It’s commonplace in the CRO community: While researchers recognize the value of strict FDA rules set for biocompatibility testing, they’re continually frustrated by ISO stipulations that aren’t necessarily relevant when evaluating implantable medical devices.
That means the researchers often spend unnecessary time and money on extractable and leachable (E&L) testing procedures that don’t result in meaningful or helpful data, reports APS Director of Analytical Services Mourad Rahi. That’s a continual source of frustration for CROs trying to maintain reasonable costs and testing timelines for clients. The International Organization for Standardization (ISO) that establishes the rules infrequently updates them. In many cases, Rahi estimates, such needlessly strict standards double the required testing time and increase final project costs by 20% to 50%.
That can be difficult to explain to product developers who want fast, efficient results. CROs like APS have little choice but to put in extra effort to meet the standards.
“The scientific community, the ones who have knowledge in this business, seem to me to have no say into how these guidelines come about,” states Rahi. “The FDA talks to all these other committees, and often create more confusion than guidelines.”
Addressing (or not addressing) ISO 10993
Rahi notes that one of the biggest conflicts he encounters in the course of his research involves ISO 10993-12. This standard dictates the types of test samples, extraction vehicles and conditions, and reference materials that can be used as controls for E&L testing.
He explains that it’s challenging enough to select the correct kind of solvent for any extraction process, given the multiple materials that can require testing within just one device. But the bigger problem is that the guidelines for solvent volumes can’t be pro-rated for differently sized medical devices, and that can result in a number of complications — from degradation of the product itself to data sets that can’t adequately prove or disprove the product’s safety.
The strict limits on solvent volumes make little sense since they’re not even close to amounts considered toxic in humans, he says.
“It’s a complete misunderstanding, and it’s frustrating that the FDA does not understand,” Rahi says of the conflict. “As a result, reporting for a large device is a phenomenal challenge for any analyst. We are generating data that doesn’t add value — it only adds cost, bureaucracy, more cost and more time.”
Another challenge he points to is the process of measuring non-volatile residue (NVR) amounts on small devices, given the lack of an appropriate microbalance tool tiny enough to get the job done. Still, the FDA won’t approve any device not subject to NVR testing, Rahi says.
Rahi notes he’s spent considerable time and effort trying to get such regulations changed by writing to the FDA, rallying other scientists and pleading his case at medical conventions — all to no avail.
“Since the guidelines are in effect, nobody’s trying to shake the tree,” he says. “Once it’s in the law or guidelines it’s almost impossible to change. It takes a lot of time and hard work, data to be presented, discussion and a lot of argument. All the scientific community agrees with me, but there’s nothing they can do.”
Planning to bring your medical device to American Preclinical Services for E&L testing? Talk to APS specialists about how our processes can meet ISO 10993-12 standards despite its many challenges.