CAPAs, Change Controls Bring Warning for Medtronic Firm

Several issues with CAPA investigations and change controls netted a warning letter for TYRX, a Medtronic subsidiary that makes absorbable antibacterial envelopes.

For example, the Monmouth Junction, N.J., company had no procedures to control and take action on devices suspected to have nonconformities, according to the June 2 warning letter posted online June 21.

It cited the company for closing a 2015 CAPA on seven lots of envelopes that were out of specification for drug content without taking action because three out-of-specification results had a “suspected common root cause.” The company’s form for nonconformance procedures doesn’t require it to verify or validate the effectiveness of CAPAs being documented.

The letter points to a November 2015 OOS event where an impurity substance was above specification in one lot and the possible root cause could not be determined. TYRX’s retest analysis was reintegrated and recalculated based on new chromatographic integration. After the reintegration, all retest results were within specification.

Failure to Investigate?

The company’s investigation found that “due to the change in the integration of the chromatograms, the raw data is the source of the error,” the letter says.

The quality assurance disposition stated that no further investigation was needed and the OOS investigation was closed without TYRX knowing the root cause of the original failure, the letter notes. The company did not verify that the updated test method would mitigate future incidents.

Similarly, a 2014 CAPA was opened to address low molecular weight of the Tyrosine polymer, which can cause higher drug elution. The company took corrective actions with the supplier related to material handling and closed the CAPA. However, two subsequent CAPAs were opened for the same issue, with one stating that the root cause was related to impurity and inconsistencies in a process. That CAPA was still open at the time of the FDA inspection.

Validation, Qualification Lacking

The letter also raised issue with validations and performance qualifications for the large TYRX Antibacterial Envelope. The letter notes that the firm failed to validate the device for drying conditions as well as the polyarylate polymer production process.

Additionally, batch records for certain validation lots that support the polymer production process documented deviations from the instructions in the batch records.

For example, one lot failed for water content due to a deviation from instructions related to mixing, and one lot had a deviation related to the company’s efforts to make up for leak detection and repair time.

Another process validation issue related to a lot manufactured under an approved process qualification protocol. The lot failed the content uniformity test for Minocycline and the process qualification report states that lots were released to commercial inventory. However, one lot was later documented as being rejected and not for commercial use.

TYRX had not performed a validation to support a device master record deviation for TRX Absorbable Antibacterial Envelopes that allowed polymer molecular weight specifications to be changed due to a change in the way the company processed molecular weight analyses.

Medtronic is committed to working with the FDA to resolve these issues in a timely manner, a spokesperson told IDDM. “We do not expect the warning letter to have a significant financial impact to the company.”

The warning letter is available at www.fdanews.com/06-23-16-MedtronicWarning.pdf. — April Hollis