Pharmacy Law January 19, 2011 Federal Food, Drug, and Cosmetic Act (a statute) 21 USC §301 et seq. Pure Food & Drug Act of 1906 First time food and drug regulation considered in US Established FDA Goal: protect health and safety associated with unsanitary and poorly labeled food and drugs – Dealt with adulterated and misbranded food and drugs in interstate commerce Food, Drug and Cosmetic Act of 1938 Expanded 1906 law Result of deadly consequences of diethylene glycol (antifreeze) in anti-infective preparation Required drugs to be safe as labeled Label must contain adequate instructions for use and warnings Later amendments provided for batch uniformity of penicillin and insulin Durham-Humphrey Amendment of 1951 Established prescription and OTC classes of drugs Established the federal caution required on all prescription drug products – “Caution: Federal law prohibits dispensing without a prescription” Establishes requirements for oral prescriptions Establishes requirements for prescription refills Kefauver-Harris Amendment 1962 Resulted from thalidomide disaster in Europe – FDA did not approve the new drug application for product in US Added safety to requirements for marketing and sales of drugs Gave FDA control of prescription drug marketing and advertising Established good manufacturing practices (GMPs) Required more research requirements and reporting of adverse drug events Prescription Drug Marketing Act of 1987 Restricts pharmacies from receiving or distributing drug samples from manufacturers Prohibits sale of drug samples by hospitals or other health care entities Establishes state licensure requirements for pharmaceutical wholesalers FDA Modernization Act of 1997 Streamlined FDA drug approval process to allow expedited availability of drugs and devices Expands manufacturers’ ability to communicate information regarding off-label uses Required FDA to establish public standards regarding approval process and a mission statement FDA Modernization Act of 1997 Established a fast-track approval process for drugs used for life-threatening diseases Established a databank with clinical trial information Authorized review of clinical investigations Gives FDA full authority to establish labeling requirements for OTC agents Other Important FDA Amendments Orphan Drug Act of 1983: expanded access to drugs for rare diseases Drug Price Competition and Patent Term Restoration Act of 1984: streamlined requirements for bringing generics to market Prescription Drug User Fee Act of 1992: requires manufacturers to pay fees to FDA for drug approval process Food and Drug Administration Amendments Update of 2007 (FDAAA): provisions designed to improve access to consumer drug info and adverse event reporting Focus of FDA Today and in the Future Appropriate prescription written prescription information for consumers and enhancements in labeling Approval of “follow-on” biologic agents Drug importation Enhanced safety in clinical trials Comparative effectiveness of certain medications compared to others – Joint efforts with other agencies Expansion of FDA’s role 2009 law now expands FDA oversight to tobacco and tobacco products – Currently, tobacco NOT regulated by FDA – New law would regulate tobacco in a manner similar to medications Global expansion with FDA-registered entities in foreign countries primarily China, India, and Canada – Inspections of foreign facilities? – FDA already has presence in South America Food versus Drug FDA Definition of Drug Recognized by official compendia in the US – USP, official Homeopathic Pharmacopoeia of US, National Formulary, or any supplement to any of them Used for the diagnosis, cure, mitigation, treatment or prevention of disease in man or other animal Intended to affect the structure or any function of the body of man or other animals ***** VAC substantially adopts FDA definition §54.1-3401 Food v Drug Food is not intended to affect the structure of the human body and is not intended to be used for disease states Drugs have stringent and long clinical testing requirements before marketing – Foods found to be drugs can be removed from market – Dietary supplements not considered drugs Suppliers must be careful when they make claims regarding products because can result in products classified as drugs by FDA – Courts will consider advertising claims made by manufacturer to determine whether a drug is marketed as food or drug – Courts also consider label and labeling of product – Often conclusions are subjective based on evidence presented Dietary Supplements Vitamins, minerals, herbs or other botanicals, amino acids, concentrate, metabolite, extract Governed by the Dietary Supplement Health and Education Act of 1994 (DSHEA) – FDA permits certain health claims so long as certain scientific agreement exists for claim • Vitamins in orange juice determined by American Heart Association to help prevent heart disease • If the claims indicated that vitamins definitely prevent heart disease, then potentially drug Pharmacists may recommend certain dietary supplements based on scientific and clinical information about the product Marketing dietary supplements Over the past several years FDA reviewed claims by certain food manufacturers and sent warning letters regarding claims Cheerios slogan: “Give us 6 weeks, we will lower your cholesterol” – FDA letter warned General Mills that its advertisement is a therapeutic claim and therefore the product is a drug subject to a new drug application Marketing of Activia by Dannon – Federal Trade Commission (FTC) action Marketing dietary supplements Appropriate claims for a dietary supplement include – Structure/function claims acceptable – May help – At least two clinical research studies have shown that product may assist in the medical claim being made – Definitive statements generally considered the realm of a drug product Foods and Dietary Supplements Payment System Implications Generally, health plans do not provide reimbursement for dietary supplements such as vitamins and minerals – Limited exceptions include Vitamin B12 and Nicacin Some payers, including state Medicaid programs, will pay for enteral food supplements such as Ensure that help to prevent wasting