Federal Regulation of Medications, FDA Amendments and Definitions

Prescription dispensing basics, label NDC number, interchange, orange and purple book, misbranding adulteration (MGL c94C, Chapter 2 and 3 Abood)

T OR F: Under MA law, opioid CII or II may be filled for a maximum of 30 day supply of such substance upon a single filling

true

T OR F: Under Mass law, all prescriptions for controlled substances shall be kept for 2 years by the pharmacy

true

Under Mass law and regulations, which of the following is not required on a prescription

time the prescription was issued

T OR F: Mass Medical Doctors may write more than 1 drug product with the same or different spending instructions on the same Rx form

false

T OR F: Patient requests their Rx for a CII partially filled, remaining amount of Rx needs to be filled no later than 30d after issue date

true

If a patient requests partial Rx CII, the remaining portion of Rx may only be filled at the ___

same pharmacy

Are electronic prescriptions required in Massachusetts?

Yes, electronic prescribing is generally required in Massachusetts, with certain exceptions.

If oral Rx for CII is issued, the practitioner

30 days

If oral CII Rx is issued, the practitioner shall cause written Rx to be delivered within

7 days

T OR F: Mass law, an oral RX issued by practitioner may be communicated to Rph by an expressly authorized employee or agent of the practioner

true

The term practitioner as defined by Mass law can include:

Physician, podiatrist, dentist, nurse practitioner

In Mass, which of the following is required on the Pharmacy label?

Pharmacy name and address, name of controlled substance

If a visually impaired patient asks for an accessible label, what font size will be used?

10 characters per inch

The first segment of the NDC number represents

labeler code (manufacturers or distributor)

The second segment of the NDC number represents

product code (strength, dosage form and formulation of the drug)

The third segment if the NDC number represents

package code (package size and type)

for interchanging biologics and biosimilars one would look to the FDA ___ book

purple

for generic substation of a drug one would look to the FDA ___ book

orange

Federal Food, Drug, and Cosmetic Act (FDCA)

provides for the comprehensive regulation of all drugs introduced into interstate commerce

What does the Federal Food, Drug, and Cosmetic Act (FDCA) intend for?

to protect consumers from adulterated or misbranded foods, drugs, cosmetics, or devices.

Under the Federal Food, Drug and Cosmetic Act, no new drug may be marketed and sold unless it has been proved both ___ for its intended use and approved by the federal Food and Drug Administration.

safe and effective

Why was the Pure Food and Drug Act (1906)implemented?

concern for the risks to public health and safety associated with unsanitary and poorly labeled foods and drugs prompted Congress in 1906 to pass the Pure Food and Drug Act

Pure Food and Drug Act of 1906

The adulteration (making products impure or unsafe) and misbranding (false or misleading labeling) of foods and drugs sold across state lines.

In ____, the Pure Food and Drug Act was amended to prohibit false and fraudulent efficacy claims.

1912

Why was the Pure food and Drug Act of 1906 hard to enforce?

it required the government to prove fraudulent intent on the part of one who made false

statements on the label.

Sulfanilamide elixir tragedy of 1937

Solvent was a found to be a deadly poison and 107 deaths were attributed to this elixir.

Did the Pure Food and Drug Act of 1906 give the FDA the power to ban unsafe drugs?

No. The law did not give the FDA the authority to ban unsafe drugs.

Why was the elixir of sulfanilamide removed from the market under the 1906 law?

It was removed based on a technicality because it was mislabeled as an elixir.

Why was the elixir of sulfanilamide considered mislabeled?

Elixirs must contain alcohol, but the sulfanilamide product did not contain alcohol.

What did the 1906 Pure Food and Drug Act NOT allow the FDA to do?

It did not give the FDA authority to ban unsafe drugs.

What was the technicality involving sulfanilamide?

It was called an “elixir,” but it did not contain alcohol.

What must an elixir contain?

Alcohol

Why was the sulfanilamide product considered mislabeled?

It was called an elixir but contained no alcohol.

Food, Drug, and Cosmetic Act of 1938 (FDCA): overview

Provided that no new drug could be marketed until proved safe for use under the conditions described on the label and approved by the FDA.

What did the Food, Drug, and Cosmetic Act of 1938 require for new drugs?

A new drug could not be marketed until it was proven safe.

Who had to approve a new drug before it could be marketed?

The FDA.

What did a drug have to be proven safe for?

Safe for use under the conditions described on the label.

What major change did the 1938 FDCA make?

