Exam 4

Question 1

sticky mixture, secretions of the sebaceous and sweat glands (ear canal is skin), hydrophobic protective covering, components (shed skin cells with keratin, sebum –> long chain fatty acids both saturated and unsaturated/alcohols/squalene/cholesterol)

Answer 1

ear wax, cerumen

Question 2

why are ear infections common in children?

Answer 2

still developing immune system, small eustachian tube

Question 3

allows drainage of fluid from middle ear, maintains middle ear pressure, most of the time it’s in a collapsed/closed form which prevents bacteria from entering middle ear, ear infection common after sore throat/cold

Answer 3

eustachian tube

Question 4

poor systemic absorption from the ear canal because covered with skin, low surface area, and cerumen barrier, middle/inner ear are inaccessible using topical delivery (tympanic membrane impermeable unless perforated or damaged or tympanostomy tube AKA grommet)

Answer 4

drug delivery to ears

Question 5

solution/suspension/oil solution, most are sterile, preserved because multidose, isotonic because ear is sensitive/easily infected/protect eardrum/relatively enclosed environment, capacity is 4 drops in adults/2-3 in children

Answer 5

otic formulations

Question 6

lack of sufficient contact time (hard to keep product in ear canal), cerumen (semisolid, sticky, solid mass, poor diffusion), eardrum (impermeable barrier), poor drug absorption through the skin, small surface area for absorption, less blood supply to skin

Answer 6

challenges in otic delivery

Question 7

increase viscosity (formulation strategy), inserting cotton wick into the ear canal and saturating the cotton periodically with medication (topical application technique), patient counseling (keep head in horizontal/lie down position, clean the ear canal by removing ear wax)

Answer 7

strategies to improve otic delivery

Question 8

occurs when ear is unable to clear cerumen due to an overproduction/narrow convoluted canal/inappropriate ear cleaning, symptoms include mild earache or pain/discomfort, tinnitus or ringing in the ear, ear fullness/plugged feeling, dizziness/vertigo, reduced or loss of hearing, treatment includes physical removal following cerumen softeners (flushing, suction, glycerin, baby oil, mineral oil) or cerumenolytic agent (carbamide peroxide)

Answer 8

cerumen impaction

Question 9

cerumenolytic agent, contains hydrogen peroxide (in presence of catalase releases water and O2 creating an effervescent foam to soften the cerumen) and urea (antiseptic and also assists in softening the wax), dispensed with droppers and bulb, examples are Clearcanal Ear Wax Softener, Clinere Ear Wax Removal Kit, GoodSense Ear Wax Removal, FT Ear Wax Removal Kit

Answer 9

carbamide peroxide (6.5%) otic solution

Question 10

inflammation/infection of the outer ear, can be treated with otic corticosteroids (hydrocortisone, dexamethasone, fluocinolone acetonide), otic antibiotics (ciprofloxacin, polymyxin B, neomycin, ofloxacin, colistin), combination of antibiotics and steroids, 2% acetic acid with or without HC as an anti-infective

Answer 10

otitis externa/swimmer’s ear

Question 11

Acetasol HC (acetic acid, propylene glycol, hydrocortisone) otic solution, acetic acid otic solution, Cetraxal (ciprofloxacin) otic solution, ofloxacin otic solution, neomycin sulfate/polymyxin B/hydrocortisone otic solution or suspension, Cortisporin-TC (neomycin, colistin, hydrocortisone, thonzonium bromide - surfactant) otic suspension, Cipro HC (ciprofloxacin and hydrocortisone), ciprofloxacin and dexamethasone otic suspension

Answer 11

otic products for otitis externa/swimmer’s ear

Question 12

otic antibiotic/corticosteroid, neomycin sulfate (interferes with bacterial protein synthesis, aminoglycoside antibiotic, ototoxic), colistin sulfate (disrupts bacterial cell membrane, colistimethate, polypeptide antibiotic), hydrocortisone acetate (decreases inflammation), thonzonium bromide (surface active agent that promotes tissue contact by dispersion and penetration of the cellular debris and exudate, now considered and active ingredient)

