QGLaw1.docx

Regulatory History: How we got here 1906 Pure Food and Drug Act (ADULTERATION AND MISBRANDING) Focused on adulteration & misbranding: had to be both to prompt federal action regarding misbranding; was not as enforceable Manufacturer focus: storing, shipping, labeling No mention of safety or ef...

Regulatory History: How we got here 1906 Pure Food and Drug Act (ADULTERATION AND MISBRANDING) Focused on adulteration & misbranding: had to be both to prompt federal action regarding misbranding; was not as enforceable Manufacturer focus: storing, shipping, labeling No mention of safety or efficacy No cosmetics In 1906, the source of drugs was primarily plants and animals 1914 – Harrison Anti-Narcotic Act (1914) – Tax it Drug abuse was an issue even then – tried to tax it away This is the early DEA 1937 – Sulfanilamide incident Diethylene glycol was used the “elixir” in the liquid formulation à targeted at children Diethylene glycol is antifreeze Keep in mind during this time, pretty much anything could be on the market, and only controlled substances required prescriptions Most drugs OTC Up to 1948, only drugs that required a prescription were narcotics Why do we find many written Rx’s from 1800/1900s then? Drugs up to 1938: Pre ’38 drugs assumed safe and effective solely by longevity of use Most OTC, unless narcotics; most not available anymore Assumed to be safe and effective Few still around: Thyroid, Morphine, Codeine, NTG 1938 – Food Drug and Cosmetic Act (SAFETY) Drug has to be safe when used as directed on the label and be approved by the FDA to be sold and marketed Also had to provide “adequate directions for use” Also created the “legend” class of drugs in name but not in practice. Called “legend” drug because the label had on it the Federal Legend Pretty much any drug statute we have today is found as an amendment to the FDCA or the Controlled Substance Act 1951 – Durham-Humphrey Amendment (Prescription Drug Amendment) - USC Established prescription drug class, even though that was sort of established by the FDCA. Obviously the FDCA didn’t do a real fine job of establishing it if it took 10 years to figure out who deemed drugs Rx or not. Touched on efficacy for the first time, but wasn’t enforceable Authorized prescription refills and oral (telephone) prescriptions/legalized verbal transmission of prescription Official Legend class of drugs Legalized refills Made exemptions to labeling requirements for prescription drugs Late 1950s-early 1960s – Thalidomide released in Europe Thalidomide was a non-barbiturate sedative Off label, it was used for morning sickness Resulted in fetal abnormalities, condition called Phocomelia Drugs from 1938-1962: DESI drugs safe but NOT effective DESI: Drug Efficacy Study Implementations 1962 – Kefauver-Harris Amendment – (SAFE AND EFFECTIVE) Drugs now had to be safe and effective to be marketed in the US Established FDA Investigational New Drug/New Drug Application Established Good Manufacturing Practices (GMP) Drugs from 1962-present: subjected to higher standards for safety and efficacy 1970 – Controlled Substance Act Essentially served to correct and consolidate a hodge-podge of controlled substance statues that existed prior. Our controlled substance laws are found in here. Federal CSA is strict, so states don’t tend to add much. Created DEA Federal Drug Statutes and Regulations Drug: Articles recognized in the Official Compendia: United States Pharmacopoeia, Official Homeopathic Pharmacopoeia of the US, or Official National Formulary Articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals Articles (other than food) intended to affect the structure or any function of the body of man or other animals Drug vs device: Same definition, device does not chemically alter the body Drug vs food: food is articles used for nutrition and energy (provide nourishment and sustain life) Dietary supplement: any product intended to supplement the diet that bears or contains: Vitamin, mineral, herb, amino acid, dietary substance for use to increase total dietary intake, concentrate, metabolite, constituent, extract, or combo of any of the above 1994 – Dietary Supplement Health and Education Act (DSHEA) Dietary supplements treated more like a type of food rather than drug “This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease” Concerns with dietary supplements (DS) Unsafe DS can be marketed and sold Consumer info lacking (ex. drug -dietary supplement interactions) Quality standards lacking: now subject to adulteration/misbranding requirements (cGMP) Health Claims Unqualified: significant scientific agreement exists 12 unqualified statements approved (Ex. calcium + osteoporosis, folic acid + neural tube defects, fiber + CHD risk) Qualified: NO significant scientific agreement Claims MUST contain qualifying language “scientific evidence suggests but does not prove…” “supportive but not conclusive research shows…” FDCA Drug adulteration and misbranding: violations will trace back to one of these Adulteration-mostly something bad with the drug Misbranding-mostly something bad with the label/labeling Prohibitions: things that someone did that the FDA didn’t like Federal Anti-Tampering Act (concerns only consumer products) Criminal acts: 1. Tampering: doing something to outside (seal) 2. Tainting: doing something to the inside (replacing) 3. Communicating false information: informing mfr that tampering has happened when it has not 4. Threatening to tamper (same as #3 but threat) 5. Conspiracy to tamper or taint, even if unsuccessful Barriers must be distinctive by design-harder to duplicate or replace Can be on the immediate container or on the secondary container (box) Reasonable handling must not routinely destroy the features Tamper-Evident Labeling: identifies evident features, must be prominently placed, in place so that it will not be lost if the tamper-evident features are removed One or more indicators or barriers, which if breached or missing will provide visible evidence of tampering Adulteration “filthy, putrid, decomposed” “prepared, packed, held under unsanitary conditions” “Drugs manufactured where: methods used, facilities and control for manufacture, processing, packing, or holding do not conform to cGMP” Drug may not feet safety, identity, strength, quality, purity standards Mainly targeted at manufacturers Examples: IS or contains an unsafe coloring agent Purports to be an official drug Strength differs from quality, purity, fall below the official compendium standards (unless plainly stated “NOT USP” on the label Misrepresentation of strength (concentration/potency does not match what it is intended to be) Ex. insulin at manufacturing plant is stored in a broken refrigerator. The intended potency is 100u/mL, because it is improperly stored, the actual potency is 50u/mL. This is a problem with the drug itself (NOT the label of the drug) Mixed with or substitution of another substance (NOT generic substitution) Devices not in conformity with performance standards Misbranding: labeling is false OR misleading If not labeled with name and place of business of the manufacturer, packer, or distributer (DRUG is misbranded, not the container) If required info is not prominently displayed: must be understandable by an ordinary individual under customary conditions of purchase and use Drug must have its established name (generic name) on its label Label must contain names of inactive ingredients, and the kind and percentage of alcohol Don’t have to compromise a Trade Secret If there is a brand/trade name and an established generic name, established name can be no less than ½ the size of the trade name Misleading containers, imitations, sold under the name of another drug (ex. labeling only the trade name when the generic equivalent is in the container) Drugs from non-registered establishments (FDA registration is a cGMP requirement) If packing or labeling is in violation of law Label vs Labeling Label: display of written, printed, graphic matter upon the immediate container of any article Labeling: all labels and other written printed or graphic matter upon any article or any of its containers/wrappers or accompanying such article Labeling includes label Commercial container: container that gets sent from the manufacturer/distributor to the pharmacy Package insert: scientific and medical info targeted at health professionals Must accompany the drug product from the manufacturer Required formatting and contents Prescription Label Contents Name and address of dispenser Serial number Date of the prescription or its filling Name of prescriber If stated in prescription: Name of patient Direction for use Cautionary statements Prescription Drug Labeling Medication Guide: GIVE W/ EVERY DISPENSING Consumer Medication Information (CMI): GIVE W/EVERY NEW PRESCRIPTION required if drugs pose “serious and significant concern” Patient Package Insert (PPI) – specific to OC, ONE WITH EACH PACKAGE DISPENSED Misbranded if not provided Institutions have to give patients PPIs initially and every 30 days during stay Risk Evaluation and Mitigation Strategy (REMS) When Med Guides, PPIs, CMIs, and BBW are not enough to protect patient FDA requires manufacturers to develop these approved risk management programs Drugs that require significantly more monitoring (ex. Clozaril, opioids, thalidomide) Legend Drugs (Rx only) Require supervision for safe and effective use Supervision by “practitioner” (defined by States) ARE NOT unreasonably dangerous ARE unavoidably unsafe OTC: deemed safe and effective for unsupervised use for intended indication OTC vs Rx only – decision that supervision is not needed with labeling (indication) Behind the Counter Drugs: “nonprescription under conditions of safe use” New Drugs Novel drug: Amlodipine 5mg New dose: Amlodipine 10mg New Indication: Raynaud’s Syndrome Contains new substance New combo of approved drug New Combo: Amlodipine/Benazepril Proportion of ingredients in combo is changed Dose, method, or duration of admin is changed New Release Form: Amlodipine IV NOT deemed GRAS or GRAE by the FDA Controlled Substances: have liability to cause dependence or have abuse potential 5 schedule classes Orphan Drugs: tx of rare diseases or conditions Rare = 200,000 or fewer Or manufacturer has virtually no chance to make profit Govt provides tax and exclusive licensing incentives Drug does not lose orphan status if found to be useful in tx common illness Biologics: derived from living organisms (antitoxins, blood products, etc.) Regulated since 1902 Licensed under Public Health Service Act (PHSA) Drug Recalls: typically voluntary FDA reporting system: MedWatch Class 1: serious adverse health consequences or death Class 2: may cause temporary or reversible AE, possibility of serious consequences is remote Class 3: not likely to cause adverse health consequences Device recalls: mandatory Pregnancy Categories (OLD) A – OK, tested and passed B – May be OK C – May be OK if benefits outweigh risks D – Known risk to human fetus X – NOT OK Pregnancy (NEW) More focused on information provision than categorization Dosing, potential risks, registry information Lactation: Drug in breast milk; potential child AEs See “Use in specific populations” National Drug Code (NDC) Manufacturer # - Drug # - Package Size The Orange Book: “Approved Drug Products with Therapeutic Equivalence Evaluations” Helps pharmacists choose bioequivalent generic product Pharmaceutical equivalent No information on therapeutic substitutions Codes A – no known or suspected bioequivalence problems AB – resolved bioequivalence problems B – NOT resolved and not considered bioequivalent Narrow Therapeutic Index/Ratio Drugs: requires careful dosage titration and patient monitoring (ex. levothyroxine, warfarin, phenytoin, lithium) Biosimilars/Biologics and Purple Book Biosimilar does not equal interchangeable Interchangeable = Biosimilar+ Prescription Drug Marketing Act: Re-importation, Diversion of Rx samples Retail pharmacies should not have legend drug samples Hospital pharmacies are specifically permitted to have, and use, legend drug samples Preferentially Priced Drugs Hospitals get special pricing for drugs They cannot resell drugs except: Another qualified hospital Nonprofit affiliate Hospitals or healthcare facilities under common control Emergencies Selling or dispensing pursuant to a prescription Laws related to FDCA (SAFETY) Pharmacy inspections: FDA does not routinely inspect pharmacies (but they can without a warrant and don’t need to state reason for being there) Board of Pharmacy, DEA, and Health Dept can also inspect Usually bring a warrant if looking for something specific 1970 -- Poison Prevention Packaging Act (PPPA) Enforced by Consumer Product Safety Commission Protect kinds under the age of 5 from accidental poisoning (hazardous household substances) Complying with standards should keep such a child from receiving a dangerous amount in a reasonable period of time NOT Child Proof Child Resistant Applies to: Oral legend drugs Controlled substances OTCs Does NOT apply to: Topicals, injectables, suppositories, eye drops, sprays, inhalers, ear drops, others “special packaging” = “safe” containers ALL oral legend drugs and ALL controlled substances do not need to be dispensed in special packaging Easy open vials with exemption or waiver from patients/patient’s rep/prescriber Prescriber can give waivers for Rxs one-by-one Patient waiver: can be a blanket waiver Exemptions: can be dispensed in easy-open caps without further permission Exemptions come from Consumer Product Safety Commission (CPSC) No safety concern for kids Must be readily available Dosepacks (prednisone) mnemonic packages (OCs) Mebendazole 6 x 100mg tabs SL NTG SL chewable ISDN Unit dose KCl Alcohol rules When unspecified: 95% ethyl alcohol Proof gallon = 1 gallon of 50% alcohol Inventories are reported in proof gallons Advertising FDA regulates prescription/legend drug advertising FTC and FDA regulate non-prescription drug