Texas MPJE: Dr. C's Review Chapter 1

What was the first legislative act that Congress passed in response to the deaths caused by sulfanilamide elixir in 1937?

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

- required new drugs to be proven safe prior to marketing

What act established the FDA?

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

- primary federal law for food, drug, cosmetic, and medical device safety

What amendment differentiated between prescription and OTC drug classes? What did these amendments additionally authorize?

Durham-Humphrey Amendments of 1951

- authorized verbal prescriptions and prescription refills

What amendment required new drugs to be proven safe and effective for their claimed use? What did this establish for the manufacturing of drugs?

Kefauver-Harris Amendments of 1962

- established Good Manufacturing Practices (GMPs) for manufacturing of drugs

What amendment gave FDA jurisdiction over prescription drug advertising?

Kefauver-Harris Amendments of 1962

- also required new drugs to be proven safe and effective

- established GMPs for manufacturing of drugs

What act bans the re-importation of prescription drugs and insulin products produced in the United States? Who is the exception to this?

Prescription Drug Marketing Act of 1987 (PDMA)

- except by the manufacturer

What act bans the sale, trade, or purchase of prescription drug samples?

Prescription Drug Marketing Act of 1987 (PDMA)

- mandates the storage, handling, and recordkeeping requirements for Rx drug samples

- also bans re-importation of drugs produced in USA (except by manufacturer)

What pharmacies are exempt from the prohibition of possessing prescription drug samples?

- owned by a charitable organization or city, state, or county government

- part of a healthcare entity providing care to indigent or low-income patients at no or reduced cost

(such samples may only be provided at no charge to patients; Class D allowed to have samples)

What act prohibits, with certain exceptions, the resale of Rx drugs purchased by hospitals or healthcare facilities? What is this law intended to prevent?

Prescription Drug Marketing Act of 1987 (PDMA)

- prevent diversion of drugs (due to price differentials because hospitals generally receive lower prices for drugs than community pharmacies)

- also bans drug re-importation and samples

What two primary topics (acts) did the Drug Quality and Security Act of 2013 (DQSA) address?

1. large-scale compounding by pharmacies -- Drug Compounding Quality Act (DCQA)

2. establishment of a framework for a uniform track and trace system for Rx drugs throughout the supply chain -- Drug Supply Chain Security Act (DSCSA)

Under the Drug Compounding Quality Act (DCQA), Section 503B in the FDCA is established. What does Section 503B allow?

Allows "Outsourcing Facilities" -- sterile-compounding facilities that are not based on patient-specific prescriptions to register with the FDA as an outsourcing facility

(note - Section 503A maintains regulation of traditional compounding)

Outsourcing 503B facilities that meet DCQA requirements are exempt from what?

- new drug provisions

- adequate directions for use

- drug track and trace provisions

True or False: outsourcing 503B facilities are not permitted to compound sterile products without receiving patient-specific prescriptions or medication orders

False -- they are permitted

- they are primarily regulated by FDA and are subject to FDA's current GMPs (cGMPs)

503A facilities may only compound pursuant to an __________________; they are permitted to do limited ___________________, and are subject to USP Chapter ______ quality standards for sterile compounding.

1. individual prescription or medication order

2. anticipatory compounding

3. 797

The 6 requirements in which outsourcing 503B facilities must abide by?

1. Licensed pharmacist provides direct oversight for the drugs compounded

2. Register as an outsourcing facility with the FDA

3. Report to the Secretary of HHS upon registering, and every 6 months thereafter, the drugs sold in the previous 6 months

4. Be inspected by the FDA (risk-based inspection schedule) and pay annual fees to support it

5. Report serious ADE experiences within 15 days and conduct a follow-up investigation / reporting to current drug manufacturers

6. Label products with a statement identifying them as a compounded drug and other specified information about the drug

When must outsourcing 503B facilities report to the Secretary of HHS?

Upon registering, and every 6 months thereafter, the drugs sold in the previous 6 months

Within what time frame must outsourcing 503B facilities report serious ADE experiences?

within 15 days and conduct a follow-up investigation / reporting to current drug manufacturers

When may outsourcing 503B facilities compound a drug product that includes a bulk drug substance?

1. The bulk drug substance appears on the 503B bulks list (for which there is a clinical need); or

2. The drug product compounded appears on FDA's drug shortage list at the time of compounding, distribution, and dispensing.