Drugs had to be proven safe and FDA-approved before marketing.

What did the Food, Drug, and Cosmetic Act (FDCA) of 1938 require on drug labels?

Labels must include clear directions for use and warnings about drugs that can cause dependence or addiction.

Besides drugs, what other products does the FDCA of 1938 cover?

Cosmetics and medical devices.

Durham-Humphrey Amendment of 1951

Amendment established two classes of drugs (prescription and over the counter)

The 1938 FDCA required all drugs to be labeled with “adequate directions for use”, Drugs on the market at this time were not safe for use except under medical supervision, what amendment was enacted to solve this issue?

Durham-Humphrey

What did the Durham-Humphrey Amendment of 1951 require labels to have/not have?

Provided that the labels of prescription drugs need not contain “adequate directions for use” so long as they contain the legend, “Caution: Federal law prohibits dispensing without a prescription”

Which Amendment states: When dispensed by a pharmacist, inclusion on the label of directions from the prescriber satisfies the “adequate directions for use” requirement.

Durham-Humphrey Amendment

What does Durham-Humphrey Amendment authorize?

oral prescriptions and refills of prescription drugs.

What does “adequate directions for use” mean?

clear instructions that anyone can understand

Food Additives Amendment of 1958

Congress amended the FDCA to require that components added to food products must receive premarket approval for safety

Food Additives Amendment of 1958: Anticancer provision, (Delaney Clause)

prohibits the approval of any food additive that might cause cancer.

Color Additive Amendments of 1960

 Requires manufacturers to establish the safety of color additives in foods, drugs, and cosmetics.

 The FDA can approve a color for one use but not the others (e.g. external use only)

Thalidomide

Popular sedative that was confirmed to cause birth defects. Due to the FDA refusal to allow marketing of the drug in the US, the number of birth defects in the US was low.

What drug caused the enactment of the Kefauver-Harris Amendment?

Thalidomide

Kefauver-Harris Amendment of 1962 overview

• Strengthened the new drug approval process by requiring drugs to be proved not only safe but also effective.

• The efficacy requirement was made retroactive to all drugs marketed between 1938 and 1962.

• Amendment also:

transferred jurisdiction of prescription drug advertising from the

Federal Trade Commission to the FDA

• established the Good Manufacturing Practices (GMP) requirements

• added more extensive controls for clinical investigations

• informed consent

• reporting of adverse drug reactions

What did the Kefauver-Harris Amendment of 1962 require?

Drugs must be proven safe AND effective before approval.

What did the Kefauver-Harris Amendment add to the drug approval process?

The requirement that drugs be proven effective, not just safe.

What happened to drugs marketed between 1938 and 1962?

They were retroactively required to prove efficacy.

Who gained control over prescription drug advertising under the 1962 Amendment?

The FDA took jurisdiction from the Federal Trade Commission (FTC).

What manufacturing requirements did the 1962 Amendment establish?

Good Manufacturing Practices (GMP).

What did the 1962 Amendment do to clinical investigations?

It established more extensive controls over clinical investigations.

What requirement was added regarding participation in clinical investigations?

Informed consent.

What safety reporting requirement was added?

Reporting of adverse drug reactions (ADRs).

What is the easiest way to remember the 1962 Amendment?

Safe + Effective + GMP + Informed Consent + ADR Reporting.

Medical Device Amendment of 1976 Overview

 Under the 1938 Act, the FDA had no

authority to review medical devices for

safety and efficacy before marketing

 Prompted by public safety concerns with

certain devices, Congress amended the

FDCA in 1976 to provide for more

extensive regulation administrative

authority regarding the safety and efficacy

of medical devices.

Before 1976, could the FDA review medical devices for safety and efficacy before marketing?

No. Under the 1938 Act, the FDA had no authority to do this.

Why was the Medical Device Amendment of 1976 passed?

Because of public safety concerns with certain medical devices.

What did the 1976 Medical Device Amendment give the FDA?

More extensive authority to regulate the safety and efficacy of medical devices.

What major change did the 1976 Amendment make?

It allowed the FDA to more extensively regulate medical devices for safety and efficacy.

What does the Medical Device Amendment of 1976 require?

 classification of devices according to their function

 premarket approval

 establishment of performance standards

 conformance with GMP regulations

 adherence to record and reporting requirements

How are medical devices classified under the 1976 Amendment?

Devices are classified according to their function

What approval is required for certain medical devices before marketing?

premarket approval

What standards were established for medical devices?

performance standards

What manufacturing requirements must medical devices follow?.

