CHAPTER

3

CHAPTER OBJECTIVES

Upon completing this chapter, the reader will be able to:

▶  Discuss the criteria by which a drug is determined to be prescription or over-the-counter (OTC).

▶  Understand how the provisions of the Durham-Humphrey Amendment affect drug classification and pharmacy practice.

▶  Describe the role of the Food and Drug Administration (FDA) in regulating written patient information.

▶  Identify the issues associated with off-label (unlabeled) drug uses.

▶  Distinguish pharmacy compounding from manufacturing.

▶  Determine the role and use of the Orange Book in pharmacy practice.

▶  Identify the scope and implications of the Prescription Drug Marketing Act (PDMA).

▶  Recognize the requirements established in the Poison Prevention Packaging Act (PPPA).

▶  Understand the legal issues related to pharmacies when advertising prescription and nonprescription drugs.

The federal Food, Drug, and Cosmetic Act (FDCA) adopts a regulatory approach that emphasizes the elimination, or at least limitation, of risks throughout the drug distribution chain—from the time a scientist first imagines that a molecule might be effective as a drug through the ingestion by a patient of a product containing that drug. Pharmacists are involved with every aspect of drug development, production, marketing, and distribution. However, the primary focus of pharmacy practice is drug dispensing. In contemporary pharmacy practice, dispensing includes more than order processing. Dispensing is a comprehensive activity that incorporates drug therapy monitoring and patient education as well as drug distribution. Because most pharmacists perform dispensing functions, the aspects of the FDCA that relate specifically to dispensing are particularly relevant to pharmacy practice.

This chapter discusses regulatory activities of the FDA that have particular significance to those who are directly involved in the dispensing function and in other patient care activities.

THE DURHAM-HUMPHREY AMENDMENT OF 1951

As discussed under “Misbranding,” § 502 of the FDCA establishes different labeling requirements for drugs, depending on whether they are prescription or nonprescription. The questions then become “How did it happen that we have two classes of drugs instead of one or three?” and “What determines if a drug is a prescription drug?” These answers can be found in the Durham-Humphrey Amendment, also known as the Prescription Drug Amendment (§ 503; 21 U.S.C. § 353).

Cosponsored by two pharmacist-legislators, Senator Hubert Humphrey and Congressman Carl Durham, this important amendment to the FDCA created the first statutory distinction between prescription and nonprescription drugs. Legislative history of the amendment discloses that the prescription distinction from OTC was not the primary focus of the bill leading to this important law. Legalization of the verbal transmission of prescriptions (as opposed to the traditional method of writing them) and the legal right for pharmacists to honor refill authorizations indicated by physicians in the initial prescription were the key provisions of the bill. The full impact of a clear dichotomy between prescription and OTC drugs may not have been fully appreciated at the time. Although the Durham-Humphrey Amendment recognized pharmacists as being instrumental in the distribution of drugs, it failed to acknowledge that pharmacists play a significant role in drug therapy.

THE LAW

The amendment, as subsequently amended by the Food and Drug Administration Modernization Act of 1997 (FDAMA), provides in part

(b)(1) A drug intended for use by man which—

(A) because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such drug; or

(B) is limited by an approved application under section 505 to use under the professional supervision of a practitioner licensed by law to administer such drug; shall be dispensed only (i) upon a written prescription of a practitioner licensed by law to administer such drug, or (ii) upon an oral prescription of such practitioner which is reduced promptly to writing and filed by the pharmacist, or (iii) by refilling any such written or oral prescription if such refilling is authorized by the prescriber either in the original prescription or by oral order which is reduced promptly to writing and filed by the pharmacist. The act of dispensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which results in the drug being misbranded while held for sale.

(2) Any drug dispensed by filling or refilling a written or oral prescription of a practitioner licensed by law to administer such drug shall be exempt from the requirements of section 502, except paragraphs (a), (i)(2) and (3), (k), and (l), and the packaging requirements of paragraphs (g), (h), and (p), if the drug bears a label containing the name and address of the dispenser, the serial number and date of the prescription or of its filling, the name of the prescriber, and, if stated in the prescription, the name of the patient, and the directions for use and cautionary statements, if any, contained in such prescription. This exemption shall not apply to any drug dispensed in the course of the conduct of a business of dispensing drugs pursuant to diagnosis by mail, or to a drug dispensed in violation of paragraph (1) of this subsection.

(3) The Secretary may by regulation remove drugs subject to section 505 from the requirements of paragraph (1) of this subsection when such requirements are not necessary for the protection of the public health.

