PATIENT PACKAGE INSERTS Mr. WHITTEN. In quoting from significant items in our Committee's Report on last year's bill, there was one concern that you did not address. We stated, "In considering available and potential alternatives, such as the U.S. Pharmacopeia Dispensing Information, FDA shall throughly investigate cost implications and exercise caution that no unnecessary inflationary costs are imposed whether directly or indirectly on consumers." What specific actions did you take in response to our expressed concern? In particular, please describe the evaluations you have conducted and are continuing to conduct of available existing alternatives to the Patient Package Insert Program. Dr. NOVITCH. A full cost analysis to the PPI regulation was published in the Final Regulation, which I will submit for the record. Very little of the cost of PPIs derives from their drafting. The major costs are associated with their distribution. Comments on the proposed regulations disputed FDA's cost analysis. Therefore, FDA decided to recast the regulation as a pilot test, reducing the number of drug categories to be covered from 375 to 10. In addition, several other features of the PPI program were changed to reduce costs. For example, PPIs were required for new prescriptions, not refills, and greater flexibility was allowed in the distribution of PPIs from manufacturer to pharmacist. The final rule also allows exemptions from FDA regulations for specific distribution sites-for example, pharmacies-where tests are beings made of alternate distribution mechanisms. The test of alternate distribution mechanisms was included as part of FDA's overall PPI evaluation plan-which is also attached for the record. This will allow data to be collected on the costs and benefits of various alternatives during the 3-year pilot test period. Although FDA is actively encouraging the solicitation of distribution alternative studies, FDA does not have the financial resources to fund those studies. Rather, funding is being left to those sites applying for the exemption. Where possible, FDA staff has and will continue to provide aid in study design. Several pharmacy chains have approached the FDA with ideas for studies. For example, Hook Drugs of Indiana intends to study a system where consumers can choose the appropriate PPI from a rack rather than having a pharmacist placing it in the bag. Several other firms have stated their desire to study alternative; however, the availability of funding remains a major obstacle. One test of distribution alternatives has been completed by the Hoffman La-Roche Company. Roche was interested in field testing of a PPI for Valium. At the FDA's suggestion, the firm incorporated two methods of delivery-first, distribution with the drug by the pharmacist and, second, placement of the PPI in a book at the pharmacy counter for the patient to consult. Pharmacists were contacted in three cities and asked to cooperate with the study. Roche conducted 45,000 interviews to find about 800 people prescribed Valium during the test period. Only 6 percent remembered receiving the PPI. It was evident from the results that the great majority of pharmacists did not distribute the PPIs. Surveys of pharmacists taken by Roche indicate that pharmacists who did cooperate preferred to distribute the PPI rather than having the book placed at the counter. 60754 Federal Register / Vol. 45, No. 179 / Friday, September 12, 1980 / Rules and Regulations DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 203 [Docket No. 79N-0186) Prescription Drug Products; Patient Package Inserts Requirements AGENCY: Food and Drug Administration. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) adopts final regulations establishing requirements and procedures for the preparation and distribution of patient package inserts for prescription drugs for human use. The package inserts will inform the patient about the drug product. This action is intended to promote the safe and effective use of prescription drug products by patients and to ensure that patients have the opportunity to be informed of the benefits and risks involved in the use of prescription drug products. The agency intends to apply the regulations to 10 drugs or drug classes during an initial implementation program. Further evaluation of the costs and benefits of the program will guide the agency in deciding whether to extend, revise, or defer these requirements. EFFECTIVE DATES: October 14, 1980. The regulations are effective with respect to particular drugs or drug classes 180 days after publication of a notice in the Federal Register applying the regulations to the drug or drug class. FOR FURTHER INFORMATION CONTACT: About this rule: Michael C. McGrane, Bureau of Drugs (HFD-30), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-4435220. About the FDA patient package inserts program: Louis A. Morris, Bureau of Drugs (HFD-107), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-443-4893. SUPPLEMENTARY INFORMATION: In the Federal Register of July 6, 1979 (44 FR 40016), FDA proposed general regulations that would require manufacturers to distribute patient package inserts to patients for prescription drug products for human use. This proposal resulted from the agency's more than 10 years experience with patient labeling for specific drugs. Note. The proposal used the term "patient labeling" to describe these leaflets. The agency has adopted the term "patient package inserts" in the final regulation. That term already enjoys considerable recognition