Phrase: "Failure of your quality unit"
When the FDA cites "failure of your quality unit to...," the regulator expects the company to fix that problem at all sites, not just the one that is the subject of the Form 483. "They're saying, 'don't make us go to all your sites,'" Mark Mynhier, a partner at consultancy PRTM, explained earlier this year.
For example, when FDA officials looked at Xian Libang Pharmaceutical's API manufacturing facility in ShanXi, China in June 2009, the agency found that the quality unit failed to ensure materials were tested appropriately and the results reported.
"Your firm used the [infrared] spectra for one lot to approve and release two subsequent incoming lots"--a practice it deems unacceptable. The practice "raises serious concerns regarding the integrity and reliability of the laboratory analyses conducted by your firm. It is essential that at least one test be conducted to verify the identity of each lot of incoming material.
"In addition, the laboratory control records should include complete documentation of all raw data generated during each test, including graphs, charts and spectra from laboratory instrumentation. These records should be properly identified to demonstrate that each raw material batch was tested and met the release specification before its use in production," the letter notes.
Another problem the inspectors noted was that the QC unit didn't detect that IR spectra were being substituted by a laboratory employee, thereby misrepresenting the results of the tested incoming material. In the same Sept. 2 response, the company said it had fired the chemist responsible for the falsified data and removed the QC and quality managers. However, the agency deemed the company's response incomplete because it hadn't "provided a more comprehensive plan to ensure the integrity of all data used to assess the quality and purity of APIs."
The aforementioned Apotex warning letter also referenced a failure of a quality unit. The agency's inspection of the company's Etobicoke, Ontario, Canada facility in December 2008 uncovered "significant CGMP violations and the failure of your quality unit to carry out its responsibilities," resulting in a warning letter of June 25, 2009. However, "[i]n your response to the FDA-483 you reported that your Etobicoke and Signet facilities are managed by the same quality unit. The violations found during the July - August 2009 inspection at Signet Drive are an indication that your quality unit continues to fail to perform its responsibilities regarding control and review, and to release products that meet specifications. Your response to the FDA-483 is inadequate in that it does not address the inability of your quality unit to conduct adequate investigations, determine the root cause, or establish adequate preventive and corrective actions for the problems found," the FDA said earlier this year.