Engineers and scientists are working hard to revolutionise the way patients take new and existing drugs.

Many of the new drugs under development are ‘biologics’, which tend to be unsuitable for taking orally (as a pill) because the liver metabolises them. A classic example of a widely-used biologic drug is insulin for diabetes mellitus.

Therefore injection is the most common way of taking biologics.

Some of the biologic drugs, particularly monoclonal antibodies, require large masses to be injected.  In order to inject a large drug mass, we have two choices: increase the injection volume, or increase the concentration of drug in the formulation.

Problems with increasing the injection volume

Injecting a large volume requires either:

• A high flow rate, which can be painful and unsightly; or
• A long duration of injection, which can be uncomfortable and difficult to maintain injector position.

In addition, many injection devices are limited to 1 mL volume because:

• Historically many autoinjectors were based on the 1 mL BD Hypak; and
• It is extremely expensive to refit the aseptic filling lines that have been built for 1 mL syringes.

Problems with increasing the drug concentration

Increasing the concentration of the drug in the liquid increases the formulation viscosity, which cannot become too great because:

• Patients are demanding thinner and thinner needles, which strongly increases the resistance to flow and would increase injection duration to unacceptable periods for viscous drugs;
• Injection devices contain typically a glass syringe, which breaks if too much force is used to drive the formulation through the needle; and
• Many drugs, especially those based on proteins, aggregate (stick together) above a certain concentration.

Autoinjectors without glass syringes

There are various autoinjector technologies which do not contain a glass syringe, such as:

• The Crystal Zenith range from West Pharmaceutical Services; and
• The Oval Medical autoinjector.

These autoinjectors may be able to deliver viscous drugs, but still tend to be limited in injection volume due to the discomfort of injecting large volumes quickly and the difficulty in holding the autoinjector steady for long enough.

The bolus injector

The solution may be a different class of injection device: the bolus injector (sometimes called a ‘patch pump’, although this term is also used for ambulatory infusion pumps).

A bolus injector may be described as a device with performance and usage between current autoinjectors and infusion pumps:

• A bolus injector is typically attached to the patient’s body for a few tens of seconds to a few hours, unlike an autoinjector which is held in the hand. Therefore a bolus injector may be able to deliver a larger volume than an autoinjector because it does not need to be manually held in position during injection, and could contain a larger drug reservoir. In addition, avoidance of a glass syringe may enable delivery of more viscous drugs.
• A bolus injector is normally designed to deliver its payload promptly, unlike an infusion pump in which the duration of delivery is a key parameter in the therapy (such as a constant, low flow rate, basal dose of insulin 24 hours per day). The bolus injector is only attached to the patient for the few minutes or hours that it is delivering its dose.

Example bolus injectors

There too many bolus injectors in development to list here but some examples are:

BD is developing the Libertas bolus injector built around a pre-filled BD Neopak syringe.

BD Libertas

West has launched the Smart Dose injector for Amgen’s Repatha drug.  The device is based on the Crystal Zenith plastic cartridge.

West SmartDose

Enable Injections is working hard on its eponymous device, which takes a different approach to the prefilled devices above:  the drug is supplied in a separate vial or syringe, then a filling pump fills the injector with the drug formulation shortly before attaching the injector to the body.  This means that the device avoids some of the regulatory hurdle of proving drug stability for many months before use.

Enable Injections

SteadyMed is developing the ‘PatchPump’ platform which uses an expanding battery to force drug out of a flexible primary drug container.

SteadyMed PatchPump (R)

Sensile Medical has various formats of pump based around its core micropump technology.

Sensile SenseTrial

Ypsomed is promoting its YpsoDose concept based on 5 mL or 10 mL prefilled glass cartridges.

Ypsomed YpsoDose

Bespak has created a prototype demonstrator of a HFA gas-powered bolus injector, called Lapas.

Bespak Lapas

There are many other devices in development, such as the NeuroDerm continuous subcutaneous infusers.  Others have been mothballed or cancelled, or otherwise fallen by the wayside such as the Roche Single Injection Device (formerly MyDose), Ratio Drug Delivery’s NuPrivo, and Unilife’s Precision Therapy.

If your organisation is developing a bolus injector and you have recommendations for improving the list above, please get in touch.

Challenges for new bolus injectors

Many bolus injector designs use a novel primary pack, and pharmaceutical companies are very reluctant to risk their drug launch on new materials and designs. Device developers are trying to reduce the risk by using materials that have been used with drugs before.

