilled syringes for the trials and regulatory approval.

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References

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Funding

Funding

BDK acknowledges an unrestricted grant to the Gavin Herbert Eye Institute from Research to Prevent Blindness.

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Authors and Affiliations

  1. Lotus Eye Hospital and Institute, Avinashi Road, Coimbatore, Tamil Nadu, India

    Ashish Sharma

  2. Division of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel

    Anat Loewenstein

  3. Department of Vitreoretina, Sankara eye Hospital, Coimbatore, Tamil Nadu, India

    Nikulaa Parachuri

  4. Madhavi Netralaya, Ara, Bihar, India

    Nilesh Kumar

  5. Intas Pharmaceuticals, Ahmedabad, Gujarat, India

    Alok Rasal

  6. University Vita-Salute, Scientific Institute San Raffaele, Milano, Italy

    Francesco Bandello

  7. Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA, USA

    Baruch D. Kuppermann

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  1. Ashish Sharma
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  2. Anat Loewenstein
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  3. Nikulaa Parachuri
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  4. Nilesh Kumar
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  5. Alok Rasal
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  6. Francesco Bandello
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  7. Baruch D. Kuppermann
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Contributions

AS: conception, analysis, drafting, integrity check, final approval. AL, NP, NK, AR, BDK; drafting, revision, analysis, integrity check.

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Correspondence to Ashish Sharma.

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Competing interests

AS: CONSULTANT: for Novartis, Allergan, Bayer, Lupin and Intas, Speaker fee Biogen. AL: CONSULTANT: Allergan, Novartis, Roche, Notal Vision, Fiorsightslabs, Beyeonics, Bayer Health Care. AR: Employee Intas Pharmaceuticals Ltd. FB: CONSULTANT: Allergan, Bayer, Boehringer- Ingelheim, FidiaSooft, Hofmann La Roche, Novartis, NTC Pharma, Sifi, Thrombogenics, Zeiss. BDK: CLINICAL RESEARCH:, Alimera, Allegro, Allergan, Apellis, Boehringer Ingelheim, Clearside, Genentech, GSK, Ionis, jCyte, Novartis, Regeneron; CONSULTANT: Alimera, Allegro, Allergan/AbbVie, Boehringer Ingelheim, Clearside, Coherus, EyeBio, Eyedaptic, Galimedix, Genentech, Glaukos, IvericBio, jCyte, Novartis, Ocular Therapeutix, Regeneron, Revana, Theravance Biopharma. The other authors declare no competing interests.

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Sharma, A., Loewenstein, A., Parachuri, N. et al. Biosimilar anti-VEGF- is prefilled syringe (PFS) a challenge?. Eye 38, 244–245 (2024). https://doi.org/10.1038/s41433-023-02698-3

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