Feature Article

DESIGN

Need for faster innovation

The United States (US) medical device manufacturing market generates in excess of US$85 billion (approximately €66.5 billion) in annual sales.¹ In addition, the US medical device industry is emerging as the most reliable growth area in medical technology. With the median age of the population increasing steadily, the industry is expected to be resilient during the current downturn.²

In addition, while the industry is growing, it is also restructuring. Five major interrelated trends that will shape the future of the industry are: continued and increasing cost pressures, a need for efficiency in innovation, increased outsourcing and offshoring, networked automation and growth in consumer-directed health care. It is estimated that the US industry spends more than US$5 billion (approximately €3.8 billion) per annum on testing new medical devices and a substantial additional amount on research and development (R&D). Cost pressures will continue to intensify as companies explore new ways to reduce costs, streamline operations and acquire new technology to innovate current operations. The medical device industry needs new technology that will improve the testing of new medical devices as well as allow for a substantial reduction in R&D expenditure, and eliminate wasted time, money and effort trying to bring a new product to market. A new technology that will trim time, expenditure and manpower while improving the quality and accuracy of testing medical devices has been developed. It provides synthetic human tissues and body parts to replace traditional methods of bench top fixtures, human cadavers and even live animals in medical device design verification and validation.

Current methods

Current methods of medical device verification and validation include the use of cadavers, live animals, mannequins, plastic components, rubber tubing and bench top fixtures. These cannot accurately replicate the end-use environment of the device, which is usually the human body. Although a procedure may be cost efficient for a company, the results and data will be of little factual use. Engineers predict the performance of a device in vivo by interpreting data drawn from in vitro results. As the differences between the actual use environment (the patient) and the model (the in vitro test) grow larger, the reliability of the resulting data as a predictor of actual performance is reduced.

Testing on a live organism that has similarities to human anatomy and structure has advantages; however there are various ways in which it does not exactly replicate human anatomy. Using live animals also makes it almost impossible to obtain consistent, reproducible results because of variations from animal to animal and test to test. Testing on live animals carries a financial and ethical burden that can make testing unfeasible for smaller medical device companies and testing organisations. For a company to test on live animals, it must comply with the relevant national Animal Welfare Act and other international protocols. To properly comply with these laws means a company must hire anaesthetists and veterinarians and must contract with outside facilities.

The use of cadavers offers a more

anatomically accurate testing medium, although death and chemical preservation significantly change the physical characteristics of the tissue and make it respond less accurately to tests. In addition cadavers are rare, expensive and become damaged during repeated testing.

Synthetic human parts

The synthetic human tissues, body parts and cadavers that have been developed meet the need for a more reliable, consistent, realistic and cost-effective solution. The technology incorporates replaceable muscles, tendons, veins, arteries and organs, which are manufactured from proprietary materials that replicate the physical and anatomical properties of living human tissue. Depending on the specific tissue in question, the materials are made from a formula that includes water, microfibres, macrofibres, fibre meshes, binders and a variety of salts. They are designed primarily for use in medical device verification and validation tests. The products closely resemble the actual live human environment and may be utilised as direct replacements of traditional models in simulated use testing. Examples of how these products have been employed include ear models used in developing a device designed to traverse the tympanic membrane, eye models used to develop tiny implants employed in the treatment of glaucoma, tissue plates used in the development of femoral puncture closure and laproscopic devices, arm and leg models used in the development of wound control treatments, and vascular models used to develop needles, guidewires and catheters.

Individual models (muscles, veins, tendon or organs, see Figures 1 and 2) are constructed so that they mimic the geometry (shape, length and diameter) and chemical and physical properties (water, salt and fibre content, strength or modulus in shear, coefficient of static or dynamic friction, surface energy, dielectric properties, heat capacity and porosity) of the particular portion of the human anatomy they are designed to match.

Although the technology is designed to replicate the structure of a specific portion of the human anatomy, individual synthetic tissue formulations are not based on tests performed on human tissues. Instead, animal models (generally porcine) are employed as the primary design basis for all of the synthetic tissues. In addition, each component of a given model is fabricated so that the interaction between adjacent components is similar to that of the target tissue. Individual anatomical components such as muscles, veins and arteries are removable and replaceable. Any replacement synthetic component will react identically to the component that it has replaced; this saves time and costs, because tests would not have to be rerun if a component needs to be replaced during a batch of data gathering.

Construction of the models

Figure 2: Synthetic deep thigh muscles. (click image to enlarge)

The synthetic human tissues and body parts are developed and conceptually divided into discrete sections at the individual component level and built up with several components to create a base model such as a thoracic aorta or human tissue layers. As an example, a model of the thoracic aorta would be divided into two separate components: the first would consist of the aorta itself and the second would comprise the surrounding tissues. For this model, two tissue analogues would be designed and fabricated to manufacture the complete sample (analogue is the termed used for the synthetic tissue that mimics actual tissue). More complex models would require more individual components to accurately replicate the required response of a target tissue and each component would require multiple tissue analogues to create the finished product. For example, the physical response of an artery to any kind of action such as penetration by a needle, abrasion by a catheter or expansion by a balloon cannot be adequately modelled by a single material such as a rubber tube. Real arteries are made from multiple layers of multiple materials, thus they respond differently than they would if they were made from a single monolithic material. Each tissue analogue is formulated to mimic one or more properties of a specific target tissue.

A winning technology

The synthetic human tissues and body part components facilitate the generation of performance data with less spent on the development programme. There is no biohazard exposure, no special training requirements and no need to hire outside specialists. Replacing the current models and apparatus of medical device verification and validation can result in simplified tests and raise validation scores. By employing the technology early in the development process, vital feedback on performance may be collected before erroneous assumptions adversely affect the device’s design and thereby the probability of costly late stage design changes is reduced. The models may be used in standard laboratory settings.

These synthetic parts address many of the requirements to reduce device testing and validation and verification costs and the person hours involved in bringing a new device from concept to production. The technology is used in the US by Fortune 500 medical device companies and its developers have received an “Excellence in Innovation” award from the US Department of Commerce.³ The company has secured three US patents for this technology and has 12 more US and European patent applications pending.

Dr Christopher Sakezles is President and Chief Technology Officer at Animal Replacement Technologies, 11523 Palmbrush Trail, Suite 106, Bradenton, Florida 34202, USA, tel. +1 941 727 0488, e-mail: c.sakezles@anireptec.com, www.anireptec.com