FDA Consumer

Cyanamid fouls fowl data

Cyanamid fouls fowl data – American Cyanamid Co. cited for inadequate research records for poultry drug testing

John Henkel

American Cyanamid Co., a major animal drug maker, received $400,000 in penalties after pleading guilty last Feb. 28 to not maintaining required records in an effectiveness study of the poultry drug Cygro (maduramicine ammonium).

Cyanamid’s monitor for the study, David L. Sharkey, Ph.D., also pleaded guilty last March 8 to not maintaining required records. He was sentenced June 24 to a $5,000 fine, two years’ probation, 100 hours of community service, and substance-abuse counseling.

The Wayne, N.J.-based company was testing Cygro to support an FDA new animal drug application. The drug was designed to be mixed with feed to protect poultry from the parasitic disease coccidiosis and to be combined with other drugs to increase bird weight and feed efficiency.

The study protocol FDA had reviewed called for independent clinical investigators to conduct feeding studies under actual-use conditions at several test sites. From those studies, Cyanamid was to collect and analyze detailed data from which FDA would determine the drug’s effectiveness for all intended uses. But, according to the government’s statement filed in the U.S. District Court for the District of Maryland, the company violated food and drug laws related to record keeping while conducting the tests between October 1987 and March 1990.

The company failed to:

* record correct results of drug assays

* record that investigators had intentionally exposed test animals to a disease agent that may have enhanced the apparent effect of the test drug

* keep accurate study records of feed consumption totals, bird numbers, bird mortality, and bird weight

* record observations of adverse conditions under which the birds were raised.

Sharkey’s misdeeds first came to FDA’s attention in January 1990, after agency officials received a tip about possible manipulation of the study at one of its sites. An FDA inspection at the site revealed enough evidence of possible fraud to warrant investigating the rest of the study’s field sites.

In August 1990, FDA officials inspected Cyanamid’s New Jersey headquarters and the study’s field-trial sites in Maryland, California, Colorado, and Missouri. The agency collected considerable evidence, including a statement from a clinical investigator who claimed he had altered data in several studies. FDA referred the case to the Justice Department for further investigation. That probe confirmed what had already become apparent: “At least half of [the clinical investigators] admitted they had changed data,” says Gerald Miller, investigator in FDA’s Baltimore district office.

In a statement to the court, the prosecutor listed examples of study fraud:

* In a test of Cygro’s effectiveness in combination with two other drugs, conducted at a Maryland field site between January and March 1989, Sharkey added organisms that cause coccidiosis to poultry drinking water. The intent, FDA officials say, was to make the drug combination appear more effective. The Cygro study protocol did not allow for intentionally infecting test animals, and Cyanamid’s final study report did not reveal the company had done so.

* In a test of Cygro and the drug virginiamycin at the Maryland site between March and May 1989, Sharkey instructed a clinical investigator to change data concerning bird weights and the number of birds under study that died or were removed. The study originally had not shown that the two drugs produce a statistically significant weight gain. But after the investigator made the changes Sharkey requested, data appeared to indicate an increase. “One of the clinical investigators told us it was common practice to falsify data this way,” says Mike Bruckheimer, compliance officer in FDA’s Newark district office.

* In a December 1989 Virginia field study, Sharkey had specific birds removed from the study. For example, investigators withdrew large birds from some pens and small ones from other pens. This, say FDA officials, had the effect of improving the apparent performance of test groups relative to the control group.

Court documents chronicled several other violations over a 2 1/2-year period, such as altering data entries originally recorded in pencil and failing to record accurate drug assays. Cyanamid withdrew all Cygro combination drugs shortly after FDA began its investigation in 1990.

FDA notes that the Cygro tests were for efficacy, not safety. And Cyanamid officials say that throughout the study, Cygro’s safety was never in question. But FDA reviewer Vernon Toelle, Ph.D., says there’s another issue to consider if an ineffective poultry drug is approved: Needless drug residue can accumulate in the bird. “Animal drugs can affect millions of people because they eat chicken and turkey,” Toelle says. “There’s no benefit to exposing humans to unnecessary drug residue. Luckily, there doesn’t appear to be a safety problem in the Cygro case.”

In the wake of the court action, Cyanamid has created a regulatory and scientific affairs department, and the company says it has “instituted new controls related to the accuracy of scientific data to prevent a recurrence of the Cygro situation.”

COPYRIGHT 1994 U.S. Government Printing Office

COPYRIGHT 2004 Gale Group