Legal and Regulatory issues in Self-Care practice

brief history of OTC drugs

1938- Federal Food, Drug, & Cosmetic Act

1951- Durham-Humphrey Amendment (categorized prescription vs nonprescription)

1962- Kefauver-Harris Amendment (mandated efficacy)

1972- FDA initiates “OTC Drug Review”

1991- Creation of Division of Non-prescription Drug Products

1997- Food and Drug Modernization Act

CARES Act- March 2020

streamlines OTC monograph process by eliminating rulemaking process, giving FDA more authority to update monographs in a timely manner (OTC drug review)

improves efficiency, timeliness, and predictability

allows FDA to collect user fees from manufacturers

what drugs can be marketed as nonprescription?

can be used by a consumer guided by the product label such that the consumer can self-diagnose, self-treat, and self-manage the condition

no health care practitioner is needed for the safe and effective use of the product

has a low potential for abuse and misuse

benefits of nonprescription availability outweigh the risks

FDCA currently prohibits marketing of same active ingredient unless

there is a meaningful difference between the two for usage

state rights and nonprescription drugs

they may not allow a prescription drug to be sold as other than prescribed, but they may restrict a drug with nonprescription status under federal law to prescription status

FDA office on Nonprescription products establishes monographs through

rulemaking

general public, manufacturers, or other interested parties may comment

nonprescription categories

category I (GRASE)

category II (non-GRASE)

category III (insufficient evidence to provide GRASE)

CARES impact on nonprescription drug categories

requires cat II drugs to be removed from the market

cat I drugs remain GRASE

cat III drugs are not automatically GRASE but will not require an NDA

CARES and rulemaking process

replaced the notice and comment process with three types of administrative orders: FDA initiated, expedited (imminent hazard), industry-initiated (OTC monograph order request tier 1 or 2)

minor changes for drugs can be implemented without administrative orders and in some cases by conducting studies and submitting data

pathways to nonprescription status

marketed in accordance with OTC review monograph for that ingredient

new drug application (NDA)

when does OTC get to market through monograph process?

pending determination under the OTC drug review process

new drug application (NDA)

required for any drug not included in OTC review monograph

reclassified (switched) from Rx to nonprescription

approved directly as nonprescription

NDAs provide FDA with following information:

the drug is safe and effective for intended use

benefits outweigh the risks

manufacturing preserves drugs identity, strength, quality, and purity

approved NDAs are

manufacturer (“sponsor”) specific

second manufacturer may submit an abbreviated NDA

type of NDA applications

direct to nonprescription

abbreviated NDA

NDA deviation

prescription to nonprescription

abbreviated NDA

used for switching a generic drug to nonprescription status (e.g. loratidine)

NDA deviation

for new nonprescription products that differ only slightly from monograph products (rarely used)

NDA supplement

allows for prescription to nonprescription switches

applies to particular product

3 years market exclusivity, label comprehension studies may also be required

citizen petition

also called petitioning the FDA

may be filed by interested parties such as manufacturers

amending the drug monograph

applies to all products with the ingredient

may need to submit NDA if product deviates from monograph specifications (i.e. indications)

considerations in Rx to OTC switches

safety

methods of use

efficacy

labeling (adequate directions)

other issues

reclassified drugs

over 700 products on the market today use ingredients or dosages that were once Rx

includes claritin/zyrtec/allegra, prilosec, miralax, zantac, flonase, narcan, etc

nonprescription safe use regulatory expansion (NSURE) initiative

In 2012, the FDA asked for comment on a docket considering

innovative technologies and other conditions of safe use to

expand which drug products can be considered nonprescription

◦ Potential candidates are medications for:

◦ Hyperlipidemia, hypertension, migraines, asthma, and allergic reactions

additional condition for nonprescription use (ACNU)

drug product that could be marketed without a prescription if an applicant implements an additional condition to ensure appropriate self-selection, appropriate actual use, or both by consumers without the supervision of healthcare practitioner

product recall

product is potential risk to public

FDA may ask for voluntary recall from manufacturer

manufacturer is responsible for notifying sellers (including pharmacists, who must notify consumers)

FDA product recall methods

Drug is misbranded, adulterated, or unapproved the FDA can seize the

product and order it be held pending review

FDA can seek a court injunction preventing further sale of the drug

product recall classification

Class I - Dangerous or defective products that predictably could cause serious health problems or death

Class II - Products that might cause a temporary health problem or pose

only a slight threat of serious nature

Class III - Products that are unlikely to cause any adverse health reaction

but violate FDA labeling or manufacturing regulations

dietary supplement and nonprescription drug consumer protection act of 2006

Requires labeling and mandatory ‘serious’ adverse events (AE) reporting by manufacturer, packer, or distributor

◦ Packaging will display name and address of entity collecting AE data and state they are responsible for FDA reporting

manufacturer initiated recall

MedWatch form 3500A by mail or online

consumers and healthcare provider initiated recall

contact FDA by phone, email, letter

online via MedWatch voluntary reporting form

a product lacking a drug facts box would be

considered misbranded

warning letter, product seizure, or injunctions can occur

drug facts labeling

clearly communicate to consumer, understand information about product benefits vs risks and how it should be taken

standardized content and format, lay terms required, minimal type size

what must be included on a drug label?

