On July 26, 2011 FDA notified pharmaceutical companies that bioanalytical studies conducted at Cetero between April 2005 and June 2010 in support of marketing applications may need to be repeated or confirmed. FDA took this action as a result of two inspections of Cetero’s bioanalytical facility in Houston, Texas conducted in 2010, as well as the company’s own investigation and third party audit. The inspections and audit identified significant instances of misconduct and violations of federal regulations, including falsification of documents and manipulation of samples.
Sponsors are responsible for addressing the concerns that FDA raised in the July 26, 2011 Untitled Letter and how those concerns relate to their individual studies.
FDA is notifying pharmaceutical companies of the current actions that need to be taken pertaining to certain time frames.
- April 1, 2005, to February 29, 2008: Studies that were previously submitted as part of an approved or pending application, or studies that will be submitted as part of a new application, will need complete reanalysis (if adequate stability data exist) or repeat of the study.
- March 1, 2008, to August 31, 2009: The Agency will accept studies for submission and review if the sponsor performs an independent third-party data integrity audit using the Bioanalytical Electronic Raw Data Audit Plan (provided by FDA). Further, studies that were previously submitted as part of an approved or pending application will also need verification of data integrity by an independent third-party audit.
- September 1, 2009, to June 15, 2010: The Agency will accept studies for submission and review without reanalysis, repeating, or further audit by Cetero or a third party.
With respect to the bioanalytical studies conducted between March 2008 and August 2009, the following are requirements for the use of third-party audits:
- Sponsors may hire independent third-party auditors, or they may use the independent third-party auditor hired by Cetero.
- Third-party auditors are independent of the sponsor and Cetero and are qualified by training and experience to conduct laboratory and vendor audits, including review of data collected by the Analyst®, AB SCIEX software.
- Independent third-party auditors must use the Bioanalytical Electronic Raw Data Audit Plan (provided by FDA).
- For all third-party audits, Cetero will permit auditors access to all raw and electronic data, data systems, and any paper records pertinent to the audited studies.
- The audit will cover 100% of the portion of each study conducted at Cetero and will be conducted following the official audit protocol agreed to and maintained by FDA.
- Along with an audit report, third-party auditors will provide a statement certifying that the audit was independently conducted.
- The sponsor will submit full audit reports of all audited studies to the FDA, regardless of the outcome of the audit.
- Cetero will immediately communicate to sponsors and to FDA any missing data or manipulation concerns identified during Cetero’s own internal investigations.
When studies with associated third-party audits are submitted for review, FDA will evaluate and make decisions concerning acceptability for each submission.
Sponsors who plan to conduct data integrity audits for studies conducted from March 1, 2008, to August 31, 2009 should contact the relevant FDA review division in the Office of Generic Drugs or the Office of New Drugs and obtain the Bioanalytical Electronic Raw Data Audit Plan prior to initiating an audit.