FDA Challenges

The FDA faces a number of important challenges in its efforts to ensure a safe food and drug supply. This section will provide a brief overview of the direction the agency is going and recent agency actions on 2 highly publicized and important matters: direct-to-consumer advertising and bioterrorism. Considering these issues provides insight into how the agency works.

Direct-to-Consumer (DTC) Advertising of Prescription Drugs

In 2001, companies spent roughly $2.7 billion on DTC promotion, and spending continues to increase (GAO, 2002). FDA regulations define advertising to "include advertisements published in journals, magazines, other periodicals, and newspapers; and broadcast through media such as radio, television, and telephone communications systems." The FD&C Act (Section 502(n)) requires that ads indicate "the established name, the brand name (if any), the formula showing quantitatively each ingredient, and information in brief summary which discusses side effects, contraindications, and effectiveness."

• The Centers for Devices, Drugs, Biologics and Veterinary Medicine each have staff assigned to review advertising and promotion.
  
  
• The Center for Drug Evaluation and Research's Division of Drug Marketing and Communication reviews most DTC ads for drugs to ensure that they are fair and balanced. DDMAC also reviews promotional materials to health care professionals before a drug is introduced into the market. Companies are not legally required to submit materials for DDMAC review before they are distributed but most choose to do so to avoid running afoul of FDA regulations. However, companies are required provide the FDA with copies of ads after they have aired on TV or the radio or been published on Web sites or in magazines and newspapers. FDA regulations about prescription drug advertising can be found at 21 CFR 202.1.
  
  
• There are 3 types of DTC ads:
  
  
  • Help-seeking ads, which advise consumers to see their doctor about treatments available for certain diseases or conditions and may mention the name of a company but not a particular drug
    
    
  • Reminder ads, which mention the name of the drug but do not mention a particular disease
    
    
  • Product claim ads, which mention both the name of its product and the disease/condition for which it is used
  
  
• Combining the first 2 types of ads may allow companies to convey the same information as in a product claim ad—telling consumers about the name of the drug and the condition for which it is indicated—without also informing consumers about the risks posed by the product. At a recent conference, DDMAC Director Thomas Abrams said that the FDA will "be looking fairly closely" at this issue and will take action against companies trying to realize the benefits of a full product ad without also presenting risk information. He recommended companies allow sufficient time between when help-seeking and reminder ads appear on TV or vary the presentational elements of the ads so consumers are not presented with product claim-type ad information without also being informed of the risks and limitations of a product.
  
  
• The agency has issued guidance documents on DTC ads in broadcast and print media. Reminder ads and help-seeking ads do not need to provide information about risks, but product claim DTC ads should contain a "fair balance" of risks and benefits associated with the product, inform consumers that they should consult with their physician, and be understandable to the public. Print product claim ads must inform consumers about the risks of the product identified in the product labeling, which is why many print ads in magazines are accompanied by a "small print" copy of the labeling material (GAO, FDA Oversight, 2002).
  
  
• TV and radio ads also must contain a "major statement" of "all of the most important risk information related to the product" as part of the sound or video ad and provide in the ad or make "adequate provision" for the distribution of product labeling. Thus, the ad may refer consumers to a web site, print ad, or 1-800/1-888 phone number where further labeling information may be obtained.
  
  
• Certain drugs have patient labeling approved by the FDA, and the agency will allow use of this labeling in DTC print advertisements to help inform consumers of the product's risks and benefits.
  
  
• Print ads, including online ads, must contain a brief summary concerning "side effects, contraindications, and effectiveness." Companies failing to follow these requirements may receive "Untitled Letters" or notices of violation from DDMAC and, in severe cases, may receive Warning Letters.
  