(note - bulk drug substances must be accompanied by a valid certificate of analysis; if an applicable USP or National Formulary monograph exists, bulk drug substances must comply with the monograph)

Section 503A limits interstate distribution of compounded drugs to ____% unless the compounder is located in a state that has entered into a __________ with ________ addressing ___________ amounts and providing for appropriate __________________ by a state.

1. 5% of the total Rx orders dispensed or distributed

2. memorandum of understanding (MOU)

3. the FDA

4. addressing inordinate amounts of compounded drugs in interstate commerce

5. appropriate investigation of complaints by a state

(adverse drug experiences, product quality issues; required info sharing with the FDA)

In states that have entered into an MOU with the FDA, when is a 503A pharmacy considered to have distributed an inordinate amount of compounded drug products in interstate commerce?

If the number of Rx orders for compounded human drug products distributed interstate during any calendar year is greater than 50% of the sum of --

1. number of Rx orders for compounded human drug products that the pharmacy sent out of the facility in which the drug products were compounded during that same calendar year; plus

2. number of Rx orders for compounded human drug products that were dispensed (e.g., picked up by a patient) at the pharmacy during that same calendar year

(note - all must still be prepared based on an individually identified patient; look at compounding page on FDA website)

The Drug Supply Chain Security Act (DSCSA) applies to Rx drugs for human use in finished form, but what certain products are exempted?

- blood & blood components

- radioactive drugs

- imaging drugs

- certain IV products for fluid replacement

- dialysis solutions

- medical gases

- compounded drugs

- medical convenience kits containing drugs

- certain combination products

- sterile water

- products for irrigation

The Drug Supply Chain Security Act (DSCSA) sets national standards for states to license __________________________________.

Drug wholesale distributors

- electronic track and trace system for Rx drugs as they move through supply chain

Under DSCSA, manufacturers are required to _______________ "Transaction Data" for each product sold; wholesalers are required to ______________ transaction data upon ____________ and subsequently provide transaction data to ______________.

Manufacturers are required to PROVIDE transaction data for each product sold; wholesalers are required to RECEIVE transaction data UPON PURCHASE and provide transaction data to BUYER (pharmacies or other wholesalers)

(note - pharmacies are required to receive, then pass this info along if they further distribute the product)

Transaction data includes transaction _______________, ________________, and a ______________, and must be maintained for _____ years by each supply chain partner.

1. Information, History, and a Statement

2. 6 years

Under the Drug Supply Chain Security Act (DSCSA), what does the Transaction Information include?

- product's name, strength, dosage form

- NDC number, container size and number of containers

- date of transaction, and names and addresses of the persons from and to whom ownership is being transferred

- unique product identifier or serialized numerical identifier (SNI) that identifies an individual bottle or unit of sale

Under the Drug Supply Chain Security Act (DSCSA), what does the Transaction History include?

paper or electronic statement that includes prior transaction information for each prior transaction back to the manufacturer

Under the Drug Supply Chain Security Act (DSCSA), what does the Transaction Statement include?

paper or electronic statement by the seller that the seller

- is authorized (licensed)

- received the product from an authorized (licensed) person - received the transaction information and history from the prior owner, if required

- did not knowingly ship a suspect or illegitimate product

- has systems and processes to comply with verification requirements

- did not knowingly provide false transaction information

True or False: under the Drug Supply Chain Security Act (DSCSA), pharmacies are required to authenticate (scan) product identifiers.

False: pharmacies are NOT YET required to authenticate (scan) those product identifiers

- pharmacies may only receive drugs with product identifiers

Under the Drug Supply Chain Security Act (DSCSA), what are the 3 elements to a product identifier?

1. Standardized numerical identifier (SNI) - comprises the NDC plus a unique alphanumeric serial number

2. Lot number

3. Expiration date

- product identifiers must be in human- and machine-readable formats

Under the Drug Supply Chain Security Act (DSCSA), pharmacies must investigate and properly handle suspect and illegitimate products. What is the distinction between "suspect" and "illegitimate"?

