The warning letter comes as Hospira’s manufacturing network continues to be cited for violations around the globe. Its manufacturing facilities in India, Australia, North Carolina and Colorado and others have received warning letters and Form 483s over the last three years. The vast majority of the letters and citations came before Pfizer agreed to acquire Hospira and sign off on, or at least remain comfortable with, the company’s quality record.
In this case, the FDA cited Hospira’s Italian facility with four specific findings from the inspection, including the company’s failure to establish procedures to prevent microbiological contamination of drugs purporting to be sterile, its failure to investigate any unexplained discrepancy or failure of a batch, its failure to control who is allowed to make changes in master production and control records, and its failure to ensure that laboratory records included complete data derived from all tests necessary.
As for the sterility issues, the agency notes that Lake Forest, Illinois-based Hospira “did not evaluate significant aseptic interventions during dynamic airflow studies (smoke studies) to determine how the movement of air and personnel during aseptic operations could pose risks to product sterility.”
And without such “smoke study data” to demonstrate how the air flows unidirectionally over critical operations and processing steps, the FDA said Hospira “cannot show that your processes are designed to prevent microbiological contamination of your products or provide adequate assurance of product sterility.”
Although Hospira says that it performed smoke studies, and made “limited modifications” to the operation to reduce risks posed by the design deficiencies, the FDA said the company’s response is still inadequate because of its failure to provide “a thorough design assessment” or a video of the new smoke studies performed.
As far as corrective actions, Hospira spokeswoman Tareta Adams told In-Pharmatechnologist.com, "Hospira is evaluating what corrective actions may be required to address the specific matters raised in the warning letter. It is important to note that we have already completed several of the corrective actions we committed to the agency in response to the May 2014 inspection observations, and the other actions are underway. The Liscate facility has not received a warning letter prior to this one."
In terms of the batch failures, the FDA cited Hospira’s failure to conduct a thorough investigation for 103 complaints related to discoloration of injectable drugs between November2011 and October 2013. The agency makes clear that any decision “to exclude non-integral units from the final run tally should be fully justified and you should fully explain the deviation in your media fill report.”
And although Hospira completed a media fill performance qualification, the FDA said the protocol “is inadequate because it does not provide criteria that adequately defines when vials are to be rejected.”
And finally, Hospira failed to exercise appropriate controls over computer and software systems to assure that only authorized personnel can make changes in master production and control records, or other records.
Specifically, FDA took issue with the company’s high performance liquid chromatography (HPLC) and gas chromatography (GC) data acquisition software, which is a TotalChrom system from PerkinElmer. This particular system “did not have sufficient controls to prevent the deletion or alteration of raw data files,” inspectors said.
The agency also noted the similarities between this deficiency and one identified in a similar inspectional finding during the December 2013 inspection of Hospira’s Irugattukottai, India, manufacturing facility, which resulted in a Form 483.
The FDA asks Hospira to specifically explain how it will implement “global corrective actions and preventive actions concerning computer controls and provide a timeline for implementation.”
The agency also seeks “specific details about the comprehensive controls in place to ensure the integrity of electronic raw data generated by all computer systems used to support the manufacture and testing of drug products.”