1

Sept. 12, 2013Chapter 3P. 117-151

Federal Regulation of Medications: Dispensing

2

Durham-Humphrey Amendment of 1951

Established the two classes of drugs: prescription and OTC.

• OTC – Safe to use without medical supervision and when accompanied by

‘adequate directions for use’

When 1938 FDCA passed, many pre-1938 drugs (which were exempt) were not safe for use without medical supervision. Durham-Humphrey Amendment addressed this

1951 Amendment established prescription legend: “CAUTION: Federal Law Prohibits Dispensing Without Prescription.” Later changed to “Rx Only” by the Food and Drug Administration Modernization Act of 1997

Essentially EXEMPTED prescription drugs from “adequate direction for use” label requirement if drug label contained Rx Legend prior to dispensing. When dispensed by a pharmacist with directions from the prescriber, it was exempt from the labeling requirements of the FDCA.

3

Durham-Humphrey Amendment of 1951 (Cont’d)

503(b)(1) drugs -

(b)(1) A drug intended for use by man which—(A) because of its toxicity or other potentiality for harmful effect, or the method of its use, or

the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such drug; or

(B) is limited by an approved application under section 505 {New Drug} to use under the professional supervision of a practitioner licensed by law to administer such drug;

shall be dispensed only (i) upon a written prescription of a practitioner licensed by law to administer such drug, or (ii) upon an oral prescription of such practitioner which is reduced promptly to writing and filed by the pharmacist, or (iii) by refilling any such written or oral prescription if such refilling is authorized by the prescriber either in the original prescription or by oral order which is reduced promptly to writing and filed by the pharmacist. The act of dispensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which results in the drug being misbranded while held for sale.

4

Durham-Humphrey Amendment of 1951 (Cont’d)

The Durham-Humphrey Amendment still allowed the manufacturer to make the Rx or OTC determination of drugs already on the market 501(b)(1)(A). If the FDA disagreed, it had to file suit and had the burden of proof to show

that the drug was unsafe for use except under the supervision of a practitioner because of its toxicity, the method of use, or the collateral measures necessary to use the drug.

The Durham-Humphrey Amendment did, however, let the FDA determine the status if it was based on section 505 (New Drug Application – NDA).501(b)(1)(B) Secton 501(b)(1)(B) allowed the FDA to apply the statutory standard and limit

a drug to prescription-only status over the objection of the manufacturer by objecting to its OTC labeling with the New Drug Application. Non-Approval of the OTC labeling allowed the FDA to do what it could not do with drugs already on the market, as stated above.

5

Durham-Humphrey Amendment of 1951 (Cont’d)

503(b)(1)(B) language at the end of the section: …shall be dispensed only (i) upon a written prescription of a practitioner licensed

by law to administer such drug, or (ii) upon an oral prescription of such practitioner which is reduced promptly to writing and filed by the pharmacist, or (iii) by refilling any such written or oral prescription if such refilling is authorized by the prescriber either in the original prescription or by oral order which is reduced promptly to writing and filed by the pharmacist. The act of dispensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which results in the drug being misbranded while held for sale.

Two of the primary purposes of the Durham-Humphrey Amendment, that did not receive much opposition and, therefore, had very little debate in congress, was to give a pharmacist the ability to take oral prescriptions and to refill oral or written prescriptions if the practitioner so authorized.

6

Explanation of Pre-Durham Humphrey Rx/OTC status (read at your leisure!)

The first truly mandatory general classification of drugs into prescription or nonprescription categories resulted from FDA regulations issued in 1944. Under the 1938 regulations, the only test for determining whether a drug was prescription-only was whether the manufacturer chose to label it accordingly. Contrary to what might be expected, manufacturers labeled many drugs that were safe for self-medication as prescription-only because they were able to make higher profits with this limitation. This practice both unduly restricted consumer access to safe and effective drugs and led to confusion among pharmacists and the public as to which products were safe for self-medication and which required supervision by a doctor. Due to the confusion and undue restrictions, pharmacists sold many safe drugs that bore the prescription label with neither a prescription (in violation of the regulation) nor adequate directions and warnings for self-use. In response, the FDA amended the regulations in 1944 and specified a definition of a prescription-only drug as one that, “because of its toxicity or other potentiality for harmful effect or the method of its use or the collateral measures necessary to its use, is not generally recognized among experts qualified by scientific training and experience to evaluate its safety and efficacy, as safe and efficacious for use except by or under the supervision of a physician, dentist, or veterinarian.” This regulation effectively created a mandatory class of non-prescription drugs—those that were generally recognized among experts as safe and effective for self-medication—for which the manufacturer was not exempted from labeling requirements and that, consequently, could not be limited to prescription-only sale. Although this distinction was mandatory, the determination as to whether a drug was safe and effective for self-medication was left to the manufacturer in the first instance, with the FDA limited to enforcement actions to insure compliance.

