(Ch 1: FDCA, PPPA, & other Misc. Federal Laws)

Question 1

I: Federal Food, Drug, & Cosmetic Act of 1938 (FDCA) and Major Amendments

Answer 1

A:

1. Established following deaths caused by sulfanilamide elixir in 1937- Congress passed the 1st legislation that REQUIRED NEW DRUGS to be PROVEN SAFE PRIOR to MARKETING
2. Established the FDA as the PRIMARY federal law dealing with food, drug, cosmetic, and MEDICAL DEVICE SAFETY today (with many amendments)

Question 2

I: Durham-Humphrey Amendments of 1951

Answer 2

B:

1. Established 2 classes of drugs: Rx and OTC
2. Authorized verbal prescriptions and prescription refills

Question 3

I: Kefauver-Harris Amendments 1962

Answer 3

C:

1. Required NEW DRUGS be proven SAFE AND EFFECTIVE for their claimed use
2. Increased safety requirements for drugs & established Good Manufacturing Practices (GMPs)
3. Gave FDA jurisdiction over Rx drug advertising

Question 4

I: Prescription Drug Marketing Act of 1987 (PDMA)

Answer 4

D:

1. Bans RE-IMPORTATION of Rx drugs and INSULIN products produced in the United States (except by the manufacturer)
2. Bans the sale, trade, or purchase of Rx drug SAMPLES
   Exception: pharmacies owned by gov that are part of a healthcare entity providing care to indigent or low- income patients at reduced or no cost. Such samples may only be provided at no charge to patients
3. Mandates the storage, handling, & record keeping requirements for Rx drugs samples
4. Prohibits, with certain exceptions, the resale of Rx drugs purchased by hospitals or healthcare facilities

Question 5

Adulterated, Misbranded or Both?

Scenario: Misfilled Rx involving the wrong strength of the drug prescribed

Answer 5

Both Adulterated and Misbranded

Question 6

Adulterated, Misbranded or Both?

Scenario: REMS drug prescribed or dispensed w/o meeting requirements of the REMS

Answer 6

Misbranded

Question 7

Adulterated, Misbranded or Both?

Scenario: An expired drug product in a manufacturer’s bottle

Answer 7

Adulterated

Question 8

Adulterated, Misbranded or Both?

Scenario: If a Rx is filled using an expired product

Answer 8

Adulterated, but may also be misbranded IF the pharmacists placed a BUD that is after the expiration date of the drug

Question 9

Adulterated, Misbranded or Both?

Scenario: A pharmacist counts a medication on a tray that has residue from another medication

Answer 9

Adulterated

Question 10

Adulterated, Misbranded or Both?

Scenario: A pharmacist stores inventory in a room or refrigerator where the temperature is not adequately controlled

Answer 10

Adulterated

Question 11

Adulterated, Misbranded or Both?

Scenario: A pharmacist stores a specific product incorrectly, such as stocking a medication on a pharmacy shelf instead of in the refrigerator as required

Answer 11

Adulterated

Question 12

Adulterated, Misbranded or Both?

Scenario: A pharmacist fails to dispense a medication in a child-resistant container when required

Answer 12

Misbranding

Question 13

Adulterated, Misbranded or Both?

Scenario: Dispensing a prescription w/o authorization even if it is labeled correctly by the pharmacist

Answer 13

Misbranded

Question 14

I: Drug Quality and Security Act of 2013 (DQSA)

Q: What are the 2 primary topics this addresses?

Answer 14

1. Large scale compounding by pharmacies
2. Track-and-Trace system for Rx drugs

Question 15

I: Drug Compounding Quality Act (DCQA)

Q: What are the 2 sections that the DCQA established and who do they pertain to?

Answer 15

1. 503A for patient-specific compounding
2. 503B is NON-patient specific compounding and considered an “OUTSOURCING FACILITY”

Question 16

Adulterated, Misbranded or Both?

Scenario: Not including medication guide or patient package insert (PPI)?

Answer 16

Misbranded

Question 17

I: DCQA section 503B details

Answer 17

1. Non-patient specific
2. must meet cGMPs
3. Registered with the FDA as an “Outsourcing Facility”
4. Outsourcing Facilities that meet the Act’s requirements are EXEMPT from new drug provisions, adequate directions for use, and DRUG TRACK AND TRACE provisions

Question 18

I: DCQA section 503A details

Answer 18

1. Patient specific
2. Limits interstate distribution of compounded drugs to 5% unless compounder has entered into a Memorandum of Understanding (MOU) with the FDA

Question 19

I: DCQA section 503A

Q: what is considered an inordinate amount of compounded drugs

Answer 19

The amount of compounded drug products in interstate commerce that the pharmacy distributed interstate during any calendar year that is greater than 50% of the sum of (the # of Rx orders compounded that the pharmacy sent out in that same calendar year PLUS the # of Rx orders dispensed and picked up by a patient at the pharmacy during the same calendar year)

Question 20

I: Drug Supply Chain & Security Act (DSCSA) Aka “Track-and-Trace system”

Q: What documents must manufacturers provide and what does it include?

