Demystifying FDA’s ASCA on Biocompatibility for Expedited Review

The FDA website will show (1) which labs are accredited and (2) what they’re accredited for as a lab could accredited for multiple methods, or just cytotoxicity for example.

• The FDA will audit both ABs and test labs as necessary.
• When a manufacturer performs testing at an accredited test lab, the lab will provide a standard report as well as a summary report.
• Provided testing takes place without unexpected results, the manufacturer can submit to FDA with a Declaration of Conformity (DOC) and summary report for pre-market submission review.

Device eligibility

It’s important to note that all devices are eligible except for liquids, creams, gels, hydrogel devices, devices containing nanomaterials, and absorbable and in situ polymerizing devices. “Things that are going to break down, or have an active integration that could polymerize such as a skin glue, because these are more of a dynamic process… the ISO standards are written more for an extraction type of environment and these may have some nuances with irritation. We may need to do some histology to characterize a bit better the reaction that’s going on," Parker explained. But for devices such as catheters, bone screws, and pacemakers, those are eligible.

ASCA labs and methods

Parker mentioned that while MEM Elution Cytotocity is included for now, other cytotoxicity methods such as the MTT and NRU may one day be added.

A list of all the methods that are currently contained within the program. A lab may be certified to one, some, or all. (Credit: Toxikon)

FDA requires training for labs for technicians, study directors, and trainers. Study directors must build up significant education, time and experience, while trainers must hold extensive experience in each technique. Proficiency evaluations ensure that the "test lab's eyes" see things the same way that accredited bodies' eyes do. “We have to provide an index of all the SOPs that are particular to the ASCA methods we’re applying for and provide all of those to the FDA,” said Parker. “We also have to supply all of our raw data sheets that we use for collecting data on a study, all of our protocols, and report templates to make sure we’re asking for the right data, we’re recording the right amount of data, and we’re reporting the right amount of data.”

Control over sample prep is key—times, temperatures, etc. Any post extraction changes that take place such pH drops or rusting may require manipulation to proceed with testing, "but then you’re not performing a standard method anymore as there could be things going on with the device that are unexpected,” he said. At that point, the FDA would likely prefer the full report versus the summary version.

Key takeaways

• The brand owner will need to prepare a DOC that includes where and when testing was performed, how test articles compare to predicate, and issues brought up by the lab that needed to be resolved. If anything was questionable, such a result that technically passed but that the lab notes from experience (in seeing thousands of devices) that it may be indicative of a future issue, then discussion of this—as well as any adverse or unusual findings—should be included.

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• If all testing is performed without issues, manufacturers receive a lab’s “stamp of approval” and then they may see expedited timelines in approval of their submission.
• Parker said he hopes for the entire industry—manufacturers, tests labs, and the FDA—to gain consistency in how they perform testing and report data through ASCA. Additionally, this represents a new open channel between FDA and test labs to get questions answered and innovate together.