COVER STORY

SURF AND TURF WARS

Pharmacists are increasingly concerned about the growth of rogue Internet pharmacies, especially those from Canada

While a hard core of rogue Internet drug sellers continues to do business virtually unchecked, a new on-line health risk has emerged in the North.

In the past year or so, dozens of Canadian pharmacies, many operating on-line, have leaped into the mail-order prescription business, using their powerful competitive price advantage to lure American consumers hammered by high medication costs. The Internet has greatly extended Canadian pharmacies' marketing reach, which was once limited to border states.

Philip P. Burgess, R.Ph., national director of pharmacy affairs at Walgreens, said Canadian pharmacies have even run full-page ads in newspapers in Arizona and Florida trying to induce consumers, mostly retirees, to save money by buying their prescription drugs on-line. He said the drug chain had identified about 100 "entities" that are shipping prescription drugs into this country by mail from Canada. "Many of them are on-line," he said.

Although most of these pharmacies require prescriptions from U.S. physicians—which are rewritten by Canadian doctors and dispensed by Canadian pharmacists—the process bypasses traditional Food & Drug Administration quality assurance safeguards as well as the drug utilization review safety net provided by American community pharmacies.

Consumer media coverage about the growth of Canadian mail-order pharmacies has generally played down the health risks and emphasized the plight of elderly individuals who have been able to save hundreds, if not thousands, of dollars a year by going on-line or crossing the border to buy their medications.

The subliminal message conveyed by this coverage is that it would be risky to political health to come down hard on mail-order prescription traffic from Canada while Congress remains deadlocked on a Medicare drug plan to benefit the elderly, about two-thirds of whom have marginal or no prescription insurance. Indeed, some politicians have abetted the personal import practice by hiring buses to take elderly constituents across the border to obtain their medications.

Even the FDA seems to have relaxed its guard on the Canadian pharmacy issue. For one thing, the agency's authority outside this country is limited to inspections of foreign manufacturing plants that make pharmaceuticals for the U.S. mar- ket. For another, while it may be illegal for a person to import drugs, the practice of individuals' obtaining medications from other countries for their own use lies in a regulatory no-man's land. Since the 1950s, the FDA has permitted patients with serious illnesses to travel out of the United States to get medications not yet approved in this country. Drugs for AIDS and Alzheimer's are past examples of this "personal use exemption" allowed by the FDA.

Even rogue sites have latched on to the FDA personal use exemption in an attempt to legitimize their clearly illicit operations, according to Carmen Catizone, R.Ph., M.S., executive director of the National Association of Boards of Pharmacy.

Most medications now being shipped through Canadian pharmacies are not covered by the stipulations of the personal use exemption. Rather, the motivation for buying north of the border has been almost entirely economic. But the FDA's political antenna is as sensitive as any officeholder's, and the agency has not been aggressive on the Canadian pharmacy issue compared with, say, its actions against domestic Internet sites selling so-called lifestyle drugs without prescriptions.

Still, that hasn't stopped individuals at the agency from speaking about the risks of buying drugs outside of the FDA's protective umbrella. Tom McGinnis, R.Ph., FDA's director of pharmacy affairs, noted that it was difficult, if not impossible, to determine whether drugs coming from Canadian pharmacies were manufactured in FDA-approved plants and thus comparable in quality to drugs available in U.S. pharmacies.

"Some of the [pharmaceutical] firms have told me that stuff made for the Canadian market is produced in their European facility, which doesn't ship to the United States, so it may not be the same formulation," McGinnis said. A slight change in formulation is going to throw off the bioequivalence, so there might be a different therapeutic response." He also said it was possible that drugs from foreign manufacturing plants that have not been inspected by the FDA could be poorly stored or even contaminated. "You always worry about that where there's no oversight of the manufacturing process," he said.