7

Durham-Humphrey Amendment (cont.)

• Exempts the pharmacy label on dispensed drugs from §502 except for certain provisions

• Specifies the minimum information that a dispensed Rx label must contain

• Expiration or beyond use dating on dispensed Rx label not required by the Amendment, but required pursuant to state laws and USP standards

8

Switching Prescription Drugs to OTC

Three Methods

• SNDA – product specific switch• Petition- product specific switch• Adding or amending an OTC drug monograph- affects all

products in the class

9

Professional Practice Considerations Related to D-H

• Prescription refill authorization issues

– Distinguish authorization of refill from transmittal authority

• Prescriptive authority issues

– Federal law leaves it up to the states to determine who may prescribe independently or in collaborative practice

– Scope of authority as determined by the state for prescribers who are not MDs or DOs is important for pharmacists to know

10

Emergency Contraception

• Example of a behind the counter drug in all states and of a pharmacist having independent prescriptive authority in some states.

• After initial rejection of Barr’s SNDA to convert Plan B from prescription to OTC, FDA finally approved for use OTC in women 18 and older.

• Court later ordered the FDA to lower the age to 17 and over and to consider that it should be available OTC without age restriction

11

Conscientious Objection• Refers to whether a pharmacist has a right to refused to dispense

prescriptions he or she has a moral or religious objection.• Many states have passed laws or regulations addressing this issue,

and pharmacy organizations have articulated procedures that should be implemented

• Courts have held that a pharmacist cannot obstruct a patient’s legal right to receive medications, and that state regulations requiring pharmacists to dispense are not unconstitutional

12

Other D-H Related Practice Considerations

• Collaborative Practice Agreements– Authority granted to pharmacists in most states

• Authority to dispense– Depends upon state law– FDA does not believe D-H dispensing standards

apply to prescribers, however, most states regulate prescriber dispensing in some manner

13

Prescription Drug Labeling Information for the Patient

Patient Package Inserts• Although the FDA originally had wanted PPIs required for

most drugs, it applies to very few including estrogen containing drugs, DES and oral contraceptives

• Duty of manufacturers and pharmacists to distribute to patients

• Law applies to institutional pharmacy as well as community

14

Prescription Drug Labeling Information for the Patient

Medication Guides and Consumer Medication Information (CMI)

• Originally FDA wanted to require MedGuides for drugs posing a serious and significant concern to public health and CMI for all other drugs

• Congress intervened to prevent FDA from implementing CMI rules and allowed private sector to develop standards for CMI

• Recent studies show private sector has not yet met the 95% “useful information” standard required by Congress

• Responsibility of manufacturer and dispenser to dispense MedGuides to patients for drugs requiring MedGuides

15

Prescription Drug Labeling Information for the Patient

Medication Guides - MedGuides• MedGuides required for BOTH new and refill prescriptions. • Special rules for patients other than at the retail level.• MedGuides are approved by FDA and have specific language

and font sizes of the lettering• MedGuides distribution is not being followed by most

pharmacists and pharmacies.• Potential tort liability for non-distribution• FDA Website for MedGuides :

http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm

16

Prescription Drug Labeling Information for the PatientREMS (Risk Evaluation and Mitigation Strategy)

Some drugs are so inherently risky that the FDA requires special procedures before they can be dispensed.

Examples: Clozaril (clozapine) – blood work reporting prior to each prescription Thalidomide Accutane (isotretinoin) – iPledge Program

CLICK ON ICON IN NEXT SLIDE TO LAUNCH WEBPAGE SHOWING IPLEDGE PROGRAM…… WILL BE DISCUSSED.

17

iPledge.mht

18

19

Prescribing & Dispensing Approved Drugs for Unlabeled Indications

• Drug products commonly prescribed for off-label uses

• Off-label prescribing and dispensing is legal under the FDCA

• Off-label prescribing and dispensing requires professional evaluation of the risk vs benefit (you’ll see that on bottom of some electronically generated Rxs (e.g., gabapentin rxs – “benefit outweighs risk”)

• Courts generally regard the labeling as evidence towards the standard of care and not as prima facie establishing the standard of care

20

Pharmacy Compounding• Pharmacies compounding for their patients pursuant to

prescription are exempt from the FDCA manufacturing provisions

• FDA 1992 compliance guide– Published by FDA over concern that some pharmacies were

crossing the line from compounding to manufacturing and were not compounding properly

