A New York book publicist has been sentenced to prison for selling an unapproved new drug espoused in a book he was promoting. The book deals with a French-born biologist living in Canada who developed a camphor-derived drug he calls 714X, which he claims can cure cancer, AIDS, and other diseases. The drug has never been approved in Canada or the United States.
Charles Pixley, 48, president of Writers & Research Inc., of Rochester, N.Y., was sentenced last July to one year and one day in prison, plus three years of supervised release and 200 hours of community service for selling 714X to Americans, including undercover FDA investigators. He arranged for the product to be brought in from Canada. He is appealing his conviction.
According to FDA forensics chemistry analysis of a sample of 714X, the product was 94 percent water, about 5 percent nitrate, 1.4 percent ammonium, less than 1 percent each ethanol, sodium and chloride, and less than one one-hundredths of a percent of camphor. A Writers & Research sales report submitted as evidence during a two-day bench trial indicated patients paid between $300 and $400 for two 6-milliliter (about 1 teaspoon) vials of 714X. According to product literature, 714X could be injected into the groin, breathed in through a nebulizer, or placed under the tongue for absorption.
While FDA believes that 714X does not pose an immediate danger to patients, its use can prevent patients from receiving proper medical treatment. Two doctors who complained to FDA about 714X expressed concern about two of their cancer patients who refused conventional therapy in lieu of treatment with 714X. Both patients died.
The agency became aware of Pixley's activities in January 1992, when a consumer called the agency's Seattle district office to inquire about 714X. The consumer heard about the treatment on a radio show and had written for and received written information from Pixley's company.
On Jan. 24 and 30, 1992, Sherry Phillips, an investigator with FDA's Buffalo district office, inspected Pixley's business, located in the front porch area of his house. She interviewed Pixley, who admitted that he brokered the sale of 714X between the Canadian manufacturer in Rock Forest, Quebec, and U.S. patients. He promoted 714X in his book, Do No Harm, which summarized the theories of 714X's inventor on the causes of disease and advocated the use of 714X. Pixley's promotional activities also included distributing flyers and other literature, giving oral presentations, and participating in radio talk shows.
Literature available at Pixley's business showed the product was promoted for various diseases. One piece of literature stated that 714X was "effective in restoring to perfect health, 75 percent of cases treated against AIDS, cancer, Lupus, MS [multiple sclerosis], rheumatoid arthritis, and other viral, immunological or degenerative diseases."
Invoices supplied by Pixley indicated that during a three-month period in 1992, Writers & Research arranged for U.S. patients to buy and receive 960 vials of 714X from Canada. The vials had a wholesale value of $96,000 and a retail value of $168,000. They were brought into the country by a delivery service or as undeclared personal items at the U.S.-Canadian border in Buffalo.
Following the inspection, Phillips informed Pixley that his activities violated federal law because FDA had never approved a new drug or investigational new drug (IND) application for 714X. In July 1992, FDA issued an import alert, prohibiting 714X from entering the United States.
However, Pixley continued to sell 714X; he sold some to undercover FDA investigators. In addition, the agency continued to receive inquiries and complaints about 714X from consumers and doctors. So, Phillips returned to Pixley's place of business in March 1993.
During the inspection, Pixley admitted to Phillips that he was selling 714X to U.S. patients and smuggling it in from Canada. Phillips observed an inventory of 714X on hand and collected records documenting the sale of 714X to patients across the country.
Pixley indicated to Phillips that, in partial fulfillment of the requirements for an IND application, he had formed an institutional review board, or IRB. These boards review clinical studies of investigational drugs to ensure that patients participating in the studies are not exposed to unnecessary risks. Pixley's IRB included himself and doctors who bought and prescribed 714X.
At the end of her inspection, Phillips told Pixley that his IRB did not comply with FDA's regulations. For example, she cited him for being a member of the group, even though he had a financial interest in the drug being studied. Also, the IRB did not provide adequate informed consent or disclose potential risks of the drug to study participants. She passed on her findings to FDA's Center for Drug Evaluation and Research.
In August 1993, center representatives held an informal hearing with Pixley and informed him that his IRB did not conform with FDA regulations, that he should stop referring to Writers & Research as an IRB, and that he should file an IND application for 714X. Later, the center informed Pixley that it was considering disqualifying his IRB.