Answer 12

Cortisporin-TC otic suspension

Question 13

during the early stages of otitis externa/swimmer’s ear water clogs in the ear canal leading to maceration and infection, clogging could be due to excessive cerumen or narrow/convoluted ear canal, otic products contain excipients that help to drain and dry the ear such as_______, _________, _________, and ________

Answer 13

propylene glycol, isopropyl alcohol, glycerin, boric acid (all are ear drying products)

Question 14

otic corticosteroid (ear drops) for the treatment of chronic eczematous external otitis, 5 drops in affected ear(s) twice daily for 7-14 days, blend of oils (isopropyl alcohol, isopropyl myristate, light mineral oil, oleth-2, fragrances, refined peanut oil - risk for allergic reactions)

Answer 14

fluocinolone acetonide otic oil (DermOtic, Flac)

Question 15

foam that stays within ear, provide better contact and extend drug release, provide metered dose, in clinical trials - no approved products yet

Answer 15

otic foam

Question 16

infection in the middle ear, common in childhood, possible causes of infection (blockage of eustachian tube, respiratory infection, damaged/ruptured eardrum), symptoms (pain, fever, inflammation), cannot be treated topically (systemic treatment/oral antibiotics, treatment via tympanostomy tube - for recurrent ear infections fluid buildup in middle ear leading to hearing loss)

Answer 16

otitis media

Question 17

steroid injection for sudden hearing loss (Meniere’s disease), fluid collects in inner ear and the pressure damages some delicate structure in the inner ear which affects both hearing and balance leading to severe vertigo), injection through tympanic membrane provides local and high concentrations of the drug into the middle ear, after injection keep the ear turned up, don’t frequently swallow, don’t pop the ears, don’t yawn, don’t blow nose

Answer 17

intratympanic injection

Question 18

incision into the tympanic membrane for draining middle ear effusions (pressure equalization tubes), offers disease-free time and improved hearing, limitations (highly invasive, otorrhea which is discharge from the external ear, persistent perforation of tympanic membrane)

Answer 18

tympanostomy tube (grommet), myringotomy is the incision

Question 19

acute otitis media treatment, Otovel (ciprofloxacin and fluocinolone otic solution), Ofloxacin otic solution, ciprofloxacin and dexamethasone otic suspension, gently pump the tragus to facilitate penetration of medication into the middle ear

Answer 19

intratympanic administration through tympanostomy tubes/grommet

Question 20

many antibiotics have the potential to do this (aminoglycosides, macrolides, salicylates, chemotherapeutic agents, loop diuretics, antimalarials), damage to cochlear hair cells, hearing loss/tinnitus, low incidence of this with topical otic products unless there is damaged perforated eardrum, tympanostomy tube, excessive skin abrasion

Answer 20

ototoxicity

Question 21

no blood supply to the ______ of the skin

Answer 21

epidermis

Question 22

most difficult epidermal barrier for drugs to cross, brick and mortar model, composed of corneocytes (keratin and water, barrier for lipophilic drugs) and intracellular lipids (barrier for hydrophilic drugs, holds cells together, keeps skin elastic and pliable)

Answer 22

stratum corneum

Question 23

ways drugs can be delivered through the skin (passive diffusion) and which does most of the drug absorption occur?

