By Vicki Ronaldson
The CRS Annual Meeting & Exposition in National Harbor, MD, U.S.A., in 2011 saw technology service providers Medimetrics present to the pharmaceutical community for the first time their ground-breaking electronic drug-delivery technology. The Philips spin-off, with offices in New York and Eindhoven, The Netherlands, presented data on their proprietary IntelliCap system, the most advanced wireless capsule available for candidate screening.
This was followed by CE certification of the device and presentation at the AAPS annual meeting and exposition in Washington, DC, where the launch of IntelliCap as a clinical research tool attracted a great deal of attention.
2012 saw Medimetrics return to the CRS Annual Meeting, this time as sponsors and with a view to securing commercial partners and end users.
Chief scientific officer Jeff Shimizu, who along with Olaf Weiner led the development of IntelliCap at Philips and the subsequent spin out of Medimetrics, talked to Vicki Ronaldson about their journey and what IntelliCap means to drug development programmes.
Q What end applications did you have in mind when designing IntelliCap?
A When we started the project, we had the view of using electronics-controlled local delivery as a therapy for difficult-to-treat intestinal disorders such as Crohn’s disease or intestinal cancers. These are great targets, but we quickly found that the capabilities of an electronic pill could be put to wider and more immediate use in the evaluation and development of compounds where delivery in the gastrointestinal tract is of interest. This applies to any oral drug where controlled, targeted, or extended release can be beneficial. We currently operate in this drug research area while at the same time keeping paths open toward therapeutic applications that, while ultimately impactful, will take longer to develop.
Q Medimetrics is a technology company—how did you identify the pharmaceutical end use/market for IntelliCap? Did you consult with pharmaceutical scientists and clinical researchers?
A This is a key consideration when bringing together technologies from different worlds, or at least from different areas of expertise. Contact with clinicians in gastroenterology was and is a must for our thinking and development. They not only understand the physiology of the gut and how our device will operate in that environment but also bring knowledge and ideas for further diagnostic and therapeutic applications for new technologies such as IntelliCap.
Clearly, as we went down the route of a research tool for drug development, insight from pharmaceutical scientists was invaluable in our development. We have these experts lead us on what capabilities are required and how best to put this new tool into practice.
Q Briefly, how does the system work?
A IntelliCap is a system based on a swallowed electronic capsule. The electronic capsule has a drug reservoir, a drug pump, a pH sensor, a wireless transceiver, and a microcontroller. The combination allows us to measure the local pH environment of the capsule, report the data in real time, and have full control over drug delivery, based on time, pH, or operator intervention. The pH data gives information on the transit parameters of the capsule. This is an important piece of data during an in vivo trial, since variation between subjects is common, and this otherwise unknown data can have a major influence on the outcome of a study, for example, a pharmacokinetic experiment.
Q IntelliCap is a clinical research tool—what kind of information will it give end users on their compound/formulation?
A Regional absorption data is important when developing any orally administered drug. This is particularly true when controlled or extended release is contemplated. Uptake in different regions must be accurately assessed. However, good in vivo data is difficult to obtain, and in silico modelling is not sufficient by itself. IntelliCap gives the researcher a tool to better and more quickly assess the properties of a drug in order to make better and more confident decisions on how or whether to advance a candidate compound.
Q There are existing electronic delivery systems—how did you identify a gap, and how does IntelliCap fill this gap?
A Concepts of an electronic delivery capsule have existed for quite some time, but it has been quite a challenge to implement the idea and put it into practice. There are a few examples of electronic capsules with diagnostic applications, for example, the capsule endoscope or camera pill for visualizing the GI tract. There are also examples of engineered capsules for drug delivery, such as the Enterion pill for targeted bolus delivery. IntelliCap is the first and only successfully applied combination of electronic control, measurement, and delivery of a compound from a swallowed capsule.
Q What were the major challenges for Medimetrics in the design process, and how were these overcome?
A There were a myriad of challenges in the design, construction, and implementation of IntelliCap. While at 11 mm diameter by 26 mm long, the capsule is large by most standards, the size is achingly small when trying to put all the various functions together in one pill. Electronics and mechanics expertise from a number of sources was needed to engineer the capsule. Next came the practical challenges of how to build the capsule in a reliable and repeatable way while working within available manufacturing techniques. There is no substitute for having a wide range of experts involved and committed to turning a new idea into a reality.
Q What preclinical work was carried out prior to CE certification?
A The aim of preclinical validation was to demonstrate that the IntelliCap system operates as designed in vivo, and that the operation supports the applications intended. Extensive bench testing in vitro was performed to show functioning elements, but the translation to in vivo use is critical to uncover any unexpected issues and pave the way to clinical use in humans. Several preclinical canine studies were performed to verify safety, validity of pH data, delivery of drug, and consistency of operation. Both targeted burst and extended release drug delivery profiles were demonstrated in preclinical pharmacokinetic studies.
Q How did you find the regulatory processes relating to medical devices in terms of the work involved and the turnaround time?
A The regulatory procedure is an important and logical process. The primary aim is to protect the safety of subjects and to bring value from any in vivo use. Further, the device must be well documented, and appropriate controls must be put into place to ensure consistent and reliable performance from individual pieces. Indeed, it does involve a significant amount of work and diligence. However, with the primary safety aim always in mind, the process is certainly manageable and in a larger sense appreciated.
Q Medimetrics recently spun out of Philips as a fully fledged technology company in its own right. What advantages were there to creating a spin out, and at what stage in the IntelliCap pipeline was this decision made?
A IntelliCap originated and was developed within Philips Research. As a novel direction in the healthcare area, the project was from the early stages put onto a corporate venturing path. That is, the application did not necessarily fit neatly into an existing business, but the potential was recognized and appreciated. As Medimetrics moved into business execution as a service organization, a number of factors pushed the venture along to establish a separate company. Operation as an independent business allows us greater flexibility and speed to meet the needs of customers in the pharma research and development arena.
Q How will IntelliCap benefit pharmaceutical companies and CROs in terms of de-risking or streamlining drug development strategies?
A This I think is the main value of IntelliCap. An IntelliCap study can be designed, planned, and executed quite rapidly and can be placed in any facility convenient to the customer. Further, by combining the transit data with control over delivery, the data becomes clearer, and fewer subjects or iterations are required to come to conclusions about the properties and behaviour of the candidate compound. In this way, risk can be greatly reduced and better decisions made using reliable in vivodata as a guide.
Q For those who are interested in using IntelliCap as a clinical research tool, how would they go about gaining access to this technology?
A Medimetrics is a service organization, so use of IntelliCap can be easily arranged by contacting us directly. Medimetrics has offices in the United States and Europe to meet the needs of customers in these two geographic areas. In addition, Medimetrics has partnered with Bio-Images Research Ltd., who can bring both clinical study execution and greater positional data through the use of gamma scintigraphy.
Becker, D, Schütz, H, Beyerbach, A, Zou, H, Shimizu, J, Iordanov, V. Mapping quantitatively regional drug absorption in canines with IntelliCap system. Controlled Release Soc. Annu. Meet. [Abstr.] 196(2011).