Case of the Month: FDA Issues Warning Letter for Unapproved Changes to Approved Assay

As a rule of thumb, FDA approvals are a snapshot applicable only to the product as it exists at the time of review and approval. So, when the product undergoes significant changes, it often triggers the need for new clearance. A California device maker just learned that lesson the hard way.

What Happened

Last year, the FDA inspected Union City, CA-based Abaxis, Inc. before it was acquired for $2 billion by animal health company Zoetis. And based on the inspection results, it sent Abaxis a warning letter, i.e., a notification of violations documented during inspections of the company’s facilities to which the company must respond. The April 12, 2019 warning letter contends that:

• Abraxis’ Piccolo Potassium assay, used with the Piccolo Xpress chemistry analyzer, is a Class III device lacking premarket approval; and
• Evidence exists that the assay is misbranded.

Specifically, FDA concluded that Abaxis changed the assay without bothering to inform the agency. According to the letter, “your firm made changes that affected the potassium assay calibration specifications and ultimately changed the performance of the device, as demonstrated by customer complaints.”

Changes to calibration set points, the FDA claims, is by its nature a change to the performance specifications that raises new issues of safety and effectiveness since a falsely low potassium result could lead to serious adverse consequences such as delay in treatment or no treatment for hyperkalemia. As a result, the change requires a new 510(k) premarket notification.

Abaxis’ Response

Abaxis has responded to the FDA’s concerns on five separate occasions but has been unable to talk the agency out of requiring a new 510(k). According to the FDA, none of the five submissions assessed “whether the modifications could have significantly affected the safety or effectiveness.”

The warning letter, of course, escalates the situation by giving Abaxis 15 business days to detail, in writing, the steps it took to fix the violations and stop similar problems from occurring again. If the corrective actions could not be completed within the 15 business days, Abaxis had to give an explanation for the delay, and a time frame for when the corrective actions would be completed.