PHCY 722 - Pharmacy Law Midterm

When do NDAs occur? (x6)

1) Addition of new chemical compound 2) New substance in existing formulation (including inactive ingredients) 3) New combination of approved drugs 4) Proportion of ingredients changed 5) New indication (intended uses; does not include off-label use) 6) New dosage, route, or duration of administration

What are all the different ways laws can be made?

1) Federal, state statutory law - made by elected officials (Fed: FDCA, Federal Controlled Substances Act; State: pharmacy practice acts, State Controlled Substances) 2) Local government ordinances - affect business aspects of pharmacy (city bans cig sales at pharmacy; NYC requires counseling in pts native tongue); still very much valid law 3) Judicial law - either via common law (principles not codified as statute, but developed by ruling; Congress may override/alter/codify common law via statute) or stare decisis (ruling sets future precedent) 4) Administrative law - rulemaking through notice + comment process; specialized laws made for specific field (pharmacy)

Investigational drug criteria (x6)

1) Indicated for a serious or immediately life-threatening condition 2) No comparable alternative therapy available 3) Drug is under investigation for the disease or condition (IND status) 4) Sponsor is actively pursuing marketing approval of the drug (NDA submission) 5) For serious diseases, sufficient evidence of safety and effectiveness for the use 6) For immediately life-threatening diseases, reasonable basis to conclude drug may be effective and would not expose patients to unreasonable and significant risk

3 branches of government and purposes (which Article of Constitution creates each?)

1) Legislative: make laws (Congress); Article I 2) Executive: enforce laws (president); Article II 3) Judicial: interpret laws (Supreme court); Article III

What additional labeling requirements are there in NC?

1) Name + address of pharmacy 2) Rx number 3) Date of Rx 4) Prescriber, patient names 5) Name, strength of drug 6) Generic name of drug 7) Directions for use 8) Cautionary statements 9) Alcohol warning for CNS depressants 10) Dispensing pharmacist first initial and full last name 11) Discard date (prior to 1yr after Rx dispensed) 12) Expiration date, storage instructions can't be covered if in original container

4 reasons for the law to step in

1) Prohibit 2) Restrict 3) Encourage specific option 4) Creation of public goods (incentives, or created by gov't themselves) - orphan drugs to tx rare diseases

Name a few examples of how compounding pharmacies got in trouble

1) Sterile eyedrops contaminated with pseudomonas (caused blindness) 2) Compounding large vats of albuterol solution 0.01% different strength than manufactured 3) New England Compounding - huge quantities of contaminated, preservative-free methylpred for injection killed dozens *led to the FDA reconsidering compounding vs manufacturing, and more regulation

What efforts have been made to increase the effectiveness of the MedWatch program? Pros/cons?

2008: all Rx's (original or refill) be accompanied by MedWatch number and to consult MD if they believe they suffer an AE on drug - Pros: more reporting of AE; part of post-marketing surveillence - Cons: way too many reports; mild or expected AE from patients; subjective reporting, need to look at patterns

It is generally easier for _______________ (legislature, agencies) to make law

AGENCIES!!! Remember "I'm a Bill" journey for legislative statutes versus relatively simple notice & comment process for agencies (takes only ~4-6mo) - This is one of the key reasons for agencies having consolidated power --- to be efficient!

Administrative agencies - are they unstoppable?

Absolutely not, important checks & balances exist: - Executive: executive appointments; agenda-setting - Legislative: make new/amend statute governing agency; oversight hearings (reprimand agency head); withdraw funding (appropriations) - Judicial: review agency's statutory authority

Case JP, a disgruntled employee at Drain Pharmaceuticals, decides to breed rats inside manufacturing facility to get back at the boss. FDA finds out and punishes the boss (as well as the employee). Is this within the FDA's scope of statutory authority?

Absolutely!!! Boss at Drain Pharma went into business with extreme externalities, and is liable via strict liability (and corporate officer liability)

FDA (Food and Drug Administration) - What is it? What creates it? - How big is it? - Lawmaking process? - What actions can it take?

Administrative agency - created by the FDCA to administer + enforce it - Largest agency: regulates ~20% of total GDP - Promulgation of rules - via same notice & comment period as for other agencies (like BOPs) - Powers: criminal proceedings, seize items/order recalls, issue warning letters

Commercial speech

Advertisements and commercials for products and services - Less 1st amendment protection to protect patients and prevent fraud - Regulation: "reasonably tailored" (regulate to avoid jeopardizing public health and safety, not outright bans) - Established by VA BOP vs VA Citizen's Consumer Council

How can drug advertising and promotion (clearly a form of speech) be regulated under the 1st amendment of the constitution?

Advertising = commercial speech (entitled to protection, but lesser protection than political speech) - May be regulated, but difficult d/t 1st amendment issues

_______ is law made by agency, while _______ is law made by legislature

Agency - rules Legislature - statutes *both have full effect of law

Notice and comment period - Does agency actually have to read all comments? - What happens if substantive changes are made during the notice and comment period?

