42
Federal Pharmacy Law
42-1. Study Guide Checklist
The following topics may guide your study of this subject area:
■ Legal responsibilities of the pharmacist and other pharmacy personnel
■ Requirements for acquiring and distributing pharmaceutical products
■ Legal requirements that must be followed in issuing and dispensing a prescription or drug order
■ Conditions for making an offer to counsel and counseling patients, including proper documentation
■ Requirements for distributing and dispensing nonprescription pharmaceutical products, including controlled substances
■ Proper procedures for recordkeeping related to pharmacy practice, pharmaceutical products, and patients, including requirements for protecting patient confidentiality
■ Qualifications, application procedures, required examinations, and internship requirements for licensure, registration, or certification of individuals engaged in the storage, distribution, and dispensing of pharmaceutical prescription and nonprescription products
■ Requirements and application procedures for the registration, licensure, and certification for a practice setting or business entity
■ Operational requirements for a registered, licensed, certified, or permitted practice setting
■ Regulatory structure and terms found in the laws and rules that regulate or affect the manufacture, storage, distribution, and dispensing of pharmaceutical products, both prescription, nonprescription, and controlled substances
■ The authority, responsibilities, and operation of the agencies that enforce the laws and rules that regulate or affect the manufacture, storage, distribution, and dispensing of pharmaceutical products (Multistate Pharmacy Jurisprudence Examination Blueprint Competency Statements, National Association of Boards of Pharmacy, www.nabp.net/programs/examination/mpje/mpje-blueprint, accessed March 31, 2014)
42-2. Federal Regulation of Drug Development, Production, and Marketing
Overview of the Federal Food, Drug, and Cosmetic Act and Other Significant Legislation
The text of the federal Food, Drug, and Cosmetic Act (FDCA) is under title 21 of the U.S. Code and can be found at the U.S. Food and Drug Administration (FDA) Web page (www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/default.htm).
Pure Food and Drug Act of 1906
This law prohibited misbranded and adulterated foods and drugs from being distributed through interstate commerce. The misbranding provision prevented false claims about the drug’s strength, quality, and purity. It did not protect consumers against false claims about the drug’s efficacy. Congress amended the law in 1912 to prohibit false efficacy claims, but the law was difficult to enforce.
Food, Drug, and Cosmetic Act of 1938
This law forms the nucleus of today’s FDCA, although it has been amended many times by the laws that are subsequently discussed in this section. It required that any new drug could not be marketed until the drug had been proved safe when used according to directions on the label. In addition, the law expanded the definition of adulterated and misbranded, and required drug labels to include adequate directions for use and warnings about habit-forming drugs contained in the product. The law applied to food, drugs, cosmetics, and medical devices. Drugs marketed prior to 1938 were grandfathered in and exempted from the requirement that they be proved safe before being marketed.
Durham-Humphrey Amendment of 1951
This amendment to the FDCA is also known as the Prescription Drug Amendment, and it established two classes of drugs: prescription and over-the-counter (OTC). A drug classified as a prescription drug did not have to include “adequate directions for use” as long as the labeling contained the legend: “Caution: Federal law prohibits dispensing without a prescription.” The pharmacist dispensing the drug pursuant to a prescription met the “adequate directions for use” requirement by including the directions from the prescriber on the label. This amendment also authorized oral prescriptions and refills on prescription drugs.
Food Additives Amendment of 1958
This amendment was passed in response to concerns that food additives could cause cancer. It required that components added to food must receive premarket approval for safety. The Delaney Clause, also known as the anticancer clause, prohibits approval of any food additive that might cause cancer.
Color Additives Amendment of 1960
This amendment requires manufacturers to establish the safety of color additives in foods, drugs, and cosmetics. This amendment also contains an anticancer clause that prohibits the approval of any color additive that might cause cancer.
