Preclinical development of an automated injection device for intradermal delivery of a cell-based therapy

Giulia Leoni,Michaela Sharpe,Alex Lyness,Paul Kemp,Gopalan Pillai,Gayatri Sharma,Natalie Mount,Rindi Schutte,Patrick Ginty

doi:10.1007/s13346-017-0418-z

Abstract

Current methods for intradermal delivery of therapeutic products in clinical use include manual injection via the Mantoux technique and the use of injection devices, primarily developed for the delivery of vaccines and small molecules. A novel automated injection device is presented specifically designed for accurate delivery of multiple doses of product through a number of adjustable injection parameters, including injection depth, dose volume and needle insertion speed. The device was originally conceived for the delivery of a cell-based therapy to patients with skin wounds caused by epidermolysis bullosa. A series of preclinical studies was conducted (i) to evaluate the performance of the pre-production model (PreCTCDV01) and optimise the final design, (ii) to confirm that a cell therapy product can be effectively delivered through the injection system and (iii) to test whether the device can be safely and effectively operated by potential end-users. Results from these studies confirmed that the device is able to consistently deliver repeated doses of a liquid to the intradermal layer in an ex vivo skin model. In addition, the device can support delivery of a cell therapy product through a customised microbore tubing without compromising cell viability. Finally, the device was shown to be safe and easy to use as evidenced by usability testing. The clinical device has since been granted European market access and plans for clinical use are currently underway. The device is expected to find use in the emerging area of cell therapies and a broad spectrum of traditional parenteral drug delivery applications.

Highlights

Intradermal (ID) delivery of therapeutic products has gained increasing attention as an alternative route of administration to the conventional subcutaneous, intramuscular and intravenous routes
Improved delivery and reduced back flow when combined with longer dwell times (4, 5 s)
For selection of the optimal device setting parameters to be assessed in the ex vivo performance study, a pilot study was conducted

Summary

Introduction

Intradermal (ID) delivery of therapeutic products has gained increasing attention as an alternative route of administration to the conventional subcutaneous, intramuscular and intravenous routes. Some of the advantages provided by targeting the ID layer include minimal invasiveness with the possibility of reduced pain, more rapid pharmacokinetics and a stronger immune response due to the presence of antigen-presenting cells and a dense vasculature [1]. ID injections have been traditionally performed manually via the Mantoux technique, which consists of inserting a fine and short hypodermic needle into the skin at an angle of 5–15° to target the ID layer [2, 3]. Though extensively used for the administration of vaccines, this method is considered technically challenging and susceptible to variability as it depends on the experience of the practitioner as well as the biomechanical properties of the skin.

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Results