Whereas adulteration deals with a drug's strength, purity, and quality, misbranding focuses on representations made by the manufacturer on the label or labeling. The FDA must approve, as part of the premarket approval process, the exact wording of a drug's label and labeling. The agency often has used the misbranding provisions of the act to prevent manufacturers from marketing products in violation of the law. Most of the misbranding provisions are also applicable to pharmacies.
That a drug's labeling shall not be false or misleading under § 502(a) is fairly self-explanatory. The FDAMA added the provision regarding healthcare economic information (HCEI). Before the FDAMA, the subject of drug manufacturers supplying pharmacoeconomic information to healthcare decision makers had been controversial. Because the FDA does not approve pharmacoeconomic data as part of the drug's labeling, the question was whether a manufacturer that provided this information would be guilty of misbranding. Now, under the law, HCEI provided to formulary decision makers is permissible as long as the information is accurate and reliable.
Before the FDAMA, § 502 contained a provision stating that the labeling of any drug containing a substance found to be habit-forming must contain a warning to this effect. The FDAMA deleted this provision, thus making whether to include the warning discretionary with the manufacturer. Manufacturers are still required to adequately describe the habit-forming characteristics of the drug in the "Drug Abuse and Dependence" section of the package insert.
Section 502(e) obviously contains a significant amount of information. The important points to note from this section are that the law requires the listing of any active ingredient for both prescription and nonprescription drugs and the quantity of each active ingredient (unless the nonprescription drug is not for human use). Section 502(e) also requires that in most situations, the labeling contains a list of the established name of each inactive ingredient in alphabetical order for both prescription drugs and nonprescription drugs (unless the nonprescription drug is also a cosmetic or not for human use). Before the FDAMA, the listing of inactive ingredients was not required.
Section 502(f) states that the labeling must contain "adequate directions for use" and "adequate warnings against use" by children and others for whom the use may be dangerous. "Adequate directions for use" in the regulations means "directions under which the layperson can use a drug safely and for the purposes for which it is intended" (21 C.F.R. § 201.5). The regulation continues by stating that the directions for use may be deemed inadequate unless the labeling contains statements of all conditions, purposes, or uses for which the drug is intended and for which the drug is commonly used. As the court held in Alberty Food Products Co. v. United States, 185 F.2d 321 (9th Cir. 1950), merely stating the proper way to take a drug is not adequate. The labeling must be complete enough to inform the consumer that the drug should be used for the consumer's particular ailment.
In addition to the statements of all conditions, purposes, or uses, "adequate" labeling of a drug must include:
The quantity or dosage for each intended use and for persons of different ages and physical conditions
The frequency of administration or application
The duration of administration or application
The time of administration or application (in relation to meals, onset of symptoms, or other factors)
The route or method of administration or application
The preparation necessary for use (e.g., shaking, dilution)
Some drugs cannot be labeled adequately to protect the consumer and meet the "adequate directions for use" requirement of § 502(f). The FDA classifies these drugs as prescription drugs, which makes them exempt from the requirements of § 502(f). Prescription drugs must contain "adequate information for use" rather than adequate directions for use (21 C.F.R. § 201.100(c)(1)). Thus, the labeling must include such information as:
The drug's indications
Side effects
Dosages
Routes, methods, frequency, and duration of administration
Contraindications
Other warnings and precautions that enable a practitioner to administer, prescribe, or dispense the drug safely
Prescription drug labeling is directed to the practitioner, not the patient. Nonetheless, the FDA has increasingly been concerned that patients receive understandable information about their prescription drug medication, as evidenced by the Medication Guide program (discussed elsewhere in the text).
Section 502(i)(2) of the FDCA provides that it is misbranding if a drug is an imitation of another drug. The FDA has invoked this section against drugs sold as imitations of controlled substances. In United States v. Articles of Drug (Midwest Pharmaceuticals), 825 F.2d 1238 (8th Cir. 1987), for example, Midwest distributed and promoted a drug containing caffeine, ephedrine, and phenylpropanolamine. Advertisements for the drug contained pictures of capsules and tablets that looked exactly like various well-known amphetamine-type controlled substances. The advertisements contained no information about the drug's ingredients, but they described the drug using various street names, such as 20/20, white mole, and mini-white. Finding for the FDA, the court held that a product is an imitation if it is:
Identical in shape, size, and color
Similar or virtually identical in gross appearance
Similar in effect to controlled substances
Section 502(i)(3) states that a drug is misbranded if it is sold under the name of another drug. Note the similarity between the definition of counterfeit drug (§ 201(g)(2)) and sections 502(i)(2) and (3). A pharmacist who dispenses a generic drug and labels it with the trade name drug might be found to have violated § 301(i)(3) as well as § 502(i)(3). A pharmacist who dispenses a placebo labeled as a certain drug might likewise have violated those two sections as well as § 502(i)(2).
Before the FDAMA, § 502 had required batch certifications for insulin and antibiotics. Early insulin preparation techniques were often crude, resulting in problems of product purity and potency. Similarly, early antibiotic preparations relied on fermentation, extraction, and purification techniques that at the time were inconsistent, resulting in variability of stability and potency. Therefore, Congress gave the FDA the authority to require that batches of insulin and antibiotics be certified by the agency before marketing. Because antibiotics and insulin products today no longer exhibit the problems they presented in earlier years, the FDA no longer has the statutory authority to require batch certification for either insulin or antibiotics.