Download Law20060112 - Dr Ted Williams

OTC Drugs
• Class of OTC drugs created by DurhamHumphrey Amendment to FDCA.
• OTC drugs are reviewed by therapeutic
class, not individually
• 100,000-500,000 individual products
• Only about 200 active ingredients
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
Non-Prescription Drug Labeling
6. Consumer cautions/warnings – “may
cause drowsiness”
7. Adequate directions for use – “shake
well”, time(s) to administer
Rx to OTC Switch
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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...
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)
“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
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)
Rx Drug Labeling
5. Net quantity in the container (no. of
tabs/caps, mL)
6. Rx legend (“Rx Only”)
7. Route of Adm, if not oral
8. Lot number
9. Container requirements to dispense (tight,
light resistant - USP Stdandsrds)
10. Expiration date
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
National Drug Code
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11 digits (XXXXX-XXXX-XX)
12345 manufacturer
6789 drug/strength
10
package size.
Unique to specific product and dose
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)
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
The New Drug Application (NDA)
• A complete application could contain
100-200,000 pages.
• Submitted electronically
• Complete evaluation of efficacy and
safety
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.
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
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
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”
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
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
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
Voluntary Reporting ProgramsPreviously Discussed
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Drug Quality Reporting System (USP)
MedWatch (FDA)
MedMaRx (USP/ISMP)
Vaccine Adverse Event Reporting
System (VAERS) (FDA)
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
Rx Ads to Professionals
• Drug misbranded unless manuf includes
in all ads
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drug name
formula
brief summary
look at examples in pharmacy & medical
journals
– must have “fair balance”
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
OTC Ads by Manufacturer
• Regulated by FTC
• FTC can’t regulate ads before they are
run
• FTC reviews Ads being run for accuracy
and claims
• OTC ads must be “reasonable”
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...
OTC Review Resulted in Three
Categories
1. Ingredients safe, effective, not
misbranded
2. Ingredients not ...and are misbranded
3. Insufficient data to permit
classification
“Third Class” of Drugs
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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
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
Patient Package Inserts
• FDA required PPIs for estrogencontaining products in early 1970s
• Now common with many drugs
• See example on FDA web site
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
Pharmacy Compounding
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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
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 can’t compound an existing Rx
product
• Can not “compound” non-approved drug
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
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
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
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
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...
OBRA 90
• Background: Requires RPh to review
patient’s 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
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)