Answer 23

through the hair follicular duct, sweat glands, and epidermis –> epidermis is where most of the drug absorption takes place because large surface area

Question 24

skin produces less oil and/or abnormal water loss from stratum corneum (could be due to low humidity that is weather related, improper formation of lipids due to aging or eczema, excessive removal of lipids due to exposure to solvent or soap, corneocyte shrink due to skin injury or infection), more difficult for drug absorption and penetration when this occurs

Answer 24

dry skin

Question 25

prevent the loss of water --> types of this (occlusive which cover the skin to prevent water loss, emollient which add oil to the lipid layer which also prevents the evaporation of water, humectant which penetrates the stratum corneum and keeps the moisture to reduce water loss), add moisture to the epidermis --> types of this (water containing products that can hydrate the skin, creams), hydrated skin increases drug absorption and penetration

Answer 25

skin moisturizers

Question 26

example of water soluble base for ointments

Answer 26

polyethylene glycols (PEGs)

Question 27

example of oleaginous base for ointments

Answer 27

hydrocarbons/oils

Question 28

examples of anhydrous base for ointments

Answer 28

hydrocarbons and surfactant (HLB < 6)

Question 29

examples of w/o emulsion base for ointments

Answer 29

hydrocarbons and water (less than 45% w/w) and surfactant (HLB < 6)

Question 30

examples of o/w emulsion base for ointments

Answer 30

hydrocarbons and water (greater than 45% w/w) and surfactant (HLB > 8)

Question 31

ability to form an impermeable barrier to moisture (occlusiveness), ability to soften skin and make it pliable (emolliency), greaseless and easily rinsed off with water without the use of soap (water rinsability and washability), ability to spread readily on the skin (spreadability), no irritation to the skin

Answer 31

properties of ointment bases

Question 32

chemical stability of the drug (is the drug stable in the base or in presence of water?), what is suitable base for a drug/patient/clinical condition (irritation, occlusiveness, emolliency), is the drug dissolved or suspended in the base (rate of release, drug penetration, grittiness)

Answer 32

formulation of dermatologicals

Question 33

what type of base should be used for dry skin?

Answer 33

occlusive and emollient base

Question 34

what type of base should be used for wet skin?

Answer 34

non-occlusive base, absorption base is preferred if there is exudate

Question 35

apply product only to indicated area, do not apply to large surface area (larger area means more penetration), do not apply to damaged skin, do not occlude skin unless indicated, avoid excess rubbing and heating of the area, stop using if skin gets irritated, wash hands after application and avoid touching other body parts before washing hands

Answer 35

how to minimize systemic adverse effects of dermal products

Question 36

gentamicin, mupirocin, retapamulin, silver sulfadiazine, metronidazole, mafenide

Answer 36

topical antibiotics for dermatologic infections, impetigo, burns

Question 37

nystatin, ciclopirox, luliconazole, clotrimazole, econazole, ketoconazole, naftifine, oxiconazole, sertaconazole, sulconazole

Answer 37

topical antifungal agents for tinea, candidiasis, dandruff

Question 38

acyclovir, penciclovir, docosanol

Answer 38

topical antivirals for herpes, HSV cold sores, genital herpes

Question 39

triamcinolone, clocortolone, fluocinolone, alclometasone, betamethasone, desoximetasone, fluticasone, hydrocortisone, mometasone, diflorasone, amcinonide, fluocinonide, halcinonide, desonide, clobetasol, halobetasol

Answer 39

topical corticosteroids for inflammation

Question 40

retinoic acid derivatives (adapalene, tretinoin, tazarotene, trifarotene), azelaic acid and benzoyl peroxide, combination with antibiotics (clindamycin, adapalene, benzoyl peroxide)

Answer 40

dermatological products for acne and rosacea

Question 41

tacrolimus, sirolimus, pimecrolimus

Answer 41

dermatological products that are immune system modifiers/immunosuppressants for dermatitis, psoriasis, eczema, vitiligo

Question 42

ruxolitinib (Opzelura)

Answer 42

janus kinase inhibitor (JAKs) for vitiligo

Question 43

calcitriol, calcipotriene

Answer 43

Vitamin D analogs for plaque psoriasis

Question 44

soften and exfoliate the horny layer of the epidermis, acne, seborrheic dermatitis, dandruff, warts (genital or perianal), anthralin, salicylic acid, cantharidin, podophyllum, resin, podofilox, sinecatechins, urea