  
• Some consumer groups and members of Congress have expressed concern that the agency is not doing enough to ensure that DTC ads are accurate and balanced and have expressed concern about a drop in the number of Warning Letters sent to companies about violative DTC ads (Alice Dembner, FDA Action on drug ads declining, Boston Globe, Oct. 19, 2002). Congressman Henry Waxman (D-Calif.), the ranking minority member of the House Committee on Government Reform, sent a letter to HHS Secretary Tommy Thompson in October 2002 expressing concern about a drop in the number of Warning Letters issued by the FDA about DTC advertising violations (House Committee on Government Reform, Minority Office, Special Investigations, 2002). Four academic and consumer group experts asked by the minority committee staff to review 100 DTC advertisements found some ads exaggerated the product’s benefits to consumers, did not convey the amount of time needed for the medication to help with their condition, and failed to adequately convey the risks of the product.
  
  
• In an informative October 2002 report, the General Accounting Office said that "FDA’s oversight of DTC advertising has limitations." (GAO, 2002). For instance, by the time manufacturers receive Warning Letters and Untitled Letters from the agency, the advertising campaign has already been completed and disseminated misleading or unbalanced information to consumers. Recent changes in the way the FDA reviews Warning Letters and Untitled Letters internally before they are issued to the public have contributed to delays in the FDA’s response to allegedly false or misleading advertisements, the report states. In addition, some companies have received multiple Warning Letters or Untitled Letters. The GAO said that the FDA is not able to ensure that it has been provided with copies of DTC ads. According to the report, to ensure companies are providing copies of ads to the FDA, the agency has hired a private firm to monitor ads on the New York City affiliates of ABC, CBS, Fox, NBC, and PBS as well as 6 cable networks: CNBC, CNN, CSPAN, CSPAN2, MSNBC, and CNNFN. However, this does not allow the FDA to monitor ads on other networks or in other areas, the report notes, pointing to the example of a "misleading advertisement" that ran for more than 2 years on a network in Puerto Rico. The GAO urged the FDA to issue Warning Letters and Untitled Letters more rapidly.
  
  
• Those supporting DTC believe that ads educate and inform consumers, raise patient awareness about their health problems and encourage patients to talk to their doctors about their health problems and follow the advice of their physicians.
  
  
• Opponents, on the other hand, have raised concerns that DTC ads may, despite FDA oversight, fail to fully inform consumers about the risks and benefits of advertised products and may be contributing to escalating health care costs because consumers may demand heavily promoted brand name drugs, which tend to be more expensive than generic drug products.
  
  
• The issue of celebrities discussing pharmaceutical products or talking about their diseases on TV talk shows or news programs has garnered increased scrutiny in recent months (Peterson, 2002; Fernandes, 2003). The FDA’s ability to regulate celebrity appearances on talk shows and how the agency would do so remains unresolved. In some cases, the involvement of celebrities may help to "raise awareness" about important health issues, such as drug complications. In other cases, however, the celebrities involved may "fail to disclose their financial links" to companies that are providing payment in return for their endorsement. In still other cases, according to the Times article, a product may be featured during a popular show without any involvement by the manufacturer. Network executives have pledged to ask celebrities if they have received compensation from health product companies before they appear on television news or talk shows about medical issues and ensure that the audience is told about any financial incentives being provided (Peterson, 2002).
  
  
• Patient education" or "disease management" campaigns in which pharmaceutical companies pay pharmacies to send mailings or make phone calls about a product to patients also have become an issue. Proponents of the program believe that these efforts can help encourage patients to refill prescriptions in a timely manner or inform them about new treatment options (for example, weekly rather than daily formulations of drugs they have been prescribed), which can improve their treatment. But critics believe that these campaigns may invade patients’ privacy. They believe that companies should have to obtain permission from patients prior to sending them reminder materials and that companies should not be using medical records or other consumer data for this purpose. Recently, some patients have filed suit against companies or pharmacies for allegedly invading their privacy by sending them unsolicited materials about such conditions as depression or HIV. A Florida woman, for instance received an unsolicited sample of Prozac Weekly from her pharmacy in a mailing that contained a letter from her doctor. She subsequently filed suit against the pharmacy chain and drug manufacturer on the basis that her privacy had been invaded. Another person in Florida filed suit against a pharmacy chain after he received "information" about an HIV medication (Elliott, 2002; Liptak, 2002; Singer, 2002; Zimmerman and Armstrong, 2002).
  