(4)(A) A drug which is subject to paragraph (1) of this subsection shall be deemed to be misbranded if at any time prior to dispensing the label of the drug fails to bear, at a minimum, the symbol “Rx only.” (Note: prior to FDAMA the law required the label to contain the legend “Caution: Federal law prohibits dispensing without a prescription.” Because of this, prescription drugs have been commonly called legend drugs.)

(B) A drug to which paragraph (1) of this subsection does not apply shall be deemed to be misbranded if at any time prior to dispensing the label of the drug bears the symbol described in subparagraph (A).

EXPLANATION OF THE DURHAM-HUMPHREY AMENDMENT

Before the passage of the Durham-Humphrey Amendment, drug manufacturers generally determined whether their products were prescription or OTC drugs. If the FDA disagreed with the manufacturer’s choice, it had to sue the manufacturer for misbranding. There was a great deal of confusion for healthcare practitioners and patients, however, because one manufacturer could label an active ingredient a prescription drug, whereas another manufacturer labeled the same ingredient an OTC drug. The amendment resolved this situation by establishing criteria for the classification of prescription drugs. All other drugs were, of course, considered nonprescription drugs. Thus, the amendment officially established two classes of drugs: prescription and OTC.

Prescription Versus Over-the-Counter Drugs

Subsection (b)(1) of the amendment provides that the FDA has the authority to categorize as prescription drugs those that are

•  Unsafe for use except under the supervision of a practitioner because of the toxicity, the method of use, or the collateral measures necessary to use the drug

•  Subject to the new drug application (NDA) approval process

(Note: Before the FDAMA this subsection also listed habit-forming drugs as those that the FDA could categorize as prescription.)

The issue of whether a drug requires the supervision of a practitioner for its use under subsection (b)(1)(A) and, thus, should be a prescription drug, was addressed in United States v. Article of Drug—Decholin, 264 F. Supp. 473 (E.D. Mich. 1967). In Decholin, the court established that the FDA must prove two issues to change the status of a drug from OTC to prescription: (1) that the toxicity and method of use require practitioner supervision, and (2) that the collateral measures necessary to use the drug require supervision.

Addressing the toxicity and method of use issue, the court stated that the FDA must show that the pharmacological and toxic effect of the drug is such that, unless it is taken pursuant to a physician’s directions, it may harm the patient. This requires evidence of the seriousness of harm resulting from the unsupervised use, including the dosage level that is likely to cause this harm, the immediacy of the harm, the effect of prolonging treatment by a physician, and the patient’s ability to recognize that the drug is not helping before real harm occurs.

Examining the collateral measures issue, the court concluded that the government also must establish that a patient who takes the drug for a condition that the drug cannot cure will suffer harm because of the postponement of a visit to the physician in reliance on the drug. This requires the government to show the seriousness of the harm resulting from the delay, the length of delay that is detrimental, the quality of advice contained on the label (e.g., whether it alerts a patient to the possibility that professional attention may be required), and the possibility that the drug may alleviate the symptoms, making a patient think that the condition has been cured when it has not.

Dispensing Written, Oral, and Electronic Prescriptions

Subsection (b)(1) also stipulates that prescription drugs may be dispensed pursuant to written or oral prescriptions promptly reduced to writing and filed. Before the Durham-Humphrey Amendment, oral prescriptions were not valid nor were refills recognized. This subsection allows for refills, as long as they are authorized either in the original prescription or by oral order.

Note that the Durham-Humphrey Amendment does not specifically authorize the electronic transmission of prescriptions. Obviously, when Congress enacted the Durham-Humphrey Amendment it could not have contemplated electronic prescriptions (e-prescribing). Nonetheless, most states have enacted laws and regulations authorizing the transmission of prescriptions by both image transmission (fax) and data transmission, and historically, the FDA has regarded electronic prescriptions very favorably. The Medicare prescription drug law (part D) specifically permits e-prescribing and preempts any contrary state restriction.

The legitimacy of electronic records and electronic signatures received a boost in 2000. In that year, Congress enacted the Electronic Signatures in Global and National Commerce Act, known as E-Sign (P.L. 106-229). E-Sign provides that electronic records, signatures, or contracts in interstate commerce are legally valid. If a law requires a signature to be in writing, an electronic signature satisfies the law. E-Sign preempts inconsistent state laws. It is not completely clear as to the extent in which E-Sign preempts laws related to prescriptions and prescription records. If completely applicable, state and federal laws requiring pharmacies to keep paper records would be invalid if the pharmacies can maintain those records electronically. Moreover, if applicable, E-Sign would invalidate laws that require prescriptions to be handwritten or signed in writing by the prescriber.