Answer 20

Transaction data that includes History, Information, and Statement

Question 21

I: DSCSA

Q: How long must transaction data be maintained by each supply chain partner?

Answer 21

6 years

Question 22

Q: Under the DSCSA, if a product is illegitimate, who must pharmacies notify, what form should be used, and when should trading partners be notified?

Answer 22

Notify FDA, Form FDA 3911, and within 24 hours

Question 23

I: Under DSCSA, for suspect/illegitimate products- pharmacies must verify product identifier of how many products?

Answer 23

@ least 3 products or 10% (whichever is greater); or all packages if fewer than 3

Question 24

Clinical Studies Phase 1

Q: Phase 1 studies are conducted in what type of volunteers?
Q: What is the primary concern?
Q: What is the goal?
Q: What is the typical range of # of subjects used?

Answer 24

Q: Healthy volunteers
Q: Primary concern is safety of the drug
Q: Goal is to determine what the drug’s most frequent side effects are and how the drug is metabolized/excreted
Q: 20 - 80 subjects

Question 25

I: Clinical Studies Phase 2 Q: What information is being seeked for the drug in question? Q: What type of trials are being used for Phase 2? Q: What continues to be evaluated & what else is studied? Q: What is the typical range of # of subjects?

Answer 25

Q: Drug EFFECTIVENESS in patients who have a certain disease or condition Q: Controlled Trials (using either placebo or a different drug) Q: Safety continues to be evaluated and short-term side effects are studied Q: A few dozen - about 300

Question 26

I: Phase 3 Clinical Studies Q: What information is continued to be gathered? Q: What populations are being studied and at what dosages? Q: What is the range of # of participants?

Answer 26

Q: Larger scale studies to gather more info on safety and effectiveness Q: Studying different populations & different dosages & using the drug in combination w/other drugs Q: Several hundred - about 3,000 people

Question 27

I: Phase 3 Clinical Studies Q: What information is continued to be gathered? Q: What populations are being studied and at what dosages? Q: What is the range of # of participants?

Answer 27

1. Larger scale studies to gather more info on safety and effectiveness 2. Studying different populations & different dosages & using the drug in combination w/other drugs 3. Several hundred - about 3,000 people

Question 28

I: After completion of clinical trials, what application may the drug sponsor submit to seek approval to market the drug?

Answer 28

New Drug Application (NDA)

Question 29

I: What is another name used to call Phase 4 studies?

Answer 29

Postmarket studies

Question 30

Postmarket studies may be required of or agreed to by a sponsor, and are conducted AFTER the FDA has APPROVED a product for marketing. Q: What information does the FDA use postmarket studies to gather?

Answer 30

To gather additional information about a product’s safety, efficacy, or optimal use

Question 31

I: After completion of animal studies, what type of application can a drug manufacturer apply for with the FDA to begin clinical testing?

Answer 31

Investigational New Drug (IND)

Question 32

I: When can clinical studies (in humans) begin?

Answer 32

After the Investigational New Drug (IND) application has been approved by the FDA and the clinical trials have been reviewed by an Institutional Review Board (IRB)

Question 33

I: What does the Investigational Review Board (IRB) check for?

Answer 33

IRB ensures that the studies are acceptable, that participants have given consent and are fully informed of their risks, and that researchers take appropriate steps to protect patients from harm

Question 34

I: Special Warning Requirements for OTC products in the FDCA Q: Must disclose presence and provide warning in “precautions” section of the label that may cause ALLERGIC REACTION in certain susceptible persons

Answer 34

FD&C Yellow No.5 (tartrazine) and No.6 (21 CFR 201.20)

Question 35

I: Special Warning Requirements for OTC products in the FDCA Q: Must contain warning in “precautions” section of labeling to the following effect: PHENYLKETONURICS: Contains PHENYLALANINE __ mg per __ (dosage unit) (CANCER Risk; CARCINOGENIC)

Answer 35

Aspartame (21 CFR 201.21) Note: artificial sweetener that is 200x sweeter than normal table sugar (sucrose) which could be recommended for patients with diabetes to reduce their sugar intake but still satisfy their desire for sweets; People with PKU (phenylketonuria) should avoid aspartame buildup (body cannot break it down on its own so buildup could lead to brain and nervous system damage, developmental/intellectual delays, and seizures)

Question 36

I: Special Warning Requirements for OTC products in the FDCA Q: Prescription drugs containing this ingredient (often used as a PRESERVATIVE) must contain an ALLERGY WARNING in the “warnings” section of the labeling

Answer 36

Sulfites (21 CFR 201.22)

Question 37

I: Special Warning Requirements for OTC products in the FDCA Q: Requires warning to only be TAKEN @ BEDTIME and NOT be used in INFANTS unless under advice of a physician. Label also cannot encourage use during pregnancy

Answer 37

Mineral Oil (21 CFR 201.302)

Question 38

I: Special Warning Requirements for OTC products in the FDCA Q: Any drug containing MORE than 5% (often used as a FLAVORING AGENT) must include warning that use other than directed may be dangerous and that should be kept out of reach of children

Answer 38

Wintergreen Oil (methyl salicylate) (21 CFR 201.303 and 201.314(g)(1))

Question 39

I: Special Warning Requirements for OTC products in the FDCA Q: Limits the amount of oral solution to NO MORE than 90 mL per OTC container. Also requires specific warnings.

