This week, FDA posted two warning letters to drug manufacturers and one to a device manufacturer. The warning letter to Stason Pharmaceuticals (Irvine, CA) includes the most granular list of requested data integrity remediation activities that I’ve seen FDA provide, to date.

And while not covered here, FDA also posted at least 10 warning letters to firms selling flavored tobacco vaping devices that are not approved.

Drug Warning and Untitled Letters

Stason Pharmaceuticals, Inc.

Stason Pharmaceuticals, Inc. (Irvine, CA) received a warning letter on July 8, 2020, based on the outcome of an inspection ending October 25, 2019. FDA recommends the firm hire a qualified consultant(s) to assist them in coming into compliance with GMPs. The warning letter identifies two deficiencies, including one in the area of data integrity, and includes a lengthy list of information and records that FDA wants in response. The requests are far more granular than the usual three-part boilerplate text that FDA usually provides for “data integrity remediation”.

Deficiencies include but are not limited to:

The firm did not adequately investigate deviations including OOS results for dissolution testing of multiple lots during stability studies and testing of retained samples. The root cause of the OOS results was not identified though the specifications were relaxed.
The firm failed to implement controls over electronic data in the laboratory. Specifically, data could be deleted from the computer associated with the spectrophotometer. FDA notes their response was inadequate because it did not include a retrospective review of how these system vulnerabilities may have impacted data integrity for previously released lots.

Signa SA de CV

Signa SA de CV (Toronto Ontario, Canada) received a warning letter on July 14, 2020, based on the outcome of an inspection at the site in Mexico ending December 20, 2019. The firm is owned by Apotex, a Canada-based generic drug manufacturer. The warning letter identifies one deficiency with multiple examples. FDA identified similar deviations at other of the company facilities and states “These repeated failures at multiple sites demonstrate that management oversight and control over the manufacture of drugs is inadequate. Your executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance.“ The firm manufactures APIs.

Deficiencies include but are not limited to:

Investigations into OOS results were inadequate. At issue is an OOS for impurity during validation runs. Potential root causes were not justified, investigations were not expanded to all batches potentially impacted and corrective and preventive actions were not implemented. Multiple failures were identified during the history of this API. At least one of the API lots was sent to the US.

Device Warning and Untitled Letters

Centurion Medical Products Corporation

Centurion Medical Products Corporation (Williamston, MI) received a warning letter on June 11, 2020, based on the outcome of two inspections at two of the firm’s sites, the latest ending November 1, 2019. The firm manufactures sterile convenience kits generally intended for use in a variety of vascular and other medical procedures. The convenience kits are not approved or cleared by FDA for marketing in the US and thus are unapproved new devices and are adulterated. Further, the lack of appropriate instructions for use renders them misbranded. The firm maintained they only re-package and sterilize already cleared/approved devices and then sterilize them. During the inspection, FDA investigators found otherwise.

Deficiencies include but are not limited to:

Device input requirements have not been adequately defined or established.
The CAPA program is not adequate because corrective actions are not verified as effective, nor have corrective and preventive actions been implemented at all of the firm’s facilities.
The firm has not defined purchasing requirements for various catheters they purchase.