Agency does have to review all comments, but can simply reject them - If any substantive changes made → re-do entire notice & comment period (whole 90d, etc.)

By default, all drugs marketed after ________ are classified as _________ (Rx, OTC)

All drugs after '62 are subject to NDA and Rx approval for safety + efficacy..... howeva: - FDA can remove drug from Rx status (and make OTC) if designation deemed not necessary for protection of public health

By default, all new medical devices are Class ___, unless......

All new devices are Class 3 (and subject to premarket safety/efficacy), unless FDA satisfied that it is substantially equivalent to pre-76 device

Dietary supplement claims (x4)

- Benefit a classical nutrient deficiency disease so long as prevalence is disclosed - Role of dietary supplement in affecting structure or function of the body - Characterizing mechanism by which a nutrient acts to maintain structure or function - Describing general well-being from consumption of nutrient

Section 503A exemptions for compounded products (x3) - Does this apply to patient-specific compounding or to outsourcing facilities? *are there any exemptions to the exemptions?

- Cannot contain FDA-removed pdt d/t safety/efficacy - Cannot be essentially a copy of commercially available product - Demonstrable difficulty for compounding that could produce AE (ex: narrow therapeutic index drugs) *applies to BOTH compounding pharmacies and outsourcing facilities *exception: listed on FDA shortage list, may get green light to compound otherwise restricted pdt

What are some strategies a drug company might try to make their drug seem more appealing in advertisements?

- Emphasize benefits; list risks as briefly as possible (small font, speed-reading) - Use cheerful celebrities to describe horrible adverse effects of drugs

More acts/amendments - Medical Devices Amendments 1976 - Prescription Drug Marketing Act - Food and Drug Administration Amendments Act 2007 - Drug Quality and Security Act

- Medical Devices Amendments 1976: specific regulations for devices; pre-market approval for safety/efficacy for some, but not all - Prescription Drug Marketing Act 1987: regulates Rx sampling (to eradicate "grey market" for drugs) - Food and Drug Administration Amendments Act 2007: authorizes FDA to require manufacturers post-marketing studies to monitor for additional risks; conduct direct-to-consumer advertising review - Drug Quality and Security Act 2013: expands federal regulation to Rx wholesalers; creates regulatory program for compounding

Dietary supplement restrictions

- No disease claims (dx, tx, cure, etc.) - Cannot include approved drug product (nor unapproved or removed products) - can't use simvastatin w/ vitamins + minerals and market as supplement that effects structure; can't sell CBD supplement products since CBD isolate is in FDA approved pdt (Epidiolex)

Classify the following: - Oat bran for breakfast - Oat bran to "help heart health" - Oat bran to treat hyperlipidemia

- Oat bran for breakfast: food - Oat bran to "help heart health": supplement (no disease claim, rather function claim) - Oat bran to treat hyperlipidemia: drug

Are the following drugs? - Paperclip - DMSO (sold as industrial solvent, some use as drug) - Kidney beans marketed for hyperlipidemia tx

- Paperclip: NO; not used in dx, tx, prevention, etc. - DMSO: NO; not intended to be used as drug; if manufacturer knew it was used ONLY as drug, it would be considered a drug - Kidney beans: YES; if intended for tx of disease (HLD), then it's a drug and needs to be proven safe + effective!! (purely theoretical..)

Examples of information asymmetry in pharmacy (how are these addressed?)

- Patient knows much less about Rx AE than pharmacist (law requires counseling about certain AE) - Manufacturer knows everything about their drug (need complete labeling; prescriber info, patient education, MedGuides)

Clinical studies - Phase I - Phase II - Phase III

- Phase I: toxicity, metabolism, bioavailability, elimination; few subjects - Phase II: larger; efficacy + dosage determined - Phase III: RTCs; use in clinical setting for safety + efficacy at determined dose; large, expensive, lengthy

Prescription Drug Marketing Act of 1987

- Prohibits sale, purchase, trade of samples - Only providers + hospital pharmacies (at MD's request) can recieve samples - Shuts down hospitals for re-selling drugs - No re-importation of drugs (Canadian imports OK if able to Secretary certifies no health or safety risk -- has not happened yet)

Off-label prescribing - Pros/cons - Regulating

- Pros: public health benefit (otherwise would not go through approval for given condition and wouldn't be allowed to use); boost sales (no need for clinical trials/approval; FDA approval for every labeled use); form of innovation - Cons: potential harm w/o proven safe + effective for given condition; inept providers use wrong drug for wrong condition - Regulation: require PA, insurance only covers if indication code included

What prompted the creation of: - Pure Food and Drug Act 1906 - Food, Drug, Cosmetic Act 1938 - Durham-Humphreys Amendments 1951 - Kefauver-Harris Amendment 1962

