Lecture #5 Flashcards
1970: Poison prevention packaging act (PPPA)
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
What does child resistant mean?
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
Covered products for child resistant packaging
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
Special packaging exemptions
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)
Notable CPSC exemptions
Sublingual nitroglycerin
* Oral contraceptives in mnemonic dispenser packages
* Steroid dose packs
* Some oral powder formulations
* Unit-dose potassium
Packaging reuse
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
1982: Chicago tylenol murders
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.
What is a recall?
The correction or removal, and notification to the company, of a product which is in violation of the law.
What are the classes of recalls?
class I, II, and III
Class I recall
Drug product may cause serious adverse health consequences including death (pharmacies notify patients who received recalled drugs).
Class II recall
Drug may cause temporary or reversible effects, but the probability of serious health consequences is remote.
Class III recall
Drug product is unlikely to cause serious adverse health consequences.
What is a seizure?
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.
Aftermath of Chicago tylenol murders
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.
What is a label?
any printed, written, or graphic material on the product container.
What is labeling?
all labels and written, printed or graphic material on the container, container wrapper, or accompanying the product.
Label vs labeling
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
What is a package insert (PI)?
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
What are the old pregnancy categories?
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
Category A
Multiple studies have been conducted, and no risk to the fetus during any trimester has been demonstrated.
Category B
No adequate studies on pregnant women have been conducted. Animal studies have not demonstrated a risk to the fetus.
Category C
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.
Category D
Evidence of risk to a human fetus has been demonstrated. A risk benefit analysis should be conducted.
Category X
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.
What are the new pregnancy categories?
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.
What are patient package inserts (PPIs)?
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
What are medication guides?
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.
What are risk and mitigation strategies?
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
What are the types of REMS?
patient friendly labeling
communication plans
elements to assure safe use (ETASU)
implementation system
Patient friendly labeling
Medication Guides and Patient Package Inserts. Something to provide patients
essential information about the drug
Communication plans
Information sent directly to healthcare practitioners informing them about the drug
and how to mitigate issues for patients
Elements to assure safe use (ETASU)
Required activities that must be done before prescribing, dispensing, or receiving a
product. Can be required from practitioners, patients, or pharmacies
Implementation system
A quality assurance process to ensure that risks are being mitigated successfully
Consumer medication information
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
Patient labeling: OTCs
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
In addition to the drug facts label, an OTC label must also have:
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
What is MedWatch?
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.”