Answer 44

keratolytics

Question 45

head lice, scabicide agents, ivermectin, permethrin, malathion, pyrethrins and piperonyl butoxide, spinosad, lindane

Answer 45

topical antiparasitic agents, pediculicides

Question 46

fluorouracil, ruxolitinib (vitiligo also), imiquimod (genital warts also), actinic keratosis, carcinoma

Answer 46

antineoplastic agents

Question 47

Tapinarof (Vtama), plaque psoriasis

Answer 47

AhR (aryl hydrocarbon receptor) agonist

Question 48

ointments, creams, pastes, gels, aerosol foams

Answer 48

semisolid dermatological products

Question 49

lotions, oils, shampoos, solutions, suspensions, sprays

Answer 49

liquid dermatological products

Question 50

powders (dusting powders), sponges, swabs, topical systems (patches), tapes

Answer 50

solid dermatological products

Question 51

used for skin treatment due to its moisturizing properties, w/o cream that contains mineral oil, white wax and cetyl ester wax (emulsifying agent sodium salts of free fatty acids from waxes), sodium borate (preservative is boric acid --> reaction in free fatty acid to create boric acid from sodium borate), water

Answer 51

cold cream

Question 52

which is preferred for the face, Zovirax cream or ointment?

Answer 52

cream

Question 53

which is preferred for genital area, Zovirax cream or ointment?

Answer 53

ointment

Question 54

for the treatment of recurrent herpes labialis, cold sores, fever blisters, excipients are white petrolatum, cetostearyl alcohol, mineral oil, poloxamer (surfactant), propylene glycol, sodium lauryl sulfate (surfactant, water washable), water, and buffer

Answer 54

Zovirax (acyclovir) cream and ointment, Xerese (acyclovir and hydrocortisone) cream

Question 55

OTC, saturated fatty alcohol, used traditionally as an emollient, emulsifier, and thickener in cosmetics, antiviral activity, treat cold sores/fever blisters on the face or lips, shorten the duration of symptoms like tingling/pain/itching/burning, penetrate deep and block the virus replication

Answer 55

Abreva (docosanol) cream

Question 56

topical treatment of acne and rosacea

Answer 56

clindamycin and benzoyl peroxide gel (Acanya, Neuac, Onexton)

Question 57

treatment of acne vulgaris, excipients are diethylene glycol monoethyl ether (polar solvent), methylparaben (preservative), acrylamide copolymer and water (determine that this is a gel), isohexadecane (hydrocarbon and texture enhancer), polysorbate 80 (wetting agent)

Answer 57

Aczone (dapsone) gel

Question 58

combination therapy (vitamin D analog and corticosteroid) for the topical treatment of plaque psoriasis, propellant is dimethyl ether and butane

Answer 58

Enstilar (calcipotriene and betamethasone) topical foam

Question 59

for treatment of acne vulgaris and rosacea, dosage forms are foam, gel, lotion, pledget/swab, solution

Answer 59

clindamycin topical --> Clindacin (foam), Clindagel (gel) Cleocin T (lotion), Clindacin ETZ or Clindacin-P (pledget/swab), solution is generic

Question 60

which clindamycin topical product has the following excipients: isopropyl alcohol, propylene glycol, purified water

Answer 60

solution (generic)

Question 61

which clindamycin topical product has the following excipients: allantoin, carbomer 934P, methylparaben, polyethylene glycol 400, propylene glycol, sodium hydroxide, purified water

Answer 61

gel (Clindagel)

Question 62

which clindamycin topical product has the following excipients: cetostearyl alcohol, glycerin, glyceryl stearate SE, isostearyl alcohol, methylparaben, sodium lauryl sarcosine, stearic acid, purified water

Answer 62

lotion (Cleocin-T)