Kefauver-Harris Amendment of 1962
This amendment is also known as the Drug Efficacy Amendment. It requires new drugs to be proved effective as well as safe. The requirement was retroactive to apply to all drugs marketed between 1938 and 1962. The retroactive provision was a huge burden on the FDA, and the Drug Efficacy Study Implementation was not completed until the 1970s. The law also transferred jurisdiction of prescription drug advertising from the Federal Trade Commission (FTC) to the FDA and required that all advertising carry labeling on possible side effects (jurisdiction of OTC drug advertising remains with the FTC). The amendment established the requirement for good manufacturing practices (GMPs), registration with the FDA by drug manufacturers, recordkeeping requirements, and regular inspections. It also requires animal testing before testing on humans, informed consent of research subjects before participating in a clinical trial, and reporting of adverse drug events.
Medical Device Amendment Act of 1976
This amendment was designed to protect consumers against potentially dangerous or useless medical devices. It provides for the classification of medical devices according to their function and requires premarket approval that parallels premarket approval for new drugs. It established (1) performance standards and conformance with GMP regulations and (2) recordkeeping and reporting requirements.
Federal Anti-Tampering Act of 1982
This law made it a federal crime to tamper with OTC products and required tamper-resistant packaging. This law is discussed in more detail later in Chapter 42.
Orphan Drug Act of 1983
This law (21 USC 360bb) was passed to create tax and exclusive licensing incentives for manufacturers to develop and market drugs or biological products for the treatment of rare diseases or conditions that affect fewer than 200,000 Americans.
Drug Price Competition and Patent-Term Restoration Act of 1984
Also known as the Hatch-Waxman Amendment, this law was intended to make generic drugs more readily available while at the same time providing incentives to drug manufacturers to develop new drugs. It achieved both purposes by streamlining the generic drug approval process and by giving patent extensions to new, innovative drugs.
Prescription Drug Marketing Act of 1987
This law addressed the problem of drug diversion by placing more stringent controls on the distribution of prescription drug products and samples, as follows:
■ Limiting the distribution of drugs beyond conventional retail sale
■ Banning the diversion of drugs from legitimate channels of distribution
■ Specifying precise storage, handling, and recordkeeping requirements for prescription drug samples
■ Banning the sale, trade, or purchase of prescription drug samples and making it illegal for a pharmacy to possess prescription drug samples
■ Prohibiting, with some exceptions, hospitals and other health care entities from reselling their pharmaceuticals to other businesses
■ Requiring state licensing of prescription drug wholesalers under federal guidelines
■ Banning reimportation of prescription drugs produced in the United States
Safe Medical Devices Act of 1990
This law amended the Medical Device Amendment Act of 1976 by giving the FDA additional authority over medical devices. It expedited the premarket device approval process and added postmarketing approval requirements. It required health care facilities that use medical devices to report problems to the FDA, and it gave the FDA new authority over recalls for medical devices.
Nutrition Labeling and Education Act of 1990
This law mandated nutrition labeling on food products and authorized health claims on product labeling as long as the claims conformed to FDA regulations. It standardized the use of labeling terms with health implications, such as “light” or “low fat.”
Generic Drug Enforcement Act of 1992
This law was motivated by a scandal involving bribery of FDA staff to facilitate the approval process for generic drug products. This act makes false statements, bribes, failure to disclose material-related facts, and other related offenses felonies.
Prescription Drug User Fee Act of 1992
This law requires manufacturers to pay fees for applications and supplements when the FDA must review clinical studies. The fees were intended to provide revenues to hire additional reviewers to speed up the new drug application (NDA) reviews.
Dietary Supplement Health and Education Act of 1994
This law created a special regulatory structure for dietary supplements that is more stringent than that for foods but less stringent than that for drugs. Manufacturers must follow GMPs, but no premarket approval by the FDA is required. The law defines dietary supplements and permits manufacturers to make certain structure or function claims that do not need preapproval from the FDA. For example, claiming that a dietary supplement “maintains a healthy circulatory system” is acceptable without prior FDA approval. However, claims that indicate the dietary supplement is intended to “diagnose, treat, cure, or prevent any disease” require FDA approval because only a drug can make those claims. The FDA aggressively polices manufacturers who make unapproved health claims that are false or misleading (www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm2006881.htm, accessed April 2, 2014).