- Pure Food and Drug Act 1906: "The Jungle" (expose of meat-packing industry in Chicago) exposed unsanitary manufacturing conditions - Food, Drug, Cosmetic Act 1938: sulfanalamine disaster (antifreeze poisoning) - Durham-Humphreys Amendments 1951: Humphrey as pharmacy assistant was worried about misbranding bc some OTC items weren't labeled for layperson - Kefauver-Harris Amendment 1962: thalidomide phocomelia birth defects; almost approved in US *previous act/amendments usually could've dealt with each of these, but they did bring up issues, so used as an excuse

Statutes - Pure Food and Drug Act 1906 - Food, Drug, Cosmetic Act 1938 - Durham-Humphreys Amendments 1951 - Kefauver-Harris Amendment 1962

- Pure Food and Drug Act 1906: prohibits knowingly adulterated (could claim ignorance), misbranded drugs; very ineffective + reactive (dangerous drugs allowed on market; no pre-market approval; gov't had to prove adulteration; ex: could have marketed unlabeled cyanide...) - Food, Drug, Cosmetic Act 1938: backbone of federal Rx regulation; proactive - required pre-market approval for safety (not efficacy) - Durham-Humphreys Amendments 1951: creates OTC vs Rx categorization by modifying "adequate directions for use" for Rx's deemed safe only under MD supervision; authorizes verbal prescriptions and refills; permits dispensing of drugs without full labeling - Kefauver-Harris Amendment 1962: adds pre-market approval for efficacy (in addition to safety) and cGMP requirements for manufacturers (adulterated if non-compliant)

State vs Federal Supreme Court

- State Supreme: each state has own; final arbiter for state laws; may have right to have case heard, or may be chosen - US Supreme: chooses to hear certain cases (~100 out of 10,000s; ex: to harmonize law; unconstitutionality; large federal implications; suits bw states)

Who is responsible for disciplining dispensing physicians who fail to comply with dispensing laws (register with BOP, comply with all pharmacy laws)?

NC Board of Medicine

Right to Try Act - National - State

National: section 561 allows eligible, terminally-ill pts access to experimental drugs after phase I - State: NC "Right to Try" act - allows for broader access; patient can go directly to manufacturer and request; manufacturer never obliged by law to provide drug

Externality - Definition, examples

Negative consequences of ones decisions affecting others (who had no involvement in decision); includes all of the downstream effects (economic, health burdens) - Ex: anti-vaxxer chooses to not immunize kids, who end up giving measles to immunocompromised neighbor - Ex: over-use of antibiotics producing resistance + superbugs - Ex: Purdue falsely promoting opioid safety indirectly triggering opioid epidemic

NDA process - What are they meant for?

New Drug Approval process - Massive submission of data about manufacturing, labeling, packaging - Premarket approval of safety ('38 FDCA) and efficacy ('62 Kefauver-Harris) for conditions prescribed, recommended, suggested in proposed labeling

Case UNC Community Pharmacy purchased amlodipine tabs from Truitt Pharmaceuticals which were contaminated with rat turds, and the incorrect strength. The FDA suspends the pharmacy's license for adulteration and misbranding violations. Is this within the FDA's scope of authority?

No way!!! Pharmacies get the 303(c) good faith exception, so if they told the FDA they got it from Truitt Pharmaceuticals, they are all good.... manufacturer will get in trouble - It would be literally impossible for pharmacies to screen all Rx's purchased, so burden of avoiding adulteration/misbranding falls to the manufacturer

How quickly has the biosimilar trend caught on? - Do manufacturers prefer biosimilar or interchangeable biosimilar?

Not that fast... most still use original biologic - More manufacturers prefer non-interchangeable biosimilar bc much faster approval process

Corporate officer liability - Pros, cons - Case example

Officers are liable for the acts of their subordinates violating the FDC; example of strict liability - Example: Sunscript got license suspended for pharmacist error

Do manufacturers prefer to have their products classified as medical devices or drugs?

Probably medical device, especially if substantially similar to pre-76 device (easy 501k approval pathway) - Drug status may be advantageous if able to get patent protection w/ innovator drug (market exclusivity)

Pros/cons of making the definition of "drug" very broad in the FDCA?

Pros: makes law more enduring (can be applied to unforseen circumstances, like biologics); confers necessary power to FDA Cons: could confer too much power to FDA!

Repackaging of drugs requires.......

Repackaging of drugs requires ALL of the labeling info required by manufacturer to not be misbranded - NOT enforced - would be impossible for LTC pharmacies to do, and unit-dose packing is for the safety + benefit of pts

Rx vs OTC categorization

Rx if: - deemed safe only under medical supervision (toxicity, method of use, habit-forming, etc.) - subject to NDA approval process (disease state claim)

Daily pharmacy prctice is more affected by _______ (state, federal) regulation - Which authorizes refills? Verbal Rx's? Electronic Rx's?

