Another FDA Warning Letter for Indian API manufacturer

The US FDA inspected an Indian API manufacturer from 4 to 12 September 2024 and found serious GMP violations. The deficiencies relate in particular to inadequate cleaning procedures and the associated risk of cross-contamination, inadequate processing of quality defects and violations of data integrity.

Inadequate Cleaning & Maintenance of Production Equipment

The FDA found that production equipment were labelled as "cleaned" even though they contained significant product residues and contamination. For example, coloured residues were found in equipment documented as cleaned, as well as in another equipment used to manufacture an intermediate product. In addition, the production buildings were in a poor condition. In one production area, the ceiling was found to be heavily stained and damaged with cracks and fallen plaster.

Although the manufacturer admitted to failing to comply with the cleaning processes, it disagreed with the risk of cross-contamination, as the equipment is used on a dedicated basis. In addition, the manufacturer assured that the damaged ceiling would be repaired.
The FDA considers the manufacturer's measures to be inadequate, as no systematic analysis of the risk from product residues was carried out. No explanation was given as to why the equipment was documented as "cleaned" even though it was still contaminated. Furthermore, the FDA states that even if no cross-contamination is possible from the manufacturer's point of view, product carryover and unknown contamination can occur if products are stored on unclean equipment. According to the FDA, there was also no evidence that the damaged ceiling had actually been repaired.

Inadequate Handling of Quality Defects

The manufacturer investigated a customer complaint about particles in an intermediate product and attributed the cause to improper cleaning of a piece of equipment. As a measure, the manufacturer decided to replace the part after a smaller number of batches. However, during the inspection, the FDA found that the equipment in question was in extremely poor condition. The internal coating was damaged and corroded. In addition, heavy rust deposits and even a dead insect were found in the system. For the FDA, the original deviation investigation is inadequate, as possible effects on other batches were not taken into account. Moreover, the possibility that the structural deficiencies and environmental contamination led to the contamination was not considered.

Batch Documentation Deficiencies & Data Integrity

The FDA discovered torn original records and batch documents in a scrap yard. When the FDA asked for the relevant batch records, a second version of these documents was provided by the management. No explanation was given as to why there were two different original documents or who had arranged for the disposal of the records. In addition, the FDA found that batch records were not maintained in a timely manner. For example, logs were not completed by the employees carrying out the work, but only later by the production manager. According to the FDA, the production manager was responsible for five different production areas at the same time, which resulted in inadequate monitoring of the documentation.

In its response to the inspection deficiencies, the manufacturer explained that some batch documents had been damaged by chemical spillages and therefore had to be replaced. The damaged pages had been replaced by the quality department, but the originals were no longer kept. It was also stated that some employees did not speak sufficient English and therefore the production manager made the entries. However, the FDA has no evidence of the alleged chemical damage to the original documents. The FDA is unable to trace the handling of GMP documents and has insufficient documentation. The FDA also doubts that the production processes were documented correctly, as the responsible employees did not make the entries themselves.

The FDA is now demanding a complete review of the company's documentation practices and measures to prevent data integrity violations. The manufacturer must ensure that all batch records are documented in real time and by the employees actually carrying out the work.

The detailed Warning Letter can be found on the FDA website.