Grand designs
Injectable and infusible drugs together represent the second largest drug market in terms of route of administration or method of delivery but in terms of technology evolution the two segments have experienced vastly different paths. While drugs delivered intravenously have benefited from evolutionary improvements in infusion pump design, the infusion sets that deliver the drug to the patient have changed very little in the past two decades.
During this period, injectable drugs that can be delivered subcutaneously or intramuscularly have undergone rapid change as vials continue to be replaced by prefilled syringes and specialty injectors, and safety syringes continue to proliferate in response to caregiver safety concerns. The former trend has been and continues to be driven by the economic and logistical issues associated with the long-term therapeutic requirements of chronic conditions such as autoimmune diseases, blood conditions and hormone deficiencies. Prefilled devices that promote dosing accuracy and patient compliance without the need to travel to a physician’s office or healthcare facility ease the burden on both patients and the caregiver infrastructure.
The thinking behind LVIDs
While there are several reasons why a drug is formulated for intravenous delivery, one of these is the sheer volume of drug required in a typical therapeutic dosing regimen. These volumes are typically well above the practical limit of 1.2-1.3mL for subcutaneous injection via a syringe or injection device. Intuitively, if there was a practical way to deliver a larger volume of a drug over a longer period of time, for example, 10mL over ten minutes, subcutaneous delivery could be accomplished without causing trauma and discomfort to the target tissue area. This is the rationale behind large volume injection devices (LVIDs).
There are currently eight LVIDs that are market-ready or in late-stage development. Two non-insulin drugs have been approved for delivery in large volume injection devices - Herceptin SC from Roche, and Ferring’s LutrePulse which delivers gonadorelin acetate from an Insulet pump - with four more in development and a number of collaborative discussions between device and drug companies under way.
The primary container is a critical component of any drug development project. Factors such as drug shelf life, efficacy and product quality are dependent on the compatibility of the drug with the primary container. Most of the LVIDs analysed in Greystone’s recent market analysis utilise a rigid drug cartridge constructed of Type 1 glass. In the case of West’s SmartDose, the cartridge consists of cyclic olefin polymer. Use of a primary container that has a large amount of stability data available and that has been FDA-approved for use in existing injectables reduces development time and risk. All of the devices in the report utilise standard legacy materials for all drug contact parts and surfaces.
LVID classification
LVIDs can be classified as electronic or mechanical, and as disposable or semi-disposable. Half of the current generation of LVIDs are electronic disposable models. Sensile Medical has developed an electronic disposable as well as electronic semi-disposable model. In terms of reservoir size, volumes range from 2-20mL. It can be argued that a 20mL drug reservoir is close to the practical limit for a wearable injection device in terms of device size and weight. Above this level ergonomics, comfort, and adhesion start to become significant issues.
The devices covered in our analysis employ a number of methods for moving the drug from the primary container, through the cannula or needle, and into the patient. Most of the devices utilise a piston or piston-type method to deliver the drug. Sensile Medical uses a precision rotary micropump to move the drug from the glass cartridge, through the cannula, and into the subcutaneous layers of the skin. The most novel approach belongs to SteadyMed, which uses a microprocessor-controlled expandable battery to push on the primary container and expel the drug.
Drug developer interest
Strategically, these devices present several interesting options for drug developers and marketers. Reformulation of brand drugs losing IP protection and/or exclusivity could be highly attractive. Resurrecting high‐volume infusible generics from the commercial graveyard and creating a new brand in a large volume device combination product will be a particularly tempting strategy, especially for smaller drug companies seeking to break out of the overcrowded generics segment.
From a therapeutic standpoint, most of the short-term activity will be centered on efforts to reformulate and/or re-brand existing approved drugs, in the process providing patients and their caregivers with new treatment options. This market will involve well-established treatments for oncology, cardiovascular conditions and blood disorders.