Lecture #5

Question 1

1970: Poison prevention packaging act (PPPA)

Answer 1

Prior to 1970, unintentional poisonings by medicine and household products were thought to be a leading cause of injury for children 5 and under, with nearly 500 deaths per year reported in the United States.
* The PPPA required prescription drugs (and harmful chemicals) to be packaged in child resistant containers (CRCs), also known as “special packaging.”
* Special Packaging is:
* Targeted at kids under 5 years old
* Not difficult for normal adults to access
* Most kids under age 5 should struggle to open, and those that can open it will be prevented from obtaining a toxic amount in a reasonable time

Question 2

What does child resistant mean?

Answer 2

A group of 50 children (age 42-51 months) are given 10 minutes with a package and instructed on how to open the package. They are told they may use their teeth.
Child resistant means 20% of children or less can open after 10 minutes
* At least 90% of adults can open after 10 minutes

Question 3

Covered products for child resistant packaging

Answer 3

Drugs for oral administration require special packaging. This includes OTC and prescription drugs, controlled substances, and samples of oral products.
* Drugs intended to be dispensed in the manufacturer’s packaging must be in CRCs
* Bulk products and unit dose containers are not required to be manufactured in CRCs
* If dispensing these products, they must be dispensed in appropriate CRCs, otherwise they may be misbranded

Question 4

Special packaging exemptions

Answer 4

There are always exemptions to special packaging:
* Non-oral Dosage Forms
* Waivers
* Prescription-by-prescription waivers (can be given by prescribers and patients),
waives CRC packaging for the life of a single prescription
* Blanket waivers (patient authorization only), waives CRC packaging for all products
* Consumer Product Safety Commission (CPSC) Exemptions (23 products)

Question 5

Notable CPSC exemptions

Answer 5

Sublingual nitroglycerin
* Oral contraceptives in mnemonic dispenser packages
* Steroid dose packs
* Some oral powder formulations
* Unit-dose potassium

Question 6

Packaging reuse

Answer 6

As a general rule, don’t reuse packaging. Plastic wears down, and can make packaging no longer child resistant. There is only one exception to this rule:
glass –> yes –> new cap used? –> yes –> reuse ok
glass –> yes -> new cap used? –> no –> don’t reuse
glass –> no –> don’t reuse

Question 7

1982: Chicago tylenol murders

Answer 7

In the fall of 1982, seven people died after taking Tylenol capsules in Chicago, including three members of the same family.
* After the discovery that all of these people took Tylenol, tests revealed potassium cyanide present in the capsules.
* It was assumed that the killer took bottles from the shelf, added cyanide, and then placed them back on the shelf.
* After copycat crimes were noted days later, Tylenol recalled 31 million bottles in circulation, and offered to replace any capsules with tablets.

Question 8

What is a recall?

Answer 8

The correction or removal, and notification to the company, of a product which is in violation of the law.

Question 9

What are the classes of recalls?

Answer 9

class I, II, and III

Question 10

Class I recall

Answer 10

Drug product may cause serious adverse health consequences including death (pharmacies notify patients who received recalled drugs).

Question 11

Class II recall

Answer 11

Drug may cause temporary or reversible effects, but the probability of serious health consequences is remote.

Question 12

Class III recall

Answer 12

Drug product is unlikely to cause serious adverse health consequences.

Question 13

What is a seizure?

Answer 13

FDA Seizure: FDA may physically isolate a drug that is adulterated or misbranded while a civil lawsuit is filed.
* DEA Seizure: DEA may physically isolate a drug that is illegal to possess or distribute while a criminal lawsuit is filed, with probable cause and a warrant when necessary.
* A drug recall is voluntary, a seizure is not.

Question 14

Aftermath of Chicago tylenol murders

Answer 14

FDA requires Tamper-evident packaging for over-the-counter human drug products:
* Must have indicators or barriers to entry which, if breached or missing, can reasonably be expected to provide visible evidence to consumers that tampering has occurred.
* Product must be “distinctive by design” and not able to be duplicated with commonly available materials.
* Any two-piece, hard gelatin capsule must be sealed using an acceptable tamper-evident technology.
* Tamper-evident features must be described on the package.
* Federal Anti-Tampering Act makes tampering a federal crime in 1983.

Question 15

What is a label?

Answer 15

any printed, written, or graphic material on the product container.

Question 16

What is labeling?

Answer 16

all labels and written, printed or graphic material on the container, container wrapper, or accompanying the product.

Question 17

Label vs labeling

Answer 17

A label is a part of the labeling but is not the only thing that fits the definition of labeling. Labeling includes anything “accompanying” the product, including advertisements and spoken words by drug representatives

Question 18

What is a package insert (PI)?