1. Suspect - one has reason to believe these products are unfit for distribution such that they would result in serious adverse health consequences or death

2. Illegitimate - credible evidence shows these products are unfit for distribution such that they would result in serious adverse health consequences or death

(potentially counterfeit, diverted, stolen, subject of a fraudulent transaction, intentionally adulterated)

Pharmacies must investigate any suspect or illegitimate product. As part of the investigation, a pharmacy must verify the product identifier of at least ____ products or ____% of the suspect product, whichever is greater, or all of the packages if there are fewer than _____.

at least 3 products or 10% of the suspect product, whichever is greater, or all of the packages if there are fewer than 3.

- pharmacies must also verify any illegitimate product in response to a notification from FDA or a trading partner.

If a product is illegitimate, pharmacies must notify _____ using form _________ and notify trading partners within ___________.

Pharmacies must notify FDA using form FDA 3911 and notify trading partners within 24 hours.

- should also work with manufacturer to prevent products from reaching patients

What must pharmacies have to "distribute" (providing a drug to anyone other than the consumer/patient)? What are the exceptions?

a wholesale distribution license, and must pass DSCSA transaction data with that distribution, unless....

- when the distribution is between 2 entities that are affiliated or under common ownership

- when a dispenser is providing product to another dispenser on a patient-specific basis

- when a dispenser is distributing under emergency medical reasons; or

- when a dispenser is distributing "minimal quantities" to a licensed practitioner for office use

a drug contains any filthy, putrid, or decomposed substance. Adulterated or misbranded?

Adulterated

A drug has been prepared or held under unsanitary conditions where it may have been contaminated. Adulterated or misbranded?

Adulterated

The methods of manufacture do not conform to current GMPs. Adulterated or misbranded?

Adulterated

a drug has been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent delays, denies, or limits an inspection, or refuses to permit entry of inspection. Adulterated or misbranded?

Adulterated

a drug container is composed of any poisonous or deleterious substance which may contaminate the drug. Adulterated or misbranded?

Adulterated

a drug contains an unsafe color additive. Adulterated or misbranded?

Adulterated

a drug product claims to meet USP standards but its strength or quality does not meet those standards. Adulterated or misbranded?

Adulterated

- if a product's strength differs from what is represented on its label, then it could be both misbranded and adulterated.

a drug is mixed or packed with any substance which reduces its strength or quality, or the drug has been substituted in whole or in part. Adulterated or misbranded?

Adulterated

- if a product's strength differs from what is represented on its label, then it could be both misbranded and adulterated.

a drug's labeling is false or misleading in any particular way. Adulterated or misbranded?

Misbranded

A prescription drug is misbranded if the manufacturer's container label fails to contain what information?

1. name and address of the manufacturer, packer, or distributor

2. brand and/or generic name

3. net quantity (weight, quantity, or dosage units)

4. weight of active ingredient per dosage unit

5. "Rx only" federal legend

6. If not taken PO, the specific routes of administration

7. special storage instructions, if appropriate

8. manufacturer's control number (lot number)

9. expiration date

10. adequate information for use (package insert, med guide, black box warnings)

(state drug labeling requirements dictate what is required on the pharmacy dispensing label)

an OTC drug label is misbranded if it fails to contain what information?

1. principal display panel, including a statement of identity of the product

2. name and address of the manufacturer, packer, or distributor

3. net quantity of contents

4. cautions and warnings needed to protect user

5. adequate directions for safe & effective use

6. content and format of OTC product labeling in "Drug Facts" panel format

What does content and format of OTC product labeling in "Drug Facts" panel format include?

1. Active Ingredients

2. Purpose

3. Use(s) - indications

4. Warnings

5. Directions

6. Other information

7. Inactive ingredients (in alphabetical order)

8. Questions? (optional) followed by telephone number

a drug liable to deterioration, unless it packaged or labeled accordingly. Adulterated or misbranded?

Misbranded

a drug's container is made, formed, or filled as to be misleading. Adulterated or misbranded?

Misbranded

a drug is an exact imitation of another drug or offered for sale under the name of another drug. Adulterated or misbranded?

Misbranded

a drug is dangerous to health when used in the dosage or manner suggested in the labeling. Adulterated or misbranded?

Misbranded

a drug is packaged or labeled in violation of the Poison Prevention Packaging Act. Adulterated or misbranded?

Misbranded

a drug that is not packaged in a child-resistant container if required. Adulterated or misbranded?

