by Charles Seife and Rob Garver, Special to ProPublica, April 22, 2013, 9:22 a.m.
(The Food and Drug Administration)
Last week, ProPublica reported that
the Food and Drug Administration allowed dozens of medications to stay
on the market, even though the research designed to prove their safety
and effectiveness was undermined by "egregious" violations at a major
pharmaceutical research laboratory in Houston. New information shows
that even after the FDA had cited the lab for falsifying data and other
misconduct, the agency issued a brand new approval to a drug tested
The FDA has refused to reveal the names of any of the approximately 100
drugs affected by the fraud at the Houston lab of the firm Cetero
Research, saying that to do so would reveal confidential commercial
information. ProPublica was able to identify five of those drugs, and
now we’ve found a sixth. This one was approved after the agency had already cited the Houston lab for misconduct.
The drug is a generic version of Tussionex, which combines a long-acting
narcotic cough suppressant with an anti-allergy medication.
Manufactured by TrisPharma, the drug has a tongue-twisting chemical
name: hydrocodone polistirex/chlorpheniraminepolistirex.
ProPublica discovered that both of the clinical trials used
to show that the generic is equivalent to the name brand — a key
requirement for FDA approval — were analyzed in May and June 2009 at the
Houston lab of the firm Cetero Research. The company, which conducted
research for scores of pharmaceutical companies, has acknowledged that
chemists at its Houston lab committed research fraud, though it says the
misconduct was limited to a handful of employees and that none of their
tests have so far proven to be wrong or inaccurate.
Cetero filed for Chapter 11 bankruptcy last year and emerged with a new
name, PRACS Institute. PRACS, in turn, filed for bankruptcy earlier this
The FDA got wind of problems at Cetero Houston in June 2009 when,
prompted by a whistleblower, the company alerted the agency of potential
On May 3, 2010, three FDA agents came to inspect the lab. The facility’s
president turned over eight flatbed carts double-stacked with file
boxes and admitted that much of the lab’s work was fraudulent, saying,
“You got us,” lead agent Patrick Stone recalled. (The lab’s president
declined to comment.)
On May 7, the FDA issued an inspection report that
cited data falsification and other laboratory violations at the
facility during the time its chemists conducted the tests for the
But five months later, in October 2010, the FDA approved Tris' drug for sale in the United States.
The FDA continued to inspect the Houston lab, and in July 2011, the agency called the
lab’s misconduct so “egregious” and pervasive that more than five years
of tests conducted at the lab were potentially “unreliable.” The agency
asked pharmaceutical companies to repeat or reanalyze any tests
conducted there during that time if they had helped win drug approval.
The FDA did not pull any drugs off pharmacy shelves, despite the fact
that dozens were approved on data the agency now said was questionable.
In April 2012 the FDA relaxed its requirements.
The agency announced that studies analyzed at Cetero Houston between
March 2008 and August 2009 — the time period in which tests for the
TrisPharma drug were conducted — would not need to be redone but instead
would require only a "verification of data integrity by an independent
Tris said it hired a consultant to perform the audit and it “came back
100 percent clean," Groner said. "Something could have happened, but in
our case, nothing did." He said Tris submitted the audit to the FDA in
the second quarter of 2012.
The FDA has reviewed the audit and found it “acceptable,” an agency
spokesperson wrote in an email. “Our earlier determination that this
product meets FDA standards was upheld.” She declined to add any
information or answer more specific questions.
The main point of that audit was to look for red flags that researchers
might have cooked the books, said Scott Groner, TrisPharma’s Director of
Regulatory Affairs and Compliance. The Cetero researchers ran blood
samples through a machine known as a mass spectrometer. By examining the
timestamps of these runs, Groner said, the auditors could tell whether
or not a rogue researcher would have been able to tamper with the
results of the experiment. "If there was some manipulation, there would
have to be some down time" for the researcher to fiddle with the samples
or the machine in order to produce the desired result, he explained.
Auditors, he added, “were looking for many other things. Were
[experiments] done late at night, on weekends?"
While the FDA declined to comment on the specifics of the Tris Pharma
case, the agency has previously said that it ran a risk assessment and
concluded that the chances were low that drugs tested at Cetero Houston
were unsafe. The fact that the FDA has since found no problems with
drugs tested there “confirmed” that risk assessment, a top FDA official
As of last week, the agency said it had completed reviewing 21 out of 53
submissions it had received from pharmaceutical companies that had
medications tested at Cetero Houston. It also said a few companies had
not yet submitted new data or audits on drugs tested there.