FDA Modernization Act of 1997
This law made significant changes that affected every aspect of the FDA’s activities. The highlights of this law include the following:
■ Streamlined regulatory procedures to ensure the expedited availability of safe and effective drugs and devices
■ Increased public accountability of the FDA
■ Required a compliance plan developed in consultation with industry representatives, scientific experts, health care professionals, and consumers
■ Created a fast-track approval process for drugs intended for serious or life-threatening diseases
■ Replaced the legend “Caution: Federal law prohibits dispensing without a prescription” with the legend “Rx only”
■ Clarified conditions under which pharmacists may perform extemporaneous compounding of prescriptions
■ Exempted pharmacists from the strict regulatory federal GMP standards and requirements for NDAs
■ Created a data bank for information on clinical trials
■ Authorized scientific panels to review clinical investigations
■ Expanded the rights of manufacturers to disseminate unlabeled use information and required specification that such use is not FDA approved
■ Encouraged manufacturers to conduct research for new uses of approved drugs and to submit supplemental NDAs (SNDAs) for these uses
■ Eliminated the manufacturers’ requirement that certain substances must carry the label: “Warning—May be habit forming”
■ Expanded the FDA’s authority over OTC drugs by establishing ingredient labeling requirements for inactive ingredients and preempted states from establishing labeling requirements for OTC drugs and cosmetics when federal requirements exist
■ Mandated priority review for breakthrough technologies for medical devices
■ Allowed the FDA to contract with outside scientific experts for review of medical device applications
Best Pharmaceuticals for Children Act of 2002
This law provided mechanisms for studying on- and off-patent drugs in children. The act extended the provision from the 1997 Food and Drug Administration Modernization Act that offered an additional 6 months of patent exclusivity for on-patent drugs being tested for pediatric use.
Medicare Prescription Drug Improvement and Modernization Act of 2003
This law added prescription drug and preventive health care benefits to the Medicare program. The law also provides extra help for persons with low incomes. The prescription drug benefits became available in 2006. All people with Medicare are able to enroll in plans that cover prescription drugs, although plans may vary. The “donut hole” limited benefits for many Medicare beneficiaries. Seniors had to pay 100% of the drug costs above $2,250 until they reached $3,600 in out-of-pocket spending. At that point, Medicare would pay about 95% of drug costs. The Affordable Care Act has minimized the impact of the “donut hole.” In 2013, covered participants received a 50% discount when buying Part D–covered brand-name prescription drugs. By 2020, the donut hole will be phased out completely.
Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006
This law established two parallel, mandatory reporting systems for serious adverse events: one for OTC drugs and the other for dietary supplements.
FDA Amendments Act of 2007
The act greatly increased the responsibilities and authority of the FDA, as well as reauthorized several critical FDA programs. It gave the FDA additional authority and requirements with regard to premarketing and postmarketing safety, including the authority to require postmarketing studies and clinical trials, safety labeling changes, and Risk Evaluation and Mitigation Strategies (REMS). It required the “side effects” statement that notifies patients to report adverse drug events (this statement is discussed in more detail later in Chapter 42). It also made changes in the rules regarding direct-to-consumer advertising by allowing the FDA to pre-review direct-to-consumer ads. Because censorship is unconstitutional, the law allows the FDA only to make recommendations about the ad. The FDA may require a change in the ad only if the change addresses serious risks associated with the drug’s use.
Family Smoking Prevention and Tobacco Control Act of 2009
This law, commonly referred to as the Tobacco Control Act, gives the FDA authority to regulate the manufacture, distribution, and marketing of tobacco products to protect public health.
FDA Food Safety Modernization Act of 2011
The act is the most sweeping reform of U.S. food safety laws in more than 70 years. It aims to ensure that the U.S. food supply is safe by shifting the focus from responding to contamination to preventing it.
Drug Quality and Security Act of 2013 (DQSA)
The DQSA creates a voluntary registration process whereby facilities that compound drugs outside the traditional practice of pharmacy may register with the FDA as an outsourcing facility that is exempt from FDA requirements, such as the FDCA’s adequate directions for use requirements, the new drug provisions, and the drug tracing provisions. Registered facilities must pay fees, be subject to inspections, and comply with labeling requirements. This law was passed in response to the events involving numerous deaths from meningitis and compounded drugs in 2012.