Question 63

which clindamycin topical product has the following excipients: cetyl alcohol, ethanol, polysorbate 60, propylene glycol, stearyl alcohol, propane, butane, purified water

Answer 63

foam (Clindacin)

Question 64

body oil, scalp oil, blend of oils that contains isopropyl alcohol, isopropyl myristate, light mineral oil, oleth-2, refined peanut oil NF, fragrances

Answer 64

Derma-Smoothe FS (fluocinolone acetonide) external body/scalp oil

Question 65

for treatment of dandruff, scalp psoriasis, scalp seborrheic dermatitis, Anti-Dandruff (selenium sulfide), Clobex/Clodan (clobetasol propionate), Ciclopirox, Ketoconazole

Answer 65

shampoos

Question 66

for fungal infections (cutaneous and mucocutaneous), dusting powder

Answer 66

nystatin (Klayesta, Nyamyc, Nystop) external powder

Question 67

PRE-OP (hexachlorophene, topical antibiotic used for surgical scrub and as bacteriostatic skin cleanser), Bioscrub (chlorhexidine gluconate, topical surgical scrub), Duraprep (iodine povacrylex, isopropyl alcohol), E-Z Scrub (povidone-iodine)

Answer 67

sponges

Question 68

apply medication or absorb discharges, Clindacin ETZ/Clindamycin-P for treatment of acne vulgaris, Ery (erythromycin for treatment of acne vulgaris), Chlorhexidine gluconate (topical antiseptic)

Answer 68

swabs/pledgets/pads

Question 69

Licart (diclofenac epolamine, for local analgesia for minor strains/sprains, local plasma concentration), Qutenza (capsaicin, for neuropathic pain associated with postherpetic neuralgia/PHN, shingles, diabetic neuropathic pain), if necessary clip the hair around the treatment area but do not shave, TOPICAL not transdermal

Answer 69

patches

Question 70

substances that control oozing/discharge/bleeding, calamine lotion/suspension, aluminum acetate cream/packet (powder)/solution, witch hazel liquid or pad for hemorrhoids or anorectal pain, used for weeping wounds, minor skin irritations, insect bites, minor rashes, coagulates proteins (protein precipitate acts as protective coat and allows new cells to grow underneath)

Answer 70

astringents

Question 71

cells filled with hard keratin much thicker than stratum corneum, impermeable to topical drugs (onychomycosis or nail fungus, infections of the nail plate), difficulty in retaining formulations here (ointments, creams, gels, polish or lacquer provides better efficacy), occlusive covering helps penetration (like covering with a bandage), system therapy if topical not working like oral or parenteral

Answer 71

nails

Question 72

which is faster transcellular route or intercellular route and why?

Answer 72

intercellular because the drug only has to undergo diffusion, not diffusion and partition (don't worry about partition because not going from oil to water or vice versa since not entering cells)

Question 73

which formulation wants to enter cells since it is water soluble and is used in buccal and parenteral formulations, fentanyl or fentanyl citrate?

Answer 73

fentanyl citrate

Question 74

which formulation doesn't want to go into cells/takes intercellular route since it is lipophilic and is used in TD patches, fentanyl or fentanyl citrate?

Answer 74

fentanyl

Question 75

drug properties (lipophilicity, ionization, size of molecule, dose/potency, non-irritating), dosage form properties (release rate, surface area/size of dosage form, drug concentration in the system), skin/stratum corneum properties (thickness, perfusion to dermis, skin hydration, temperature, massage, occlusion)

Answer 75

factors affecting drug absorption through the skin

Question 76

- semisolids (ointments/gels) and liquids (solution) --> difficult to maintain dose uniformity because not unit dosage forms - patches/films (transdermal therapeutic system TTS) --> control the drug release accurately, drug reservoir system with or without membrane, easy to use - device and novel forms/systems --> iontophoresis, phonophoresis, microneedles

