FDA Exam 3

Advertising of Prescription Drugs

• Manufacturer to professionals 

  • FDA regulations mandate both substance of information (to be included or not to be) in advertising and the manner in which it is presented (size of type, order of information) 

  • True statement of information in brief

Violation of True Statement 

• Advertising false or misleading 

• Does not present a fair balance between side effect and contraindication information, 

• Fails to reveal material facts 

• Same scope, depth and detail of information for side effects and contraindications as effectiveness 

Advertising Direct to Consumer 

• Advertisers may provide a summary of risks in audio or video form if there is adequate provision for the consumer to obtain full labeling information from 4 sources: 

  • Referral to a print advertisement or available brochure 

  • Toll free number 

  • Internet web page address 

  • Referral to a health care provider

Advertising - DTC

• Manufacturer to consumer - non-product specific - institutional - does not mention the name of the manufacturer

• Product specific must meet FDA regulations for advertising - written at a level consumers can understand 

Device Definition

• A device is: 

  • Instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory which is: 

    • Recognized in a National Formulary or USP or supplement 

• Intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment or prevention of disease in man or other animals OR

• Intended to affect the structure or any function of the body of man or animal and 

• Which does not achieve any of its principal intended purposes through chemical action within or on the body of man or other animals 

• And which is not dependent upon being metabolized for the achievement of any of its intended purpose 

Classes of Devices

• I - requires least regulations (pose least potential harm to users) - general controls are adequate - manufacturer’s register their facility, list their products with FDA, provide premarket notification where required, maintain records and reports and adhere to GMP - needles, toothbrushes, scissors, stethoscopes 

• II - general controls are insufficient to ensure safety adn effectiveness, have specific performance standards - insulin syringes, diagnostic reagents, thermometers, heating pads, infusion pumps 

• III - must have premarket approval, are life supporting or life sustaining, present a potential unreasonable risk of illness or injury - pacemarkers, soft contact lenses, replaceable heart valves 

Devices

• Post 1976 devices put into Class III until found otherwise 

• FDA may require recall, repair, refund or replacement. They can also seize, enjoin shipment, withdraw approval or reclassify 

District Ethical Principles

A consensus of ethicists recognizes these: 

• Honesty 

• Promise-keeping 

• Nonmaleficence 

• Beneficence 

• Autonomy 

• Justice 

Honesty

• Our obligation to tell the truth in our dealings with others 

• Are we bound to do this in all circumstances?

• Is it always in our best interest to “Tell the truth, the whole truth and nothing but the truth?”

Promise-Keeping

• Most moral people feel an obligation to keep the promises they make. 

• Are we bound to keep them forever, even if circumstances change?

• Are there some things we should never agree to do?

Nonmaleficence

• Do not harm 

• Ever? To anyone?

• Cannot we protect our family, our friends, our country?

Beneficence

• Do good

• Act in a positive way in our dealings with others 

• Prevent harm to others if it is in our power 

• At what personal and professional cost?

Autonomy

• People have the right to live their lives the way they see fit, without the interference of others.

• Are there limits to this right?

• Where do we draw the line?

Justice

• All people should receive respect

• The benefits conferred upon one should be conferred upon all 

• Must all people be treated alike all the time?

Dilemma

• What happens when one or more of these principles come into conflict in a particular situation?

• Which principle is most dominant in you value system?

• Which will do the most good?

• Which will do the least harm?

• Which are you willing to face the consequences of your actions for?

Cosmetic Definition

• 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 

• Articles intended for use as a component 

Cosmetics

• Premarket approval not necessary but manufacturers must substantiate the safety of product and its ingredient 

• Manufacturer does not have to follow GMP or register with the FDA (it is voluntary) 

Manufacturer must: 

• Labeling-ingredients listed in descending order of amount contained in product 

• Have fragrances and flavors listed as such 

• Place ingredients on the outside of the package or container so the customer can read them at the point of purchase 

• Special warnings-self pressurized containers, hair dyes containing coal tar

Cosmetic Misbranding

• Misbranded if: 

  • Labeling is false 

  • Misleads the customer 

  • Lacks the required information 

  • Label information is not clear enough to read and understood by average consumer 

  • Violates the Poison Prevention Packaging

Cosmetics

• If safety not yet determined there must be warning panel saying this

Cosmetic Adulteration 

• Adulteration if: 

  • Contains poisonous or deleterious substances 

  • Contains filthy or putrid or decomposed substance 

  • Prepared under unsanitary conditions 

• Container contains a substance that may contaminate the contents 

• Contains an unsafe color additive but is not a hair dye

Food and Dietary Supplements 

• Nutritional Labeling and Education Act of 1990 prohibits disease prevention claims in food labeling unless they conform with FDA regulations - dietary supplements added in 1994 under Dietary Supplement Health and Education Act (DSHEA) 

• FDA will authorize health claims if the supplier submits a petition containing considerable information and evidence supporting the claim 