Labeling Requirements

Without the Durham-Humphrey Amendment, pharmacists would be required to label every dispensed prescription drug pursuant to the same requirements that manufacturers must meet. Subsection (b)(2), however, recognizes that some of the information mandated by § 502 would be impractical for drugs dispensed pursuant to prescription and should fall under the discretion of the healthcare provider. Thus, subsection (b)(2) exempts the dispensing pharmacist from the labeling requirements of § 502 except for the following:

•  The label must not be false or misleading.

•  The drug dispensed must not be an imitation drug.

•  The drug must not be sold under the name of another drug.

•  The packaging and labeling must conform to official compendia standards.

•  If it is a drug liable to deterioration, it must be packaged and labeled appropriately.

•  It must be packaged in conformance with the PPPA (15 U.S.C. § 1571 et seq.).

In the case of the Pharmaceutical Manufacturers Association v. Food and Drug Administration (reported in the case studies section), the physician and pharmacist plaintiffs unsuccessfully argued that the exemption accorded in subsection (b)(2) precludes the government from mandating that healthcare providers distribute written information to patients for certain prescription drugs. The plaintiffs argued that because subsection (b)(2) gives them discretion regarding what information to provide to a patient, the government could not mandate that they provide written information to patients. The court disagreed, finding that it was not the intent of the provision to give complete discretion to healthcare providers to the exclusion of the government.

Subsection (b)(2) also specifies the minimum information that the pharmacist must include on the label of a dispensed drug. Most state laws require additional information on the label such as

•  The name, initials, or license number of the dispensing pharmacist

•  The expiration date of the drug, if any

•  The drug’s name and strength

•  The address of the patient

•  The name of the manufacturer or distributor

•  The lot or control number

State Standardized Prescription Labels

Recently, there has been increased awareness that many patients cannot read or understand the label effectively, thus leading to adverse drug events. A 2006 study published in the Annals of Internal Medicine revealed that 46% of patients misunderstood one or more instructions printed on the container labels of five commonly prescribed medications (http://annals.org/article.aspx?articleid=731144). In an effort to improve this situation, the United States Pharmacopeia (USP) (http://www.usp.org) and the National Association of Boards of Pharmacy (NABP; http://www.nabp.net) have proposed that states develop standards to establish patient-centered standardized labels; and California and New York were the first two states to do so. Generally, the requirements for a patient-centered standardized label include that the label should be organized in a patient-centered manner such that critical information (i.e., name of patient, name and strength of drug, directions for use, purpose or condition) is grouped together, prominently displayed, and clear; that the critical information should be in an appropriate font size; that directions for use should be standardized and explicitly describe dosage and intervals; and when possible, the labeling should be in the patient’s preferred language. California and New York require that the label be interpreted in certain languages other than English.

Other Subsection (b)(2) Considerations

Previously, subsection (b)(2) provided that if the dispensed drug was an antibiotic or insulin product subject to batch certification, then the product must have come from a batch-certified source. However, the FDAMA has since eliminated batch certification requirements.

Subsection (b)(2) does not exempt drugs from § 502 if they are dispensed pursuant to diagnosis by mail. The purpose of this provision is to help protect the consumer against fraud and quackery. It does not apply to the typical mail-order drug outlets. This provision may, however, apply to situations in which patients, who have never established a legitimate, personal physician–patient relationship, are being diagnosed and prescribed for by means of the Internet. Neither the FDA nor the courts have ever considered the application of this clause to Internet prescriptions, however.

Expiration or Beyond-Use Dating

The manufacturer is required to include the expiration date on the label of its product. This date identifies the time during which the drug may be expected to meet the requirements of the USP monograph for the drug. Correspondingly, almost every state requires that the pharmacist include an expiration date on the label of the dispensed drug product; however, this date may or may not be the same date as the manufacturer’s expiration date, depending on state law and other factors. The USP states that “The dispenser shall place on the label of the prescription container a suitable beyond-use date (emphasis added) …” (http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/revisions/m4908-general-chapter_7.pdf). The “beyond-use date” is defined as the date after which the drug should not be used, and it must not exceed the manufacturer’s expiration date. The USP provides that in determining the beyond-use date, the pharmacist shall take into account the nature of the drug, the container in which it was packaged by the manufacturer, the characteristics of the dispensed container, expected storage conditions, and other factors. The USP further states that for multiple-unit containers (the typical prescription vial), absent data to the contrary, the beyond-use date “shall not be later than (a) the expiration date on the manufacturer’s container, or (b) 1 year from the date the drug is dispensed, whichever is earlier.”