  
• A 1999 FDA survey released in 2002 indicated that DTC ads were prompting patients to ask doctors about certain diseases or conditions but were not visiting doctors specifically because of what they heard in advertisements. A majority of consumers said the ads were helping to "make them aware of new drugs" and help patients "decide if they should discuss the product with a doctor." The survey also found that about half of the time doctors did not prescribe the drug requested. A majority of patients surveyed also said that the ads "make drugs seem better than they really are" and fail to give enough information about risks of using the product.
  
  
• Preliminary results from a more recent FDA survey of medical doctors suggests that physicians believe DTC ads serve an educational function, help patients ask "thoughtful questions," and allow patients to become "more involved in their healthcare." But many physicians also believe that DTC ads also may leave patients with an exaggerated view of the product’s effectiveness and may not fully explain the benefits and risks of the advertised drugs. In addition, some patients may request drugs not warranted for their condition, and physicians may have to take time to address patient "misconceptions" about an advertised medication (FDA, FDA Releases Preliminary Results, 2003; Aikin, 2003).
  
  
• The DTC may expose companies to additional legal liability from consumers who believe that the advertisements highlighted the benefits of a product but failed to fully inform them of its risks. Traditionally, courts have ruled that for prescription products it is sufficient for a company to warn the doctor about side effects as opposed to informing the patient directly. The doctor as the so-called learned intermediary between the company and the patient could evaluate the risks and benefits of prescribing the product, inform the patient of relevant risks, and explain to his or her patient why the drug was appropriate. In part the reason for this approach was because drugs were, traditionally, advertised to doctors, and consumers were thought to lack the sophistication to understand adverse effects and could become intimidated by the medical terminology. In addition, almost all drugs pose some degree of risk under certain conditions.
  
  
• However, with drugs now being promoted to patients as well as doctors, should companies be forced to provide patients with similar risk information? In Perez v. Wyeth Laboratories (1999), the Supreme Court of New Jersey ruled that patients can sue companies that directly advertise their products to consumers for failure to properly warn them about the side effects of prescription drugs even though the physician, who prescribed the drug (in this case, Norplant) was warned of the side effect.
  
  
• In light of the U.S. Supreme Court's decision in Thompson v. Western States Medical Center, which struck down the FDA's restrictions on advertising of compounded drugs (drugs custom-made by pharmacists rather than pharmaceutical companies), it may be more difficult for the FDA to regulate advertising. A majority of the court found that the FDA should have considered "non-speech related means" of accomplishing its goal.
  
  
• Following the verdict in Western States, the FDA published a notice in the Federal Register asking for comments about how it regulates DTC advertising and health claims as well as other First Amendment issues.

Bioterrorism

• The FDA was actively involved in responding to incidents involving letters contaminated with anthrax spores and has taken a number of actions to help ensure an adequate response to future incidents of bioterrorism. Steps taken by the FDA include these:
  
  
  • Hiring new staff to work on counterterrorism initiatives, especially with regard to imported foods: The FDA has hired roughly 650 new staff members in the 2002 fiscal year, according to Deputy Commissioner Lester Crawford.
    
    
  • Working with the Federal Trade Commission and states to crack down on companies illegally marketing ciprofloxacin (Cipro) and other legitimate medical products to consumers without a valid prescription or selling dietary supplements and devices as "cures" for anthrax and other potential bioterrorism agents
    
    
  • Developing tests to detect agents that could be used by terrorists
    
    
  • Taking steps even before recent events by approving ciprofloxacin as a treatment for anthrax after a person has breathed in anthrax spores, advising physicians on the use of other treatments such as doxycycline, and working with manufacturers to revise labeling
    
    
  • Publishing food security guidance documents for (a) Food producers, processors, transporters, and retailers; and (b) Food Importers that suggest measures companies can take to safeguard the food supply such as conducting background checks of employees, restricting access to computer systems, and scrutinizing their suppliers
    
    
  • Revising guidance regarding the use of potassium iodide pills after exposure to radiation: These pills can prevent one type of radiation from accumulating in the thyroid gland after radiation exposure.
    
