OTC Drugs

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OTC Drugs

• Class of OTC drugs created by Durham-Humphrey
  Amendment to FDCA.
• OTC drugs are reviewed by therapeutic class, not
  individually
• 100,000-500,000 individual products
• Only about 200 active ingredients

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NonPrescription Drug Labeling

• 1. Product Name
• 2. Name, address of manuf, packer or distributor
• 3. Net contents
• 4. Established name of all active ingredients
  and quantity of certain other ingredients, active
  or not i.e..., alcohol, dyes
• 5. Name of any habit forming drug

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Non-Prescription Drug Labeling

• 6. Consumer cautions/warnings may cause
  drowsiness
• 7. Adequate directions for use shake well,
  time(s) to administer

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Rx to OTC Switch

• Authorized by Durham-Humphrey
• Manufacturer or FDA can initiate
• Insurance company can initiate (e.g. Prilosec)
• OTC Drug Review Process primary mechanism by
  which drugs are switched
• There is a committee at FDA which advises on Rx
  to OTC switches
• Rx examples switched to OTC Benadryl, Actifed,
  Hydrocortisone, Drixoral, Dimetapp, Monistat,
  Ibuprofen, Zantac, Tagamet, Pepcid, Aleve,
  Claratin, Prilosec...

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Prescriptive Authority

• Durham Humphrey states that legend drugs may be
  prescribed by a practitioner licensed by law to
  administer such drug
• Determined by state practice acts (MD, DO, NP,
  PA, DVM, NP, OD)

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Unapproved Use of Prescription Drugs

• Called off-label, unlabeled, or unapproved
  use
• Legal for prescriber to use a drug for any
  indication (ethical in every case?)
• Promotion of unlabeled uses by manufacturer is
  restricted
• See NYT article 1/11/06
• Drug Makers Scrutinized Over Grants

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Prescription Drug Labeling

• Labeled for the health professional, not general
  public-and contains
• 1. Name, address of manufacturer, packager or
  distributor
• 2. Established name of drug product
• 3. Ingredient information-quantity and proportion
  of active ingredients
• 4. Quantity in terms of weight or measure (mg)

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Rx Drug Labeling

• 5. Net quantity in the container (no. of
  tabs/caps, mL)
• 6. Rx legend (Rx Only)
• Route of Adm, if not oral
• Lot number
• 9. Container requirements to dispense (tight,
  light resistant - USP Stdandsrds)
• 10. Expiration date

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Package Insert

• FDCA regulates what must be placed in package
  insert
• And in what order
• Can not be promotional
• Often negotiation between FDA and Manufacturer
• Provides legal cover for manufacturer

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National Drug Code

• 11 digits (XXXXX-XXXX-XX)
• 12345 manufacturer
• 6789 drug/strength
• 10 package size.
• Unique to specific product and dose

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Investigational New Drug (IND) Application

• Prescription drugs must be approved by FDA prior
  to marketing
• Must be proven safe and effective (?)
• Usually only effective vs. placebo and not vs.
  similar drugs
• IND is first step in process and leads to the New
  Drug Application (NDA)

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Investigational New Drug (IND) Application

• There are three IND types
• Investigator IND
• Emergency Use IND
• Treatment IND
• IND application must contain
• Animal Pharmacology and Toxicology Studies
• Manufacturing Information
• Clinical Protocols and Investigator Information

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The New Drug Application (NDA)

• A complete application could contain 100-200,000
  pages.
• Submitted electronically
• Complete evaluation of efficacy and safety

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Goals of the NDA

• Provide enough information to permit FDA to make
  the following key decisions
• Whether the drug is safe and effective in its
  proposed use(s), and whether the benefits of the
  drug outweigh the risks.
• Whether the drug's proposed labeling (package
  insert) is appropriate, and what it should
  contain.
• Whether the methods used in manufacturing the
  drug and the controls used to maintain the drug's
  quality are adequate to preserve the drug's
  identity, strength, quality, and purity.

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Abbreviated or Supplemental NDA

• Abbreviated NDA
• Generic drug
• New combination of approved drugs
• Proportion of ingredients in combination is
  changed
• Supplemental NDA
• New intended use of the drug (labeling change)
• Dose, method or duration of administration is
  changed
• Change in manufacturing process or location

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Clinical Trials in Humans

• 3 phases
• Phase I - small number of patients (healthy
  males)
• Phase II - tested on patients with the disease
• Phase III - safety and efficacy on hundreds or
  thousands of patients
• Must have informed consent from patient before
  testing proceeds

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FDA New Drug Rating Classification System

• Rates new drugs by chemical type and therapeutic
  potential
• Rating determines how rapidly drug will get
  through NDA process
• Standard review vs. Priority review

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Post Marketing Surveillance

• FDA MedWatch Drug Quality Reporting System
• Anything that deals with product quality - label,
  bad pills
• USP Drug Quality Reporting System (DQRS)
• Product quality, an adverse reaction-any type of
  problem
• These are sent by USP to FDA
• Phase IV clinical trials
• voluntary vs. mandatory

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Drug Price Competition and Patent Term
Restoration Act

• Streamlined the approval process for generic
  drugs
• Generic manufacturer now needs to establish that
  their product is bioequivalent to the reference
  drug
• See FDA Orange Book

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Drugs Intended to Treat Serious Diseases (AIDS,
Avian Flu...)