In February 1994, Beverly Ritter, an investigator in FDA's San Francisco district office, called Writers & Research, posing as a patient. Using an alias, she ordered $22 worth of patient literature on 714X, a $15 physicians' handbook on 714X, and $400 worth of 714X. The literature and the first of what were considered two orders of 714X arrived at an undercover address within one month.
Checks FDA sent as payment for the literature and 714X were returned to FDA's undercover location, stamped as paid. The stamped information indicated the checks had been deposited to an account with a Rochester, N.Y., bank. Under subpoena, the bank provided information about the account that showed it was held in the name of Writers & Research and that between April 1, 1993, and March 31, 1994, more than $472,000 had been deposited to the account. One check made out for more than $7,000 in cash was stamped to indicate it had been credited to the account of Pixley's 714X supplier in Canada.
In July 1994, special agents with FDA's Office of Criminal Investigations requested and obtained a search warrant for Pixley's place of business. They seized various documents related to 714X, including correspondence between doctors and other clinicians; records of telephone calls from customers; product order forms; customer sales receipts; patient and physician literature, cassettes and videotapes; and copies of FDA statutes and regulations.
On Oct. 25, 1995, a grand jury for the U.S. District Court for the Western District of New York returned a 19-count indictment against Pixley and Writers & Research. Count 1 charged both parties with conspiracy to defraud FDA by selling an unapproved new drug. Counts 2 through 19 charged Pixley with illegal interstate commerce of an unapproved new drug. Counts 2 through 19 each represented a date on which an individual had received 714X.
During the bench trial April 10 and 18, 1996, U.S. District Judge Michael Telesca heard testimony from various FDA employees, including Paul Goebel, in FDA's Center for Drug Evaluation and Research, who testified on the appropriateness of IRBs, and forensics chemist Rick Flurer, Ph.D. Also, David Feigal, M.D., director of FDA's division of anti-viral drug products, and Gerald Sokol, M.D., a medical reviewer in FDA's division of oncology and pulmonary products, testified in writing that they consider 714X a new drug because it is not generally recognized among scientific experts as safe and effective. Another FDA employee, Elaine Abraham, Ph.D., also testified in writing that she had searched FDA files and found that neither IND nor new drug applications for 714X had ever been filed.
Pixley's lawyer argued that 714X is a homeopathic drug and therefore not subject to FDA regulation. As a homeopathic drug, the defense argued, 714X is considered safe and effective based on the listing of its ingredients in the Homeopathic Pharmacopoeia. However, when questioned about the chemical name (trimethylbycyclonitraminoheptane-chloride) placed on the 714X vial, defense witness Harris Coulter, Ph.D., editor and chief of the eighth edition of the Homeopathic Pharmacopoeia, said he did not understand that label and would not know the contents of the vial based on the label.
On April 19, 1996, Telesca found Pixley and Writers & Research guilty of count 1 and Pixley guilty of counts 2 through 19 of the indictment. In his decision and order, Telesca wrote that the "overwhelming proof at trial" established 714X as a drug and therefore subject to the regulations governing the marketing of new drugs in the United States.
"[T]here is absolutely no proof that 714X is a homeopathic drug," he wrote. "It was not listed as such in the Homeopathic Pharmacopoeia nor was it labelled as such on vials of the substance which were marketed to individuals."
Telesca sentenced Pixley and Writers & Research on July 9. In addition to a prison sentence, supervised release, and community service, he ordered Pixley to refrain from "possessing, distributing, or aiding in the distribution" of unapproved drugs and assessed him $500. He fined the company $1,000 and assessed it $200.
Pixley filed a notice of appeal in the U.S. Court of Appeals for the 2nd Circuit on July 9.
Paula Kurtzweil is a member of FDA's public affairs staff.
As a result, on July 8, FDA sent a warning letter to Warren Zerra, operator of the party's laser light show, telling him that the light display at the May 17 party was operated in a "grossly hazardous manner," and that Zerra must stop his show until he takes steps to bring it into compliance with the agency's safety standards.
The letter followed an FDA inspection in which Gary Zaharek, electrooptics specialist with FDA's Pacific regional staff, identified serious problems, including the unsafe practice of striking people directly with laser beams. There were no known injuries.
FDA regulates laser light shows, along with all other laser equipment--from surgical instruments to compact disk players--under the Radiation Control for Health and Safety Act and the Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act.
An informant alerted FDA to Zerra's violations. FDA sent Zaharek to inspect the light show operation at the party, which was held on a dance floor at a San Francisco restaurant and club.
