Q: What extra steps do companies need to take to have a drug approved for use in a self-administrative form?

Kaufman: Generally, a biological drug will need to be first approved as an independent drug, regardless of whether or not it is to be used in a self-administrative form. For the device constituent of a combination product, the medical device manufacturer will generally support biopharmaceutical companies by filing a master access file and/or 510K to help with the customer's submission process.

Self-administered biological drugs can generally be placed inside a primary container such as a pre-filled syringe or cartridge, which will then reside in a device that possesses the mechanical system to perform the injection. The two together is a drug/device combination product that, although not yet official, has been identified by the FDA as an area that requires regulatory guidance. Companies that wish to introduce a drug in a self-administrative form will need to start regulatory planning at a very early stage to ensure that approval times do not become a potential bottleneck to a successful global launch.

Mark Novara

Potter: Any pharmaceutical product in development must undergo clinical trials. In addition, a product that is to be self-administered needs to undergo trials with volunteers and patients to ensure that the delivery system can be safely used by different patient groups in a non-clinical setting. Some of these trials may be userhandling trials, with no drug involved, just to demonstrate that the volunteer can safely use the delivery system. These trials are far simpler and cheaper to conduct than active drug trials. Once trials have been carried out for a first product, then further trials to investigate the handling and use of the delivery technology may only be required if the product is for a different patient group (e.g., elderly patients or patients with rheumatoid arthritis who may struggle to handle a delivery device).

Q: How are designers and manufacturers of selfadministration devices approaching the challenges of ensuring sterility and accurate dosing outside of healthcare settings?

Kaufman: Accurate dosing is achieved through specially designed delivery mechanisms, rigorous testing and precise manufacturing. For example, in a mechanical device, highly accurate dosing can be achieved using the appropriate spring technologies. Thus, the design and testing of such devices is paramount. Sterility is ensured again by designing a suitable device for the primary container selected by the biopharmaceutical partner; for example, a pre-filled syringe that is assembled into an auto injector under controlled procedures in line with related regulations and standards.

Sadowski: First, it is important to consider the fact that the product will be used without the direct supervision of healthcare professionals. Companies should conduct extensive background research and ethnographic studies to fully understand the patient and the likely environment of use. The design can be established based on the findings of the investigations and the pilot device can be tested with the patient in a variety of expected actual-use settings to confirm that the product will perform as intended.

Q: The ability to offer adjustable doses, for example in diabetes, has great potential. What progress is being made in this area?

Kaufman: We see progress in the development of unique and robust mechanical designs that can accommodate the need to offer adjustable doses. This allows for the device to remain cost effective, as some drugs do not have a market price that justifies complex drug delivery technology. However, we do see a renewed drive to incorporate electronics into some of the more expensive devices, which is perhaps inspired by the trend of cutting-edge designs related to smart phone and tablet innovations.

Sadowski: Technologies that provide dose adjustability have already been developed and commercialised. Cartridge-based, multidose pens, for example, have achieved excellent acceptance in the administration of insulin. Companies are now working on improving dose adjustability and confirmation of correct dose by applying advanced electronics that aids ease of use and adds intelligent features.

Q: What are the challenges of manufacturing devices suitable for selfadministration?

Kaufman: Main challenges include anticipating numerous device usage scenarios against which to test the device, ensuring quality consistency and providing robust production lines to respond to mass production needs. To address these challenges, device manufacturers should work closely with biopharmaceutical companies to better understand end-user feedback and use it to more accurately reflect and construct usage scenarios for device testing. In addition, device manufacturers need to continually invest in the latest in-house capabilities and processes.

Novara: In most cases, customers will want some level of customisation; they rarely want off-the-shelf devices. The challenge for manufacturers is delivering these differentiated customised devices at an affordable cost – for both the customer and the manufacturer. Companies are utilising modular platform technology to develop and customise devices.

The market place is also uncertain and highly dynamic. Manufacturers are B2B businesses selling devices to pharma and biotech companies. If their business changes, suffers, or is impacted, so is that of the device manufacturer. This requires methodical portfolio management and operational planning to optimise the business.

When customers choose a device partner, they make device-based decisions, but also company-based decisions. They will be looking for factors such as a global reach and full service support, including support with global registration, and the ability to offer a differentiated benefit.

Sadowski: The most important aspect of making devices for self-administration is ensuring that they perform as intended in the hands of the patient. That means we need to first understand the patient. There are well-established ethnographic research methodologies that can be used to learn about patients and the environment in which they will use medicine. However, even today, many companies delay addressing this aspect in clinical programmes. As a consequence, products have been launched in a configuration that is clearly not well suited for self-administration. Only later, after the product fails to meet market expectations, does the company initiate programmes to address the needs of self-administration. It can be argued that keeping the configuration as simple as possible (e.g., in a vial) reduces development risk and cost, but this must be balanced against the resulting market risk, particularly when competitors introduce a product that better addresses self-administration challenges.