Misbranded

Dispensing a prescription without authorization, even if it is labeled correctly by the pharmacist. Adulterated or misbranded?

Misbranded

- Rx drug product is only exempt from the manufacturer's labeling requirements when it is dispensed pursuant to a valid prescription

Misfilling a prescription with the wrong ________, __________, or ________________ will always cause the drug to be misbranded. If a misfilled prescription involves the wrong __________ of the drug prescribed, it would also be adulterated.

- the wrong drug, strength, or directions for use will always cause misbranding.

- the wrong strength of the drug makes it also adulterated.

(adulteration definition: when the strength differs from or quality falls below that which it represents)

A drug is subject to a REMS and it is prescribed or dispensed without meeting the requirements of the REMS. Adulterated or misbranded?

Misbranded

- REMS program is part of the official labeling of the drug

The advertising or promotion of a compounded drug is false or misleading. Adulterated or misbranded?

Misbranded

An expired drug product in a manufacturer's bottle. Adulterated or misbranded?

Adulterated -- the strength cannot be assured after the expiration date.

- if a prescription is filled using an expired product, it may also be misbranded

(if the pharmacist placed a beyond-use date that is after the drug expiration date)

A pharmacist counts a medication on a tray that has residue from another medication. Adulterated or misbranded?

Adulterated

A pharmacist stores inventory in a room or refrigerator where the temperature is not adequately controlled. Adulterated or misbranded?

Adulterated

A pharmacist stores a specific product incorrectly, such as stocking a medication on a shelf instead of in the refrigerator as required. Adulterated or misbranded?

Adulterated

OTC warning requirements for FD&C Yellow No. 5 (tartrazine) and No. 6

must disclose presence and provide warning in "Precautions" section label - may cause allergic reaction in certain susceptible persons

OTC warning requirements for Aspartame

must contain warning in "Precautions" section label - Phenyl-ketonurics: Contains phenylalanine ____ mg per _____ (unit)

OTC warning requirements for Sulfites

must contain an allergy warning the "Warnings" section label (often used as preservative)

OTC warning requirements for Mineral Oil

Requires warning to only be taken at bedtime and not be used in infants unless under advice of a physician. Label also cannot encourage use during pregnancy.

OTC warning requirements for Wintergreen Oil (methyl salicylate)

any drug containing more than 5% (often used as flavoring agent) must include warning that use other than directed may be dangerous and be kept out of reach of children

OTC warning requirements for Sodium Phosphates

Limits the amount of oral solution to no more than 90 mL per OTC container; also requires special warnings

OTC warning requirements for Isoproterenol Inhalation Preparations

Requires warning not to exceed dose prescribed and to contact physician if difficulty in breathing persists

OTC warning requirements for Potassium Salt Preparations for Oral Ingestions

Requires warning regarding nonspecific small-bowel lesions consisting of stenosis, with or without ulceration, associated with the administration of enteric-coated thiazides with potassium salts

OTC warning requirements for Ipecac Syrup

1. "For emergency use to cause vomiting in poisoning. Before using, call physician, the poison prevention center, or hospital emergency room immediately for advice." (boxed in red letter)

2. "Warning: Keep out of reach of children. Do not use in unconscious persons."

3. Dosage must be present (1 tablespoon / 15 mL over 1 yrs old)

4. May only be sold in 1 oz (30 mL) containers

OTC warning requirements for Phenacetin (acetophenetidin)

Must contain warning about possible kidney damage when taken in large amounts or for a long period of time

OTC warning requirements for Salicylates

1. Must have special warnings for use in children including warning regarding Reye's syndrome

2. Retail containers of 1.25 grain (pediatric) ASA cannot be sold in containers holding more than 36 tablets

OTC warning requirements for OTC Drugs for Minor Sore Throats

Any OTC product that states "For the temporary relief of minor sore throats" must include: "Warning---Severe or persistent sore throat or sore throat accompanied by high fever, headache, nausea, and vomiting may be serious. Consult physician promptly. Do not use more than 2 days or administer to children under 3 years of age unless directed by physician."

What OTCs are required to have a warning for Alcohol?