Supplement Definition

• Product intended for ingestion to supplement the diet and contains: vitamins, minerals, herbs, or other botanicals, amino acids, dietary substances for use by man to increase dietary intake, concentrates, metabolites, constituents, extracts, combinations

• If its claims involve diagnosis, cure, mitigation, treatment, it is a drug 

Supplements

• Forms include 

  • Tablets

  • Capsules 

  • Powders 

  • Energy bars

  • Drinks

Purpose (supplements)

• To help ensure we get adequate amounts of essential nutrients or help provide optimal health and performance 

• They may also have unwanted effects on part of the population or may interact with certain drugs 

Approval Process

• Not evaluated by FDA for safety and effectiveness 

• Manufacturers have responsibility for ensuring products are safe and that label claims are accurate and truthful 

• After DSHEA - NDI’s must give pre-market safety notification to FDA

FDA’s Role

• FDA can take actions against product that presents a significant of unreasonable risk of illness or injury 

• FDA has burden of proving this

• Usually determined after the product is on the market - except NDI 

• FDA responsible for evaluating adulteration and misbranding 

• Firms cannot market contaminated products or products whose label contains information that is false or misleading 

• Cannot claim ingredients that are not actually present - labeling issue 

• FTC controls advertising regulations

Unreasonable Risk

• Risk benefit calculation that weighs a products risk against the benefits under conditions of use recommended or suggested in the product labeling, or if silent, under ordinary circumstances 

• Feb 2004 FDA applied this standard to supplements containing ephedrine alkaloids

Supplement Claims

• Product will benefit a classical nutrient deficient disease, prevalent in US 

• Describe role of supplement in affecting the structure or function of the body 

• Characterize the documented mechanism by which it acts to maintain structure or function claims 

• Statements describing general well being derived from consumption but product must contain a disclaimer 

• “This has not been evaluated by the FDA. Product is not intended to diagnose, treat, cure, or prevent any disease.” 

Claims

• Must have substantiation they are truthful and not misleading - FDA attempting to define substantiation - new focus in 2005 

• Looking at regulation and case law 

• Manufacturers must draft labeling claims carefully and review support for each claim - how it relates to a specific product, is scientifically sound and adequate

Reliable Scientific Evidence

• Tests, analyses, research, studies or other evidence 

• Look at expertise of professionals (relevant area) 

• Conducted and evaluated in an objective manner by a qualified person, using generally accepted procedures

NDI’s

• New dietary ingredients 

• Under DSHEA - dietary ingredients not marketed in US before October 15, 1994 

• Pre-market safety notification to FDA required (shifts burden of proving safety to the manufacturer) 

• Adulterated - unless contains only dietary ingredients present in food supply as food OR procide history of use or other evidence of safety when used under recomnmended conditions 

• Reasonably expect to be safe and provide information on which conclusions are based 

• Provide at least 75 days before produc goes into interstate commerce

Poison Prevention Packaging Act

• Now enforced by Consumer Product Safety Commission 

• Requires: use of child resistant container for packaging some OTC’s and most prescription drugs the pharmacist will dispense to consumers 

• Manufactured so that 80% of children under 5 cannot open but 90% of adults can 

• Drugs dispensed only once in resistant containers or vials since continued use compromises effectiveness of container 

• Permits reuse of glass containers if they have a new closure 

• As of 1/29/02 oral dosage OTC’s switched from prescription must have child resistant caps unless falls under exemption

Reverible Containers Allowed

• Pharmacist may dispense in reversible containers (closures child resistant when used on one side but not child resistant on the other ) if they are dispensed in a child resistant mode 

Dispensing Exemptions 

• Drugs dispensed under a prescription are exempt if: 

  • Physician prescribing requests 

  • Patient requests 

• Request can be oral but pharmacist should document the requast 

• Can have patient sign statement that they requested 

Poison Prevention Packaging Act

• Patients may make a blanket request that all medications be dispensed in a noncompliant container 

• Prescribers may not 

Manufacturer’s Exemption

• Manufacturers may market one size of an OTC for the elderly or handicapped in a noncompliant package 

• Must contain statement this package for households without young children 

• If label is too small - contain warning - Not Child Resistant 

• If popular size - must also market in a child resistant form 

Institutional Exemption 

• Drugs dispensed to institutionalized patients are exempt if administered by institution’s employees 

Exceptions to Law

• Sublingual nitroglycerine 

• Sublingual and chewable isosorbide dinitrate 10mg or less 

• Sodium floride products not more than 254 mg of substance per package

• Anhydrous chloestryamine powder 

• Methylprdenisolone tablets no more than 84 mg of drug

Exceptions

• Mebendazole tablets not more 600 mg 

• Betamethasone tablets not more than 12.6 mg

• Potassium supplements in unit dose forms not more that 50mEq per unit dose 

• Etythromyacin ethylsuccinate granules for oral suspension and oral suspensions not more than 8g of erythromyacin 