Lack of pharmacists' care

McGinnis also pointed out that patients who obtain drugs from Canadian or other foreign pharmacy sites normally don't share that information with their pharmacists. "The thing I worry about is that those patients are not getting the benefit of what pharmacists do and that's the drug utilization review," he said. "They're really missing out on the pharmacist and pharmaceutical care when they do this type of thing, so even though it's a little bit cheaper, in the long run it may be detrimental to their health."

David J. Fong, Pharm.D., senior v.p., pharmacy, at Longs Drug Stores, sounded the same theme. "Who is managing the total profile of prescriptions a patient is getting to ensure there is a system of checks and balances" to prevent interactions and contraindications? he asked. "My gut feeling is that the Canadian pharmacies that are sending prescriptions by mail to the United States are not going through the same depth in evaluating the patient," he said.

Even though Walgreens operates three U.S. mail-service pharmacies in response to managed care demands, Burgess said, "we still do not believe that the ideal model for people to get their prescriptions is through the mail. The ideal model is for face-to-face communication and interaction with the patient." He said the "very nature" of mail service is that it eliminates personal contact. "Now you're adding the whole dynamic of another country," he said. "You have a U.S. physician initiating a prescription, a Canadian physician who is rewriting the prescription, and now a Canadian pharmacist who is filling the prescription. The margin of error just keeps building in that scenario."

The target of most Canadian pharmacy promotional activity has been senior citizens. Burgess noted that was the age group "least able to handle multiple drugs coming from multiple sources. A lot of studies show that senior citizens get more sensitive to drugs as they get older, so when they get their refills from Canadian pharmacies," who is monitoring these sensitivities?

Another risk in ordering from on-line Canadian pharmacies was described by Susan Winckler, R.Ph., J.D., v.p., policy and communications, at the American Pharmaceutical Association. "The sites I've gone to ask the patient to sign a very significant disclaimer basically saying, 'Even if you send me the wrong medication, I can't come after you,' " she said. "If there were a problem with the medication or anything else, the consumer in the United States would have little recourse."

Burgess also mentioned a new wrinkle involving drugs shipped from Canada. "The scenario that is playing out now is that there are Canadian wholesalers shipping drugs to American physicians" who are dispensing them to their patients, he said. "That's a real prescription for disaster. Those are nonpharmacist wholesalers that are shipping those drugs. There are no checks and balances."

The system of pharmacy checks and balances is also totally lacking at rogue Web sites. They use the anonymity of the Internet to purvey a cornucopia of potentially dangerous drug products and dietary supplements without prescription or regard for adverse events. For several years, these sites have been a shadowy target for federal and state regulatory and law enforcement agencies. While these agencies have had some success in closing down sites, prosecuting their operators, and revoking licenses, a hard core remains that is difficult to track and bring to ground. Call them shape-shifters. Once cornered, they shut down and assume another guise.

"What we see today is that there is a core made up of maybe three dozen sites that are very active, very aggressive," said Catizone. "They're willing to fight the system and challenge it legally. They've created hundreds of pages that make people think there are more of them than there really are. But when you track down the core of these sites and the distribution centers, the credit card processing, and the domain owners, it comes down to these three dozen or so primary sites."

Catizone said these sites "are spamming everybody." That is, they are sending millions of promotional e-mail messages to consumers across the country, trying to lure them with offers of easy access to lifestyle medications like Viagra, Propecia, and phentermine, as well as other potentially dangerous dietary supplements. These sites promise to deliver products without a prescription, requiring only that consumers fill out a form allegedly reviewed by a physician for potential risks.

But Dale Austin, executive v.p. of the Federation of State Medical Boards, said many of these forms are a sham. FSMB, which is the clearinghouse for rogue site investigations, has been tracking their activities for more than two years. Austin said more than half of the medical questionnaires FSMB has looked at in investigating hundreds of sites have been filled out with the correct answers already inserted in the blanks.