Answer 18

Required as part of the labeling of prescription drugs and biological products, these are sometimes referred to as “prescribing information” or a “drug monograph.”
* Must contain many things in a predefined order, including but not limited to:
* Boxed warnings
* Indications
* Dosages
* Contraindications
* Warnings
* Use in special populations
* Clinical pharmacology
* Adverse Reactions
* Drug Interactions
These are intended for healthcare professionals, though they can be given to patients.
* If a drug on a shelf does not have a PI, it is misbranded

Question 19

What are the old pregnancy categories?

Answer 19

Before July 1, 2017, all products were categorized into one of the following: A, B, C, D, X
Some older PIs and some prescribers still use this terminology

Question 20

Category A

Answer 20

Multiple studies have been conducted, and no risk to the fetus during any trimester has been demonstrated.

Question 21

Category B

Answer 21

No adequate studies on pregnant women have been conducted. Animal studies have not demonstrated a risk to the fetus.

Question 22

Category C

Answer 22

No adequate studies on pregnant women have been conducted. Animal studies show a potential for fetal risk or have not been conducted. A risk benefit analysis should be conducted.

Question 23

Category D

Answer 23

Evidence of risk to a human fetus has been demonstrated. A risk benefit analysis should be conducted.

Question 24

Category X

Answer 24

Evidence of a risk to a human fetus has been demonstrated, and those risks outweigh any possible benefits of the drug. This drug is contraindicated for use during pregnancy.

Question 25

What are the new pregnancy categories?

Answer 25

In place of the previous pregnancy categories, now labeling contains 3 sections related to reproduction: * Pregnancy * Lactation * Females and males of reproductive potential * This new system allows for greater discussion and nuance around the use of drugs within each patient subset. * Better for patient counseling, developed to improve information shared when making decisions around drug use.

Question 26

What are patient package inserts (PPIs)?

Answer 26

FDA-approved labeling written in patient-friendly language which covers: * Drug uses * Risks * Precautions * Must be dispensed with the drug they correspond to whenever that product is dispensed. Failure to do this results in misbranding. * These requirements apply to any person who dispenses medications, including institutions and practitioners * Currently, the only drugs requiring PPIs are estrogens and oral contraceptives * Other drugs may have PPIs, but they are not required to be distributed

Question 27

What are medication guides?

Answer 27

FDA-approved labeling written in patient-friendly language that explains issues related to a drug or drug class * Must be provided with new and refill prescriptions for patients in an outpatient environment * Not under the direct supervision of a healthcare professional * MedGuides are required when one or more of the following exists: * Labeling could help prevent serious adverse effects * Serious risks of use exist which patients should be made aware of * Patient adherence to directions is crucial to drug effectiveness * Hundreds of drugs require MedGuides, failure to dispense a MedGuide with a required drug is misbranding.

Question 28

What are risk and mitigation strategies?

Answer 28

Used to address serious risks associated with using a medication or class of medications. * Can be required by the FDA as part of a drug’s labeling * Goal is to reduce issues with drug products but should not be construed as preventing all drug issues. * There are four types of REMS, which can be used alone or in combination

Question 29

What are the types of REMS?

Answer 29

patient friendly labeling communication plans elements to assure safe use (ETASU) implementation system

Question 30

Patient friendly labeling

Answer 30

Medication Guides and Patient Package Inserts. Something to provide patients essential information about the drug

Question 31

Communication plans

Answer 31

Information sent directly to healthcare practitioners informing them about the drug and how to mitigate issues for patients

Question 32

Elements to assure safe use (ETASU)

Answer 32

Required activities that must be done before prescribing, dispensing, or receiving a product. Can be required from practitioners, patients, or pharmacies

Question 33

Implementation system

Answer 33

A quality assurance process to ensure that risks are being mitigated successfully

Question 34

Consumer medication information

Answer 34

Patient information provided when medication is dispensed by a pharmacy, but is not classified as PPIs or MedGuides * Not regulated by the FDA, and not legally required to be dispensed to patients * Does not take the place of formal counseling provided by pharmacists

Question 35

Patient labeling: OTCs

Answer 35

All over-the-counter products are required to have a Drug Facts section, which includes: * Active Ingredient(s) * Purpose(s) * Use(s) * Warning(s) * Directions * Inactive Ingredients * Other Information

Question 36

In addition to the drug facts label, an OTC label must also have:

Answer 36

The expiration date on the label, when applicable. If no expiration date is on the label, the drug should be considered expired three years after purchase. * Lot or batch code * Name and address of manufacturer, packer, or distributor * Net quantity of contents * A description of the type of tamper-evident packaging utilized

Question 37

What is MedWatch?

Answer 37

MedWatch is the FDA’s voluntary reporting system for adverse events with drug products, biologics, medical devices, nutritional products, cosmetics, and dietary supplements. * This allows both Health Professionals (FDA Form 3500) and Patients (FDA Form 3500B) to report serious adverse events associated with drugs or FDA-covered products * All reports are confidential. * Although voluntary, the FDA “emphasizes that it is a moral obligation of healthcare professionals to furnish the agency with information.” * In 2007, a law was passed “mandating that pharmacies provide patients with notification of a toll-free number so they can report adverse events.”