STATE!!! - Federal: Rx v OTC; verbal, Rx refills; dispensing w/o full labeling (DHA) - State: faxing, electronic prescriptions, other pharmacy practice laws

Outsourcing facilities - What legislation creates? - Capabilities - Requirements? Exemptions?

Section 503(b) exempts outsourcing facilities from labeling requirements + NDA - Requirements: register with FDA; cGMP compliance, specific labeling ("compounded pdt not FDA approved") - Must begin as sterile facility, then implied in statute you can also produce non-sterile - May compound: bulk or patient-specific prescriptions

Compounding in pharmacy - Requirements - Qualification

Section 510(g) - exempt from manufacturing requirements (cGMPs, labeling, NDA) if they do not manufacture, prepare, propagate, compound or process drugs or devices for sale other than in the regular course of their business of dispensing at retail NOT allowed: - "Office use" compounding - Stockpiling or selling to pharmacies/clinics (outsourcing) - Compounding of drug available on market - Use of bulk ingredients not FDA-approved; or from do-not-compound list

Information asymmetry

Situation in which one party is more informed than another bc of having more info - MANY laws (esp in regards to mislabeling) seek to remedy information asymmetry for consumers

Dispensing authority - Who can dispense? What can they prescribe? - Who governs who can dispense? - Requirements for dispensing?

State law - pharmacists, PAs, NPs, and MDs can dispense, and all must register with BOP - PA, NPs: can dispense any drug allowed to prescribe (if in clinic with pharmacy permit + subject to consulting pharmacist oversight)

Prescribing authority: - Who can prescribe? - Who governs who can prescribe?

States govern who can prescribe, and extend of prescriptive authority. In NC: - Physicians (MDs) prescribe - PA and NP have limited prescribing - CPPs have most limited prescribing ("quasi-prescribing," strictly limited by specific collaborative practice agreement)

How did the Pure Food and Drug Act of 1906 address the sulfanilamide elixir disaster?

Sulfanilamide elixir made with diethylene glycol (antifreeze) - Only could address on grounds of mislabeling, since elixirs are supposed to contain EtOH, which this did not (could have been labeled liquid and would not have addressed) - However, it did prompt the creation of the FDCA, which then required proof of safety prior to marketing

Perez vs Wyeth Laboratories - Which court? - Issue - Outcome - Significance

Superior court (trial court) - Issue: Norplant (implantable contraceptive) mass marketing, direct-to-consumer advertising campaign targeting women (consumers) and did not warn about AE (scarring, pain from removal; weight gain, facial hair, etc.); Wyeth argues learned intermediary doctrine (trained professionals, MD's, responsible to relay that info to patients) - Outcome: if advertising to consumers (seeking to influence pt choice), must warn about AE - Significance: evolution of drug advertising necessitates presentation of balanced risk/benefit info for pts....... however the learned intermediary doctrine has surprisingly been upheld in other instances

_____________ clause says that ________ (state, federal, local) law prevails when they are in conflict

Supremacy clause - Federal trumps state laws when in conflict; state law trumps local law

Heckler vs Chaney - Which court? - Issue - Outcome - Significance *which case is this similar to?

Supreme Court - Issue: death row inmates were being executed via lethal injection using drugs not labeled for execution, sued FDA since drugs weren't proven safe + effective - Outcome: FDA wins; agencies have discretion about what to enforce, and they chose not to enforce this one (but also - how could safety ever be proven for a lethal injection?) - Significance: agencies are best suited to decide how to allot resources and enforce own rules (courts can't compel agencies to take action) *similar to KB pharmaceuticals, where court did not compel FDA to act against compounding pharmacies

United Pharmacal vs Missouri BOP - Which court? - Issue - Outcome - Significance

Supreme court - Issue: Pharmacal selling animal drugs w/o pharmacy license; BOP argues statutory authority over animal drugs, while Pharmacal says BOP's rule about animal drugs came from a website FAQ - Outcome: FAQ is not a rule (would have to go through notice + comment, etc.) and has no legal effect; Board can take action based on interpretation of rule, not on grounds of FAQ (statute doesn't distinguish human v animals, so license is needed) - Significance: agencies make law through rules, but must go through procedure w/ notice + comment period; agencies often publish their thinking on particular matters, but it does not have the effect of law (though this doesn't mean they won't go after you for violating rule/law in place)

TRUE/FALSE Pharmacists in NC can refuse to fill prescriptions if they deem it would be harmful to patient or question its validity

TRUE!! And they should! - However, w/o indication codes usually included it can be difficult for pharmacists to piece it together

TRUE/FALSE If someone gets put in jail for beating someone up and causing permanent damage under criminal law, they can still go to civil court to pay for damages for injuries suffered

TRUE!!!