When nonsterile solid and liquid drug products are repackaged into unit-dose or single-unit containers by pharmacies or shared service establishments, however, the appropriate standard for the beyond-use date is less clear. USP guidelines provide that the beyond-use date is the earlier of one year from the date of repackaging or the expiration date on the original bulk container, unless stability data or the manufacturer’s labeling indicates otherwise. These guidelines depend upon two conditions: (1) that the dispenser maintains the facility at a mean temperature of 25 degrees Celsius; and (2) that the dispenser uses packaging material that affords better protection than polyvinyl chloride (PVC). Many pharmacies, however, use PVC packaging because it is much less expensive. If this is the situation, then there is no applicable USP guideline.

To confuse the matter further, the FDA final compliance guide issued in 1995 establishes a different guideline: That the expiration date not exceed six months; and that the six-month expiration period not exceed 25% of the remaining time between the date of repackaging and the expiration date on the unopened original manufacturer’s bulk container. (This was the same as the USP guideline before it was changed as described above.) In an effort to match the latest USP guideline, the FDA issued a draft compliance guide in 2006 changing the six-month based standard to the one-year standard articulated by the USP (http://www.fda.gov/ohrms/DOCKETS/98fr/05d-0174-gdl0001.pdf). However, the draft guide has yet to be finalized and the FDA has stated that until it is finalized, the six-month standard applies (http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124785.htm).

The question of course is how should pharmacies deal with this situation for unit dose drugs if they repackage in PVC containers. Because the USP now has no standard, it would seem that the FDA’s six-month standard should be followed until the latest compliance guide is finalized. More importantly, however, state law is determinate and pharmacists should follow it.

State law permitting, many pharmacies have adopted the USP beyond-use date guidelines for multiple unit containers, leading to some consumer confusion. A good example of this occurred in 2003 in California. State law in California requires the label to contain “The expiration date of the effectiveness of the drug dispensed” (CA B&P Code 4076(a)(9)). Rite Aid pharmacies typically affixed on the label the expiration date as being one year from the date of dispensing or the manufacturer’s expiration date if it was sooner, pursuant to the USP guideline. At the behest of a group of consumers, the State of California brought a lawsuit against Rite Aid contending the chain engaged in consumer fraud for placing a misleading expiration date on the label. The suit alleged that the misleading date induced consumers to discard their medications prior to the manufacturer’s expiration date and replace them, thus unfairly generating more business for Rite Aid. (A similar suit was filed directly by consumers against Walgreens in Illinois in 2003.) Once Rite Aid pointed out it was merely conforming to the USP standards, the suit was dropped.

SWITCH OF PRESCRIPTION DRUGS TO OVER–THE-COUNTER DRUGS

As discussed earlier, subsection 503(b)(3) of the Durham-Humphrey Amendment authorizes the FDA to switch prescription drugs to OTC status by regulation when the conditions warrant. A switch may occur in three ways:

1.  The manufacturer may request the switch by submitting a supplemental application to its approved NDA.

2.  The manufacturer may petition the FDA.

3.  The FDA may add or amend an OTC monograph.

The OTC drug review process was initially the primary mechanism by which drugs were switched from prescription to OTC status. Under the review process, the advisory review panels may recommend such a switch to the FDA. If the agency agrees, it publishes a final OTC drug monograph to this effect, which becomes binding on manufacturers of that active ingredient. Today most switches occur through the supplemental new drug application (SNDA). Using this manner generally allows the manufacturer to obtain market exclusivity for the product.

Some switches have justifiably confused pharmacists because, on occasion, a product from one manufacturer is a prescription drug and an identical product from another manufacturer is an OTC drug. (Note: Differentiate this issue from how adequate directions for use labeling can cause a drug to be both OTC and prescription as discussed under “Misbranding.”) This situation can result when a switch to OTC status occurs through FDA approval of a manufacturer’s supplemental application to its NDA. Approval for one NDA holder to switch does not automatically apply to other manufacturers of products containing the same ingredients. Each manufacturer must submit a supplement for approval. Therefore, switches for identical products can occur at different times. Pharmacists must abide by the label and not sell a prescription drug without a prescription, even though the competitor’s product may be sold OTC. A switch in status pursuant to a monograph, on the other hand, generally applies to all other manufacturers’ products at the same time.

The petition route to a switch had essentially been a nonissue until Blue Cross (now WellPoint Health Networks) submitted a citizen petition to switch the nonsedating antihistamines (Allegra [fexofenadine], Claritin [loratadine], and Zyrtec [cetirizine]) from prescription to OTC in 2001. Although the regulations do not specify who may petition, no party other than a product’s manufacturer had ever submitted a petition. WellPoint’s petition raised the issue of whether the FDA could legally approve a petition by a party other than the manufacturer over the manufacturer’s objections. Ultimately an FDA panel voted to support the petition, but the FDA took no action, leaving it up to the manufacturers. Schering-Plough switched Claritin in 2002, Zyrtec switched in 2007, and Allegra in 2011.

