RX 526: Exam 1

What is a law?

"the system of rules which a particular country or community recognizes as regulating the actions of its members and which it may enforce by the imposition of penalties." -Oxford dictionary

Constituent is what?

citizen

Legislative is what?

Congress, Indiana General Assembly

Legislative does what?

- Makes laws

- Statutes

Executive is what?

President/Governor

Executive does what?

- Make rules/regs and enforce statute, rules, regs

- Executive orders

- Administrative agencies (rules/regulations)

Judicial is what?

courts

Judicial does what?

- Interpret laws

- Case law

Statute = ___

law

Statutory law passed by US Congress is what?

United States Code (USC)

Statutory law passed by state legislature is what?

Indiana Code (IC)

USC

United States Code

IC

Indiana Code

Administrative Law is what?

Rules, Regulations

Administrative agencies are given authority by what to create rules and regulations?

statute

Administrative Law Example: FDA

Food, Drug, and Cosmetic Act

Administrative Law Example: IN Board of Pharmacy

Indiana Code, Title 25

Enforcement of statute, rules, and regulations are also given by what to agencies?

statute

Federal rules/regulation creation

- Federal agencies must publish draft rules in The Federal Register

- Public comment period & Agency review

- Final rules are also published In The Federal Register and Code of Federal Regulations

--- Promulgation

Examples of Federal rules/regulation creation

FDA, CMS, DEA

State rule/regulations

- State agencies must also publishdraft rules

- Public comment period needed

- Comments reviewed before final rules established

State rule/regulations Example

- pharmacy technician vaccine administration

- IPLA ->> Board of Pharmacy, Medical Licensing Board

Validity of regulations

- Rule/regulation MUST be within the scope of the agency

- It must be based on statute that gives the agency authority to promulgate the rule

- It must have a relationship to public health, safety, and welfare.

Common law

law made by the courts

Courts make laws through what?

Judicial opinions

stare decisis

Ruling is enforceable as law and binding on lower courts

stare decisis Only applies to what?

courts in same jurisdiction

When does Common law and statutory law overlap

when courts asked to interpret meaning of statutes

Example: PBM Law

- Arkansas passed Act 900 in 2015

--- PBMs must pay Arkansas pharmacies at rates equal or higher to drug acquisition cost

- Arkansas District Court and Eight District Court ruled in favor of PBMs

- U.S. Supreme Court reversed the lower court rulings

- PCMA vs. Rutledge

--- PCMA vs. Rutledge

Hierarchy of Laws

1. U.S. Constitution

--- Federal statute

--- Federal rule/regulation

2. State constitution

--- State statute

--- State rules/regulations

3. City/county charters

--- Local laws and ordinances

--- Local agency rules/regulations

Preemptive Doctrine

Federal law preempts state law, unless state law is stricter. Follow the stricter law when federal and state law conflictPreemptive Doctrine Example Indiana limits on initial days' supply for opioid dispensing

True or False? State law can be more strict than federal, but not less strict

True

Executive Orders

- US Constitution gives president broad executive and enforcement authority

- Congress also gives this authority to the president

- In states, this is also designated by state constitution and/or legislature

Civil Law

Private party sues another (Injury alleged). Civil action compensates a party "wronged" by another. Decision based on common law and/or statutory law

Criminal Law

Law (statute) violated -> Criminal action stated by government. Criminal charge may only occur if a statute exists prohibiting what occurred

Administrative Law

Statute or regulation violated. Agency investigates and takes action. Actions include: warnings, fines, license revocation or suspension, probation

Standard of care

level of practice, skill, and diligence that a reasonably competent professional would provide under similar circumstances

Bright line

a clearly defined, objective legal standard that leaves little room for interpretation and produces predictable, consistent outcomes

Right touch

a regulatory philosophy that applies the minimum level of regulation necessary to manage risk, focusing on outcomes, proportionality, and evidence‑based decision‑making

Policy

- Outline of what WILL or WILL NOT be done

- Not law

- Involves many players: government, special interest groups

Policies can lead to what?

