Early-phase contract research organisation (CRO) Cetero Research has hit back at the US Food and Drug Administration for representing as pervasive misconduct what Cetero insists was an isolated incident of data falsification at its bioanalytical laboratory in Houston, Texas.
The US-based CRO is also standing by its own “rigorous scientific analysis” of the problems at Houston, stating: “The research conducted on behalf of our pharmaceutical sponsors can be, and has been, properly validated”.
This is despite the FDA’s claim that the company’s internal investigation, in the wake of an employee complaint about falsification and manipulation of sample data at Houston, was too narrow to determine the extent and impact of the alleged violations.
The agency also argues that the corrective actions subsequently proposed by Cetero were inadequate to address what an independent third-party audit suggested had been several years of misconduct by laboratory staff.
The CRO’s main beef is that the FDA’s announcement last week – notifying pharmaceutical companies with bioanalytical studies conducted by Cetero at its Houston facility between April 2005 and June 2010 that the studies might need to be repeated or confirmed – rode roughshod over the company’s own findings.
Cetero also says the announcement and publication of an Untitled Letter sent to the company by the FDA on 26 July were the agency’s first feedback on both the CRO’s plan for a “thorough and robust” investigation of the alleged violations and its responses to Form FDA 483 notices of observations issued following the agency’s inspections of Cetero Research, Houston in May 2010 and December 2010.
According to Cetero, it “remains fully committed to maintaining the quality and integrity of the data collected in each of its facilities, including the Houston, Texas bioanalytical laboratory. It is this commitment that makes the broad action announced publicly by FDA on July 26, 2011, even more difficult to understand”.
The FDA’s letter to Roger Hayes, president, bioanalytical of Cetero Research, said the agency’s inspections had revealed “objectionable conditions” and “significant instances of misconduct and violations” at Houston, raising concerns about the integrity of the bioequivalence and bioavailability data generated by the facility between April 2005 and June 2010.
These violations, the letter added, included the “widespread falsification of dates and times in laboratory records for subject sample extractions, and the apparent manipulation of equilibration samples to meet pre-determined acceptance criteria”.
Cetero launched its own internal investigation at Houston more than two years ago, when it “discovered the recording of inaccurate day/time data by a small number of research chemists”, the CRO notes in its response to the FDA announcement.
The company then “proactively contacted the FDA to self_report its preliminary findings, as well as seek agency feedback on its comprehensive investigation plan”. Cetero clients were also contacted to make them aware of the situation.
The CRO’s preliminary finding was that six chemists at the Houston facility had misreported the dates when samples were extracted prior to analysis. The chemists did this, Cetero claimed, “to seek additional compensation through weekend pay and pay for hours when they did not actually work”.
According to the FDA’s letter, though, not only was this explanation unsupported by documentation but the problems of data-tweaking at Houston went much wider.
For example, it noted, “your firm focused initially on the weekend extraction records, and you failed to consider whether any weekday extraction records were falsified”.
Following the FDA’s May 2010 inspection, however, Cetero “decided to investigate further, and you found that employees falsified timecards and laboratory records on both weekends and weekdays”.
The “narrow scope of your internal investigation of the falsification of laboratory records, the lack of a consistent and credible explanation for the time and date discrepancies in timecards and sample extractions, and the failure of your QA [quality assurance] procedures to detect the falsification, call into question the validity of all of the information documented on your AP [analytical procedure] sheets”, the agency’s letter stated.
By failing to accept the “results of our rigorous scientific analysis”, the FDA’s letter “discredits the Company’s 1,200 dedicated and experienced employees”, Cetero contended.
What was most important, though, was that “the processes being used today at Cetero are state_of_the_art” and in “full compliance” with FDA regulations and bioanalytical industry standards, it added.
“We intend to continue to work closely with FDA and our clients, and request the same in return, as we work to successfully resolve the issues raised by the FDA,” Cetero Research stated.
Some commentators have blamed the problems at Houston on pressure to cut the costs of drug development, leading to increased outsourcing of clinical research functions but a question mark over whether this always comes with a cast-iron assurance of quality.