Third Class of Drugs

Since at least the 1970s, pharmacy organizations and others have contemplated a “third class of drugs,” later called “Behind-the-Counter” (BTC) drugs and most recently a class of drugs that are “Nonprescription Under Conditions of Safe Use.” Although the exact definition for a third class of drugs has varied, it was generally agreed that it would include certain nonprescription drugs that could be sold only by a pharmacist. The rationale for a third class of drugs included that some of the drugs being switched could jeopardize a patient’s health unless a pharmacist provided appropriate consultation and that such a class of drugs would allow the FDA to switch drugs that could not otherwise be switched because of safety concerns. Some examples of a third class of drugs do exist presently, including the sale of some Schedule V drugs in states that permit their sale as exempt narcotics.

Some question has always existed regarding whether an amendment to the Durham-Humphrey Amendment would be necessary to establish a third class of drugs on a national basis or if the FDA has the statutory authority to do so by regulation. The FDAMA included provisions for the national uniformity of nonprescription drugs, thus making it unlikely that a state would have the authority to establish a third class of drugs. Regardless, the FDA traditionally had opposed pharmacists on this issue. In 1974, FDA Commissioner A. M. Schmidt issued a policy statement that was later summarized in a 1984 petition response:

It would be inappropriate to restrict the sale of OTC drugs to pharmacies based on anything less than proof that a significant safety issue was involved. Restricting certain OTC drugs to pharmacies only could decrease the number of outlets where the consumer could purchase OTC drug products, limit competition, and raise some OTC drug prices, with no attendant public health benefit. Recognizing at all times the important contribution of pharmacists to the health care system, the FDA has continued to conclude that limiting certain drugs to sale-by-pharmacists only is unnecessary because a public need for such a limitation has not been demonstrated. (Poole, 1991)

The FDA, however, first signaled a likely change in its position in 2007 by announcing a public meeting to obtain comments regarding the creation of BTC class of drugs (72 Fed. Reg. 56769, Oct. 4, 2007). The hearing was held in November 2007 where pharmacy organizations spoke in favor of a BTC category of drugs, while some other organizations, most notably the American Medical Association, opposed the category. Subsequently, the General Accounting Office issued a report on the BTC issue in 2009, comparing the U.S. regulation of nonprescription drugs to that of four European Union countries (http://www.gao.gov/new.items/d09245.pdf). The report describes pro and con arguments and identifies important policy considerations but concludes: “The classification of drugs in other countries and the existence of other classes provide little insight into the likely effect of a BTC drug class on nonprescription drug availability in the United States.”

In February 2012, without mentioning the BTC discussions, the FDA announced that it is considering the creation of a class of nonprescription drugs that could be made available to patients “under conditions for safe use” (77 Fed. Reg. 12059, Feb. 28, 2012). The FDA noted that conditions for safe use would be specific to the drug product and could include various means, such as requiring pharmacist intervention, or using innovative technologies, like diagnostics, in the pharmacy or other settings. The agency held hearings in March 2012, where predictably, pharmacy and insurance organizations supported the concept and medical organizations opposed it (http://www.fda.gov/drugs/newsevents/ucm289290.htm).

PROFESSIONAL PRACTICE CONSIDERATIONS

The Durham-Humphrey Amendment directly or indirectly raises several issues of importance to professional pharmacy practice, as discussed here. State laws address many of these issues with much more specificity.

Prescription Refill Authorization

As stated in the law, a prescription may not be refilled unless there is specific authorization, either orally or in writing, from the prescriber. A physician’s employee or agent, including office nurse, cannot legally authorize a refill of a prescription unless state law has specifically granted the person this authority, nor can a prescriber legally delegate authority to an employee or agent not authorized by state law. The physician’s employee or agent may, however (state law permitting), simply transmit or communicate the refill authorization (or new prescription) from the prescriber. In practice, this means that if a pharmacist calls a prescriber’s office for refill authorization and speaks to an employee of the prescriber who immediately grants authorization, the pharmacist should question who is really authorizing the refill.

Prescriptive Authority

The Durham-Humphrey Amendment provides that prescription drugs may be prescribed by a practitioner “licensed by law to administer such drug.” Healthcare practitioners are not licensed by federal law, however, but by state law. Thus, each state determines if a practitioner in that state has the authority to prescribe. Some states have granted various degrees of prescriptive authority not only to allopathic physicians (MDs), osteopathic physicians (DOs), dentists, podiatrists, and veterinarians but also to nurse practitioners, physician’s assistants, optometrists, naturopathic doctors, and pharmacists. Pharmacists must know which categories of practitioners can prescribe in their state and be able to distinguish who falls into those categories. For example, pharmacists must understand the legal difference in their state between registered nurses and advanced practice registered nurses (APRNs). Depending on state laws, APRNs may have either independent or collaborative prescriptive authority.

