Warning Letter to Indian Manufacturer: Dead Legs and Missing Validation

An Indian pharmaceutical manufacturer has received a Warning Letter due to the deficiencies identified during an inspection conducted by the FDA in February 2020. The main reasons for this were deficiencies in equipment design, validation and incoming goods inspection.

Deficiencies in the incoming goods inspection

According to the FDA, the Indian manufacturer has not tested components used in the production of homeopathic products for purity, content or quality. Furthermore, the FDA criticizes the lack of qualification of the suppliers of the components and the resulting lack of scientific proof that the components meet their requirements or specifications. The FDA now expects an overview of the microbiological and chemical specifications of the components and the corresponding instructions on how the quality control tests are carried out. A programme of how contract laboratories responsible for incoming inspections are to be managed is also required.

Deficiencies in validation

A serious deficiency is the lack of process validation. The FDA writes that there is no validation of the manufacturing process for products that contain toxic components, among other things. Batches of these products were distributed in the USA without data that supports the product quality or homogeneity.
The Indian manufacturer wrote in its reply that it was developing a validation master plan. However, the FDA lacks detailed validation protocols and timelines as to when the validation of all affected manufacturing processes will be completed.

Deficiencies in equipment design

Defects in equipment design and cleaning of manufacturing equipment are also part of the Warning Letter. In detail, the FDA describes "dead legs", dripping and the use of threaded piping in equipment used for the formulation of homeopathic medicinal products.
The FDA also saw cause for complaint in the cleaning of equipment. During the inspection, multipurpose process equipment with unidentifiable residues was found, which was marked as "cleaned".

In its response, the manufacturer had sent photographs showing adjustments to the system and temporary corrections of the design flaws. They also agreed to perform a gap analysis, but without further support documentation.
The FDA now expects a remediation plan regarding design, inspection, cleaning and maintenance of the manufacturing system. In addition, the FDA requires validation reports for all systems after the design flaws have been corrected and a detailed risk assessment for batches manufactured with the defective equipment and distributed to the USA, including measures such as recall of affected batches.

The Warning Letter to the Indian manufacturer can be found on the FDA website.