The second challenge is that a new primary drug container is likely to be incompatible with the pharmaceutical companies’ aseptic filling lines, which are extremely expensive and time-consuming to build and validate.

In addition, some bolus injectors have advanced features such as automatic needle insertion and electronic control which increase development complexity.

Finally, new devices must meet the newly raised regulatory demands on usability (human factors).

The future

The drug delivery device industry is working hard to define the requirements and test methods for acceptable bolus injectors, which is likely to become ISO 11608 part 6.

We expect that bolus injectors will become a familiar part of the drug delivery device space, and that they could enable exciting new therapies such as regenerative medicine.

If you would like to know more about bolus injectors, or have a need to procure or develop one, please get in touch. Springboard develops injection technologies, and conducts technology scouting, technology procurement, due diligence and usability engineering projects for our clients.

Full disclosure: the author has worked on numerous injection device developments for pharmaceutical companies and device manufacturers, and has been asked to attend the meetings to draft ‘ISO 11608-6 Needle-based injection systems for medical use – Requirements and test methods – Part 6: Bolus Injectors’.

This post was originally posted on 19 September 2013 and has been updated since.

We have received a great number of enquiries for the latest information on wearable bolus (large volume) injectors, especially since our article “The Rise of the Bolus Injector” was published.

Therefore, Springboard’s Director of Drug Delivery Device Development, Tom Oakley has written a brand new article for OnDrugDelivery featuring the latest technical, commercial and regulatory developments in the world of bolus injectors.

Head over to OnDrugDelivery to read the latest news on bolus injectors, or read the whole edition devoted to large volume injectors.

Devices covered in the OnDrugDelivery magazine include:

• Unilife Precision-Therapy
• Sensile Medical SenseCore
• West SmartDose
• Enable Injections
• BD Libertas
• SteadyMed PatchPump

If you are from a pharmaceutical company or medical device developer and would like to find out more about bolus injectors and their development, please contact Tom Oakley on +44 (0) 1223 422 273.

Springboard’s Tom Oakley recently presented the latest developments of bolus (large volume) injectors at 2 major international conferences: the Management Forum in London and SMi America in New Jersey. Here is an update on the other hottest topics in injectable drug delivery… At the Management Forum, Amgen’s Mathias Romacker explained the trend to:

• Higher concentration formulations; and
• Larger doses with less frequent injections.

Interestingly, both of these trends point to an increased need for bolus injectors. 3P Innovation’s Tom Bailey and XstalBio’s Barry Moore showed the increased need for reconstitution devices, driven by the increased number of biologics being developed for subcutaneous delivery, especially therapeutic proteins. SHL’s Mats Persson described trends such as:

• Moving treatment from the hospital to the home for increased patient convenience and lower treatment cost;
• Using the injection device for drug product life-cycle management;
• Larger volume and higher viscosity injections required by new drug formulations;
• Increased emphasis by regulators on human factors studies;
• Interest in polymer, as opposed to glass, syringes;
• Autoinjectors for cartridges as opposed to syringes;
• Instructions for use on and in devices; and
• True end-of-dose indicators.

At the SMi America conference, Merck’s Scott Brown described the most common pitfalls of drug delivery device development, and Beroe’s Chanderkanth Gautam explained the opportunities and threats to electronic autoinjectors. In summary, developments in devices to inject drugs are being driven by:

• New biologics which may require larger injection volumes, higher viscosities, or reconstitution;
• Regulatory demands for human factors studies; and
• The need for increased adherence, which may be addressed by electronic functionality in devices.

If you work at a pharmaceutical company or medical device manufacturer and want to know more, please contact Tom Oakley.

Springboard has been asked to present ‘The rise of the bolus injector‘ at the Management Forum on Injectable Drug Delivery.

We will build on a recent research project by the Cambridge University Judge Business School that Springboard sponsored.

The presentation will answer the most important questions for drug delivery professionals, such as:

• The changing needs of patients and new drugs
• Could autoinjectors and infusion pumps meet the needs?
• Bolus injectors: a new class of injection device
• Example devices
• What to expect from the draft standard ‘ISO 11608-6’ on bolus injectors

The Management Forum on Injectable Drug Delivery is one of the leading meetings of pharmaceutical and device professionals, and we highly recommend it to managers and executives working in pharmaceuticals, medical devices, clinical medicine, government, academia and patient support groups.

If you would like a face-to-face meeting at the event, please contact Springboard on +44 (0) 1223 422 273.

The presentation will be made available to Springboard’s current and potential clients after the congress so please get in touch if you are interested.