advertising TN FDCA Prohibited Acts (53-1-103) Manufacture, sale, or delivery, holding, or offering for sale of any food, drug, device, or cosmetic that is adulterated or misbranded Adulteration or misbranding of any food, drug, device, or cosmetic Sale by vending machines of any drugs that are capable of causing physical or mental harm if taken internally in overdoses 53-1-108 Adulteration Very similar to FDCA Filthy, putrid, decomposed substance Prepared, packed, held under unsanitary conditions Drugs differently than they claim to be (strength, quality, purity) Fall below compendium standards, unless stated on label Mixed w/ anything that alters quality of strength or substitutes for drug 53-1-109 Misbranding False or misleading labeling Label doesn’t contain name and address of manufacturer/packer/distributor, quantity, directions, warnings Packaging and labeling requirements not met Label not easily readable Imitations sold under name of another drug Deteriorative drugs not specified on labeling “Warning – may be habit forming” TCA 53-10 Legend Drugs 101: Any item that federal law prohibits dispensing without a prescription from a licensed doctor, dentist, optometrist, or veterinarian 102: exemptions Wholesalers selling to pharmacists Pharmacists selling to physicians, dentists, vets, optometrists 103: BOP enforces and collects fines TCA 53-10-104 Who can prescribe Physician, Dentist, Optometrist, Vet, PA, authorized nurse TCA 53-10-104 Drugs to cause/perform abortion Under no circumstances shall NP or PA be delegated authority to prescribe these drugs TCA 53-10- (105-109) 105: Prescription not necessary for possession of legend drugs 106: Misbranded drugs are deemed to be adulterated 109: “No amphetamine classified as a Schedule II stimulant under 39-17-408d shall be prescribed for the purpose of assisting a patient to gain or lose weight 110 Indication of Rx label: SHALL include indications on label if requested and provided by prescriber, patient, or caregiver Dispenser is not liable for injury from failing to include indication if it wasn’t requested If reasonably relying on indication from sources above Doesn’t apply to inpatient, nursing home, prisons, etc. 111 Death of prescriber CII NOT dispensible – NO CONTROLS CAN BE DISPENSED AFTER PRESCRIBER DIES New prescription, never filled fill within 90 days CIII, CIV, CV refills void 90 days after death (NO CONTROLS FEDERALLY) Non-scheduled refills void 180 days after death 112 Prevention of Drug Abuse Professional judgment shall be protected/respected Shall make reasonable effort to prevent abuse of drugs A pharmacist may decline to dispense Lack of therapeutic value Lack of legitimate medical purpose Class A misdemeanor: knowingly restrict or interfere with a pharmacist’s duty to counsel & exercise professional judgment 113 Off Label Drug Use TN allows truthful promotion of off-label uses 202-204 Generic Dispensing 202: pharmacists should substitute with generic to save $$$ 204: prescriber shall allow for substitution unless Brand is medically necessary Prescribers must not on Rx if brand is necessary Generic not available Anti-epileptic drug 205: dispense least expensive generic equivalent in stock and covered by plan Make reasonable attempt to contact prescriber if new generic available If brand is cheaper, dispense it Comply with patient requests Dispense what is cheapest and makes the patient happy and what insurance covers 207: Label Contents Label on immediate container (name and address of manufacturer) Pharmacist shall notify if generic substitution by noting on the Rx label (not inpatients) 208: Generic Substitution Can substitute with A, NOT with B Professional judgment if not rated 210: Anti-epileptic drugs Interchange Change in mfr Generic brand Brand generic Generic different generic Notification PRIOR TO interchanging if epilepsy/seizures are currently controlled Patient/relative/close personal friend AND Prescriber Not applicable to institution patients 211: Biologics interchange Substitutions allowed Follows same requirements as non-biologics If substituted: within 5 days, communicate to prescriber the specific product provided to the patient (including name of product and mfr) 401: Tamper-proof prescriptions Applies to all written and printed Rxs from TN prescriber Except: Verbal, fax, electronic Rx Rx from another state with different laws Vet, inpatients, facilities Pharmacists shall not fill, but can give emergency supplies based on third party payers CMS standards apply Prevent copying of prescription forms, erasure/altering info on forms/making counterfeit forms Can include serial numbers, but pharmacists don’t bear liability