Warning letter due to insufficient container-/closure integrity

A site of the company Hospira in Italy received a comprehensive FDA Warning Letter at the end of March which criticises among others defects concerning the closure of vials and the related possible microbiological contaminations. Main problem for the FDA is that operators carried out operations over the vials that pose a microbiological risk for the product. Furthermore, the company did not perform smoke studies to demonstrate unidirectional airflow as protection for the product. This is aggravated by the fact that the FDA has criticised this already in 2013 and nothing has changed. According to the FDA this means that the sterility of the products produced since then is questioned. The FDA is clearly missing a video demonstrating the airflow and thus the protection of the product as well as a detailed assessment of the filling equipment design.

The FDA also criticised the approach as concerns the media fill, in other words the proof that the manufacturing process guarantees sufficient sterility. For example, several times numerous vials were rejected during the media fill and not assessed microbiologically (incubated) without sufficient explanation.

Another item in the Warning letter refers to the complaints processing that is handled inadequately according to the FDA. 103 complaints for discoloration of a sterile product have not been investigated adequately, for example.

Furthermore, the computerized systems in the QC laboratory were criticised because of insufficiency of the data integrity. The HPLC and GC systems did not have adequate controls to prevent the deletion or alteration of raw data files.

The detailed FDA findings can be seen in the Warning Letter.