• FDAMA 1997– Delineated which activities might cross the line from compounding

to manufacturing and added other requirements regarding compounding

– Stripped the FDA of authority to consider compounded drugs as “new drugs”

21

Pharmacy Compounding• U.S. Supreme Court ruled that advertising restrictions in FDAMA

were unconstitutional but failed to consider if all of FDAMA’s compounding laws were now invalid as ruled by the Ninth Circuit, or whether the unconstitutional provisions were severable

• FDA 2002 compliance guide

– FDA adopted Ninth Circuit’s position that FDAMA compounding laws were not valid, but reinstituted most of the requirements of FDAMA in the 2002 compliance guide

– Reestablished position that pharmacy compounded drugs are new drugs

• FDA inspection authority

22

Pharmacy Compounding

FDCA Inspections

• FDCA prohibits FDA from inspecting pharmacies that are not manufacturing

• Court determined that the FDA could inspect for the purpose of determining whether a pharmacy is compounding or manufacturing

23

Pharmacy Compounding: New Drug Issue

• Pharmacy plaintiff’s challenged FDA’s position that pharmacy compounded drugs are new drugs.

• Fifth Circuit disagreed with Ninth Circuit and found that the unconstitutional advertising provisions of FDAMA are severable. Further found that compounded drugs are thus exempt from the new drug provisions provided the pharmacy meets all the conditions established in FDAMA

24

Pharmacy Compounding: Patent Issues

• A pharmacy’s right to compound cannot override a manufacturer’s patent rights

• Minoxidil and Rogaine serve as an example

25

Orange Book and Generic Substitution

State Generic Substitution Laws• Every state now permits pharmacists

to substitute generically in some manner

• State laws differ considerably• Labeling must accurately differentiate

generic product from brand

26

ORANGE BOOK• Evaluates pharmaceutically equivalent products on the basis

of bioequivalence• Pharmaceutical equivalence – products contain same active

ingredients and are identical in strength and dosage form• Bioequivalent pharmaceutical equivalents are generally

presumed therapeutically equivalent – having same clinical safety and efficacy

• Orange Book uses 2 letter rating system and for some products 2 letters and a number (AB, AB1, AB2: e.g., birth control pills, nifedipine ER (Adalatt CC vs. Procardia XL)).

• Pharmacists must comply with state law when substituting and exercise professional judgment substituting B rated products

27

Narrow Therapeutic Index (NTI) Drugs

• Drugs with less than a two-fold difference between median lethal dose and median effective dose or two-fold difference between minimum toxic concentrations and minimum effective concentrations.

• Some controversy exists as to whether FDA’s statistical parameters for bioequivalence are accurate enough for certain NTI drugs

• Pharmacists should exercise particular professional judgment when called upon to substitute B rated NTI drugs

28

Prescription Drug Marketing Act

• Requires state licensing of wholesalers• Bans reimportation of Rx drugs except by

manufacturer• Bans sale, trade, or purchase of Rx drug

samples• Mandates requirements for Rx drug samples• Prohibits resale of Rx drugs purchased by

hospitals or health care facilities

29

Prescription Drug Marketing Act of 1987

Drug Samples• Establishes restrictions to limit misbranding and

adulteration situations• Defined as a unit of drug not intended to be sold

and intended to promote the sale of the drug• Establishes requirements for distribution to

prescribers• Prohibits community pharmacies from receiving

samples

30

FDA Inspection Of PharmaciesP.148

• FDA can inspect a pharmacy to determine if the pharmacy is compounding or manufacturing and can extend the search if probable cause exists that the pharmacy is manufacturing

• FDA may search without a warrant.

31

Use Of Alcohol In Pharmacy Practice

• Tax paid alcohol– Used in compounding in community pharmacies– Obtainable from outlets that sell liquor at retail

• Tax free alcohol (190 proof ethyl alcohol) – Available to hospitals for medicinal, mechanical

and scientific purposes and in treatment of patients. May be used only for inpatients

– Charity clinics may use for medicinals for out-patients if they do not charge

32

Poison Prevention Packaging Act of 1970 (PPPA)

• Intent of Act to protect children from accidental poisonings due to “household substances”

• Administered by the Consumer Product Safety Comms• The law establishes the standards for child resistant containers• Container may not be reused unless glass or threaded plastic

and then with new closure • Exemptions

– Pharmacies– Manufacturers– Commonly dispensed drugs

33

Poison Prevention Packaging Act

Exemptions• Prescriber requests• Patient requests• Institutionalized patients• Certain drug products such as SL nitroglycerin and SL & chewable

isosorbide dinitrate• For manufacturer

– May market one size in noncompliant package with appropriate statement

– READ PPPA DOCUMENT – ON SWEENEY WEBSITE

34

35

Next time -- 171-201