in the health care community. Thus, "patient package inserts" will also be used throughout Purposes and Benefits of Patient Patient package inserts represent a significant initiative for improving health care for Americans. Through their use patients will be able to participate increasingly in decisions having to do with the use of prescription drugs, substances which, like few others, affect human life. When used properly, prescription drugs have enormous potential for reducing human suffering and economic loss. When used less than optimally, however, this potential can be seriously diluted. Traditionally, the extent of patient knowledge on prescription drugs rested solely with the treating physician; information on prescription drugs was not available independently to patients. It has been only recently that information on prescription drugs has achieved some degree of general availability. The Physicians' Desk Reference, long the sole province of physicians and pharmacists, is now found in book stores, albiet at substantial prices. Its contents, however, consist of no more than the official professional labeling of drugs, labeling which is fully understood only by health professionals. Other information is available to patients in the form of privately authored treatises on drug actions, such volumes reflect only the views of their authors, consumers are not necessarily aware of their availability or their veracity, and again, they must be purchased at not insubstantial prices. Finally, randomly available information in the press is at best piecemeal, and often confusing. Thus, generally, today's users of prescription drugs are still not routinely exposed to information about proper drug use, except insofar as that information is imparted, usually orally. by the prescribing physician. FDA believes that providing complete and readily understandable information on drugs to patients can help achieve maximum benefits from their use, and reduce their potential for causing harm. Patient package inserts for prescription drugs, through which information about a drug will be provided in lay language directly to patients at the time the drug is dispensed, are intended to increase patient knowledge about prescription drugs, and thereby promote their optimal use. FDA's research confirms that patient package inserts will, in fact, fulfill these important purposes. Overall, existing patient package inserts are read and understood by a high proportion of patients. Consumers hold favorable attitudes towards patient package inserts and support developing them for Existing FDA Patient Package Inserts Since the late 1960's, FDA has on several occasions required that package inserts written in nontechnical language be provided directly to patients when certain prescription drug products are dispensed. In the Federal Register of June 18, 1968 (33 FR 8812), FDA required that each isoproterenol inhalation drug product dispensed to a patient bear a two-sentence warning on the container (now codified in 21 CFR 201.305). In the Federal Register of June 11, 1970 (35 FR 9001), FDA issued a regulation requiring certain information about the use of oral contraceptive drug products to be made available to patients (now codified in 21 CFR 310.501). In issuing patient labeling requirements (21 CFR 310.515) in the Federal Register of July 22, 1977 (42 FR 37636) for estrogenic drug products, which are drugs used primarily to treat menopausal symptoms in women, FDA expanded significantly the scope of its patient labeling requirements. Unlike oral contraceptives, which are normally marketed in unit-of-use packages that contain a one-cycle supply, estrogenic drug products are usually custom packaged by the dispenser each time a prescription is filled. The unit-of-use packaging of oral contraceptives ⚫ permitted manufacturers to include the leaflet in the package so the labeling was automatically dispensed with the package. (Separate, longer leaflets were required to be available from prescribing physicians.) Such was not the case, however, for estrogenic drug products, where the labeling is not affixed directly to the dispensing package by the manufacturer. Accordingly, the patient labeling requirement for these products placed significantly greater obligations on the Federal Register / Vol. 45, No. 179 / Friday, September 12, 1980 / Rules and Regulations dispenser to ensure that the labeling is In the Federal Register of January 31, FDA has also established a patient labeling requirement for intrauterine devices (IUD's) for contraception that are regulated as prescription drug products (21 CFR 310.502), for IUD's regulated as medical devices (21 CFR 801.427), and for progestational drug products (21 CFR 310.516). FDA requirements for patient package inserts for prescription drug products bave centered on largely elective drug products that present significant risks to patients. They have as a consequence also been intended to afford patients the ability to participate with physicians in choosing whether to use the products. In these cases. FDA concluded that patients needed information upon which to decide whether to take or to continue to use the drug product. Following the development of the patient labeling requirement for oral contraceptives in 1970, FDA began evaluating the usefulness of patient package inserts for prescription drug products generally and studied ways to present the information to patients. In response to suggestions from the National Food and Drug Advisory Committee, FDA in 1974 