In addition to ascertaining if a healthcare practitioner has prescriptive authority, a pharmacist must consider the practitioner’s scope of prescriptive authority. State law (called state practice acts) defines a practitioner’s scope of practice to diagnose and treat, which, in turn, determines the practitioner’s scope of prescriptive authority. State laws grant physicians broad treatment authority and thus the authority to prescribe almost any drug. This applies even to specialists such as psychiatrists and radiologists who, because they are physicians, can legally treat conditions outside their specialty. Other prescribers such as dentists, veterinarians, and podiatrists have much narrower treatment and prescriptive authority. For example, a dentist who treats a patient for acne has very likely exceeded the scope of practice for dentistry. If the dentist then prescribed tetracycline for the treatment of the acne, the prescription would be invalid, and the pharmacist who knowingly dispensed the drug might then be in violation of the state practice act.

In reality, because a pharmacist is not usually privy to the diagnosis, determining if a practitioner is prescribing within the scope of his or her authority might be difficult to impossible in some cases. Thus, a pharmacist would not likely be held legally accountable for dispensing a prescription from a prescriber who has exceeded his or her prescriptive authority, if the pharmacist dispensed the prescription in good faith after making an attempt to ascertain the condition for which the drug was prescribed. It is important that pharmacists contact the prescriber when aware that a prescription might be outside the prescriber’s scope of practice, if merely to determine if the correct drug has been prescribed.

In states that authorize nurse practitioners, physician’s assistants, or optometrists to prescribe medication, there are generally certain limits on the prescriptive authority of these professionals. The pharmacist must be aware of these limits.

Emergency Contraception (Plan B)

Before its ultimate evolution to an unrestricted OTC drug, the emergency contraception (EC) drug, Plan B, was an example of pharmacist independent prescriptive authority in some states and a third class of drugs in all states. The original Plan B, marketed by Barr Laboratories (now Teva), contains two 0.75 mg tablets of levonorgestrel to be taken 12 hours apart. EC is a method of preventing pregnancy after contraception fails or after unprotected sex and is not intended for routine use. The FDA approved Plan B as a prescription-only medication in 1999, at which point some states passed laws authorizing pharmacists to independently prescribe the drug provided they met certain requirements. Since that time Plan B has enjoyed a colorful, contentious, confusing, and tortuous history.

In 2001, several medical, public health, and reproductive organizations filed a Citizen Petition with the FDA asking the agency to switch Plan B to OTC status without age restrictions. Later, in 2003, Barr submitted an SNDA to the FDA requesting a switch of the drug to OTC status without age restrictions. Despite approval for the switch by two FDA advisory committees for all age groups, the FDA rejected the SNDA application. The FDA’s decision raised public outcry by many over whether politics outweighed science. The FDA, however, suggested that Barr could reapply by presenting evidence that girls under the age of 16 could use the drug over the counter safely. Barr then submitted another SNDA in 2004. The FDA then replied that it could not reach a decision because of three issues: (1) Whether the same active ingredient could be marketed both Rx and OTC based solely on the age of the user (rather than for different indications), (2) whether and how age-based distinctions could be enforced, and (3) whether the Rx and OTC versions may be marketed in a single package.

After considerable public controversy and FDA deliberations with Barr, the agency announced, in 2006, that it had approved the amended version of Barr’s SNDA application. The FDA acknowledged that Barr had submitted adequate information to demonstrate that Plan B is safe and effective for use under the labeling conditions established. Those conditions included that Plan B be sold only from BTC in pharmacies staffed by a licensed pharmacist, and that the purchaser must present personal identification showing proof of age (18 or older).

The FDA set the OTC age at 18 or older despite the fact that FDA staff agreed that Barr’s SNDA established that the drug was safe and effective for 17-year-olds. Meanwhile, after a five-year delay, the FDA denied the Citizen Petition that had been filed in 2001 seeking that the drug be available OTC for all ages. This denial prompted a lawsuit by the petitioners (Tummino v. Torti, 603 F. Supp. 2d 519 (E.D.N.Y 2009)). Finding for the plaintiffs, the court found that the FDA’s decision had been influenced by political and ideological considerations and it had acted in bad faith and abused its discretion in denying the petition. The court ordered the FDA to make the drug available to 17-year-olds and also vacated the FDA’s denial of the Citizen Petition, ordering the agency to reconsider the petition without political intrusion.