• NDA process criticized over the years as being
  too slow to approve breakthrough drugs
• FDA modified its process
• FDA Modernization Act of 1997
• codified fast-track approval of break through
  drugs

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Voluntary Reporting Programs-Previously Discussed

• Drug Quality Reporting System (USP)
• MedWatch (FDA)
• MedMaRx (USP/ISMP)
• Vaccine Adverse Event Reporting System (VAERS)
  (FDA)

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Drug Advertising

• FDA regulates Rx Advertising
• FTC regulates OTC Ads
• Lanham Trademark Act allows private parties a
  cause of action against false ads
• Also regulated by State Pharmacy Practice Acts

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Rx Ads to Professionals

• Drug misbranded unless manuf includes in all ads
• drug name
• formula
• brief summary
• look at examples in pharmacy medical journals
• must have fair balance

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Direct to Consumer Advertising

• No Federal regulations specifically on this
  subject
• two categories of these ads
• non product specific - no drug names usually
  discusses a medical condition and states see
  your doctor!
• product specific - i.e.., Cialis, Levitra,
  Detrol, Neulasta
• Recent FDA hearing on DTC advertising

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OTC Ads by Manufacturer

• Regulated by FTC
• FTC cant regulate ads before they are run
• FTC reviews Ads being run for accuracy and claims
• OTC ads must be reasonable

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OTC Review

• Kefauver-Harris Amendments applied to OTC and Rx
  Drugs
• OTC products reviewed on a class basis
• Were OTC products effective as marketed?
• Antihistamines as daytime sedative Sominex...

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OTC Review Resulted in Three Categories

• 1. Ingredients safe, effective, not misbranded
• 2. Ingredients not ...and are misbranded
• 3. Insufficient data to permit classification

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Third Class of Drugs

• Historic Issue
• Drugs sold only by a pharmacist
• ie.,those that just came off Rx status
• Common in many other countries
• Only in Florida so far
• Proposal for EC

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Prescriptive Authority

• Granted by the State
• RPhs can prescribe Formulary items in some states
  (but not in Oregon)
• Practitioners - MD, DO, DDS, DVM, PA, NP,
  ND, OD
• Restrictions on prescribing

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Patient Package Inserts

• FDA required PPIs for estrogen-containing
  products in early 1970s
• Now common with many drugs
• See example on FDA web site

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Approved Drugs for Unlabeled Indications

• MD, DO (Doctor of Osteopathy) Practitioners may
  prescribe any drug for any indication
• Others must stay within their scope of practice

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Pharmacy Compounding

• Controversial Area
• RPh may compound pursuant to a Rx
• Or in anticipation of an Rx
• Is regulated by State law and is not considered
  manufacturing

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Pharmacy Compounding

• Is manufacturing if product is sold to another
  pharmacy
• It is manufacturing if pharmacy repackages OTC
  products for sale to other health providers
• Pharmacy cant compound an existing Rx product
• Can not compound non-approved drug

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FDA Orange Book

• Publishes FDA Classification of drugs therapeutic
  equivalence
• AA-no bioequivalence problems
• AT-topical -no problems
• AB-drugs meeting necessary bioequivalence
  requirements
• BC-Extended release with problems

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FDA Ratings-CON'T

• BT-Topical with problems
• BX-insufficient data
• B-No determination will be made until other
  questions answered
• See FDA web-site

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Federal Alcohol Tax

• Federal government does not tax alcohol when used
  by
• Gvt for scientific/mechanical purposes
• Schools/colleges for scientific/ mechanical
  purposes
• Labs for research
• hospitals etc for patient care
• pathology labs for patient care

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Poison Prevention Packaging Act

• Intended to prevent child poisonings
• Established child resistant safety cap
• Established that household substances must be
  child proof
• Hazardous substances, economic poisons
  (insecticides), food, drug or cosmetic or
  household fuel in a portable container

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Poison Prevention Packaging Act

• Enforcement by Consumer Product Safety Commission
• Exempts some drugs from safety cap
• If either MD or patient requests ez open caps
• Some OTCs used by elderly or handicapped
• Hospital drugs i.e..., unit dose and some other
  Rx items i.e..., OCs, nitroglycerin...

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OBRA 90

• Background Requires RPh to review patients
  medication therapy--counseling
• Rebates from drug manuf to state Medicaid
• DUR-Retrospective and Prospective
• Mandated Patient Counseling, RPh document
  counseling activities, enforcement of RPh
  activities by state board of pharmacy
• Applies only to Medicare/Medicaid patients
• Most states broadened to apply to all patients
• Will discuss under State laws

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Reimportation of Rx Drugs

• Personal use exemption for limited quantities
• Internet purchases from outside US technically
  illegal
• Common practice
• Drugs sold from outside of US are not FDA
  approved (even if made in same factory as
  FDA-approved version)