began a patient prescription drug labeling project to investigate whether FDA patient package inserts efforts should be expanded to apply to a variety of prescription drug products. Since the project began, FDA has (1) discussed patient package inserts issues with interested and potentially affected persons, (2) reviewed scientific literature about patients' needs and desires for patient package inserts, (3) conducted research projects to evaluate existing and model patient package inserts, and (4) reviewed existing methods for communicating drug information to patients. Between September 1974 and June 1975, FDA officials met individually with nine organizations representing physicians, pharmacists, and the pharmaceutical industry, and in July 1975 met with consumer representatives to discuss the general concept of patient package inserts. The minutes of each meeting have been placed on file in the office of the Hearing Clerk (HFA-305), Food and Drug Administration, Rm. 462, 5600 Fishers Lane, Rockville, MD 20857. On March 31, 1975, FDA was petitioned by a consortium of consumer organizations to require written warning information on labels of some prescription drug products. The petitioners expressed concern that physicians may not always provide patients with the information needed to use drugs safely and effectively, that patients may not understand the information provided orally and may be reluctant to ask questions, and that patients may need written material in case they forget the information that was provided orally (Onek, et al., 1975). A copy of the petition has been placed on file in the FDA Hearing Clerk's office. A notice published in the Federal Register of November 7, 1975 (40 FR 52075), reviewed briefly the consumer petition and the opinions and views on patient package inserts that had been obtained from the professional, trade, and consumer groups that had met with the agency. The notice asked for comments to help formulate a policy on patient package inserts for prescription drug products. The notice specifically asked for comments on the consumer petition, and also asked for comments on patient package inserts generally. The agency received more than 1,000 comments on the November 7, 1975. notice. The agency carefully reviewed the comments and either adopted them in the proposed patient package inserts regulations or responded to them in its preamble. To explore and focus further the issues relating to patient package inserts, FDA hosted a series of four separate meetings in May and June 1976, in which FDA officials met with a group of consumer advocates and representatives from the pharmaceutical industry, medical associations, pharmacy associations, and allied health professions. Minutes of these meetings have also been placed on file in the FDA Hearing Clerk's office. In 1976, FDA invited the Drug Information Association (DIA), an independent nonprofit professional group interested in drug information, to arrange a symposium on patient package inserts for prescription drug products at which a diversity of views 60755 could be presented. FDA and DIA were joined by the American Medical Association (AMA) and the Pharmaceutical Manufacturers Association (PMA) as cosponsors of the symposium, which was held in November 1976. The symposium was attended by more than 700 health professionals, consumer representatives, and members of the press, and focused on the issues related to patient package inserts for prescription drug products. The symposium proceedings were published as a special supplement to Volume 11 of the Drug Information Journal January 1977). FDA continued to solicit public contributions to the patient package inserts program. In December 1978, FDA sponsored a 2-day conference on the content and format of patient package inserts. Approximately 300 participants attended, including pharmaceutical industry representatives, physicians, pharmacists, other health professionals, marketing and advertising representatives, and consumers. The conference was concerned with the information that patient package inserts for prescription drug products should be required to contain and how the information should be presented to benefit people most likely to read it. The proceedings of the conference are on file in the FDA Hearing Clerk's office. In February 1979, the Institute of Medicine of the National Academy of Sciences, under contract to FDA, sponsored a public hearing to solicit comments on how patient package inserts should be objectively evaluated, once they are used on a widespread basis. A copy of the presentations at that hearing is also on file in the FDA Hearing Clerk's office. FDA also reviewed the literature on patient information for prescription drug products to determine the extent of current efforts to communicate drug information to patients. A discussion of the agency's literature review appears in the proposal (44 FR 40019-40021; July 6, 1979). FDA's literature review showed that most patients are not exposed to information about prescription drug products. Those that are exposed to oral information are not attentive to it. In addition, health care professionals use language that patients do not understand, and patients are unwilling to ask for clarification. Moreover, even if oral information is provided and patients are attentive to and understand it, they may not accept its validity. Finally, patients often do not remember medical information that is presented orally. Thus, the agency's proposal was based upon its belief that patient |