Product: pharmaceutical manufacturing facilities
Investigators from the U.S. Food and Drug Administration (FDA) identified significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug products to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 351(a)(2)(B), in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
We have conducted a detailed review of your firm?s responses and note that they lack sufficient corrective actions.
We also acknowledge receipt of your firm’s additional correspondence dated October 2, 2013.
Our investigators observed specific violations during the inspection, including, but not limited to, the following
Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).
Chikalthana Facility (FEI 3002808503):
The inspection documented that all of your QC laboratory computerized instruments ((b)(4) HPLCs) were found to be stand-alone, and laboratory personnel demonstrated that they can delete electronic raw data files from the local hard drive. Your firm deleted multiple HPLC data files acquired in 2013 allegedly to clear up hard drive space without creating back-ups. Your QC management confirmed that there is no audit trail or other traceability in the operating system to document the deletion activity. Furthermore, your analysts do not have unique user names and passwords for the computer and laboratory information systems; your QC analysts use a single shared user identifier and password to access and manipulate multiple stand-alone systems.
Waluj Facility (FEI 3004540156):
The (b)(4) HPLC systems in operation at the Waluj facility are also stand-alone, and during our inspection, an employee demonstrated to the investigator that data can be deleted through the local hard drive of the data acquisition system. As with the Chikalthana facility, all Waluj facility employees use a shared password to access the operating system. During the inspection, your firm?s management informed our investigator that (b)(4) back-ups of data are performed. However, we are concerned that your system and procedures permit deletion of HPLC files and that (b)(4) backed up data may not represent all the original data generated.
You are responsible not only for having controls to prevent alteration or loss of the data, but also for recording any changes made to existing data, which should include the date of change, identity of the person who made the change, and an explanation or reason for the change.
In response to this letter, provide your evaluation of all laboratory equipment that may be affected by the lack of adequate controls to prevent data manipulation. In addition, address the root cause of your quality unit’s failure to control and detect the manipulation or alteration of laboratory documents and describe actions to prevent recurrence. In response to this letter, provide your procedures to manage all computerized data and how the data will be used, retained and stored to ensure its integrity.
FDA District Office: CDRH