• Colestipol powder up to 5g in packet 

• Etythromyacin ethylsuccinate tablets containing no more than 16g of drug 

• Preparations in aerosol containers intended for inhalation therapy 

• Pancrelipase preparations 

• Prednisone tablets not more than 105mg

Other Products Covered by Law 

• Furniture polish 

• Methyl salicylate 

• Sodium and potassium hydroxide 

• Turpentine 

• Kindling and illuminating preparations 

• Methyl alcohol 

• Sulfuric acid 

Other Products Covered

• Ethylene glycol 

• Iron containing drugs 

• Dietary supplements containing iron 

• Solvents for paint and other similar surface coating materials 

Tamper Resistance 

• Federal Anti Tampering Act of 1982 - federal offense to tamber with consumer products 

• Tampering-improper interference with product for purpose of objectionable or unauthorized changes to the product 

• OTC’s, cosmetics, devices to be manufactured in tamper resistant packaging 

• Violation can be deemed adulteration, misbranding or both

• Product has an indicator or barrier to entry which if broken or missing can reasonably be expected to provide visual evidence to consumers that tampering has occurred

Policy (FDA Enforcement)

• FDA as a science-based law enforcement agency bases its enforcement activities on medical and technical evaluations of product safety and effectiveness and of statements in product labeling 

• 3 sources of power: law passed by Congress; regulations promulgated by the FDA; policy guidance documents issued by the agency

Enforcement Objective

• To make sure that food, drugs, medical devices, and cosmetics comply with the laws and regulations the agency enforces 

• They believe compliance will be achieved voluntarily 

• 85-90% of inspections reveal substantial compliance 

• Enforcement powers are 2 kinds: administrative and judicial

Administrative Enforcement

• Agency can exercise on its own 

  • Tools: 

    • Inspections 

    • Inspectional Observations (Form FDA 483) 

    • Warning Letters 

    • Adverse Publicity 

    • FDA initiated recall and monitoring company initiated recall 

    • Delay, withdrawal, or suspension of product approval 

    • Preclusion of government contracts 

    • Detention and refusal of entry into US of imported products 

    • Assess civil money penalties 

    • Debar individuals and corporations

Devices

• May also order a detention 

• Order a company to cease marketing a device 

• Tell users to stop using it

• Order a recall 

• Order a company to repair, replace or refund a device

Biologics

• May also order a recall 

• Revoke or suspend biologic licenses

• Order the retention, recall, destruction, and cessation of manufacturing for human cell, tissue, and cellular and tissue based products

Informal administrative actions 

• Meet with company representatives to “encourage” voluntary compliance 

• Monitor voluntary compliance and corrective action plans 

• Obtain agreements to correct problems 

• Refer problems to state and local authorities to take enforcement action under state law 

Judicial Enforcement Powers

• Civil seizures 

• Civil injunctions 

• Criminal prosecutions 

• Seek court orders assessing civil money penalties 

• Under case law - equitable remedies 

• Restitution (refunds to customers) 

• Disgorgement (surrender of ill gotten gains) 

• Enforcement litigation is bought by the Department of Justice on a recommendation of FDA Chief Counsel 

Prior Notice

• First step in any enforcement action: gives prior notice of any alleged violation unless the agency believes these violations are intention, gross or flagrant or create a danger to health

Factors

• 6 Factors that help the agency decide if it is going to take enforcement action: 

  • The seriousness of the problem 

  • The number of people affected 

  • The degree to which people would be affected 

  • The strength of the evidence that laws or regulations are being violated 

  • The likelihood of success in seeking to remedy the problem 

  • The need for federal resources to resolve the problem

• 6 Factors that help the agency decide if it is going to take enforcement action: 

  • The seriousness of the problem 

  • The number of people affected 

  • The degree to which people would be affected 

  • The strength of the evidence that laws or regulations are being violated 

  • The likelihood of success in seeking to remedy the problem 

  • The need for federal resources to resolve the problem

what are the 6 Factors that help the agency decide if it is going to take enforcement action?

gives prior notice of any alleged violation unless the agency believes these violations are intention, gross or flagrant or create a danger to health

whats the first step in any enforcement action?

• law passed by Congress; regulations promulgated by the FDA; policy guidance documents issued by the agency 

(from Policy - FDA Enforcement) what are the 3 sources of power?

• Honesty 

• Promise-keeping 

• Nonmaleficence 

• Beneficence 

• Autonomy 

• Justice 

A consensus of ethicists recognizes these principles - what are they 6

I

(which class of device?)

• requires least regulations (pose least potential harm to users) - general controls are adequate - manufacturer’s register their facility, list their products with FDA, provide premarket notification where required, maintain records and reports and adhere to GMP - needles, toothbrushes, scissors, stethoscopes 

II

(which class of device?)

general controls are insufficient to ensure safety adn effectiveness, have specific performance standards - insulin syringes, diagnostic reagents, thermometers, heating pads, infusion pumps

III

(which class of device?)

must have premarket approval, are life supporting or life sustaining, present a potential unreasonable risk of illness or injury - pacemarkers, soft contact lenses, replaceable heart valves