    
  • Attempting to educate consumers and members of the media through its Web site and other publications
    
    
  • Finalizing a rule known as the "animal efficacy rule" that allows approval of products based on testing in animals when human clinical studies are not ethical or feasible
    
    
  • Approving a treatment that can be provided to those who have been exposed to Soman, a type of nerve gas. The treatment, known as pyridostigmine bromide, has been approved for use by the military and is intended to be taken when exposure to Soman is a possibility. In combination with 2 other drugs, the treatment may help improve the possibility of survival, according to an FDA press release, which also points out that the rule is the first time a drug was approved under the "animal efficacy rule"
    
    
  • Inviting pharmaceutical manufacturers to submit new drug applications for Prussian blue (ferric hexacyanoferrate(II)), which can be used as a treatment after exposure to radioactive cesium and radioactive or non-radioactive thallium. Exposure to radioactive isotopes of these compounds could occur as the result of an incident involving nuclear materials
    
    
  • Working with vaccine manufacturers to ensure biologic and drug products intended to treat anthrax, smallpox, and other potential bioterrorist agents are safe and effective and issuing guidance concerning blood donations from those who have received the smallpox vaccine, which will help "reduce the very slight risk of blood borne exposure to the smallpox vaccine among certain small populations that may develop adverse reactions to the vaccine," such as persons with HIV or cancer
    
    
  • Working with the US Customs Service, US Department of Transportation, and other government agencies to explore anti-counterfeiting technologies and ensure that FDA-regulated products are not compromised en route to the United States.
    
    
• The Public Health Security and Bioterrorism Preparedness Act of 2002 (Public Law No: 107-188) will provide the FDA with significant new authority regarding imported food and other aspects of food security. At a conference, Deputy Commissioner Crawford described President Bush's signing of the law on June 12, 2002, as "one of the proudest days in FDA history." Among other things, the law does the following:
  
  
  • Requires the FDA to draft a regulation that requires domestic firms that manufacture or process foods for animal and human consumption and foreign companies exporting food to the United States to register with the FDA. In January 2003, the FDA published a proposed rule in the Federal Register (68 FR 5377). According to an FDA press release and CFSAN document explaining the regulation, "more than 400,000" food firms will be impacted by this regulation, including roughly 202,000 domestic companies and 205,000 foreign firms (FDA, FDA Proposes Regulation, 2003; FDA, Protecting the food supply, 2003). The rule requires manufacturers of foods, food additives, dietary supplements, drinks, and infant formula to provide contact information to the agency and tell the agency what types of foods it manufactures or processes, the press release states. Registration was required by December 2003.
    
    
  • Requires food importers to provide prior notice to the FDA and indicate the origin of the product. The FDA published a proposed rule that would implement this section of the bioterrorism bill in January 2003 (68 FR 5428). In addition to indicating which country the product originated from, the name of the importer, manufacturer and shipper also must be provided, according to an FDA press releases. The FDA believes that up to 20,000 of these notices will be provided each day once the rule is implemented in December 2003 (FDA, Prior Notice of Imported Food Shipments Proposal, 2002; Center for Food Safety and Applied Nutrition, 2003).
    
    
  • Provides for the FDA to make grants to the states to conduct inspections and allows the FDA to commission officers from other federal agencies, such as the U.S. Customs Service, to assist the agency in conducting inspections.
    
    
  • Allows the FDA to temporarily detain items for up to 30 days if "credible evidence or information indicating that an article of food presents a threat of serious adverse health consequences or death to humans or animals."
    
    
  • Gives the FDA the authority to prohibit (debar) individuals who violate import regulations, thereby preventing them from importing food items into the country.
    
    
  • Reauthorizes the Prescription Drug User Fee Act, which provides for manufacturers to pay user fees when they submit drug or device applications for the FDA's review and possible approval.