laws

Pharmacy Policy Issues

- Opioid crisis

- Pharmacist provider status

- COVID-19 response

- Contraception access

Pharmacy Policy Issues: Opioid crisis

1. Overdose deaths skyrocketed

2. Groups advocated for change

3. Laws, regulations passed

4. Changes in practice

Pharmacy Policy Issues: Pharmacist provider status

1. Scope of pharmacists increasing

2. Insurance companies did not pay pharmacists for claims

3. National organizations started campaign for change

4. State pharmacy associations advocated for state recognition

Pharmacy Policy Issues: COVID-19 response

1. COVID-19 pandemic stress on health care system

2. Advocacy by multiple groups to expand access

3. Pharmacists given more authorities

4. State laws changed

Pharmacy Policy Issues: Contraception access

1. Contraception access lacking

2. 2013 -California became the first state to permit pharmacists to "furnish" without a prescription

3. Consumer, pharmacy, other health care groups joined to expand access in other states

What is the purpose of Board of Pharmacy?

to protect the public from pharmacy

What is the purpose of State Pharmacy Association?

exist to protect, advance, and advocate for the profession of pharmacy at the state level.

FD & C Landmark Laws

- Pure Food and Drug Act of 1906

- Food, Drug, and Cosmetic Act (FDCA) of 1938

- Durham-Humphrey Amendment of 1951

- Kefauver-Harris Amendment of 1962

- Medical Device Amendments of 1976

Pure Food and Drug Act of 1906

- Prohibited adulteration and misbranding of foods and drugs in interstate commerce

--- DID NOT include that misbranding includes false or misleading efficacy claims

- This led to Pure Food and Drug Act of 1912

--- Required the government to prove fraudulent intent

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

- No new drug could be marketed until proven safe for use described on the label and approved by the FD

- Expanded definitions of adulteration and misbranding

- Labels must include "adequate directions for use" and warnings about habit-forming potential of certain medications

- Exempted drugs marketed before 1938 to be proven safe

- Added cosmetics and devices

Durham-Humphrey Amendment of 1951

- Created prescription and over the counter classes*

- "Caution: Federal law prohibits dispensing without a prescription"

--- Pharmacist placing label of directions on prescription satisfies "adequate directions for use"

- Authorized oral prescriptions and refills of prescription medications

Kefauver-Harris Amendment of 1962

- Drugs must be proven safe AND effective

- FDA given jurisdiction over prescription drug advertising

- Established Good Manufacturing Practices (GMP)

- Informed consent of research subjects and reporting of adverse drug reactions in clinical trials

Thalidomide led to what law/amendment?

Kefauver-Harris Amendment of 1962

Medical Device Amendments of 1976

- Classification of devices

- Premarket approval

- Performance standards

- GMP regulations

- Record and reporting requirements

Drug definition

1. "Articles recognized in the official compendium or any supplement of the official compendium."

2. AND intended for the use in diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animal

3. AND article (other than food) intended to affect the structure or any function of the body in man or other animal

4. AND articles intended for use as a component of any article specified in any of the above bullet points

Cosmetic definition

Articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applies to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, AND articles intended for use as a component of any such articles

- Except that such term shall not include soap

Are Articles drugs or cosmetics?

Articles can be a drug AND a cosmetic (ex. Medicated shampoos)

Food

1. Articles used for food or drink for man or other animals

2. Chewing gum

3. Articles used for components of articles in 1 and 2

Prescription Drug Definition

- Rx-only or legend drug

- Supervision for safe and effective use

--- Supervision = practitioner

- Concerns with toxicity, potential for harmful effects, how it is administered/used, collateral measures for use

- "Unavoidably unsafe" but not "unreasonably dangerous"

Over-the-counter (OTC) definition

- Safe and effective for use without supervision

- OTC vs Rx status can vary by indication

Behind-the-counter definition

- Third, "unofficial" class

- Proposals or state-specific

- Example: PSE

Orphan Drug definition

- Drugs for Rare Diseases

- Used for a condition that:

--- Affects less than 200,000 people in the US OR

--- Affects more than 200,000 people but the cost of developing and making the drug will not be covered from sales

- If found to have another use, it does NOT lose orphan drug status

Dietary Supplement

Product (other than tobacco) intended to supplement the diet that contains one or more of the following:

--- Vitamin

--- Mineral

--- Herb or other botanical

--- Amino acid

--- Dietary substance for use by man to supplement the diet by increasing the total dietary intake OR

--- Concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause A through E

Pre-1938 drugs definition

Assumed safe and effective due to length of use

DESI: drugs marketed from 1938-1962

Proven to be SAFE but NOT effective

DESI

drug efficacy study implementation

Post-1962 Drugs definition

- Subject to higher standards for safety AND effectiveness

- Must go through full FDA approval process, including INDA/NDA

Pre-'38 Drugs examples

- Thyroid hormone

- Morphine

- Codeine

- Nitroglycerin

DESI Drugs

- Drug Efficacy Study Implementation

- Drugs introduced between 1938-1962

--- Safe but NOT known to be effective

- Effectiveness had to be proven or removed from market

New Drug

- Not generally recognized as safe (GRAS) and not generally recognized as effective (GRAE)

--- GRASE (not generally recognized as safe and effective)

- New condition or new dosage form

- Must go through new drug application for FDA approval

Device definition

Instrument or related article that is:

1. Recognized in USP, NF, or any supplement AND

2. Intended for use in the diagnosis of disease or other condition, or in the cure, mitigation, treatment, or prevention of disease in man or other animal, AND

3. Intended to affect the structure or any function of the body in man or other animal, and which does not achieve its primary intended purposes through chemical action and which is not dependent upon being metabolized for the achievement of its intended purpose

Drug or Device?

- Is the product intended to deliver drugs to the patient, but is not prefilled by the manufacturer?

- Is the drug component included solely to make the product safer?

- Is the drug component intended to have a therapeutic effect?

Medical Devices: Classes

- Class I

- Class II

- Class III

Medical Devices: Device types

- Restricted

- Custom

- Banned

Class I Devices

- Least dangerous; "low risk"

- Do not support life, sustain life, or present an unreasonable risk of illness or injury with use

- Subject to "general controls"

--- Must conform with cGMP

Class I Devices examples

Stethoscope, scissors, toothbrushes, ventilator tubing

Class II Devices

- More "dangerous" than class I

--- Moderate risk

- Require special controls

--- Performance standards set by experts

--- Most likely to require premarket notification

Class II Devices examples

Syringes, tampons, condoms, HbA1c immunoassay

Class III Devices

- Most serious/"dangerous"

--- "High risk"

- Support life, sustain life, prevent the impairment of human health, or present unreasonable risk of illness or injury

- REQUIRE pre-market approval

--- Similar to new drug

Class III Devices examples

Pacemakers, replacement heart valves, implanted spinal cord stimulators

Device Types: Restricted

- Require prescriptions

- May restrict to patients who are trained

Device Types: Custom devices

Ordered to fit the needs of a patient

Device Types: Banned

- Banned from use in the US

- Prosthetic hair fibers

Adulteration

- Entire product or part is filthy, putrid, decomposed

- Prepared, packed, held under unsanitary conditions

- Methods used, facilities, and controls used for manufacture, processing, packaging, or holding do not conform to Current Good Manufacturing Practice (CGMP)

- Container is an issue (poisonous or deleterious)

- Contains unsafe coloring agent or is an unsafe coloring agent

- Claims to be official drug and strength, quality, purity different from the compendium standards

--- UNLESS plainly stated on the label (e.g. "Not USP")

- Not an official drug and the strength or purity falls below what is claimed

- Mixed or packed with a substance to reduce its quality or strength or complete substitution (entire drug or parts of it)

- A drug is considered adulterated, even if it is pure when:

