API Testing is also relevant for the FDA - Warning letter to Indian Manufacturer

The FDA inspected the manufacturing facility of Bhargava Phytolab Private Limited from 22 to 26 July 2024 and found serious violations of Current Good Manufacturing Practices (CGMP). The main findings include

1. Deviations in the Manufacturing of Active Pharmaceutical Ingredients (API)

Inadequate testing for each API batch:

• Toxic raw materials are used for the manufacture and distribution of APIs without sufficient testing.
• For example, there was a lack of limit tests for potentially harmful substances.
• The results were based solely on supplier certificates (CoA) without validating the reliability of the supplier data.

Lack of process validation:

• No validation was performed to ensure that production processes were reproducible and produced APIs of consistent quality and specification.

FDA requirements:

• Independent peer review of design and process control.
• Introduction of supplier qualification procedures.
• Validation of production processes and detailed timelines for implementation.

2. Lack of Sufficient Testing of Raw Materials

Reliance on supplier certificates (CoA):

• Important tests for harmful contaminants were missing.
• There are no validated procedures for checking the reliability of external test laboratories.

Lack of qualification of raw material suppliers:

• No comprehensive testing plans to ensure identity, purity and quality of raw materials.

FDA requirements:

• Review material system to qualify all suppliers and verify shelf life and test data.
• Implement robust testing plans for raw materials, including chemical and microbiological testing.
• Validation of CoA data and regular revalidations.
• Develop a programme to qualify and monitor external testing laboratories.

3. Deficiencies in the Manufacture of Finished Medicinal Products

Problems in the system:

• The system was poorly designed, e.g. with ‘blind spots’ and lack of continuous circulation, increasing the risk of biofilm formation.
• Insufficient monitoring was carried out to ensure that the system was functioning properly and was suitable for production.

FDA requirements:

• Validation of the system, including design, maintenance and continuous monitoring.
• Implementation of programmes to monitor and record microbiological and chemical parameters.
• Implementation of a risk assessment plan to evaluate the impact of system failures on the quality of drugs distributed in the US. This will include customer notifications and recalls as appropriate.

General measures:

The FDA requires the company to submit comprehensive corrective actions and timelines. These include

• Detailed process validation programmes (PPQ) for active ingredients and finished drug products.
• Systematic identification and control of process variability.
• Monitoring and qualification of production facilities and equipment.
• Risk assessment and preventive measures for products already on the market.

In addition, the company is expected to implement measures to ensure that all manufacturing processes comply with regulatory requirements and ensure the safety, quality and efficacy of the products. Read more deficiencies and the complete FDA Warning Letter on the website.