FDA Warning Letter: No Compendial Methods established? Develop appropriate Testing Procedures by yourself!

Recommendation

Monday, 29 April 2024 10.00 - 16.00 h

Introduction to the AQCG’s new ECA Guide for an Integrated Lifecycle Approach to Analytical Instrument Qualification and System Validation
Includes USP Speaker Update on the Analytical Procedure Lifecycle

The U.S. Food and Drug Administration (FDA) has issued a Warning Letter to Global Treat Srl. The firm manufactures "HemoTreat Hemorrhoid Ointment", an unapproved new drug. During an inspection from September 9 to 13, 2019, at the companies' drug manufacturing facility located in Galati, Romania, the FDA found significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals.

Release of drug products without conducting identity and strength testing

According to the FDA, the firm released drug products without conducting identity and strength testing. For example, the company released drug products without testing active ingredients like camphor, white petrolatum, and lanolin for identity and strength. The FDA points out that "Testing of each batch for strength and identity before release is essential to determine if the drug products you manufacture meet appropriate specifications."

In the responses to the Form FDA 483, the company stated that it will test active ingredients for which there are testing methods. The FDA has classified this response as inadequate. A manufacturer is responsible for ensuring each batch is tested for strength and identity before release to ensure the drug products meet appropriate specifications."This may require the development of appropriate methods where compendial methods are not established."

Failure to test incoming components for identity, strength, purity, and other appropriate quality attributes

Furthermore, the company failed to test incoming components. Instead, the company relied on certificates of analysis (COA) from unqualified suppliers. The company's response to the Form FDA 483 lacked sufficient details for how it will ensure each component possesses the identity, strength, and other appropriate quality attributes before use. Also, Global Treat Srl provided no evidence that methods are validated or suitable for use.

Failure to establish an adequate quality control unit

In the Warning Letter, the FDA says that the company's quality unit (QU) failed to ensure that adequate procedures are available and did not provide adequate oversight of the manufacturing activities. The FDA gives several examples of this, such as that "production personnel instead of the QU received and reviewed final microbiological test results and signed off on the product data sheet, releasing the product for distribution" and that neither the general manager nor the QU, reviews and approves procedures that are related to production and quality.

In conclusion, the FDA is not aware of sufficient evidence to show "HemoTreat Hemorrhoid Ointment," as formulated and labeled, is generally recognized as safe and effective. Based on the nature of the violations that were identified, the FDA strongly recommends engaging a consultant to assist Global Treat Srl in meeting CGMP requirements.

To find out more, please see the complete Warning Letter issued to Global Treat Srl.