FDA finds data integrity problems in recent warning letters

The US Food and Drug Administration (FDA) has issued four warning letters to companies in China, India, and the US for various violations of good manufacturing practices (GMPs) related to the production of sterile drugs and over-the-counter (OTC) products. Two of the warning letters identified data integrity issues, and failures in component testing were a recurring theme in the others.

One warning letter was issued following a records request, and another was sent to an outsourcing facility. The FDA published the letters on 25 March.

Aspen cited for inadequate contamination safeguards

Aspen Biopharma Labs Private Limited, located in Hyderabad, India, received a warning letter following an inspection conducted in September 2024. The inspection revealed numerous issues within the facility, which manufactures active pharmaceutical ingredients (APIs). The company was criticized for the facility's state of "disrepair" and for producing higher-risk APIs in an area that lacks appropriate separation.

Inspectors reported that manufacturing areas lacked adequate protection from the outdoor environment, resulting in exposed materials.

FDA stated that the company inadequately validated its processes and failed to complete process validation for commercial-sized lots of its APIs, instead relying on studies conducted on development lot sizes rather than for commercial production.

The company also failed to ensure adequate document control over paper and electronic records. The company “provided a written statement on firm letterhead admitting to backdating a QC lab document and you signed a declaration confirming commercial drugs shipped to the US were not supported by appropriate original data.”

On 15 January, the company was placed on an import alert. A day later, on 16 January, the company agreed to recall all drugs destined for the US market.

Yangzhou Sion chastised for GMP failures

FDA issued a warning letter to Yangzhou Sion Commodity due to violations concerning component testing, quality control oversight, and data integrity issues. This company, located in Jiangsu Province, China, manufactures OTC products, including toothpaste and tooth gels.

The company relied on its suppliers’ certificates of analysis (COAs) without additional testing of incoming lots of components. FDA reminded the company that the use of high-risk APIs “has resulted in various lethal poisoning incidents in humans worldwide.”

Additionally, the quality control unit did not conduct assay testing to assess the strength of the active ingredient, implement an adequate stability program, or ensure that personnel received proper training.

Finally, there were discrepancies between the original and rewritten versions of the testing records and COAs related to both active and inactive ingredients used in the manufacture of over-the-counter (OTC) drug products. Additionally, the company used correction fluid to amend paper records documenting microbial analyses.

“These documentation practices raise concerns about the integrity, authenticity, and reliability of all your data and quality of your drug products,” FDA wrote. “Document control is essential to maintaining an adequate quality system.”

FDA advised the company to retain an independent third-party qualified consultant to audit its operation and assist in data integrity remediation.

The company is under an import alert and has 15 days to address the violations.

Hangzhou Glamcos faulted for inadequate testing

FDA issued a warning letter to the Chinese OTC manufacturer Hangzhou Glamcos Biotech after placing the company on an import alert on 30 September. The warning letter was issued following a review of the company's records.

According to the letter, Hangzhou Glamcos Biotech, located in Tongly, Hangzhou, violated GMP requirements by failing to conduct testing on its finished products. The company produces antibacterial wet wipes.

FDA reminded the firm that “without adequate testing, you do not have adequate scientific evidence to assure your drug products conform to appropriate specifications before release.”

According to the FDA, Hangzhou Glamcos did not conduct identification testing on incoming components such as glycerin and propylene glycol, which carry a high risk of contamination with diethylene glycol (DEG) or ethylene glycol (EG).

The company may have misrepresented its claims regarding the shipment of products to the United States. The letter states, “In response to FDA’s initial records request, you asserted that you have not manufactured drugs for the United States in three years. After FDA provided you information regarding shipments of drugs from your facility as recent as of January 8, 2024, you then provided the requested information. FDA is concerned that you may have falsely alleged that you do not manufacture, process, pack, or hold drugs for the United States.”
The company has 15 days to respond to the warning letter.

Outsourcing facility Annovex warned for GMP failure

Annovex, an outsourcing facility based in Lorton, VA, received a warning letter due to GMP failures associated with its 503B outsourcing operations.

During an inspection conducted last summer, FDA inspectors identified “serious deficiencies in your practices for producing drug products which put patients at risk.”

The warning letter highlighted violations related to Annovex's non-compliance with the statutory provisions of 503B. Specifically, the company failed to submit a report to the FDA identifying the drug products compounded at the facility during the previous six-month period. These included sterile drugs heparin, sodium chloride IV bags, and phenylephrine. Additionally, the company did not submit reports on adverse events.

The remaining observations were tied to the company’s failure to follow GMPs. The firm was taken to task for making drugs under insanitary conditions, such as not performing media fills under “challenging or stressful” conditions. In addition, the company continued to produce and distribute sterile products “despite positive growth being identified in 10% of filled until during your January 2024 media fill.”

Another violation was the firm’s failure to perform smoke studies to demonstrate unidirectional airflow within the ISO 5 areas. The company also failed to investigate batch failures.

The company must reply to the letter within 15 days.

Aspen Biopharma, Yangzhou Sion Commodity, Hangzhou Glamcos Biotech, Annovex Pharma,

FDA finds data integrity problems in recent warning letters

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