"We had to observe the person actually committing these illegal acts," says Frank Mackison, a consumer safety officer in FDA's Center for Devices and Radiological Health, "just like a policeman has to actually observe you speeding before he issues a ticket."
Zaharek observed numerous violations by the light show operator. The most dangerous, according to the investigator, was the absence of a safe distance between the audience and the lasers. For light shows like Zerra's, FDA requires beams to be at least 3 meters (3.3 yards) above the floor.
"People were being struck directly with the laser beams," Zaharek says. "That's the most dangerous aspect of illegal laser light shows. If a beam hits someone directly in the eye, it could cause serious eye burns."
The setup was especially dangerous, according to Zaharek, because a stationary beam hit people as they walked up or down a staircase at the party. A moving beam is less hazardous, he says, because in the mere blink of an eye, the beam has passed.
Other serious violations included:
FDA will monitor Zerra's operations and is prepared to reinspect. If Zerra continues to operate illegal light shows, he may be subject to a fine of up to $1,000 per violation and a court-imposed injunction of the illegal shows.
The warning letter is one of at least nine FDA has sent to laser light show operators since January. "We want to get the message out to operators that are putting on shows in a haphazard manner," Zaharek says. "Shape up before something serious happens."
Slenders and Absher, owners of D & S Calf Co., Chowchilla, Calif., signed the decree, which the U.S. District Court for the Eastern District of California entered on April 23, 1996, after an FDA investigation documented illegal residues of penicillin, tetracycline, gentamicin, neomycin, streptomycin, sulfamethazine, and sulfamethoxazole in D & S calves.
A calf that is treated with a drug or that has nursed from a drug-treated cow must be withheld from the market until the drug withdrawal time is complete. Drug residues in edible animal tissue may cause allergic reactions in some people consuming meat from these animals. The residues also may cause changes in the intestinal microflora, affecting such processes as vitamin synthesis, therapeutic drug metabolism, and development of antibiotic-resistant bacteria.
FDA investigator Robert J. Anderson first inspected D & S Calf in July 1989, after the U.S. Department of Agriculture found excessive drug residues in four calves sold for slaughter by Slenders. When calves are sent to slaughterhouses, USDA collects liver, kidney, and sometimes muscle tissue samples from a certain percent of the animals. If the samples indicate the presence of illegal drug residues, the carcass is condemned, and USDA notifies the producer and FDA.
FDA's inspection revealed that D & S Calf did not maintain adequate records showing where the calves were bought, the medications given to the calves, or the withdrawal periods for the medicated calves. On Sept. 18, FDA's San Francisco district office sent a regulatory letter to Slenders warning him that he must maintain the required records if he continues to sell calves in interstate commerce.
FDA's Anderson returned to D & S Calf in October 1990 after USDA again found illegal residues in several calves sold by D & S Calf. Slenders told Anderson he would record the source and medicated status of the calves he sold for slaughter as food.
The level of violations did diminish after that inspection. "He cleaned up his operation for awhile," recalls John Reves, a compliance officer with FDA's San Francisco district. But in late 1994 USDA again detected illegal residues of antibiotics in a calf Slenders sold for slaughter.
When FDA returned to D & S Calf in January 1995, Slenders admitted to the investigator that he knew the calf was medicated but had forgotten to tell the slaughterhouse. On March 17, FDA's San Francisco office again warned the firm to stop delivering medicated calves for slaughter for food and advised it to maintain proper records. In response to that warning, Slenders told the agency he would not purchase or sell medicated calves for slaughter.
But his assurances were false.
From September 1995 through March 1996, USDA detected illegal drug residues in more than 40 calves sold by Slenders and Absher. That brought the total since October 1994 to more than 50. "That's a phenomenal number of violations in such a short period of time," says Reves.
Because the agency's warnings did not result in compliance, on March 15, 1996, FDA asked the U.S. Department of Justice to initiate injunction proceedings against D & S Calf. After the department contacted the defendants, they agreed to sign a consent decree to settle the case without admitting or denying any wrongdoing.
Under the decree, the defendants agreed not to sell animals for slaughter for human food until residue avoidance systems were in place.
FDA and the Department of Justice worked with the defendants to establish an acceptable residue avoidance plan. The resulting plan requires Slenders and Absher to:
--Isadora B. Stehlin