Drug Supply Chain Security Act
This law, title II of the DQSA, establishes requirements for tracing prescription drug products through the pharmaceutical supply distribution chain. The purpose of this law is to protect consumers from exposure to drugs that may be counterfeit, stolen, contaminated, or otherwise harmful.
Definitions
Drug
The definition of a drug is divided into four parts (21 USC 321(g)).
Part A
Article recognized in the official United States Pharmacopoeia/National Formulary (USP/NF, U.S. Pharmacopeial Convention, www.usp.org), or the official Homeopathic Pharmacopoeia of the United States (HPUS, Homeopathic Pharmacopoeia Convention of the United States, www.hpus.com), or any supplements of these references
Part B
Article intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans or other animals
Part C
Article (other than food) intended to affect the structure or any function of the body of humans or other animals
Part D
Article intended for use as a component of any articles specified in the above but not including devices or their components, parts, or accessories
Food
The term food means articles used for food or drink for humans or other animals, chewing gum, and articles used for components of any such article (21 USC 321(f)). Special categories of food have been recognized to avoid regulating these foods as drugs.
Special dietary foods supply a special dietary need that exists by reason of a physical, physiological, pathological, or other condition, including conditions of disease, convalescence, pregnancy, lactation, infancy, allergic hypersensitivity to food, underweight, overweight, or the need to control the intake of sodium.
Medical foods are foods that are formulated to be consumed or administered enterally under the supervision of a physician and that are intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation (21 USC 360ee).
Cosmetic
The term cosmetic means articles intended to be rubbed, poured, sprinkled, or sprayed on; introduced into; or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance. The term also includes articles intended for use as a component of any such articles. The term does not include soap (21 USC 321(i)). The FDA does not have premarket approval for cosmetics, and manufacturers are not required to register with the FDA or to follow GMPs. Cosmetics must list the ingredients on the label in descending order of predominance. Warnings regarding the following are also required: (1) inhaling contents under pressure may be harmful or fatal; (2) the safety of the product has not been determined; and (3) the presence of coal tar in hair dye. The FDA may remove a cosmetic from the market if it is misbranded or adulterated or is a health hazard. Cosmetics must conform to the Poison Prevention Packaging Act (PPPA), or they are considered misbranded. A cosmetic may be considered a drug if it claims to treat a condition. For example, a shampoo that treats dandruff is considered to be both a cosmetic and a drug.
Dietary supplement
A dietary supplement is a product that is intended for ingestion, intended to supplement the diet, and contains any one or more of the following: a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by humans to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of the above (21 USC 321(ff)). The FDA regulates dietary supplements less stringently than drugs, but claims by the manufacturer that the dietary supplement treats a disease (rather than maintaining health) may bring the product under FDA regulation as if it were a drug.
Medical device
The term device means an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory that is (1) recognized in the USP/NF or any supplement to it; (2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in humans or other animals; or (3) intended to affect the structure or any function of the body of humans or other animals, and that does not achieve its primary intended purposes through chemical action within or on the body of humans or other animals and that is not dependent upon being metabolized for the achievement of its primary intended purposes (21 USC 321(h)). Questions arise when a drug is used with a medical device—is it a drug or a medical device? For example, an intrauterine device that delivers hormones would be treated as a drug.
Registration
Each year, every person who owns or operates any establishment in any state engaged in the manufacture, preparation, propagation, compounding, or processing of a drug or drugs must register with the Secretary of Health and Human Services (HHS) his or her name, places of business, and all such establishments. Registration must occur before engaging in any of the listed activities, and a separate registration must be made for each establishment that engages in the activities. Pharmacists who compound are exempt from registering as manufacturers if they “do not manufacture, prepare, propagate, compound, or process drugs or devices for sale other than in the regular course of their business of dispensing or selling drugs or devices at retail.” Compounding “in the regular course of business” means to compound a drug pursuant to a prescription or in reasonable anticipation of receiving a prescription (anticipatory compounding). If a pharmacist compounds a drug product outside the regular course of business, the FDA will deem that pharmacist a manufacturer and all the requirements that apply to manufacturers will apply to that pharmacist, including registration, GMPs, labeling and packaging requirements, NDA requirements, and so on. Under the DQSA, facilities that compound outside the regular course of business may voluntarily register with the FDA as an outsourcing facility to avoid these FDCA requirements.