Answer 76

transdermal dosage forms

Question 77

type of patch where membrane controls drug release and absorption, suitable for fast-penetrating and potent drugs

Answer 77

membrane-type patch

Question 78

type of patch that has no membrane, stratum corneum controls the absorption rate giving the skin the responsibility to control absorption, for slow-penetrating drugs

Answer 78

matrix patch

Question 79

type of patch that has multiple drug layers, multiphasic delivery is possible (loading and maintenance doses)

Answer 79

matrix-membrane combination patch

Question 80

flexible film/laminate that is polymer based, protects the patch, prevents transfer of drug to others, provides occlusive property, serves as product identification, can provide a cosmetic nature, caution because some patches contain metallic components (aluminum, Catapres-TTS)

Answer 80

patch backing layer

Question 81

keep the patch securely attached to skin, Bioclusive or Tegaderm, transparent/breathable/flexible/adhesive film dressing, need to consider drug being delivered, duration of wear and skin sensitivity, examples that can use this are Fentanyl Transdermal Patch, Butrans (buprenorphine) transdermal patch

Answer 81

adhesive dressings

Question 82

controlled release, lag time between application to skin and appearance of drug in the blood that depends on release from this/penetration of the drug/diffusion through the stratum corneum, not suitable for acute/emergency situations, skin acts as drug-reservoir leading to accumulation of the drug in stratum corneum, drug persists in the body/blood after removed

Answer 82

pharmacokinetics of transdermal delivery systems

Question 83

used for prevention of angina, not for acute angina, apply once a day for 12-14 hours and then remove, apply patch around same time each day, zero order drug delivery

Answer 83

Nitro-Dur (nitroglycerin) transdermal 24 hour patch

Question 84

antihypertensive alpha 2 adrenergic agonist, free base of drug, controlled release once a week (0.1mg/day/week), therapeutic level is reached after 2-3 days (that's the lag time), after removal therapeutic levels maintained for 8 hours, half life of oral tablets is 12 hours so BID dosing so this is a significant advantage for patient compliance

Answer 84

Catapres-TTS (clonidine)

Question 85

absorption varies from site to site so stick to manufacturer's specified sites because of skin thickness variation, recommended locations are based on convenience/product design/penetration, large patient to patient variability in stratum corneum due to age/gender/environmental conditions/skin disease if any, firm and complete contact with skin (clean/wash the site with water and no soap because possible irritation and removal of skin fat, remove large hairs but don't shave, adhesive dressing could be used), rotate the sites of application (possible irritation and lag time issue), if patch removal is difficult an oil based product like petroleum jelly or olive oil may be applied to edges to aid removal

Answer 85

transdermal drug systems site of application information

Question 86

where is Transderm-Scop (scopolamine) patch applied?

Answer 86

behind the ear

Question 87

where is Butrans (buprenorphine) patch applied?

Answer 87

upper arm, chest, back

Question 88

where is Daytrana (methylphenidate) patch applied?

Answer 88

hip area avoiding the waistline

Question 89

where is Xulane (ethinyl estradiol and norelgestromin) patch applied?

Answer 89

buttock, lower abdomen

Question 90

suited for extender release, non-invasive, avoids the risks and inconveniences of parenteral therapy, alternative option to oral drug delivery for patients unable to take oral meds/to avoid first pass metabolism/GI tract problems like nausea and vomiting, easily identified/removed if dose termination is required (rapid termination but blood level may persist for a while)

Answer 90

advantages of TDS

Question 91

few drugs penetrate stratum corneum sufficiently (mostly suitable for lipophilic/potent drugs), many drugs and excipients can irritate the skin (patient acceptance could be a problem, irritation may change nature of stratum corneum and therefore absorption), therapeutic blood level attained slowly (lag time, not suitable for acute effect)