Good Manufacturing Practices (GMP)

What recordkeeping requirements apply to medical devices?

They must follow record and reporting requirements.

Orphan Drug Act of 1983 Overview

 Pharmaceutical manufacturers had urged Congress to recognize that the NDA process was too expensive to warrant development and marketing of drugs for diseases that affected few people.

 In 1983, Congress passed legislation to provide tax and exclusive licensing incentives for manufacturers to develop and market these drugs or biologicals

 “rare diseases or conditions” (defined as those affecting fewer than 200,000

Americans.)

Why was the Orphan Drug Act of 1983 created?

The drug approval process was too expensive for drugs treating rare diseases.

What did Congress provide to encourage development of orphan drugs?

Tax incentives and exclusive licensing incentives for manufacturers.

What are “orphan drugs”?

Drugs or biologicals developed to treat rare diseases or conditions.

How did the 1983 Act define a “rare disease or condition”?

One affecting fewer than 200,000 Americans.

Who benefits from the incentives provided by the Orphan Drug Act?

Pharmaceutical manufacturers developing and marketing drugs for rare diseases.

What is the main idea of the Orphan Drug Act?

Rare disease → expensive development → incentives to encourage drug development.

Drug Price Competition and Patent Term Restoration Act of 1984 Overview

 AKA Waxman-Hatch Amendment

 Enacted to streamline the generic approval process while giving patent extensions, in certain circumstances, to innovator drugs.

 The intent is to make generic drugs more readily available to the public while providing incentives to manufactures to develop new drugs.

What is another name for the Drug Price Competition and Patent Term Restoration Act?

The Waxman-Hatch Amendment.

What was the main purpose of the 1984 Waxman-Hatch Amendment?

To streamline generic drug approval while providing certain patent extensions for innovator drugs.

What did the the Waxman-Hatch Amendment do for generic drugs?

Made generic drugs more readily available to the public.

What did the the Waxman-Hatch Amendment provide for innovator drugs?

Patent extensions in certain circumstances.

Why did the the Waxman-Hatch Amendment address both generics and innovator drugs?

to increase generic availability while incentivizing development of new drugs.

What are the two main goals of Waxman-Hatch?

Easier generic approval + incentives for new drug development.

Prescription Drug Marketing Act of 1987 Overview

 Due to growing alarm that a secondary

distribution system for prescription drugs was

threatening the public health and safety and

creating an unfair form of competition.

 Law establishes sales restrictions and record

keeping requirements for prescription drug

samples.

 Prohibits hospitals and other health care entities

from reselling their pharmaceuticals to other

businesses and requires state licensing of drug

wholesalers.

Why was the Prescription Drug Marketing Act of 1987 passed?

Concern that a secondary drug distribution system threatened public safety and created unfair competition.

What did the Act establish for prescription drug samples?

Sales restrictions and record-keeping requirements.

What did the Act prohibit hospitals and other healthcare entities from doing?

Reselling their pharmaceuticals to other businesses.

What licensing requirement did the Act establish for drug wholesalers?

State licensing of drug wholesalers.

What are the main requirements of the Prescription Drug Marketing Act?

Restrict drug-sample sales, require records, prohibit certain resales, and license wholesalers.

Safe Medical Devices Act of 1990 overview

 This act further strengthened the Medical Device Amendment giving the FDA

additional authority especially related to post marketing requirements and premarket notification and approval, while expediting the premarket device approval process.

What did the Safe Medical Devices Act of 1990 do?

It strengthened the Medical Device Amendment and gave the FDA additional authority.

What area did the 1990 Act strengthen after a device was marketed?

Post-marketing requirements.

What did the Act strengthen before a device could be marketed?

Premarket notification and approval requirements.

What happened to the premarket device approval process?

It was expedited

What are the key points of the 1990 Act?

More FDA authority + stronger post-market rules + premarket notification/approval + faster approval.

The Generic Drug Enforcement Act of 1992 Overview

 Occurred when some FDA staff accepted bribes

from generic drug industry personnel in order to

facilitate the approval process of certain generic

drug products.

 FDA to ban individuals or firms from

participating in the drug approval process if

convicted of related felonies.

 Imposes severe civil penalties for any false

statements, bribes, failures to disclose material

facts and other related offenses.

What event led to the Generic Drug Enforcement Act of 1992?

Some FDA staff accepted bribes to help certain generic drugs get approved.