TRUE/FALSE If you develop simvastatin that uses a different sustained-release mechanism than the innovator simvastatin XR, then you can qualify for an ANDA

TRUE!!! - Different sustained-release technology can be used and still qualify as generic

TRUE/FALSE Pharmacists are potentially liable for filling an Rx a prescriber is not authorized to issue

TRUE!!! - May be very difficult to assess in practice though (unless super obvious)

Biologics - Drugs? - Generics? Which act codified? - Regulation - Interchangeability

Technically drugs, but regulated under both FDC Act and the Public Health Service Act - Biologic Price Competition + Innovation Act 2010 - biosimilars and interchangeable biosimilars - Biosimilar: faster approval, but can't switch for innovator (must be prescribed biosimilar) - Interchangeable biosimilar: more similar (not identical), harder approval; may sub for biosimilar if product selection permitted ----- must notify provider if switched!

Virginia BOP vs Virginia Citizen's Consumer Council - Which court? - Issue - Outcome - Significance

US Supreme Court - Issue: VA had rule prohibiting advertising of drug prices; BOP argued pricing is too banal to be considered in medical decisions, Citizen's Council argued it was to eliminate need to compete for pricing and drives up drug prices - Outcome: Citizen's Council wins; pricing advertising permitted - Significance: commercial speech can be regulated, but MUST be in support of legitimate gov't interest (advancing public health and safety, not to make an extra buck)

US vs Rutherford - Which court? - Issue - Outcome - Significance

US Supreme Court - Issue: does FDC act preclude terminally ill pts from getting Laetrile (not FDA-approved), does this infringe on constitutional rights; what does safe/efficacious mean for terminally ill? Drug seized by Border Control since shipped across state lines w/o NDA ever being filed - Outcome: FDA wins; exceptions for terminally ill not provided in FDCA; drug may worsen/hasten death so safe + efficacious still has meaning; if ruled for terminally ill, manufacturers could omit safety + efficacy approval process and argue everyone is terminally ill; court advises petition to Congress to amend, create exception and define terminally ill in statute - Significance: word is important in law; gold standard of safety + efficacy taken very seriously

What act codified the ANDA process? What was the compromise?

Waxman-Hatch Act - 502(b) pathway = ANDA - Trade off for establishing easier approval process (ANDA) for generics was to extend innovator patent protection form 2yr → 5yr

If the FDA says regardless of what happens when manufacturers provide access to experimental drugs, it won't impact their drug approval, why do manufacturers not always provide access?

While FDA says they don't take it into account, if people die in a horrible way, it'd be (inadvertently) considered in drug's approval (but never officially)

Direct to consumer advertising raises concerns about misleading uninformed layperson into misusing expensive drugs, potentially to their detriment. Should DTC advertising be banned? Can it be banned?

Would never survive 1st amendment scrutiny! (constitutional law trumps all) - Instead of banning, FDA provides requirements, can conduct "pre-review" to provide recommendations, or step in if advertisements are misleading *only US and New Zealand allow for direct to consumer advertising

If you were a drug manufacturer and made a highly-effective therapy for skin cancer that was still in clinical trials for those >18yo, would you provide access to a 16yo petitioning for access to your life-saving drug? *what if your patient meets the NC, but not the federal, criteria for the Right to Try?

Yes: desire to relieve human suffering (identifiable individual); may be super effective but also huge leap of faith.. No: pt falls outside inclusion critera; looks awful if AE or ineffective (causing worse/quicker death), which could sway approval, preventing potential benefit for a greater number of pts ($400 million + 10-15yr leap of faith) *never ever provide access if only eligible based on state Right to Try act -- amounts to misbranded interstate commerce otherwise!

Cosmetics definition

Articles to be rubbed, poured, sprinkled, sprayed on, or otherwise applied to the body (except soap) - No premarket approval for safety nor efficacy - Some may voluntarily register w/ FDA - Compounding pharmacies sometimes make cosmetics

Definition of food

Articles used for food or drink for any animal; chewing gum; any part of such articles

Prompted by a rash of dispensing errors attributable in part to overworked and distracted pharmacists, the North Carolina General Assembly passes, and Governor Cooper signs, Auxiliary Pharmacy Personnel Act of 2018 ("APPA"). APPA states: "When engaged in pharmacy practice activities, a pharmacist shall be assisted by at least two registered technicians." Pharmacist Brickley provides consulting services to long-term care facilities. He does not engage in any dispensing activities. The Board of Pharmacy, which enforces the APPA, fines Pharmacist Brickley $1,000 for not using two registered technicians to assist him while engaged in consulting services. Pharmacist Brickley appeals the fine to the Wake County Superior Court. The Court rules that, since the General Assembly passed APPA as a result of dispensing errors, the phrase "pharmacy practice activities" in the statute refers only to dispensing activities. Therefore, the Court holds, Pharmacist Brickley did not violate the APPA when conducting consulting services without technician assistance. The Court vacates the Board of Pharmacy's fine. The Court's ruling: A. Is an improper exercise of judicial law making because the General Assembly passed the APPA and the courts therefore have no authority to interpret it. B. Is a proper exercise of judicial power (and obligation) to interpret laws to reflect the intent of the legislature that passed them. C. Is an improper reversal of an administrative agency's decision because administrative agencies are themselves empowered to exercise judicial power. D. Is a proper exercise of judicial power to fashion common law rules of decision to resolve a dispute when no statute governs the dispute at hand.

