FDA cites companies for CGMP, marketing authorization, and clinical trial violations

The US Food and Drug Administration (FDA) issued warning letters to a medical device manufacturer and a homeopathic drug manufacturer for failing to meet current good manufacturing practices (CGMP) requirements. The agency also cited another device maker for marketing products without authorization and failing to comply with clinical trial requirements.

Beta Bionics

FDA issued a warning letter to California-based medical device maker Beta Bionics for failing to meet CGMP requirements and medical device reporting (MDR) violations. The company makes iLet Dosing Decision Software and the iLet ACE Pump, which are used in its iLet Bionic Pancreas System.

Among the quality system regulation (QSR) violations cited in the letter, FDA inspectors said Beat Bionics failed to establish and maintain corrective and preventive action (CAPA) procedures to adequately analyze quality data, including product complaints, to identify nonconforming products and those that don't meet quality expectations. More specifically, the agency said it failed to implement CAPA procedures to address complaints about device malfunctions that later may have led to serious adverse events.

"Investigators observed [redacted] complaints reporting hypoglycemic episodes that were attributed to Use Error – Unintended Insulin Delivery associated with the patients’ incorrectly changing the insulin cartridges," said FDA in one example. "107 complaints were submitted to the FDA as serious injury Medical Device Reports for severe hypoglycemia or intervention required to prevent severe hypoglycemia.

"Your firm's User-Related Risk Analysis, RA000021, identified that use errors with the iLet Bionic Pancreas System could trigger unintended insulin doses potentially large enough to cause death (classified as the highest risk level, Severity [redacted])," the agency added. "Despite this identified safety risk, your firm closed 56 related complaints without implementing corrective actions to address the identified use errors or documenting justification for why corrective actions were deemed unnecessary."

FDA also cited Beta Bionics for medical device reporting (MDR) violations and provided examples of several instances in which the company failed to report adverse events to the agency as required by regulations. The inspectors noted that in several instances, patients using their iLet Dosing Decision Software experienced hyperglycemia and required medical intervention to prevent potential organ damage and death. While the company was required to submit reports to FDA within 30 days of learning about the incidents, it never filed the MDRs.

Inspectors also noted that, in several instances, patients reported that their iLet ACE Pump malfunctioned, with issues including Bluetooth connectivity problems, unresponsive touchscreens, and unresponsive sleep/wake buttons. They note that the malfunctions may be linked to defective hoverboards that caused at least one serious injury, but the company never submitted an MDR about them.

Finally, the FDA cited Beta Bionics for corrections and removals violations. More specifically, the company updated its software after discovering issues but did not notify regulators within the required 10-day period. In one example, FDA noted that the company discovered that its iLet Dosing Decision Software was using delayed readings to dose patients with insulin that risked their health and issued a software update.

"This action constitutes a medical device correction or removal initiated to reduce a risk to health posed by your device or remedy a violation of the Act caused by your device which may present a risk to health, under 21 CFR 806.10(a)," said FDA. "You have not already provided this information as set forth in 21 CFR 806.10(f) (see 21 CFR 806.10(a)(2)), nor was the correction or removal action exempt from the reporting requirements under 21 CFR 806.1(b) (see 21 CFR 806.10(a)(2)).

"You were therefore required to submit a Report of Correction or Removal to FDA within 10 working days of initiation, under 21 CFR 806.10(b)," the agency added.

ExThera Medical

FDA cited ExThera Medical, another California-based medical device manufacturer, for marketing its products without premarket authorization and for failing to comply with clinical trial requirements, including obtaining agency approval before making changes to its clinical trial investigational plan. The agency stated that the company sent its Seraph 100 Microbind Affinity Blood Filters to a hospital for emergency/compassionate use (CU) before getting permission.

"Your firm’s email communications with [redacted], [redacted] Hospital dated April 27-28, 2024, indicate that these devices were shipped for treatment of a patient under the CU pathway," said FDA. "However, FDA approval for CU was not obtained prior to the devices being distributed.

"Furthermore, your firm failed to adhere to work instruction, WI017, 'Use of Unapproved Devices in United States,' which states 'For Compassionate Use Case, FDA approval is required prior to use of the unapproved device,' and specifies that 'If there is an [investigational device exemption (IDE)] for the device, ExThera Medical (IDE sponsor) needs to submit an IDE supplement requesting approval for a compassionate use under section §812.35(a) to treat the patient,'" the agency added.

Inspectors noted that ExThera never submitted a report to FDA after distributing the devices to treat patients. They also emphasized that IDE devices are intended only for use in accordance with an approved investigational plan and are limited to the study parameters, investigational sites, and patient population described in the study protocol.

"Distribution of an investigational device for compassionate use to patients not enrolled in the study constitutes a change to the investigational plan requiring prior FDA approval," said FDA. "Obtaining prior approval for compassionate use is essential to ensuring that the rights, safety, and well-being of patients being treated under compassionate use are adequately protected.

"Furthermore, distributing investigational devices for compassionate use without prior approval has the potential to introduce additional risks, including inadequate device accountability, which can lead to unapproved uses of the device that further compromise the protective safeguards for patients and threaten public health safety," the agency added.

FDA cited ExThera for failing to properly monitor investigational trials and to ensure clinical investigators complied with the investigational plan. Inspectors noted that the company was unable to provide documentation to prove that it had obtained informed consent from patients who received the devices in trials and that they were properly monitored afterward.

Exthera was also cited for distributing the Seraph 100 without obtaining premarket approval (PMA), IDE approval, or 510(k) clearance. The agency said that it made false and misleading statements regarding the device's regulatory status.

"FDA has reviewed your company’s website at https://extheramedical.com, and various public statements by your firm’s officials as described below," said FDA. "Your firm’s promotion of the device is in violation of FDA’s regulations and the Act.

"For example, ExThera’s Chief Medical Officer, Lakhmir 'Mink' Chawla, M.D., stated that the Seraph 100 device is approved in the US, is safe, and is effective for a range of intended uses," the agency added.

A. Nelson & Co.

FDA issued a warning letter to homeopathic drugmaker A. Nelson & Co. for CGMP violations. The agency noted that it conducted an unannounced inspection of the company's London manufacturing facility in the fall of 2025 and found that it failed to conduct appropriate laboratory tests to ensure the products were not contaminated with microorganisms.

Inspectors said that instead of testing every batch of drugs, the company only tested some batches and did not conduct antimicrobial testing before releasing certain drug products. Furthermore, they said the company extended the expiration dates for certain drugs without basing the decision on adequate stability data.

A. Nelson was also cited for failing to have written responsibilities and procedures that the quality control unit (QU) should follow and was told its documentation deficiencies raised significant concerns about data integrity.

"Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture," said FDA.

A. Nelson said it had brought in a third-party consultant to help the company address its CGMP violations. FDA, however, emphasized that the buck stops with the company's executive management.

Warning letters

FDA cites companies for CGMP, marketing authorization, and clinical trial violations

Related topics

Recommended content

Welcome to the new RAPS Digital Experience