Answer 39

Sodium Phosphates (21 CFR 201.307)

Question 40

I: Special Warning Requirements for OTC products in the FDCA Q: Requires a warning not to exceed dose prescribed and to contact physician if difficulty in breathing persists

Answer 40

Isoproterenol Inhalation Preparations (21 CFR 201.305) Note: used to treat conditions like asthma, bronchitis, emphysema

Question 41

I: Special Warning Requirements for OTC products in the FDCA Q: Requires warning regarding nonspecific small bowel lesions consisting of stenosis, with or w/o ulceration, associated with the administration of enteric-coated thiazides with this ingredient

Answer 41

Potassium Salt Preparations for Oral Ingestions (21 CFR 201.306)

Question 42

I: Special Warning Requirements for OTC products in the FDCA Note: This product is no longer available but the regulation is still in place Q: The following statement (BOXED and in RED LETTERS) must appear: “For emergency use to cause vomiting in poisoning. Before using, call physician, the poison prevention center, or hospital emergency room immediately for advice.” Q: The following warning must appear: “Warning: Keep out of reach in children. DO NOT USE IN UNCONSCIOUS PERSONS.” Q: The dosage of the medication must appear. The usual dosage is 1 Tablespoon (15 mL) in individuals over 1 year of age Q: May only be sold in 1 oz (30 mL) containers

Answer 42

Ipecac Syrup (21 CFR 201.308)

Question 43

I: Special Warning Requirements for OTC products in the FDCA Note: This product is no longer available but the regulation is still in place Q: Must contain warning about possible kidney damage when taken in large amounts or for a long period of time

Answer 43

Phenacetin (acetophenetidin) (21 CFR 201.309)

Question 44

I: Special Warning Requirements for OTC products in the FDCA Q: Must have special warnings for use in children including warning regarding Reye’s Syndrome. Retail containers of (1 1/4) grain (pediatric) ASA cannot be sold in containers holding more than 36 tablets

Answer 44

Salicylates (21 CFR 201.314)- Aspirin and other salicylates drugs

Question 45

I: Special Warning Requirements for OTC products in the FDCA Q: Any OTC product that states “For the temporary relief of minor sore throats” must contain this warning: “Warning—Severe or persistent sore throat or sore throat accompanied by high fever, HA, 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.”

Answer 45

OTC Drugs for Minor Sore Throats (21 CFR 201.315)

Question 46

I: Special Warning Requirements for OTC products in the FDCA Q: Internal analgesics and antipyretics including APAP, ASA, ibuprofen, naproxen, ketoprofen, etc., are required to have a warning for persons consuming 3 or more alcoholic beverages per day and to consult with a doctor before taking

Answer 46

Alcohol Warning (21 CFR 201.322)

Question 47

I: Special Warning Requirements for OTC products in the FDCA Q: These are subject to several warning requirements including one that states “Sexually transmitted diseases (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

Answer 47

OTC Drugs for Vaginal Contraceptive and Spermicide Use containing Nonoxynol 9 as the Active Ingredient (21 CFR 301.325)

Question 48

I: Special warnings Requirements for OTC products in the FDCA Note: Has 2 parts (APAP and NSAIDS) Q: Acetaminophen 1) Must have “acetaminophen” prominently displayed 2) Must warn about LIVER TOXICITY 3) Must warn not to use with other products containing acetaminophen & to talk to a Dr or Pharmacist before taking with warfarin Q: NSAIDs 1) Must include the term “NSAID” prominently on the label 2) Must contain “STOMACH BLEEDING” warning

Answer 48

OTC Pain relievers (21 CFR 301.326)

Question 49

I: Special warnings Requirements for OTC products in the FDCA Q: Must provide the following warning: “Accidental over-dose 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.” Q:This warning requirement also applies to dietary supplements containing iron as indicated in 21 CFR 101.17

Answer 49

OTC Products Containing Iron in Solid Oral Dosage Form (21 CFR 310.518)

Question 50

Adulterated, Misbranded or Both? Scenario: OTC products (that are not exempt) not packaged in tamper-evident packaging

Answer 50

Adulterated and Misbranded

Question 51

I: Special warnings Requirements for OTC products in the FDCA ~ Additional OTC Requirements ~ Q: Tamper-Evident Packaging

Answer 51

1. Manufacturers and packagers of OTC drugs for sale at retail must package OTC products in a tamper-evident packaging 2. Certain products are exempted (dermatologicals, dentifrices (aka toothpaste), insulins, and lozenges) 3. OTC products not packaged in tamper-evident packaging would be considered adulterated and misbranded