A manufacturer of sterile ophthalmics (preparations for use in the eye) has recently received a Warning Letter from the US FDA. Container leaks and the associated risk of microbial contamination were the main points of criticism.
During the inspection, the FDA had noticed numerous documented cases of leaking containers in the production area. The company changed process parameters in these cases and afterwards released the batches concerned. This led to market reclamations because of leaking containers. According to the FDA, leaking containers were also found in media fills. The FDA therefore questions the manufacturer's ability to safely produce sterile medicinal products.
The missing validation of production processes and the fact that the equipment had not been qualified are at least as serious. Furthermore, the FDA criticizes the missing root cause analysis of issues such as the leaks described above. When the findings of such cases are not considered when it comes to process design and validation, a continuing state of control is not possible according to the FDA.
Parts of the container/closure system are obtained from an external supplier. The FDA criticizes that the information on the supplier certificate were not verified. Moreover, there was no rationale for acceptance criteria. According to the FDA, this can lead to leaks in the packaging and result in loss of sterility.
Another issue criticized by the FDA is the fact that the stability studies for at least two products were missing. Without stability studies, no reliable shelf life can be determined. The container tightness as well is addressed again, as it must be included in the stability study.
The FDA suggests that the manufacturer read FDA's Aseptic Guide and strongly recommends to hire an external consultant in order to become familiar with GMP requirements and compliance.
Get more details in the Warning Letter of the FDA to Opto-Pharm Pte Ltd..