Austin said that even when an FSMB investigator deliberately replaced the supplied answers with ones that, by a manufacturer's labeling standards, indicated a contraindication, the drugs were still shipped. "That tells you what the intent is," he said. "The intent is to sell drugs."

Though the danger of getting adulterated or even totally different substances is always a possibility, Austin said that manufacturer tests of some of the products ordered by FSMB had turned up no "watered-down versions" or ingredients different from those ordered. He said the products had not been tested for age or possible contamination, however.

FSMB's clearinghouse role was determined about three years ago at a Washington, D.C., meeting of organizations and agencies that included the FDA, NABP, Drug Enforcement Administration, postal authorities, and some manufacturers. FSMB has had a full-time investigator tracking the sites for about two years. Austin said information from these investigations had been turned over to a number of boards or agencies, depending on jurisdiction.

Austin added that these entities have sometimes done their own investigations or relied on the information provided by FSMB and "have begun to take actions. There are individuals who have lost their licenses or had their licenses put on probation. There are pharmacies that have been sanctioned by boards of pharmacy. The last time I looked, there were about 11 physicians [against whom] action had been taken based on information we turned over."

Actions against on-line physicians have been based on the fact that medications are ordered in production-line fashion, using only the flimsiest of self-reported clinical information and no direct contact or physical examination. One state that has taken vigorous action against these practices is California. There the state medical board maintains a full-time Internet Crimes Unit that delves into on-line prescribing practices of both state and out-of-state physicians. The unit is staffed and supervised by full-time career peace officers.

Candis Cohen, a spokeswoman for the California board, said the unit had investigated well over 50 cases since beginning its investigations in July 2001, more than half from out of state, which have been turned over to those states with jurisdiction. She said "a couple of arrests" had been made and about 30 investigations are pending.

Alberto Perez, supervisor of the Internet Crimes Unit, said the unit has also been involved in the high-profile investigation in which the California Board of Pharmacy in May imposed more than $88 million in fines against a Los Angeles pharmacy and two pharmacists for Internet dispensing. He said the medical board has "done something similar to that" and is actually in the process of developing a parallel case, which he could not discuss.

Lack of jurisdiction

One giant stumbling block to effective law enforcement against rogue sites has been the issue of jurisdiction. State medical and pharmacy boards control only the actions of practitioners within their own state lines, as do state attorneys general. But the nature of the Internet is that it is interstate—indeed international—in scope. Cyberpharmacies and physicians can slip across state lines, in both the literal and figurative sense, or even into other countries to avoid penalties, even when investigators are able to track them down.

"The really egregious players are those who have the high-powered attorneys and the ones who have the resources to move, create sites, and open distribution centers across the country," said Catizone.

That factor combined with the difficulty in pinpointing perpetrators in the first place has limited the number of prosecutions nationwide. While it wasn't possible to find a full accounting of all cases that have been brought—not even the National Association of Attorneys General had such statistics—a representative handful are given in the box above.

However, regulatory and law enforcement efforts, including such simple devices as warning letters, have had a deterrent effect. Austin said that "early on" a lot of people who got involved in on-line prescribing and dispensing were what he described as "naive" players. When cease-and-desist letters were sent to these individuals, he said, they quickly backed off. "The core individuals who remain now know exactly what they're doing," he added. "They're in it for the buck and wear many faces on the Internet."

At the federal level, the FDA continues to monitor the activities of Internet rogue sites, both domestic and foreign, according to McGinnis. He added that the agency conducted a comprehensive Internet search about a year and a half ago that identified about 3,600 sites selling prescription drugs, but when they "drilled down" to the core, there were slightly fewer than 400, about 200 of which were domestic and the rest foreign. The agency has no regulatory authority over foreign sites, but it has tried to work with its counterparts in other countries to curtail these activities, with varying success.

The agency has also sent letters to foreign sites whose practices it deems questionable and has had some success in deterring those operations. A complete list of letters sent by the FDA can be found on the agency's Web site at www.fda.gov/cder/warn/cyber/cyber2002.htm.