B!!!! Recall that when interpreting a law, the court should always consider what the original intent of legislature passing the bill

Adulteration or misbranding - Simvastatin 10mg labeled as simvastatin 15mg

BOTH! - Adulteration: strength differs from what claimed - Misbranded: product differs from what label says

14th Amendment

Bill of rights applicable to states - prior to 14th amendment, states actually could restrict speech

"Authorized generics"

Brand-name product is relabeled and marketed under generic product name - Generic made by innovator (same exact tab)

In 2013, the United States Congress passed, and the President signed into law, the Drug Quality and Security Act ("DQSA"). The DQSA prohibits a pharmacy from compounding a prescription drug product that is "essentially a copy" of an FDA-approved drug product on the market. In 2018, the FDA issues a guidance document that says a compounded product is "essentially a copy" of an FDA-approved drug product if it is the same dosage form, contains the same active ingredient, and the dose differs from the commercial product by 10 percent or less. Pharmacist Doug Markey routine compounds sildenafil tablets containing 105 mg of active ingredient. Pfizer, a pharmaceutical manufacturer, markets an FDA-approved sildenafil 100 mg tablet under the brand name Viagra. The FDA charges Pharmacist Doug Markey with violating the DQSA by compounding a product that is "essentially a copy" of Pfizer's product. The FDA is likely to: A. Succeed in punishing Pharmacist Markey because it published a guidance document defining a compounded product as "essentially a copy" of a commercial product if the dose differs from the commercial product by 10 percent or less, which is true of Markey's product. B. Fail in punishing Pharmacist Markey because Congress has no authority under the United States Constitution to regulate prescription drug compounding activities. C. Succeed in punishing Pharmacist Markey if the FDA convinces a court that its view that Markey's product is "essentially a copy" is correct under the language of the DQSA. D. Fail in punishing Pharmacist Markey because an administrative agency lacks the authority to enforce a statute that it administers.

C!!! Guidance docs (like website FAQs) do not have the effect of law/rules, but if you choose not to follow, the board may come after you for violating existing statute

Imperial Prosthetics develops and wishes to market a new form of prosthetic leg, which is surgically grafted onto the distal head of the femur to replace the knee joint and the entire lower leg and foot. CEO of Imperial Prosthetics, Sheev Palpatine, approaches you for advice on how to get the new prosthetic to market. You advise CEO Palpatine: A. Because the prosthetic will be classified as a Class I medical device, Imperial Prosthetics need only register the device with the FDA and may begin marketing it immediately. B. Because the prosthetic will be classified as a Class II medical device, Imperial Prosthetics will need to comply with specific performance standards, but will not have to obtain premarket FDA approval of safety and efficacy. C. Because the prosthetic will be classified as a Class III medical device, Imperial Prosthetics must obtain premarket FDA approval of safety and efficacy unless the company can show that the prosthetic is substantially equivalent to one marketed before 1976. D. Because the prosthetic also meets the definition of a "drug" under the federal Food Drug & Cosmetic Act, Imperial Prosthetics may not, under any circumstances, market the prosthetic unless and until it obtains premarket FDA approval of safety and efficacy.

C!!!! Remember that all medical devices are automatically considered Class III and subject to safety/efficacy pre-market approval unless proven substantially equivalent to pre-76 device

Types of court (in descending order of superiority)

Can be federal or state: 1) Supreme Court: final arbiter 2) Court of Appeals: review trial court decisions based on legal errors (wrong law applied, or law doesn't apply); may review facts, but cannot present new facts (will never win based on saying witness lied in trial); super rare to re-open based on new evidence; stare decisis effect 3) Trial courts (district, superior courts): fact-finding (hears case, testimony/documents); convince judge/jury your side is right *very important to consider what court a particular case is being heard in (ex: if Appeals, must be arguing on procedural grounds)

Dietary Supplement Health and Education Act of 1994 (DSHEA) - Requirements (x2) - Issues? (x3)

Commands FDA to treat dietary supplements more like food than drugs; cGMP regulations apply (but do not need to prove safety/efficacy for approval); reactive regulation - Must report serious ADRs to FDA w/in 15d and list contact info to report ADRs on labeling Issues: - allows for potentially unsafe supplements to reach market (reactive); burden on FDA to prove unsafe - lack of consumer info about DDI w/ Rx's - lack of quality standards (strength, purity) bc don't need approval *pharmacists can help remedy the information asymmetry w/ supplements

REMS programs - Purpose - What can they consist of? - What do they apply to?

