The FDA have notified pharmaceutical companies that bioanalytical studies conducted by Cetero Research between April 2005 and June 2010 in support of marketing applications may need to be repeated or confirmed. Cetero is a contract research organization (CRO) that performs bioequivalence and pharmacokinetic testing for a number of pharmaceutical companies.
The FDA is asking drug sponsors to identify those tests conducted by Cetero during the designated time frame that were used to support New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs). Drug sponsors will need to determine whether any of the testing performed by Cetero should be re-done.
Also, the FDA will send letters to drug sponsors with pending applications, requesting that they either repeat the bioequivalence testing done by Cetero or retest drug samples using a different test laboratory or contractor.
It is unlikely that these concerns relating to data integrity affect the overall safety and efficacy of drugs already on the market and, at this time, there is no evidence of problems with the safety, quality, purity or potency of drugs already approved. However, as a precautionary measure the FDA is asking drug sponsors to review the testing in question conducted by Cetero to make sure that data are completely reliable.
FDA is taking 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.
The pattern of misconduct was serious enough to raise concerns about the integrity of the data Cetero generated during the five-year time frame. FDA concurs with the assessment of Cetero’s independent auditor who stated, “This misconduct appears to be significant enough to cast doubt on the data generated…If the foundation of the laboratory is corrupt, then the data generated will be also.” As noted in a letter FDA sent to the company, Cetero also failed to conduct an adequate internal investigation to determine the extent and impact of the violations and failed to take sufficient measures to assure data integrity within the 5 year time frame.
As noted in the July 26 letter sent to Cetero, “FDA has reached this conclusion for three reasons:
(1) the widespread falsification of dates and times in laboratory records for subject sample extractions
(2) the apparent manipulation of equilibration or ‘prep’ run samples to meet pre-determined acceptance criteria
(3) lack of documentation regarding ‘prep’ runs that prevented you from conducting an adequate internal investigation to determine the extent and impact of these violations.”