and cachexia Medicare Part D program excludes payment for dietary supplements and for enteral food supplements Adverse Event Reporting for Dietary Supplements and OTCs FDAAA includes provisions to report adverse drug events associated with dietary supplements and OTC medications by requiring reporting of serious adverse effects associated with the product – – – – – – Death Life-threatening experience In-patient hospitalization Persistent or significant disability or incapacity Congential anomaly or birth defect Requires medical or surgical intervention to prevent one of the outcomes described above Responsibility is the distributor, packer or manufacturer that appears on the label – Retailers including pharmacies do not have to report directly but must communicate incidences to the proper entity Information must be submitted to FDA within 15 days of event and new medical developments reported within the first year of event Label and Labeling Definition: Label Written, printed, or graphic matter upon the immediate container of any article – Includes container or wrapper ***** VAC substantially adopts FDA definition under § 54.1-3401. Definitions Definition: Labeling Definition includes information on label and all other written, printed, or graphic matter upon any article or any of its containers or wrappers Much broader than label and many more implications Information not sent directly with the drug may be considered labeling if part of the integrated distribution process Includes OTC and Rx labeling ***** VAC substantially adopts FDA definition under § 54.1-3401. Definitions Rx v. OTC Labeling Basic information same with some differences – Rx must contain the “Federal Caution” – OTC must contain very specific information related to warnings to stop use – OTC must contain specific information regarding the dosages and the patient population intended • Rx provides information related to the recommended and usual dosage – OTC must contain specific information regarding the route of administration, appropriate time of administration, etc – Rx contains information for type of container used to dispense Professional Package Insert Included in the labeling of the prescription drug Must accompany the drug product and provide essential scientific and medical information needed for the safe and effective use of the drug by health care professionals Rules implemented June 2006 streamline information in professional package insert and must be fully implemented for all by 2013 Attempts to remove much of the legal jargon in package insert and highlights the most important information up front including boxed warnings Boxed warnings FDA approved warnings required for products with certain contraindications or serious warnings, particularly those that may lead to death or serious injury – Information appears in a text box in the package insert • Contains warnings or contraindications, special or restricted uses, risk mitigation strategies, testing or other special requirements for use of the product – Information about common off-label uses with unacceptable risk • For example: antipsychotics for dementia in seniors – Products approved with black box warnings may or may not require consumer-focused warnings, such as MedGuides Patient Package Insert FDA law requires leaflets to be included with certain medications, including products containing estrogens, DES, oral contraceptives and intrauterine contraceptive devices Manufacturer must notify pharmacist to insert leaflet in each prescription dispensed Must provide general information regarding the risks associated with use and potential adverse effects, and pulmonary embolism Applies in both community pharmacy and institutional settings (modified form) – In institutions can be provided upon administration of first dose and then once every thirty days Medication Guides (MedGuide) Required for certain products posing a “serious and significant concern” other than estrogencontaining products if FDA finds – Patient labeling could help prevent serious adverse effects – Product has serious risks that patient could benefit from knowing – Patient adherence crucial to effectiveness of drugs MedGuide must be approved by FDA Must be in English – Any document not in English that purports to be a MedGuide has not been FDA approved Medication Guides (MedGuide) Manufacturer not required to provide MedGuide leaflet with products but must – Provide information in professional package insert regarding the requirement to provide MedGuide with approved products and – Must provide pharmacies with a mechanism to obtain MedGuides through a website, distribution center, etc. MedGuide required for Accutane, Lariam, all antidepressants and others – Complete list: http://www.fda.gov/Drugs/DrugSafety/ucm085729.ht m MedGuides v Pharmacy generated consumer medication information Pharmacies may also provide consumer medication information from its computer systems or other source of information – Pharmacy-generated consumer medication information not FDA approved and currently does not have to be in a standard format – Pharmacies that provide its own information must also conform to FDA required consumer medication information requirements Misbranded Drugs FDA definition VAC §54.1-3462 Considers whether the label or labeling of a drug is false or misleading FDA must approve information Misbranded Drugs: Key Points Label or labeling must not be false or misleading Package must contain information on manufacturer, packer, or distributor Must contain all statements, words or designs required or approved by FDA, including package inserts, MedGuides, etc Controlled substances must contain “Warning-May be Habit Forming” Prescription drugs must have established name or ingredient prominently displayed – Proprietary name must be included in type 1/2 the size of established name – VA Board of Pharmacy may grant exceptions Misbranded Drugs: Key Points Information regarding dosages that might be dangerous to health or unsafe Information related to dangers of use in children Special packaging requirements to prevent deterioration, etc. If it fails to meet conditions of the Poison Prevention Packaging Act Adulterated Drugs