Development and Approval of New Drugs
Legend drugs versus over-the-counter drugs
Legend drugs are prescription-only drugs, and federal law requires the legend “Rx only” on the labeling of these products. The FDA classifies drugs as prescription drugs when the supervision of a physician is required for its safe use. OTC drugs do not require either the supervision of a physician for their safe use or a prescription. Federal law requires that these drugs be labeled with adequate directions for use that inform the consumer of what type of ailments the drug is designed to help and how to safely use the product. “Behind-the-counter” drugs are not officially recognized as a third classification, but, in reality, these are drugs that may be sold only by pharmacists.
Investigational new drug
Before a new drug can be marketed, the manufacturer or other sponsor must complete an extensive testing process to ensure that the new drug is safe and effective for its proposed use. The first step in this process is to submit an investigational NDA to the FDA. The application must include any animal studies that reflect on the safety of the drug and the proposed clinical protocols to be used in testing the drug on humans. Within 30 days, the FDA determines whether the investigational new drug is suitable for testing.
Phase 1
Phase 1 clinical trials are designed to test the safety of the new drug and to assess its toxicological, pharmacokinetic, and pharmacological properties. In a Phase 1 trial, a small group of healthy individuals is given the drug.
Phase 2
Phase 2 clinical trials are designed to test the effectiveness of the drug. Investigators give the drug to a larger group of human subjects (100 or more) who have the disease or symptoms of the condition to be treated by the new drug. This stage of the research not only tests the effectiveness of the new drug, but also provides information about dosage, relative safety, and adverse effects.
Phase 3
Phase 3 is the final phase of a clinical trial before FDA approval. This phase involves thousands of patients and multiple clinical research sites that are part of a controlled clinical study. Usually, an experimental group is given the drug being tested, and a control group is given a placebo. The studies are “double blinded,” meaning that neither the patient nor the investigator knows to which group the patient has been randomly assigned. This phase provides data about the drug’s effectiveness compared to the control group receiving the placebo. If the drug satisfactorily completes each of the three phases, the manufacturer or sponsor files an NDA with the FDA for marketing approval.
Phase 4
Phase 4 is the postmarketing surveillance of an approved drug. Health professionals are encouraged to report any problems with the drug, and manufacturers submit yearly reports on new information about the drug. The FDA uses Phase 4 to determine whether the drug should stay on the market.
Exception for immediate and life-threatening diseases
The Food and Drug Administration Modernization Act modified the FDCA to allow an investigational new drug to be accessible outside a clinical trial to treat patients with immediate or life-threatening diseases for which no satisfactory alternative treatment is available if there is reasonable basis to conclude that the drug may be effective and would not expose patients to unreasonable and significant risk.
New drug application
An NDA is submitted to the FDA by the manufacturer or sponsor after Phases 1, 2, and 3 of the clinical trials have been successfully completed. The FDA has at least 6 months to review the application, and experts and others have an opportunity to comment on the submission. If the FDA approves the application, the manufacturer may begin to market the drug.
Risk Evaluation and Mitigation Strategy
The FDA Amendments Act of 2007 authorized the FDA to require sponsors to include an REMS in a pending NDA when the FDA believes that it is necessary to ensure that the benefits of the drug outweigh the risks (21 USC 355-1). The FDA may also mandate a postmarket REMS when it believes an approved drug may have a patient safety issue. An REMS may require one or more methods for protecting the consumer from potentially dangerous drugs. For example, an REMS might require distribution of medication guides, a patient package insert, a communication plan aimed at health care professionals, specialized training for prescribers, or restrictions on the type of health care setting from which the drug may be dispensed.
Expedited approval (fast track)
The FDA may grant a new drug “fast track” status if it is intended for treatment of a serious or life-threatening condition and addresses an unmet medical need. The sponsor must agree to conduct postapproval studies to validate the product’s use.
Drug classifications
During the approval process, the FDA classifies new drugs based on their chemical and therapeutic characteristics.
