The engineering of a medical device constitutes only one aspect of its viability. In order to obtain regulatory approval, a device also needs to comply with biocompatibility and sterilization standards. Raw materials, packaging, and design may all impact a device’s safety and compatibility, and a preclinical assessment of all these factors is a critical step in verifying the device’s market potential.
Although preclinical testing for medical devices has become fairly standardized, device developers still face a number of unique challenges throughout each device’s testing process. But by crafting a set of strategies for addressing likely scenarios in the testing stage, a development team can anticipate many of the most common issues, and streamline the process with each new iteration.
The following five hurdles are frequently encounered in the preclinical testing stage.
1. Lack of toxicity data
Some medical devices are made using materials that have not been previously tested on human subjects. If mutagenicity and genoticity data for those materials are not available, it may be necessary to perform biocompatibility testing in order to verify the device’s viability. The ISO 10993-1 standard provides guidelines on specific tests that should be performed.
Since some of these tests may require significant time and resource investment, it’s crucial to plan for them early-on, to prevent a shortfall of toxicity data later in the application process. The sooner a device’s toxicity or incompatibility can be established, the more time the development team will have to develop designs based on alternate materials.
2. Unclear success metrics
Although safety and biocompatibility are both crucial measures of a device’s usability, a range of other metrics may be useful in determining whether additional improvements are needed. In some cases, data from toxicity and biocompatibility studies may be just as relevant as data on the device’s functionality. If the device falls short in any of these areas, a set of clear success metrics will prove critical in engineering improvements.
To evaluate the device’s performance in all relevant areas, it’s necessary to perform tests over a period at least equivalent to its duration of intended use. Whatever metrics are used, it’s essential to perform preclinical studies using a broad sample base composed of male and female subjects, with diverse body and organ mass, pathology, histology, and other biometric variables.
3. Unexpected sensitivities
A device’s efficacy and durability depend heavily on the design of its packaging. Preclinical tests may reveal unexpected light or temperature sensitivities in certain components of the device. Such sensitivities may create a need for packaging that shields the device from light or heat. Moisture-sentitive devices must be shielded from acqueous compounds.
All these sensitivities, and many others, may be revealed in the preclinical testing process. The sooner these sensitivities can be established, the more time the packaging design team will have to engineer a container that accomodates the device’s requirements, and preserves its functionality and usability all the way to the final point of use.
4. Incompatible sterilization measures
In addition to moisture and temperature sensitivities, many devices must be kept sterile, or be sterilized after each use. By establishing a set of clear sterilization parameters in the preclinical testing stage, the manufacturer can design a method for sterilization, develop instructions for end users, or even provide a sterilization kit if necessary.
Sterilization methods may include gamma, x-ray or e-beam irradiation, dry heat, steam, or ethylene oxide. Each of these methods interacts with different materials in different ways; for example, famma radiation can affect the tensile strength of polymers, while ethylene oxide can leave a hazardous residue, and dry heat may cause damage to temperature-sensitive materials. Thus, the choice of materials may depend on the desired sterilization method; though in some cases, the reverse may be true.
5. Lack of insight on the submission process
As crucial as materials, packaging and sterilization are, the marketability of a device ultimately depends on its regulatory approval. For this reason, it’s highly useful to work with a partner who understands the regulatory submission and approval process, and can approach the application in a way that minimizes delay and unnecessary cost.
For example, some South American and Asian regulatory agencies will grant approval to devices in a shorter period than European bodies, whose scrutiny is much more stringent. At the same time, markets in which devices undergo the closest examination are often those with the wealthiest potential customer bases. Timing can be crucial; meeting prerequisites in some markets first may streamline the approval process for others.
A submission must include an overall assessment of the device’s materials and performance, along with all data gathered in preclinical tests. Once the application has been submitted, the regulatory body may evaluate it for several weeks of months before responding. For this reason, it is often useful to submit in multiple markets simultaneously, if the regulatory agencies in these markets permit this practice.
Although the process of preclinical device testing involves many moving parts, a partnership with an experienced testing organization can help simplify and orchestrate many of the relationships between these parts. A clear toxicity dataset can help minimize the costs of redesigns, for example, while measurements of sensitivities and sterility requirements can inform the design of more protective packaging. All this data feeds into the regulatory approval process, which represents the final key challenge in bringing a medical device to the clinical trial stage.
