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

NonPrescription Drug Labeling

1. Product Name2. Name, address of manuf, packer or

distributor3. Net contents4. 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

• 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 product3. Ingredient information-quantity and

proportion of active ingredients4. 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 oral8. Lot number9. 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

• 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 Programs-Previously Discussed

• 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– 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

• 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 estrogen-containing 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

• 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)