Subsequently, in February 2011, Teva Women’s Health Inc. submitted an SNDA seeking to make Plan B One-Step (single dose 1.5 mg levonorgestrel approved in 2009) available OTC for all girls of reproductive age. In December 2011, the commissioner of the FDA approved the SNDA; however, the secretary of the Department of Health and Human Services (DHHS) overruled the commissioner’s decision (http://www.hhs.gov/news/press/2011pres/12/20111207a.html). The commissioner agreed with FDA experts that well-supported, science-based evidence existed that established Plan B is safe and effective for use in all females of child-bearing potential. Nonetheless, the secretary felt there were not enough data presented considering the significant cognitive and behavioral differences among girls of different ages. At the same time, the FDA denied the Citizen Petition for the original Plan B (two dose) that had been remanded by the federal district court. Teva then submitted an amended SNDA to make Plan B One-Step available OTC to women 15 years of age and older.

The Secretary’s and FDA’s decisions prompted the individuals and organizations that had filed the Citizen Petition to once again sue the FDA in the same federal district court (Tummino v. Hamburg, 936 F. Supp. 2d 162 (E.D.N.Y. 2013) to require the FDA to make EC available without age or point of sale restrictions. On April 5, 2013, the court issued its decision, again finding for the plaintiffs. The judge commented that the Secretary’s directive to the FDA to reject Plan B “forced the agency to ride roughshod over the policies and practices that it has consistently applied in considering applications for switches in drug status to over-the-counter availability.” The court concluded that the Secretary’s decision with respect to Plan B One-Step and the FDA’s decision with respect to the Citizen Petition (original Plan B) were arbitrary, capricious, and unreasonable. The court reversed the FDA’s decision and remanded the Citizen Petition to the FDA with orders to approve it and make EC products available without a prescription and without point-of-sale or age restrictions within 30 days. The court ordered no point-of-sale restrictions after examining evidence that the current BTC restriction obstructed many women from being able to obtain the product.

On April 30, 2013, the FDA approved Teva’s amended SNDA that Plan B One-Step be available for sale to those under 15 years of age “‘proof of age required’ not for sale where age cannot be verified” (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm350230.htm). The product would be available only in retail outlets with an onsite pharmacy, but inventoried in an aisle and available during the retailer’s normal operating hours whether the pharmacy is open or not. The announcement noted that the FDA’s decision was independent of the litigation and not intended to address the court’s decision. Then, one day later the Department of Justice announced it would appeal the district court’s decision and seek to delay the decision.

On appeal, a three-judge panel of the Second Circuit Court of Appeals on June 5, 2013, refused to delay the district court’s order for two-dose (0.75 mg) EC products, thus requiring the FDA to make them available immediately without age restriction (Tummino v. Hamburg, 2013 WL 2435370 (2d Cir. 2013). The panel did stay the district court’s order for Plan B One-Step pending an expedited appeal. Ultimately, however, the FDA decided not to appeal, and on June 20, 2013, it issued an announcement that it was complying with the district court decision and had approved an amended SNDA from Teva for Plan B One-Step without age or point-of-sale restriction (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm358082.htm). Teva received three years of exclusivity on Plan B One-Step.

Conscientious Objection

Prescriptions for EC drugs, abortifacient drugs, and oral contraceptives have raised a very contentious issue: whether a pharmacist has a right to refuse to dispense prescriptions to which the pharmacist has moral or religious opposition. This issue has been labeled as one of conscientious objection and has been the subject of discussion among the media, Congress, state legislators, and professional organizations. It has resulted in legislation and/or board of pharmacy regulations in many states as well as professional organization guidelines; however, no consensus has really emerged. Some states have passed laws or regulations requiring pharmacists to dispense prescriptions regardless of their moral beliefs. Some states have enacted laws establishing “conscience clauses,” such that pharmacists may refuse to dispense prescriptions that violate their conscience.

Professional organizations and state boards of pharmacy generally have taken a compromise position, attempting to respect the pharmacist’s beliefs, while ensuring that patients receive the medications to which they have a legal right. Under this philosophy, a pharmacist should notify the employer in advance and in writing of his or her objections to dispense particular drugs. The employer, provided it can do so without undue hardship, should develop procedures such that the pharmacist is not placed in a situation where he or she would be required to dispense the objectionable prescriptions, and yet that still allow the patient to receive the drug with minimal inconvenience. For example, another pharmacist on duty could dispense the medication, or the patient could be referred to a nearby pharmacy.