See FDA definition VCA definition §54.1-3461 Adulterated Drugs Includes drugs that consist in whole or in part of filthy, putrid, or decomposed substances Drugs prepared, packed or held in unsanitary conditions Drugs prepared, packaged, processed or held under conditions that violate GMPs Drugs that purport to be those recognized in official compendia but quality or purity falls below the standards Drugs mixed or packed to reduce quality or strength Adulterated Drugs Applies to preparation conditions for the drugs, not the drug itself Mostly applies to manufacturers but can apply to pharmacies if – A pharmacy receives an adulterated drug and then sells the drug – A pharmacy compounds medications under conditions that result in adulteration • State implications different from federal law implications Current Good Manufacturing Practices (CGMPs) FDA regulations that establish minimal requirements for the methods, facilities, or controls used in the manufacture, processing, packaging, or holding of a drug product Ensures product meets FDA quality and purity requirements Only apply to manufacturers except if a pharmacy engages in activities deemed manufacturing Manufacturer Compliance with CGMPs and FDA Registration Manufacturers required to register with FDA – Pharmacies NOT required to register with FDA but in some cases could be inspected Manufacturer registration with FDA valid for two years and FDA will inspect one time within the two year period Purpose of inspections – Production and control procedures to ensure proper identity, strength, quality, and purity of drugs – Identify deficiencies and provide follow-up for correction Manufacturer could be required to recall drugs from market or FDA could seize all adulterated drugs Product Tampering Violations associated with intentional product tampering the joint authority of FBI, Department of Agriculture, and FDA FDA rules require some OTC products to be in tamper-resistant packaging – Must ensure that packaging provides visible evidence that tampering has occurred FDA Drug Approval Process New Drug Approval Process Applicant must provide – Reports of drug safety and efficacy – Drug components and composition – Methods, facilities, and controls used in manufacturing, processing, and packaging – Samples of drugs – Proposed labeling Definition: New Drug Drug not generally recognized by qualified experts as safe and effective for use under the conditions recommended in the labeling – Generally recognized as safe (GRAS) – Generally recognized as effective (GRAE) Must be used for a “material” amount of time for indications in the labeling FDA determination on new drugs considered final authority; not court decision Sometimes applies to new drugs for different indications, forms, etc §201(p) FDCA New Drug Application Process Investigational new drug application – Drug name, composition, manufacture and quality control data, preclinical animal investigations regarding pharmacological, pharmacokinetic, and toxicological evaluations – Approval if IND within 30 days, then drug moves to clinical trials Clinical trials in humans – Phase I: examines adverse effects in small studies, toxicity, metabolism, bioavailability, elimination and other pharmacological effects – Phase 2: tested for efficacy on patients with the disease/condition – Phase 3: large clinical trials for safety and efficacy – Phase 4: post-marketing surveillance IND for Treatment Used for individuals with serious or life-threatening injuries meeting following requirements – – – – – Serious or immediate life-threatening disease or condition No comparable or satisfactory alternative Drug is under investigation for treatment of condition Sponsor seeking marketing approval Sufficient evidence of safety and effectiveness for serious diseases – Reasonable basis to conclude the drug may be effective and would not expose individuals with immediate life-threatening diseases to unreasonable and significant risk FDA MedWatch Program Voluntary system for healthcare professionals to report ADRs to FDA Information can be found at www.fda.gov/medwatch/index.htm Voluntary and confidential Move to make process more transparent, required? FDA Risk Evaluation & Mitigation Strategies (REMS) Another form of surveillance implemented by FDA in 2008 to establish formal protocols to communicate information about safety and efficacy concerns with certain medications – Many medications already approved for REMS have MedGuides – REMS developed by manufacturers and approved by FDA – A list of currently approved REMS available at http://www.fda.gov/cder/drug/DrugSafety/REMS.htm – More REMS expected in the future http://www.fda.gov/Drugs/DrugSafety/InformationbyDrug Class/ucm163647.htm REMS components REMS include at least one of the following elements designed to ensure safety of use – Practitioners must be certified or have training to prescribe medication – Pharmacies and other dispensers or those who administer must have special certification – Drug distribution is limited to only certain settings such as clinics or hospitals – Patients who receive the medication must receive special information regarding safe use, including required lab testing – Patients must be monitored when using the medication – Patients must be enrolled in a registry to use drug Manufacturers that fail to comply with REMS requirements subject to fines and penalties, including misbranding of products REMS components Review “Fictitious Drug REMS” beginning on page 30 of the following document to understand components of REMS http://www.fda.gov/downloads/Drugs/GuidanceComplia nceRegulatoryInformation/Guidances/UCM184128.pdf FDA Drug Safety Website Provides comprehensive information on postmarketing surveillance for consumers and professionals http://www.fda.gov/Drugs/DrugSafety/Postmark etDrugSafetyInformationforPatientsandProvider s/default.htm For Next Week Review definition of OTC drug under FD&CA Review compounding provisions under FD&CA and general info on FDA website Review FDA generic equivalency information http://www.fda.gov/cder/consumerinfo/generic_equivalence.htm Skim DEA regulations http://www.deadiversion.usdoj.gov/21cfr/index.html Section 1300.01; 1301; 1306