FDA warns two companies over CGMP deviations, device violations

The US Food and Drug Administration (FDA) has sent warning letters to two companies after the agency identified issues during inspections of their facilities.

FDA said an inspection of an ALI Pharmaceutical Manufacturing facility produced evidence of “significant deviations” from current good manufacturing practices (CGMP) for active pharmaceutical ingredients (API). The agency’s inspection of WAVi Co. found that a device the company claims is used for research has been distributed for non-research purposes without a pre-market approval application or an approved application for investigative device exemption (IDE).

FDA noted that in both cases, the companies did not provide adequate explanations when responding to these issues. Both companies were instructed i to correct the outlined issues as soon as possible or face potential regulatory action.

ALI Pharmaceutical Manufacturing

FDA’s warning letter to ALI Pharmaceutical Manufacturing notes that, following an inspection of the company’s drug manufacturing facility, the agency identified several deviations from CGMP for API, such as not being able to validate their porcine thyroid API manufacturing processes, including for a specified intermediate; the agency also noted that the validation process differed from the current manufacturing process. The report of the process also “lacked information about the material of construction (e.g., thickness and composition) of the drums, whether liner bags were used in the drums, and the quantity of intermediate in each drum,” the agency said.

Since the API manufactured by ALI Pharmaceutical Manufacturing is used in a treatment for hypothyroidism, “proper blending and manufacture of your intermediate that is appropriately evaluated through process validation is essential to prevent patients from receiving insufficient or excessive doses,” the agency said.

FDA noted the company provided an inadequate response to the deviation by not including the impact of microbial results on a separate distributed porcine thyroid API that is potentially within a re-evaluation period. “You do not provide sufficient details of your plans to assess and remediate your validation program,” they wrote.

ALI Pharmaceutical Manufacturing also did not create and follow written procedures for when intermediates and API lots fail to meet specifications or critical deviations occur. In one instance, the company did not investigate the manufacturing process or retain samples when a customer complained about an out-of-specification (OOS) microbiological result; rather, the company performed a retrospective evaluation of similar complaints. ALI Pharmaceutical similarly did not investigate the manufacturing process when they received an OOS microbiological result that was six times the allowable limit, instead performing a “limited Phase 2 investigation.”

While the company committed to further corrective action and preventive action (CAPAs) to assess the failures, FDA said the response was not sufficient because it did not address the issues of failing to investigate the manufacturing process or evaluate retained samples.

In addition, ALI Pharmaceutical did not conduct analytical testing that would prevent the blending of API lots. The company committed in its response to performing top, middle, and bottom sampling for intermediates in process for their finished API, but FDA stated in their warning letter that the company commitment did not include full testing for lots before blending, and “lacks a commitment to evaluate lot uniformity of other strengths of distributed porcine thyroid API previously manufactured at your firm that may still be on the market.”

FDA said ALI Pharmaceutical should establish proper process validation, a proper ongoing program for process control, adequate quality systems that meet CGMP, and a plan for investigating test results that are out of specification.

The agency also outlined CGMP issues seen during the inspection, such as certificates of analysis from a contractor used by ALI Pharmaceutical to release lots even though they did not meet current GMP requirements.

“Based upon the nature of the deviations we identified at your firm, we strongly recommend engaging a consultant qualified to evaluate your operations to assist your firm in meeting CGMP requirements,” FDA wrote.

WAVi Co.

FDA’s warning letter to WAVi Co. noted that their device, WAVi Desktop, designed to to aid assessment and diagnosis of patients with neurological disorders, is being promoted and distributed by the company to customers despite not having an application for pre-market approval or approved application for an IDE.

While the company claimed WAVi Desktop is for research purposes, citing studies that were IDE exempt, FDA said this was not evidence that the device has an approved IDE application or is exempt from needing an IDE application. FDA also pointed to the company’s website, which contains statements indicating the device is not being used solely for research purposes.

“Specifically, during the inspection, you provided a list of recent publications and studies accompanied by a list of recent academic partners. However, your list of customers that was collected by our investigator is far more extensive than these academic partners,” they wrote.

The website also contains testimonials and claims that appear to show the device is being used in clinical practice, FDA noted, as well as specific mentions of locations where customers can use the WAVi Desktop device. “This statement, along with your firm’s customer list, suggests that you have distributed the device to non-academic partners for purposes other than research,” they said.

Further, FDA’s inspection of a WAVi Co. facility identified Quality System regulation violations. In their warning letter, FDA said WAVi Co. failed to perform validation of device software, to validate the test fixture of the device’s electrical processing unit, to maintain device history record and master device records, and to create and establish quality audits.

Warning Letter 1, 2

FDA warns two companies over CGMP deviations, device violations

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