Answer 91

limitations of TDS

Question 92

- apply only to clean, dry, non-irritated skin - use only recommended sites of application - remove the protective liner just before use - press the patch firmly to the skin - rotate sites of application as recommended and watch for skin irritation (report if any) - avoid applying on skin where friction is likely - dispose securely and properly because lots of drug remaining in patch - wash hands after application - be aware of swimming, showering, or engaging in vigorous activity - avoid heating the site of application - advise what to do if edges of patch peel away or patch does not stick well - discuss need to take an intermediate dose at beginning if necessary

Answer 92

patient counseling on TDS

Question 93

gels and ointments for systemic applications, nitroglycerin ointment (Nitro-Bid), testosterone gel (AndroGel, Fortesta, Testim, Vogelxo, Vogelxo Pump), estradiol gel (Divigel, Estrogel), Gelnique (oxybutynin chloride gel for overactive bladder), applied with suitable applicators (measuring device), cost effective and suitable for patients with allergic reactions to alternative, suitable to titrate the dose for personalized therapy

Answer 93

transdermal semisolid dosage forms

Question 94

solution for actuation/sprays, Evamist (estradiol), testosterone solution

Answer 94

transdermal solutions

Question 95

temporarily alter the nature of stratum corneum, provide moisture, loosen and delaminate stratum corneum, examples are ethanol, dimethyl sulfoxide, urea, oleic acid, propylene glycol

Answer 95

penetration enhancers

Question 96

ultrasound pulses through a probe into the skin to enhance drug delivery, fluidize the lipid barrier (cavitation force), commonly used in physical therapy/chiropractic, topical steroids for deep local action

Answer 96

phonophoresis/sonophoresis

Question 97

driven by electric field, useful for ionizable molecules, hair follicles and sweat ducts, provide deeper local action or systemic effect, Ionsys (fentanyl) Iontophoretic Transdermal System (discontinued), decrease the patient to patient variability because stratum corneum is not rate limiting step, as needed delivery that is patient controlled, eliminates the problem of a long lag time, has no accumulation of drug in stratum corneum, delivery programs can be preprogrammed for dose adjustment

Answer 97

iontophoresis

Question 98

painless injection, delivery of large molecules, no lag, no persistence, questions about safety because may increase susceptibility to infections, design (this followed by drug reservoir or this coated with drug/integrated)

Answer 98

microneedles

Question 99

prohibited the interstate commerce in adulterated and misbranded food and drugs, established FDA to regulate food and drug

Answer 99

Pure Food and Drug Act

Question 100

all marketed drug products must be safe and pure as of stated strength, companies are required to submit a new drug application (NDA)

Answer 100

Federal Food, Drug, and Cosmetic Act

Question 101

all marketed products must be safe and effective, required to conduct clinical trials, phases 1/2/3

Answer 101

Kefauver-Harris Amendments to Food Drug and Cosmetic Act

Question 102

created an abbreviated mechanism for approval of generic copies of all drugs approved after 1962 by stating that preclinical trials and clinical testing does not have to be repeated for generics (ANDA), gave companies greater access to market for generic prescription drugs and innovator companies' greater patent life

Answer 102

Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act)

Question 103

created an abbreviated approval pathway for biological products shown to be biosimilar to or interchangeable with an FDA licensed reference biological product, part of Affordable Care Act

Answer 103

Biologics Price Competition and Innovation Act

Question 104

- drug products that are identical or comparable to brand name products in terms of drug substance (active ingredient), dosage form, strength, route of administration, quality, performance characteristics, intended use - work the same as brand name medications, must meet high standards to receive FDA approval, approved medications are generally sold only after patents and exclusivities protecting brand name version end, COST less than brand names (whole point of them!)

Answer 104

generic drug products

Question 105

cost saving therapeutic alternatives that reduce costs, increase drug use, and prevent drug shortages, there for social and economic justifications not therapeutic justification, may not be appropriate for all drugs (hormones because of personalized dose, drug with critical dose and narrow therapeutic ratio)

Answer 105

generic substitution

Question 106

generic must be therapeutically equivalent (TE), meet the same requirements for identity/strength/purity/quality (pharmaceutically equivalent PE), be manufactured under the same strict standards of FDA's good manufacturing practice regulations required for brand products

Answer 106

have to meet this to have FDA approval

Question 107

what is the FDA's bioequivalence range?