Review classifications
■ Type P classification means that the new drug is given priority review either because no other effective drugs are available to treat a particular illness or because the new drug has a significant advantage over currently marketed drugs.
■ Type S classification means a standard review because the new drug is similar to other drugs currently on the market.
■ Type O classification indicates the drug under review treats a rare disease affecting fewer than 200,000 Americans.
Chemical classifications
■ Type 1 classification indicates a new molecular structure from existing drugs used for the therapeutic purpose. This classification indicates a new and unique drug.
■ Type 2 classification indicates a new derivative of a molecular structure already approved in the United States.
■ Type 3 classification indicates a new formulation of a drug already marketed in the United States.
■ Type 4 classification indicates a new combination of two or more drugs.
■ Type 5 classification indicates a drug being manufactured by a new company.
■ Type 6 classification means a new therapeutic indication for a drug that is already approved.
■ Type 7 classification indicates that the drug is already marketed without an approved NDA.
■ Type 8 classification indicates that the product is an over-the-counter switch.
■ Type 10 classification indicates that the product is a new indication submitted as a distinct NDA, not consolidated.
There is no type 9 classification. For more information, see www.fda.gov/Drugs/InformationOnDrugs/ucm075234.htm.
Drugs for rare diseases or conditions
The FDA may authorize an investigational new drug or device, prior to FDA approval of the drug or device, to be used for the diagnosis, monitoring, or treatment of a serious disease or condition in emergency situations. For an individual patient to obtain a new drug or device in this situation, the following conditions must be met (21 USC 360bbb):
■ A licensed physician must determine that the person has no comparable or satisfactory alternative therapy available to diagnose, monitor, or treat the disease or condition involved and that the probable risk to the person from the investigational drug or investigational device is not greater than the probable risk from the disease or condition.
■ The FDA determines that there is sufficient evidence of safety and effectiveness to support the use of the investigational drug or device.
■ The FDA determines that provision of the investigational drug or investigational device will not interfere with the initiation, conduct, or completion of clinical investigations to support marketing approval.
■ The sponsor, or clinical investigator, of the investigational drug or investigational device submits to the Secretary of HHS a clinical protocol describing the use of the investigational drug or investigational device in a single patient or a small group of patients.
Naming new drugs
The responsibility for designating the generic name for a new drug is held by the United States Adopted Names Council (USANC). The Secretary of HHS gives final approval. The name must be short, distinctive, and not likely to be confused with other existing names. The name should also provide some indications of the therapeutic or chemical class to which the drug belongs.
National Drug Code
The Drug Listing Act of 1972 requires registered drug establishments to provide the FDA with a current list of all drugs manufactured, prepared, propagated, compounded, or processed by them for commercial distribution (see section 510 of the FDCA [21 USC 360]). Drug products are identified and reported using a unique, three-segment number, called the National Drug Code (NDC), which serves as a universal product identifier for human drugs (FDA Web site, www.fda.gov/drugs/informationondrugs/ucm142438.htm). If a prescription drug product has an NDC of “0137-0145-10,” the “0137” is assigned by the FDA and identifies the manufacturer or distributor (known as the “labeler’s code”). The “0145” is assigned by the manufacturer and identifies a specific strength, dosage form, and formulation for that particular manufacturer. The “10” is also assigned by the manufacturer and identifies the trade package size and characteristics, such as blister pack or bottle of 100 tablets. An NDC does not denote FDA approval of a drug. (Note: The FDA’s standard 10-digit number conflicts with HIPAA’s 11-digit standard for NDC. The FDA suggests adding an asterisk to the product code or the package code, instead of 0, to comply with both HIPAA and the FDA standard. For more information, see www.fda.gov/drugs/developmentapprovalprocess/ucm070829).
Brand-name or proprietary drugs
A brand name is the name assigned to the drug by the manufacturer. If the drug is a proprietary drug, the manufacturer is the innovator company to first market the drug and holds a patent on the drug, giving the manufacturer exclusive rights to market the drug.
