FDA warns firm in India for falsified logbooks; two other companies warned for lax testing

The US Food and Drug Administration recently issued warning letters to an over-the-counter (OTC) drugmaker in India for submitting falsified logbooks to the agency. The agency also warned two other OTC firms for multiple violations of good manufacturing practice (GMP), including testing violations.

Additionally, FDA warned US-based device company Koven Technologies for using its Doppler ultrasound device to monitor fetal heartbeats, an indication that it was not approved for, as well as a clinician for violating the terms of the investigational study plan.

Dabur India Limited   

FDA issued a warning letter to Indian OTC drugmaker Dabur India Limited concerning the company’s sites in Saily, Silvassa, Dadra and Nagar Haveli and Daman and Diu for multiple GMP violations, including falsifying records, and inadequate cleaning practices.

The company providing the investigator with its equipment usage logbook for several days during the inspection. When the logbook was finally produced, FDA remarked that it appeared to be “newly created.” The original logbook was later found in the document room. FDA said that “a comparison of the two logbooks revealed that the version provided to our investigator was falsified.” The logbook also omitted multiple US marketed OTC drug products that were documented in the original logbook.”

The investigator found several discrepancies between the source data and the final values recorded in the batch manufacturing records or certificates of analysis. For instance, in multiple batches, the reported values for quality attributes, such as residue on ignition, melting range, pH, and viscosity, did not match the original data.

FDA indicated that although these inaccuracies did not involve out-of-specification results, the quality unit signed off on these records without verifying the consistency and accuracy of the data.

Another problem was the company’s failure to demonstrate the adequacy of its cleaning practices in removing potential contaminants. The company relied on visual inspections instead and its cleaning procedures lacked maximum allowable carryover limits, residue testing, or direct surface sampling of difficult-to-clean areas.

FDA advised the company to hire a consultant to assist in meeting CGMP requirements. The agency has placed the company’s products on import alert.

Thomas Brunner Hygiene

FDA issued a warning letter for multiple GMP violations after requesting records from Thomas Brunner Hygiene GmbH, located in Baden-Württemberg, Germany. The company produces OTC antiperspirants.

FDA said the firm did not provide evidence that it adequately tested its products. For example, the company failed to conduct an assay test to measure the active ingredients of these products.

The agency said that “testing is an essential part of CGMP to ensure that the drug products you manufacture conform to all predetermined quality attributes appropriate for their intended use. Drug products must be tested for identity and strength of the active ingredient before their release and distribution. Without adequate testing, you do not have scientific evidence to ensure that your drug products conform to appropriate specifications before their release.”

Furthermore, the company did not adequately validate its manufacturing and cleaning processes. It also failed to demonstrate that it had validated procedures for cleaning non-dedicated manufacturing equipment.

Another problem was the firm’s failure to test its water quality. The agency reminded the company that “water must be suitable for its intended use and must routinely be tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.”

Woodbine

FDA issued a warning letter to Woodbine Products, a manufacturer of OTC drugs in Medina, Ohio, for failing to test incoming products containing glycerin, propylene glycol, and ethanol. The company also reportedly used nonpharmaceutical-grade propylene glycol to manufacture its drug products.

FDA states that “the use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide.”

The company also failed to adequately validate the processes used to manufacture its OTC drug products. FDA told the company that “you have not performed process performance qualification (PPQ) studies, nor do you have an adequate ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality. Your firm also failed to validate your cleaning processes for non-dedicated equipment used to manufacture your OTC drug products.”

In addition, FDA faulted the company’s quality unit for failing to perform adequate oversight over drug manufacturing. For example, the quality unit failed to establish an appropriate testing program to assess the stability characteristics and to use of this testing to determine appropriate storage conditions and expiration dates.

The letter states that “significant findings in this letter demonstrate that your firm does not operate an effective quality system in accordance with CGMP. In addition to the lack of effective management oversight of your production operations, we found your quality unit is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements.’

Koven Technologies

FDA issued a warning letter to Koven Technologies, a company based in Saint Louis, MO, for expanding the uses of its Bidop 3 Dopplers for fetal ultrasounds without securing the necessary approval for this use.

The letter states that “your firm did not document design and development changes related to expanding the indications for use of the Bidop 3 (K954397) to include a fetal application which was not cleared as an intended use. During the inspection, the Bidop 3 operations manual noted the indications for use include detection of fetal heart sounds.”

The company also failed to document its risk management processes for using this product as a fetal monitor. “For one of the fetal dopplers, the risk management report was revised to include an indication for use as a fetal heart rate doppler. However, the report fails to evaluate risks to the fetus, despite the device being labeled for determining fetal heart rate and sounds.”

In addition, the company failed to evaluate returned devices related to device failures. The investigator reviewed 29 Returned Goods Authorizations (RGAs) forms and found that 13 were not evaluated as complaints. “Your firm did not consider these reports as complaints and did not initiate or complete a complaint form as required by its complaint procedure.”

FDA warns clinical investigator for not following plan  

Clinical investigator Maria E. De La Torre Silva was issued a warning letter for failing to ensure that a clinical investigation was conducted in accordance with the investigational plan. The plan specified that subjects were not allowed to be enrolled in more than one study simultaneously. However, one patient was enrolled in multiple trials, which violated the terms of the investigational plan.

The clinical investigator also did not maintain proper records of the drug's disposition, including dates, quantities, and subjects' usage. “Your failure to maintain adequate drug-accountability records, including documents recording study drug used, unused, and returned, raises significant concerns about the adequacy of your oversight and control of investigational drug, and raises concerns about the validity and integrity of the data collected at your site,” FDA said.

Dabur, Thomas Brunner, Woodbine, Koven Technologies, Maria E. De La Torre Silva