The Customs Service has also succeeded in blocking some of the drugs being mailed into this country from foreign Internet sites. "Customs is getting real good at spotting prescription drugs—any drugs actually," McGinnis said, adding that consumers may finally learn to stop ordering such drugs if their packages never arrive because Customs has grabbed them and they have lost their money. The foreign sites remain undeterred by seizures because the drugs are paid for in advance by credit card.

In this country, McGinnis said, FDA investigations of rogue sites have resulted in close to 100 arrests and 50 convictions. Several attempts to get the details of these cases from the Justice Department were unsuccessful.

Over the past few years, the number of rogue sites has waxed and waned depending on the number of law enforcement activities and on market events. The deadly anthrax mailings two years ago fostered a flood of sites selling ciprofloxacin on-line. Several of the pharmacists interviewed for this article pointed out the health risks of unmonitor- ed antibiotic use, particularly in creating resistance. But the sites, which once numbered about 100, no longer have a consumer market and so have disappeared.

Fortunately, the illegal activities of rogue sites haven't stained the reputations of legitimate on-line pharmacies that continue to provide millions of patients with responsible care. The NABP offers a seal of approval called VIPPS (Verified Internet Pharmacy Practice Site) to on-line operations that have undergone a rigorous vetting process. So far, 12 sites have been authorized to display that seal on their home pages, Catizone said, and another 10 "are in the queue." He said the sites represent about 8,000 to 10,000 Internet and brick-and-mortar pharmacies.

Catizone also said NABP was "weeks away from signing an agreement to bring the VIPPS program to Canada to certify Canadian pharmacies." He added that recent dialogues with FIP, the international pharmacy federation, indicated that that organization was also willing to move forward with a VIPPS program "after working out some logistics."

One thing pharmacists can do to curtail indiscriminate drug purchases over the Net is to educate patients about the dangers they face in buying medications from sites without a doctor's prescription or pharmacist's oversight—or even from a Canadian pharmacy whose products may come from foreign factories not scrutinized by the FDA. Both the FDA and APhA (www.aphanet.org) offer materials that can be used as talking points for pharmacists who encounter questions from customers about the low prices charged by Internet pharmacies.

Fong said pharmacists at Longs have been active in explaining the risks to customers who approach them with questions about Internet pharmacies. "They're not saying, 'Don't do it,' " Fong explained. "They're saying, 'Make sure you know all of the facts and consult with your doctor before doing this because you're not dealing with somebody you see every day.' "

Bruce Buckley

The author is a New York-based pharmacy journalist.

Federal bill, if passed, could fuel growth of rogue sites

Legislation to control rogue sites by forcing them to disclose their names and locations has languished in the current Congressional session. But a bill that would allow individuals to import Food & Drug Administration-approved drugs from Canada for their own personal use has been given a fair chance of becoming law. The measure also allows commercial shipments of approved drugs from Canadian drug wholesalers to licensed U.S. pharmacies.

"It would legitimize some of these sites," said Susan Winckler, R.Ph., J.D., v.p., policy and communications, at the American Pharmaceutical Association. "That's what a lot of people are nervous about, including the FDA." She added that it wasn't "so much the integrity of the Canadian drug supply" that was worrying people. It's that "you create a really strong incentive for unscrupulous people to come in and corrupt the Canadian drug supply or set up sham organizations that could send a counterfeit product directly into the United States."

David Fong, Pharm.D., senior v.p. of pharmacy for Longs Drug Stores, also expressed strong reservations. "From the legislative perspective, it's sexy," he said. "It shows we're working with consumers out there and looking for low-cost alternatives. From a professional and regulatory perspective, though, it creates all kinds of questions and concerns," including the possibility of counterfeit drugs. "Who's ensuring that the quality of what's being dispensed is comparable" to that of drugs produced under FDA scrutiny? he asked.