active ingredients, purpose, use, warning, directions, other information, inactive ingredients, FAQs

flag the label

voluntary program to alert consumers on changes to a product

should be carried on the label for at least 6 months after change

significant changes to a drug product include

(1) expansion or limitation of the claims,

◦ (2) modification of the dosage level,

◦ (3) change in active ingredients or directions for use,

◦ (4) new warnings or contraindications, and

◦ (5) any other significant new information

product line extensions

include new strengths, formulations, combinations of ingredients, and even a different therapeutic entity

manufacturers capitalizing on name brand: add suffix or prefix

consumer confusion—pharmacist role in selection

examples of product line extensions

dulcolax stool softener now contains docusate sodium

dulcolax tablets and suppositories still contain bisacodyl

dulcolax milk of magnesia contains magnesium hydroxide

OTC packaging

nonprescription products must have one or more barriers to entry that if breached would signal to consumer tampering

must contain unique designs or other characteristics that cannot be duplicated

must contain statement of feature to alert consumer

poison prevention packing act (PPPA)

requires child resistant packaging for a number of products—aspirin, acetaminophen, ibuprofen, methyl salicylate

OTC expiration date labeling

must indicate this on labeling

product should not be used due to loss of stability, potency, strength, or quality

must also include storage conditions

which products are exempt from expiration date labeling?

products that do not have a dosage limit and are stable for at least 3 years

e.g. some topical drugs, skin protectants, lotions, or astringents

OTC products advertising regulated by

federal trade comission (FTC)

the FTC’s truth in advertising law regarding OTC and dietary supplements can be summarized by two principles

advertising must be truthful and not misleading

advertisers must be able to substantiate all claims made within the advertisement

third class of drugs

after Durham-Humphrey, some advocated for this

these would be available without a prescription but a pharmacist would be required to be involved with the sale

models in Australia, Canada, France, New Zealand, the UK

availability would benefit both quality and costs of healthcare

DeFacto 3rd classes

schedule V—Codeine

dextromethorphan

pseudoephedrine (combat methamphetamine epidemic act)

contraceptives

immunizations

combat methamphetamine epidemic act

limits access: stored behind the counter at pharmacies or locked cabinet

limits quantities: no more than 3.6g per day or 9g in 30 days

if mail-order, no more than 7.5g in 30 days

purchaser must show ID and be 18 years of age to obtain

sellers maintain written/electronic log book (packages less than 60 mg exempt)

cosmetics that may be drugs

topical antimicrobial products (soaps)

skin protectants

sunscreen products

antiperspirant products

nail hardeners

teeth whiteners with bleach

indoor and oral tanning preparations

hormone creams

eye wrinkle creams

wrinkle eradicators or anti-aging creams

dietary supplement

defined as product taken by mouth that contains one or more dietary ingredients

dietary ingredients

vitamins, minerals, amino acids, herbs or other botanical, dietary substances (e.g. enzymes), concentrate, metabolite, constituent, or extract

dietary supplement labeling

responsibility of FDA

not allowed to make claims product will diagnose, cure, mitigate, treat, or prevent disease

must list as supplement, ingredients, net contents of package, manufacturer information, and a supplement facts panel

dietary supplement marketing

print or media advertising regulated by federal trade commission (FTC)—truth in advertising law

dietary supplement labeling requirements

statement of identity

supplemental facts panel

structure/function claim

directions

supplements facts panel

ingredients or proprietary blend

name of manufacturer, packer, or distributer

advancing DSHEA

concerns about misbranded or adulterated dietary supplements have increased in recent years

FDA wants to increase communication and safety related to DS

including new 75 day premarket notification requirements for new dietary ingredient (NDI) notification and implementation of a dietary supplement ingredient advisory list

regulation of homeopathic products

by FDA for manufacture and distribution

monographs must be approved by HPCUS in the HPUS

homeopathic monographs

manufacturing must occur as approved by HPCUS to be considered safe and effective

records of properly conducted provings are required for entry of new materials into HPUS

all point-of-care laboratory testing in pharmacies is subject to regulation by

the Centers for Medicare and Medicaid services as part of the clinical laboratory improvement amendments (CLIA) program

point-of-care and community pharmacies/health screenings

most are considered CLIA-waived

must get CLIA certificate

depending on state regulation also register with DOH and follow rules and regs

CLIA-waived tests examples

international normalized ratio (INR), blood glucose, glycosylated hemoglobin (HgA1C), lipid profile, HIV, rapid strep, etc

nonprescription product liability

most cases brought upon manufacturers, not pharmacists

nonprescription product liability

strict liability could apply to pharmacists for failure to effect timely removal of a recalled or expired product from the shelves when a patient is harmed

nonprescription advice liability

pharmacists can be sued for malpractice and negligence for inaccurate advice (with liability requiring affirmative misrepresentations) regarding nonprescription drugs that harm the patient