Warning Letter to an Indian Manufacturer of OTC Products

The FDA inspected the Indian manufacturer of sterile OTC products in December 2025. Serious deficiencies included the absence of a protective barrier in Area A, the inadequate aseptic design of the production line and violations of data integrity.

Data Integrity in the Microbiology Laboratory

The FDA has identified serious and recurring data integrity violations at the laboratory relating to critical microbiological tests and monitoring data. Specifically, the laboratory failed to provide complete and original raw data demonstrating that the required tests had actually been performed.

For example, the FDA noted that agar plates used for staff monitoring which had shown visible growth were found in the incubator the following day with identical labelling, but without growth. The FDA was informed that the original plates had been discarded and replaced with new ones. This means that the ISO 5 environmental conditions of the aseptic line were incorrectly represented. Additionally, the FDA objects to the fact that monitoring samples (including environmental and personnel samples, as well as any other samples required) were frequently not collected in accordance with the SOP. Furthermore, the FDA cites discrepancies in sample descriptions and identification, and in pre-filled laboratory forms containing microbiological results from sterility tests, for example. The FDA therefore considers the documentation to be unreliable. It is also noteworthy that the FDA observed microbial contamination on multiple occasions during the inspection, as soon as samples were taken in the ISO-5 process environment and the tests were being monitored by the FDA.

Filling Line Design and Airflow Visualization

The FDA objects to the lack of a physical barrier separating and protecting the ISO-5 (Grade A) filling area of the aseptic filling line for sterile OTC products from the surrounding Grade B zone and its personnel. According to the FDA, this lack of separation poses an unacceptable risk to product sterility. Contaminants can be carried from the less-controlled area by airflow and personnel movement.
In addition, according to the FDA, several pieces of equipment that came into direct contact with the product, the containers, and the closures were not sterilized. The FDA emphasizes that only sterile equipment may come into direct contact with the sterile formulation, containers, and closures.The FDA also criticises the ergonomics and the flow of personnel and materials. For instance, there is insufficient space in the aseptic work area and the equipment is in poor condition. The FDA also notes rust on the HEPA filters and their diffuser grilles above the filling line.
They also state that the aseptic process simulations (media fills) were not sufficiently representative of commercial aseptic manufacturing.

One of the main issues raised in the objections is that the airflow visualisation (smoke studies) was not conducted under dynamic conditions in order to assess the risks posed by interventions in the aseptic line. The visualisation is described as static and too limited. The FDA also notes deviations observed in employees' aseptic practices, including leaving skin exposed while wearing safety goggles during aseptic production. In this regard, the FDA refers to its Aseptic Guide, 'Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice'.

The full text of the Warning Letter sent to the Indian manufacturer can be found on the FDA's website.