According to Tom McGinnis, director of pharmacy affairs at the FDA, in opposing similar legislation in the past, U.S. health officials have said they could not certify that drugs imported in such an alternative supply chain would be as safe and effective as those available in U.S. pharmacies.

Fly in the ointment

Drug manufacturing plants are subject to Food & Drug Administration inspections as long as they make products that are shipped to the United States. The agency has no jurisdiction if a foreign factory is shipping only to, say, Canada—an issue that the FDA cites in opposing on-line pharmacy sales originating from our neighbor to the north.

Inspectors who travel to other countries to see whether factories are adhering to the agency's stringent standards learn to be extremely sensitive to the smallest clue that might reveal evidence of product contamination, according to Tom McGinnis, R.Ph., director of pharmacy affairs at the FDA.

For example, said McGinnis, what tipped off one inspector that something was amiss was flies—or rather, the absence of flies. "There are always flies in big warehouses and manufacturing facilities," as he tells it. So the suspicious inspector asked what was going on behind a closed door. It turned out that they were making a pesticide that was killing the flies but also cross-contaminating the drug products.

"I always tell people that they may be getting the USP label amount of a drug product," said McGinnis, but "it's the other stuff that might be hurting them."

A sampling of Internet-related legal actions

• In May of this year, $88.7 million in fines was demanded by the California Board of Pharmacy in three citations against a Los Angeles pharmacy and two pharmacists for allegedly filling Internet prescriptions in violation of state law, which makes it illegal to dispense without a "good faith prior medical examination" by a California-licensed physician. The cases are under appeal.

• The Texas Board of Pharmacy alleged that a pharmacy and a pharmacist in San Antonio dispensed controlled substances with invalid prescriptions to 41 states and Canada. The licenses of the pharmacy and pharmacist were revoked in May 2002. Also a total of $11.4 million in administrative penalties were imposed.

• The Medical Board of California sought an indefinite suspension of the license of a physician in Colton, Calif., for allegedly prescribing drugs after talking with patients around the country referred to him by a Texas-based Web site.

• An Australian citizen and a U.S. citizen have been sentenced on charges relating to illegally offering prescription drugs over the Internet through a Web site in Clanton, Ala. The sentence handed down in February of this year was the result of 23 counts brought against them in an indictment returned in July 2000. The case was prosecuted by an assistant U.S. Attorney.

• An Oklahoma physician was sentenced to 51 months in prison for his role in a conspiracy to distribute drugs through Internet prescriptions requested by patients from a national Web site. This is according to a Department of Justice press release mentioned in a current newsletter from the National Association of Boards of Pharmacy.

Is insurer ignoring risk in covering foreign drugs?

Despite the risk inherent in using prescription drugs obtained from foreign countries, AARP's healthcare insurer, UnitedHealth Group Inc., has begun reimbursing members of the senior organization for low-cost medications purchased from pharmacies outside the United States, many using the Internet to do so.

An individual who buys prescription drugs from a foreign source is operating outside the law, according to the Food & Drug Administration, except when the purchase meets the agency's "personal use exemption," which covers lifesaving drugs not yet approved in this country. But, in practice, the FDA has not come down hard on seniors and others who cross the border or go on the Internet to buy low-cost medications from Canada.

In a letter to 97,000 AARP members in September, Jim Pogue, a United- Health executive, wrote, "We have made an administrative decision to waive the requirement that a prescription drug be purchased in the Unites States or one of its territories."

A UnitedHealth spokesman insisted the cost-saving reimbursement plan was not a change in policy, and that "elements of this were in place before. The letter gives it more import than it should." And Julie Alexis, manager of health products for the AARP unit that provides the insurance, added that all 400,000 AARP members who have drug insurance would be eligible for reimbursement, not just the 97,000 who received the letter.

 

Bruce Buckley. SURF AND TURF WARS. Drug Topics 2002;21:42.