When it comes to medical device design and manufacturing, there is no such thing as knowing too much about the components and the manufacturing processes involved. The consequences of not knowing enough can be disastrous, potentially leading to recalls and patient injury or death. From improperly age-testing a polymer part to not figuring out the effects of the molding process and not understanding leachables and extractables, there are many ways to be caught unawares in medical device design.

Getting Aging Down Right

Sticking a plastic medical device part or some plastic packaging in an oven to figure out how it will age years from now--it sounds like a good idea. But there are plenty of ways to botch up the testing, says Karl Hemmerich, president of Ageless processing Technologies (Sandy, UT; www.agelessprocessingtechnologies.com). "One way is using a temperature that's too high," says Hemmerich who will speak about accelerated aging tests on Thursday, February 13, at MD&M West in Anaheim, CA.

Hemmerich recalls a resin company that had a propylene part that was supposed to age well, but it actually had problems down the road because the testing had been conducted at a too-high temperature of 176°F. "in real-time aging, it was actually less stable than competitive resins. They drove a stabilizing reaction inappropriately," Hemmerich adds.

With its TIR 17 rules in the 1990s, the association for the advancement of Medical instrumentation recommended 140°F as a limit for using heat to speed up aging and figure out whether knit lines or other issues could cause problems down the road, Hemmerich says. Obviously, the melting temperature should be avoided when using heat to test a polymer's aging properties. But Hemmerich points out two other important temperatures: The glass transition temperature, at which the molecules inside the polymer start moving and potentially relieve stress to a part; and the crystalline temperature, which will cause the polymer's properties to change after it is cooled.

Issues can crop up with other age-acceleration techniques, such as high-oxygen environments. On top of that, Hemmerich finds that few companies understand sample size, either by using a sample that is too large and drives up costs or using a sample that is too small to properly define the quality of a part. "If the potential defect is life threatening (a critical defect), a larger number of samplings needs to be tested. If it's a minor defect (cosmetic, etc.), you can keep your costs down by testing fewer samples."

There are good reasons to use accelerated aging tests, Hemmerich notes. "You're trying to project forward in time, and you can't wait for the product to sit around for five years before you launch."

Watch Your Molding Knit Lines

A medical device designer might look up a polymer's physical properties to gauge how a part made of the polymer will withstand stress. But start molding the part, and it might not hold up anyway. Molding adds an entirely new dimension to what needs to be tested out. There's temperature, mold pour rate, mold geometry, and the injection location, remarks Eric Hill, president of Impact Analytical (Midland, MI; www.impactanalytical.com). However, Hill finds it a common problem: Molding isn't properly taken into account in part design. Many younger companies simply don't have the resources to anticipate issues beforehand.

"You can form all kinds of knit lines and all sorts of things within the material when it's molded that can be in direct line with where the stress is going to be," Hill says. Knit lines can potentially be thought of as similar to the grain of a piece of steak. In the case of polymer molding, molecules orient themselves in the direction of the flow of the material into the polymer mold. If stress later on is parallel to the knit lines, they can snap. "As soon as that part or material is stressed, it can be real conducive to fracture, cracking, and breaking just because of the way it's been molded. All the while, the material could be the correct material," Hill says.

Knit lines can also be an issue for polymer parts with glass particles added to them.

The whole point is that medical device designers need to have an experienced molder on board to think about these issues while the mold is being designed. "That will get you a large percentage of the way there," Hill adds.

When it's time to go beyond the prototype, mold a couple of parts and test them in terms of performance. If breaks or failures occur, a laboratory such as impact analytical can conduct microscopy work to determine the cause of the failure. By studying the material under a microscope, impact can find the knit lines.

A change in where the injection molding takes place can potentially fix the problem. "Then you can go back and make adjustments," Hill says. It is important to find a lab with experience with polymers--and the know-how when it comes to what to look for and how to interpret the data. Impact analytical has not yet seen 3-D printed parts in need of testing for failures, but Hill agrees that 3-D printing could open up a whole new set of issues as it becomes more ubiquitous. "3-D printing is going to give people access to forming all sorts of innovative and useful materials. You have to resist the temptation to mold these unique shapes that may have an application but not to take the time to do the proper modeling beforehand or the proper testing after you've made the device to show that it can withstand the stress," Hill says.

Leachables and Extractables

"Some people don't understand that there is a difference between extractable and leachables," comments Thor Rollins, a biocompatibility specialist at Nelson Laboratories (Salt Lake City; nelsonlabs.net). "Extractable are chemicals that can come off your device under exaggerated conditions. Leachable are compounds that can be extracted from materials or contaminants of a medical device under clinically simulated conditions. Leachables are always a subset of extractables."

Both leachables and extractables can be toxic or carcinogenic. To ensure that device materials are not going to release potentially lethal chemicals into patients' bodies, device companies first need to evaluate their devices for leachables and extractables by preparing samples using either extraction or direct analysis. Extraction parameters include patient exposure and the extraction solvent, type, time, and temperature.

The next step is to determine the methods for analysis of the compounds, which can include Fourier transform infrared spectroscopy, differential scanning calorimetry, gravimetric extractable surface residue, and so forth.

The final step is to evaluate the results. "We have to determine the quantity of the extractable or leachable compound and what the relevant human daily exposure is," Rollins remarks. "We base this on a 70-kg weight, which is an average human weight. If you have a target population, you would have to change that weight."

Examples of compounds for which tests should be performed include phthalates used as plasticizers, volatile organic compounds, nonvolatile residue, semivolatile organic compounds, and metallic compounds. "The same concerns that exist in phthalates used in water bottles also exists in medical devices," Rollins states. In addition, he recommends that manufacturers take a thorough survey of all the metals used in a device that might shed. "They can still cause issues long term with a patient," he explains.

There are several avenues manufacturers can follow to determine if a device is safe or not. One such avenue is Toxnet, a toxicology data network that enables users to enter the compounds they have found to determine if they are safe. Ideally, no observed adverse effect levels will be discovered. Less ideal are lowest-observed-adverse-effect levels or the median lethal dose, which is denoted as 'lethal dose, 50% (LD50). "LD50s basically mean that half of the population died after exposure to this compound," Rollins explains. "I don't like working with them. I would much rather work with no observed adverse effect levels, if possible."

Chris Newmarker is senior editor of MPMN and Qmed. Follow him on Twitter at @newmarker and Google+.