In no situation should a pharmacist obstruct a patient’s legal right to receive a lawful medication. In the case of Noesen v. State, Dept. of Regulation and Licensing, 754 N.W.2d 849 (Wis. 2008), a Wisconsin pharmacist informed the employer of his conscientious objection to dispense birth control prescriptions, but did not tell the employer that he would not transfer refills upon the request of another pharmacy. When a patient attempted to refill her birth control prescription, the pharmacist told her he could not dispense it and that there was no other pharmacist on duty. The patient then went to another pharmacy but the pharmacist refused to transfer the prescription to the pharmacy, resulting in the patient missing a dose. The State Board of Pharmacy found the pharmacist guilty of unprofessional conduct because his failure to transfer the prescription constituted a danger to the health and safety of the patient and substantially departed from the standard of care of a pharmacist. The Board ordered that the pharmacist inform all future employers in writing that he would not dispense birth control prescriptions and outline the steps he would take to ensure that a patient has access to the medication. The pharmacist sued the Board, but the Wisconsin court of appeals upheld the Board’s decision.

However, in a situation in Idaho, a prescriber phoned in a prescription to a pharmacist for Methergine, a drug generally used for the prevention and control of postpartum hemorrhage. The pharmacist asked if the drug was for postabortion care, and the prescriber replied that she could not disclose that information because of confidentiality. The pharmacist said she would not dispense the prescription and hung up when the prescriber requested a referral to another pharmacy. A complaint was filed with the board of pharmacy that found no violation of Idaho pharmacy laws or regulations under Idaho’s conscience clause law (NABP Newsletter, 2011).

In a state of Washington case, the issue centered upon whether board of pharmacy regulations requiring pharmacies to dispense lawfully prescribed drugs except under certain circumstances violated the plaintiff pharmacists’ constitutional rights (Stormans, Inc. v. Selecky, 844 F. Supp. 2d 1172 (W.D. Wash. Feb. 22, 2012)). After four years of litigation, a federal district court determined that the Washington regulation violated the plaintiff pharmacy’s and pharmacists’ First Amendment rights to the free exercise of religion as well as their rights to equal protection under the Fourteenth Amendment. Similarly, an Illinois state appellate court held that the state conscience clause prohibits the enforcement of a governor order requiring pharmacists to dispense Plan B when the pharmacists have a religious objection (Morr-Fitz, Inc. v. Quinn, 976 N.E.2d 1160 (IL. App. 2012).

Collaborative Practice Agreements

Pharmacists do not have general independent prescriptive authority in any state. However, most states have enacted legislation allowing pharmacists to initiate or adjust drug therapies in collaboration with a physician. This collaborative arrangement requires a written contractual agreement in the form of protocols and procedures. The extent to which a pharmacist may engage in drug therapy management often depends upon state law, the collaborative agreement, and the practice setting. Authority granted to the pharmacist can range from following a restrictive drug formulary to having complete discretion to select any drug the pharmacist deems best.

Authority to Dispense Prescription Drugs

The FDCA does not specify who may or may not dispense prescription drugs; this again is the jurisdiction of the states. Pharmacists licensed to practice under state law may dispense prescription drugs, of course, as may any other practitioner who is authorized to do so under a state’s laws, including physicians.

Physician dispensing increased significantly in the 1980s as physicians sought ways to supplement their incomes, lowered as the result of both managed care and governmental cost containment efforts. Pharmacists strongly oppose physician dispensing on economic and ethical grounds and were particularly irked that physicians in many states did not conform to the same dispensing standards required of pharmacists. Some physicians, for example, poured tablets and capsules in sacks and either wrote the directions on the sack or merely told the patient the directions. Looking for ways to curb the practice of physician dispensing, or at least to hold physicians to dispensing standards, pharmacists asked the FDA to step in and apply the Durham-Humphrey Amendment’s standards to physicians. On the basis of its interpretation of congressional intent, however, the FDA took the position that the labeling requirements of the law apply only to pharmacists, not physicians.

The wisdom of the FDA’s interpretation aside, many states enacted legislation in the 1980s mandating that dispensing physicians meet the same or similar dispensing requirements as pharmacists. One state pharmacy board went a step further, and proposed regulations placing greater dispensing restrictions on physicians than pharmacists. This prompted the Federal Trade Commission (FTC) to threaten legal action against the pharmacy board. The FTC viewed the proposed regulations as anticompetitive in violation of the antitrust laws, because one group of competing professionals was unduly restricting another group for economic advantage. The board subsequently amended its regulations to impose the same restrictions on physicians as pharmacists.

Federal law does place some restrictions on physician dispensing through the Medicare/Medicaid fraud and abuse statutes. Federal law also prohibits physicians from referring Medicare and Medicaid patients to pharmacies that they own.

  TAKE-AWAY POINTS