Answer 107

80-125%

Question 108

Cmax, tmax, and AUC are part of this type of equivalence, compares the rate and extent of absorption between products

Answer 108

bioequivalence (BE)

Question 109

list of approved drug products with TE evaluations that is approved based on safety and efficacy from an NDA or ANDA, helps to identify multi-source products (products that are available in more than one TE product), helps to determine products that are TE to each other (TE codes --> A__ is yes, B___ is no), assists the generic company in identifying reference products (RLD and RS)

Answer 109

FDA's Orange Book

Question 110

RS or RLD is given for in vivo bioequivalence studies

Answer 110

RS

Question 111

multi-source drug products with two or more reference listed drugs coded how?

Answer 111

AB1, AB2, AB3....

Question 112

what code means that two products are TE and passed a bioequivalence test and we can assume the two products are equally safe and effective?

Answer 112

AB

Question 113

substitution of drug products that contain different chemical entities but should produce similar treatment effects/same pharmacological action, example is celecoxib for ibuprofen or fentanyl for morphine

Answer 113

therapeutic substitution

Question 114

products that are NOT PE, for example same API but different routes of administration/dosage forms/strengths/salts, NOT compared for TE so generic products cannot submit ANDA for these products and are not part of generic substitution

Answer 114

pharmaceutical alternatives

Question 115

one small PK study, less than 30 normal healthy adults that are volunteers, single dose (two treatment crossover study design), collect data of [plasma drug] at various times, AUC, Cmax, test results should be within the 80-125%, if yes than products are PE, BE, TE and get an AB code

Answer 115

human PK trial

Question 116

blood levels may not be seen/relevant, need to assess local bioavailability of the test (generic) to the reference (brand), drug release, clinical therapeutic effect, case by case basis

Answer 116

BE of topical products

Question 117

granted for Class I (high solubility high permeability) immediate release oral drug products because no anticipated absorption problems, human PK study not required, generic manufacturers can do an in vitro dissolution study to compare their product to reference/brand (if both are similar in vitro dissolution profiles then they are BE and get an AB code, some don't need either PK or dissolution study --> Class I solutions - liquid dosage form - using similar solvents, products are PE, drug is already dissolved, solvents are similar, test and reference assumed to be BE)

Answer 117

FDA waivers

Question 118

products in conventional dosage forms not presenting BE problems code

Answer 118

AA

Question 119

injectable aqueous solutions and in certain situations intravenous non-aqueous code

Answer 119

AP

Question 120

injectable oil solutions code (type of oil should be identical)

Answer 120

AO

Question 121

solutions and powders for aerosolization code

Answer 121

AN

Question 122

topical products code

Answer 122

AT

Question 123

drug products that FDA at this time considers not TE to other PE products

Answer 123

B codes

Question 124

extended release products that aren't BE code

Answer 124

BC

Question 125

drugs with documented BE problems code

Answer 125

BD

Question 126

delayed release (enteric coated) products B code

Answer 126

BE

Question 127

products in aerosol-nebulizer drug delivery systems B code

Answer 127

BN

Question 128

potential BE problems code

Answer 128

BP

Question 129

rectal dosage forms for systemic delivery B code

Answer 129

BR

Question 130

topical products with BE issues code

Answer 130

BT

Question 131

insufficient data submitted code

Answer 131

BX

Question 132

products having drug standard deficiencies code

Answer 132

BS

Question 133

biologics with same mechanism of action, control of manufacturing process, extensive lab testing, animal safety studies, human safety/potency studies, human immunogenicity studies, clinical efficacy and safety

Answer 133

biosimilarity