Conditional approval of drug; risk > benefit only if conditions are met - Includes: restricted distribution, education, teaching for MD or pt *Special procedures to manage risky drugs

Which law gives Congress the power to regulate drugs? Federal law aims to protect from what 2 things

Constitution - Interstate Commerce Clause to protect from: 1) Adulteration (contamination) 2) Misbranding (label not what's in bottle)

The __________ creates the federal gov't in the US

Constitution - specifically grants certain powers to Fed (if not specified, then they don't have it) - "Certain" powers: may be very broad (ex: interstate commerce clause allows regulation of pretty much all goods) - Short (3-4p), but super vague to confer large amount of power

Adulteration of drugs - What does it apply to? How could drugs be adulterated?

Contamination of product or of facility where product was produced - Ex: rats in facility w/ 100% contamination free tablets = adulterated (risk of contamination is enough) - Definition allows enforcement of facilities (including overseas!) - Adulterated if: cGMP violation; strength or purity differs from what claimed; contamination or risk of contamination *proactive regulation

CVS vs NC BOP

Court of Appeals - Issue: 3 separate CVS pharmacists commit dispensing errors; CVS gets reprimand, but argues beyond statutory authority bc rule says pharmacists (not pharmacies) can be reprimanded - Outcome: BOP wins; w/in statutory authority to revoke, suspend, refuse to renew license or reprimand pharmacist.... reprimand is so much less serious than other punishments, so they're allowed to reprimand pharmacy (if CVS had won case, then BOP probs would have just revoked license); deferential to BOP - Significance: pharmacy is liable for pharmacist actions (just like in Sunscript case); BOP allowed to give less harsh punishments

Nutraceutical v Eschenbach - Which court? - Issue - Outcome - Significance

Court of Appeals - Issue: FDA banned Ephedra sales in US; Nutraceutical sells Ephedra products as supplements and argues FDA failed to provide evidence of Ephedra health risk - Outcome: FDA wins; actually had loads of evidence it was unsafe -- pull from market - Significance: FDA will pull unsafe supplements from market (DSHEA = reactive); you can't use ingredient pulled from market in supplements (nor in compounding)

Nutrilab vs. Schweiker - Which court? - Issue - Outcome - Significance

Court of Appeals - Issue: FDA classifies starch blockers as drugs and asks for removal until approval of safety/efficacy; Nutrilab argues not drug since derived from food (amylase protein extracted from raw kidney bean) - Outcome: FDA wins; drug since intended to affect structure/function of body - Significance: illustrates breadth of definition of drug

Sunscript vs NC BOP - Which court? - Issue - Outcome - Significance

Court of Appeals - Issue: pharmacist working under Sunscript licenese commits dispensing error w/ phenytoin resulted in death; both pharmacist + Sunscript permit penalized; Sunscript argues beyond scope of authority to be punished based on vicarious liability (pharmacy itself didn't engage in misconduct) - Outcome: pharmacies act through pharmacists; upholds Sunscript's license penalty (deference to BOP) - Significance: pharmacy and individual can be penalized for SAME misconduct; ambiguity in rule's language to protect public health

Cohen vs Missouri BOP - Which court? - Issue - Outcome - Significance

Court of Appeals - Issue: whether BOP exceeded statutory authority by imposing a penalty against Mr. Cohen; Cohen got 1yr suspension + 5yr probation, BOP finds violations after 5yr probation expired + issues probation extension by 1yr, then revokes license; BOP punishment options: revoke or put on probation up to 5yr - Outcome: Cohen wins -- BOP could have issued new probation (rather than extending) or simply revoked license, but exceeded it's statutory authority by exceeding the 5yr max for probation (non-deference) - Significance: word is everything; had court ruled for BOP, it would set precedent for BOP to hand out any punishment it deemed fit (if NC BOP had heard case, they might have ruled differently..)

Abigail Alliance v. Von Eschenbach - Which court? - Issue - Outcome - Significance

Court of Appeas - Issue: Alliance argues IND process is too lengthy for terminally ill; want access after Phase I; argue implicit constitutional right to self-preservation - Outcome: no fundamental (implicit) right "deeply rooted in our nation's history" for terminally ill access to experimental drugs; encourages Alliance to petition Congress; started policy discussion about IND drug access (MD can get treatment IND w/in 1 day now!) - Significance: courts reject implicit arguments + very reluctant to amend constitution; real argument would have been for personal freedom in any medical decision (including drug abuse), which has never been a part of US law

Majority of cases in pharmacy law are heard in ______ court

Courts of Appeal

In general, courts _____ (have; do not have) deference to agencies - Is this good or bad?