Patent issues
Without patents, manufacturers would have little financial incentive to research and develop a new drug because nothing would prevent other companies from marketing generic versions of the drug after it has been approved by the FDA. Patents prevent this situation by giving the innovator company the exclusive rights to market the drug for a period of years. However, generic drugs keep the cost of pharmaceuticals down. The laws try to balance the two competing interests by extending certain patent rights of innovator companies to encourage research and development of new drugs and by streamlining the approval process for generic drugs.
Supplemental new drug application
An innovator company submits an SNDA when it wants to make changes in an approved drug product.
Generic drugs
Definition
When a patent for a proprietary drug expires, generic versions of the drug may be marketed by other companies. The generic version is usually cheaper than the proprietary drug.
Abbreviated new drug application
An abbreviated new drug application (ANDA) is submitted by a company that wants to market a drug after the innovator company’s patent expires. Compared to an NDA, this process is streamlined and requires proof that the new drug product is similar to the innovator’s drug product in pharmacokinetic properties, bioavailability, and clinical activity. An easy way to distinguish this application from an SNDA is to remember that an ANDA is submitted by another company, while an SNDA is submitted by the same company that first marketed the drug.
Drug recalls
If a marketed drug is determined to have problems, the FDA encourages the manufacturer to issue a drug recall notice. A pharmacy that sells a recalled drug product is probably violating the FDCA because the product is most likely to be considered adulterated or misbranded. It is the manufacturer’s responsibility to send wholesalers and pharmacies written recall notices of Class I and Class II recalls.
Drug recalls fall into three classes:
■ Class I recalls are the most significant and mean that the drug product may cause serious adverse health consequences including death. This recall should include stocks in pharmacies and notice to patients to whom the drug has been dispensed.
■ Class II recalls mean that the drug product may cause temporary or reversible effects, but the probability of serious adverse effects is remote. This type of recall usually involves only stocks in pharmacies.
■ Class III recalls mean that the drug is unlikely to cause any adverse health consequences.
Unapproved Drugs
In 2006, the FDA estimated that thousands of prescription and OTC drug products that have never been approved by the FDA are being marketed illegally. Pharmacists should use professional judgment before dispensing or selling an unapproved drug. (Note: Distinguish between an unapproved drug and an unapproved or off-label use of an approved drug.)
Current Good Manufacturing Practice
GMP is a set of regulations that specify the minimum standards required to manufacture pharmaceutical products in the United States. A manufacturer must be registered with the FDA and must describe its manufacturing and production processes as part of the NDA process.
Labeling Requirements
Definitions
The term label is defined as a display of written, printed, or graphic matter on the immediate container of any article. The label must appear on the outside container or wrapper of a retail package, or it must be easily legible through the outside container or wrapper.
The term labeling is defined to include all labels and other written, printed, or graphic matter on any article or its containers or wrappers, or accompanying such article. For example, a package insert is considered part of a drug’s labeling.
Labeling requirements for the manufacturer
Extensive regulations control what a manufacturer must put on the product’s labeling. To avoid having the product deemed misbranded, a manufacturer must include the following on the product’s labeling (21 CFR 201.1, 201.55, 201.100):
■ Name or address of the manufacturer, packer, or distributor
■ Established name of the drug or drug product
■ Ingredient information, including quantity and proportion of each active ingredient
■ Names of inactive ingredients if not for oral use (with some exceptions)
■ Generic and proprietary names
■ Quantity in terms of weight measure (e.g., 100 mg)
■ Net quantity of the container (e.g., 100 tablets)
■ Statement of the recommended or usual dosage or reference to the package insert
■ Identifying lot or control number
■ Legend “Rx only”
■ Specific route or routes of administration (e.g., oral, subcutaneous injection)
■ Special storage instructions, if appropriate (e.g., refrigeration)
■ Expiration date established by the manufacturer
Unit-dose packaging and labeling
Unit-dose packaging is more cost effective for health care facilities because it cuts down on wasted drugs prescribed for inpatient use. To meet this need, manufacturers provide their products in single-dose or unit-dose packaging that is too small to contain the required labeling information. The FDA has issued guidelines about what information should be contained on each unit-dose package:
■ Generic name and trade name, if appropriate
■ Quantity of active drug or drugs present
■ Name of manufacturer, packer, or distributor
■ Repackager’s lot number
■ Expiration date
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