Internal analgesics and antipyretics including APAP, ASA, ibuprofen, naproxen, ketoprofen are required to have a warning for persons consuming 3+ alcoholic beverages per day and to consult with a doctor before taking

OTC warning requirements for Vaginal Contraceptive and Spermicide Use Containing Nonoxynol 9 as the Active Ingredient

"STDs alert: This product does not protect against HIV/AIDS or other STDs and may increase the risk of getting HIV from an infected partner."

OTC warning requirements for Acetaminophen

1. must have "acetaminophen" prominently displayed.

2. must warn about liver toxicity

3. must warn not to use with other products containing APAP and to talk to a doctor or pharmacist before taking with warfarin.

OTC warning requirements for NSAIDs

1. must include term "NSAID" prominently on label

2. must contain "stomach bleeding" warning

OTC warning requirements for Products Containing Iron in Solid Oral Dosage Form

"Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately."

- also applies to dietary supplements containing iron

Manufacturers and packagers of OTC drugs for sale at retail must package OTC products in a ______________________ packaging

tamper-evident

What OTC products are exempt from tamper-evident packaging?

dermatologicals, dentifrices (toothpaste), insulins, lozenges

True or False: OTC products not packaged in tamper-evident packaging would be considered adulterated and misbranded.

True

A pharmacist that repackages OTC products would be subject to what requirements?

cGMP requirements and all additional requirements including manufacturer labeling and tamper-evident packaging if offered for sale to the public.

True or False: When an OTC product is prescribed and filled as a prescription, the OTC labeling requirements have to be followed.

False

- prescription drug labeling requirements would apply and would include the prescriber's directions for use, any instructions for refills, and beyond-use dates (valid for one year).

If a patient wishes to purchase an OTC drug in a smaller package size than what is commercially available, can a pharmacist break open the product and sell the lesser quantity by placing it in a vial and labeling it?

No, patient must have prescription for the smaller quantity and the OTC drug is filled as a prescription.

FDA Drug and Device Recall Class I

Reasonable probability product will cause either serious adverse effects on health or death

FDA Drug and Device Recall Class II

May cause temporary or medically reversible adverse effects or where probability of serious adverse effects is remote

FDA Drug and Device Recall Class III

not likely to cause adverse health consequences

Prescription drug advertising is regulated by ____________

FDA

OTC drug advertising is regulated by ______________

Federal Trade Commission (FTC)

The advertising of prescription drug prices is exempt from FDA regulations provided that which conditions are met?

1. only purpose is to provide info on price (not safety, efficacy, indications for use, etc.)

2. contains proprietary name of the drug (if any), generic name, strength, dosage form, and the price charged for a specific quantity of the drug

3. advertising may include other information, such as the availability of professional or other types of services, as long as it is not misleading

4. the price stated shall include all charges to the consumer; mailing and delivery fees, if any, may be stated separately

Patient Package Inserts (PPIs) are required to be given to patients in the community setting when new and refill prescriptions for what products are dispensed?

1. Oral contraceptives

2. Estrogen-containing products

For hospitalized or institutionalized patients, when must a PPI be provided to a patient?

prior to the first administration of the drug and every 30 days thereafter

Failure to provide a PPI and/or a Medication Guide when a dispensing a drug that requires one would cause the drug to be ______________

misbranded

FDA requires Medication Guides for all new and refilled prescriptions dispensed in the community when:

1. Patient labeling could prevent serious adverse effects

2. Product has serious risks relative to benefits

3. Patient adherence to directions is crucial

True or False: FDA maintains a searchable Medication Guide database on its website

True

True or False: Consumer Medication Information (CMI) is written patient information that is substitutable for FDA-regulated and mandated PPIs and MedGuides

False

Why are pharmacies and pharmacists required to distribute a "side effects statement" to patients when dispensing all new and refill prescriptions in the outpatient setting?

To enable consumers to report side effects of prescription drugs to FDA

What must the "side effects statement" provided with each prescription drug read?

"Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088"

What can the "side effects statement" be distributed on?

1. Sticker attached to the pharmacy container

2. Preprinted pharmacy prescription vial cap

3. Separate piece of paper

4. Found within CMI or MedGuides

When does FDA requires a REMS?

If FDA finds that it is necessary to ensure that the benefits of the drug, drug class, or biological product outweigh the risks of the product.

What must a REMS include?

a timetable for assessment of the REMS

What can a REMS include?

MedGuide, PPI, communication plan, elements to assure safe use, and an implementation system