Identity Testing and Stability Studies criticised in an FDA Inspection

The U.S. Food and Drug Administration (FDA) has issued the first warning letter of the year, dated January 9, 2020, to Huaian Zongheng Bio-Tech Co., Ltd. The contract manufacturer produces over-the-counter (OTC) drug products, including versions specifically marketed for children.

During an inspection carried out from July 1 to 5, 2019 at the company’s plant in Huaian, China, significant violations of current good manufacturing practice (cGMP) regulations for finished pharmaceuticals were found. Due to these findings, the FDA placed the firm on Import Alert on November 8, 2019.

Among others, the FDA was concerned about the following points:

  • Drug products were released without adequate testing, including identity and strength testing for each active ingredient. 
  • Huaian Zongheng Bio-Tech Co., Ltd. failed to test incoming components used to manufacture the drug products to determine their identity. It was not ensured that at least one specific identity test was conducted for each lot of active ingredients.
  • The company failed to validate the manufacturing processes for its drug products adequately. According to the FDA, the company performed process validation for only one of its drug products. However, numerous drug products with different formulations and with multiple active pharmaceutical ingredients are manufactured at the plant.
  • Furthermore, the company failed to use equipment in the manufacture that is appropriate for its intended use and in its cleaning and maintenance.
  • The company’s drug products contain glycerin as an ingredient. In this context, the FDA points out that “the use of glycerin contaminated with diethylene glycol (DEG) has resulted in various lethal poisoning incidents in humans worldwide.” To help the company to meet cGMP requirements when distributing glycerin for use in drug products, the FDA recommends following the guidance document “Testing of Glycerin for Diethylene Glycol.”

Stability Studies in the Focus

Another important point mentioned in the warning letter concerns the stability testing program.

In general, a stability testing program should demonstrate that the chemical properties of the drug products remain acceptable throughout their labeled expiry period.

In the warning letter, the FDA summaries the minimum requirement as follows:

  • A stability program should include the stability-indicating methods and a detailed definition of the specific attributes to be tested at each station (timepoint).
  • Stability studies should be carried out for each drug product in its marketed container-closure system before distribution is permitted.
  • There should be an ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid.


The FDA highlights that Huaian Zongheng Bio-Tech Co., Ltd. is responsible for the quality of drugs produced as a contract facility, regardless of agreements in place with the product owners. Based on the nature of the violations, the FDA strongly recommends engaging a consultant to assist the firm in meeting cGMP requirements. Until all violations are entirely corrected, the FDA may withhold approval of any new drug applications or supplements listing the firm as a drug manufacturer.

To find out more, please see the original warning letter to Huaian Zongheng Bio-Tech Co., Ltd.

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