--- Prepared, packaged, or held in conditions where it MAY have been contaminated

--- Exposed to a container that MAY have contaminated it

--- Manufactured under conditions that do not conform to CGMP

- Issues/potential issues with product itself

- Adulteration can occur in pharmacies

--- Improper storage

--- Mixed incorrectly

--- Counted without cleaning the tray

Current Good Drug Manufacturing Practice

- Set of regulations that establish minimum requirements for:

--- Methods, facilities, or controls used in the manufacture, packaging, or holding of a drug product

- Test small part of a batch for quality

- Applies to manufacturers

- Only applies to pharmacies if registered as an outsourcing facility or engage in activities deemed as manufacturers

- Manufacturers inspected by FDA every 2 years

Misbranding

- Drug that has false or misleading labeling

- Required information must be prominently displayed

--- Must be understandable by an ordinary individual under customary conditions or purchase and use

- Misleading container or limitations or sold under the name of another drug

- Dangerous to health when used in the dose, frequency, or duration described on label

- Packaging or labeling in violation of Poison Prevention Packaging Act

- Color additive for coloring only and not labeled as such

- Failure to comply with REMS

- Fails to bear product identifier (Rx-only)

- Drug comes from non-registered establishment

- Issues with the words associated with the product

- Prescription label requirements fall under misbranding

- Products can be adulterated AND misbranded

Adulteration VS. Misbranding

- Adulteration = something is wrong (or could be wrong) with the medication "INSIDE" the bottle

- Misbranding = issues with the "OUTSIDE" of the bottle/the label

Adulteration AND misbranding

- The capsules from this bottle of elderberry supplements were found to have contained no elderberry extract at all, but rather they were packed with bulking fillers.

- The capsules are adulterated because the supplement was substituted with another ingredient AND

- The capsules are misbranded because the capsules contain substances other than what was listed on the label

Pharmacist Adulteration Case in Indiana

- Compounding pharmacy in Indiana

- 2013-2016: 70 potency test failure notices

--- Medications under or over-potent

--- Drugs shipped to hospitals before receiving potency test results

--- Infants injected with over-potent morphine

United States v. Elmer

- 10-count indictment

--- 1 count of conspiracy to defraud the U.S.

--- 3 counts of distributing an adulterateddrug in interstate commerce

--- 6 counts of adulterating drugs while held for sale after shipment of a drug component in interstate commerce

Dietary Supplement Health and Education Act (DSHEA) 1994

- Manufacturers can make statements related to a structure or function of the body if the statement:

--- Claims product will benefit a classical nutrient deficiency (as long as prevalence of the disease in the US is disclosed as well)

--- Describes the role of dietary supplement in affecting the structure or function of the body

--- Characterizes the documented mechanism by which a nutrient or dietary supplement acts to maintain structure or function

--- Describes the general well-being from consumption of a nutrient or dietary ingredient

Dietary Supplements Requirements

- Manufacturers must have evidence for statements

--- Truthful, not misleading

- Label must contain "This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease"

- No premarket approval required

- Do not need to submit proof to FDA that product is safe or effective

DSHEA Concerns

- Marketing of unsafe dietary supplements occurs and FDA unable to act aggressively to protect the public

- Lack of consumer information about dietary supplements interacting with certain OTC and prescription medications

- Lack of quality standards; manufacturers not required to register

--- MUST comply with CGMP

Non-generic drugs must apply for and obtain approval of ___ from ___

NDA from FD

NDA

New Drug Application

What is needed for clinical trials before NDA can be approved?

IND

Who must apply for approval FDA?

Rx-only AND OTC drugs

New drug definition

drug that is not generally recognized by qualified experts as safe AND effective (GRASE) for use under the conditions recommended in the drug's labeling

Some drugs have been marketed for several years without FDA approval. If FDA decides these drugs need approval, then...

manufacturer could demonstrate the produce is GRASE and use to a "material extent and for a material time" to avoid product being labeled new drug