Courts usually have deference to agencies (don't try to tell them what to do) - Deference is good - agencies were created to provide expert opinion for specialized areas; bolsters agency's statutory authority

Criminal vs Civil Law

Criminal: gov't suing individual for violating societal interests; consequence = punishment (fine, prison, death penalty!) Civil: private dispute; consequence = money for damages (to make another "whole")

cGMP Regulations - Introduced by ____ act - Features - Applies to....

Current Good Manufacturing Practices - Kefauver-Harris Amendments '62 established - Comprehensive, strict, costly - Applies only to manufacturing/outsourcing (not compounding

Sobey Pharmaceutical ("Sobey") obtains FDA approval to market Pharmawake for the treatment of narcolepsy. Pharmawake is a different class of chemical and operates by a different mechanism of action than Provigil (modafinil) and Nuvigil (armodafinil), which Sobey views as its primary market competitors. Sobey's scientists believe that, because of these differences, Pharmawake will be twice as effective as Provigil and Nuvigil and will have a much lower side-effect profile. Sobey has conducted no trials to establish these claims. Sobey introduces Pharmawake to the market with an advertisement campaign stating "Twice as effective as Provigil and Nuvigil, and safer too!" FDA charges Sobey with a misbranding violation of the federal Food Drug and Cosmetic Act. The FDA's charge is most likely: A. Invalid because the Pharmawake advertising campaign is based on good faith predictions by scientists of the drug's effectiveness and safety profile as compared to other products. B. Valid because under no circumstance may a prescription drug advertisement make any statement comparing the advertised product to other prescription drug products on the market. C. Invalid because prescription drug advertisements are not part of the drug "label" and therefore not subject to FDA regulation. D. Valid because, without studies establishing Pharmawake's efficacy and safety profile as compared to Provigil and Nuvigil, the claims are at best misleading.

D!!! Drug is definitely misbranded if making unsubstantiated claims - Good faith exemptions are for pharmacists who inadvertently dispense adulterated drug, then tell FDA where they got it from - Comparisons are certainly allowed between prescriptions - Labeling includes ALL published info AND advertisements (print, commercials)

The United States Congress is concerned that direct-to-consumer marketing of prescription drugs causes health care providers to prescribe far more "brand" drugs than are necessary, increasing the federal government's drug coverage costs through programs like Medicare and Medicaid. Congress is also concerned that direct-to-consumer marketing of prescription drugs cause patients to demand prescription drugs that are unnecessary for them, ineffective for them, or both. Congress passes, and the President signs into law, the Consumer Responsibility and Protection Act of 2018 ("CRAP Act"), which prohibits all direct-to-consumer advertising by pharmaceutical companies. Amgen, a pharmaceutical manufacturer, files suit in federal court and asks the court to enjoin (i.e., bar) enforcement of the CRAP Act. Amgen's suit is likely: A. To succeed, because the CRAP Act's stated purpose is to reduce costs to the federal government, which is never a proper basis for legislative action. B. To fail, because protection of public health is a legitimate governmental interest, and the CRAP Act advances that interest. C. To fail, because prescription drug advertising is "commercial speech", and therefore entitled to lesser First Amendment protection. D. To succeed, because the CRAP Act violates the First Amendment of the U.S. Constitution.

D!!!! Drug advertising will never be banned d/t contradicting the 1st amendment (cannot violate constitution) - Reducing costs is a legitimate reason for legislation, just not in this case - Advancing public health is always a good reason, just can't violate 1st amendment - Commercial speech is entitled to lesser protection, but there still is some, and an outright ban is NOT allowed

What happen if Congresses passes as statute that violates the Constitution?

Deemed void by the Supreme Court - Supreme Court will also void laws if Congress exercises power not granted by Constitution - This is what would happen if we tried to OUTRIGHT ban drug advertising

Definition of a drug depends on the intent of the _______ - Key question to ask

Depends on intent of seller/manufacturer - Has therapeutic or structure/function claim been made?

Would a manufacturer prefer to have their product classified as drug or as dietary supplement?

Dietary supplement!! MUCH easier to get it into market - Still can market to affect structure/function, but don't have to go through clinical trials to substantiate their efficacy or safety - Manufacturers fight FDA hard to try and get/maintain supplement status

Bicameralism

Division of Congress into 2 chambers (Senate, House of Reps) - designed to be inefficient + create more deliberate laws, that will truly provide societal benefit

Drug Quality and Security Act of 2013 - Office use compounding - Standards for compounding - Violation notification

Drugs must be compounded on the prescription order for one patient: - Limited quantities (reasonable) of compounding before receipt of valid prescription order based on prescribing patterns allowed, but not to be dispensed until prescription order recieved from licensed physician - "Office use" compounding: NOT allowed; flagrantly illegal (bc not for one patient) - Incorporates USP standards into LAW - Requires FDA to notify BOP if determines compounding pharmacy breaking 503A exemptions (also requires BOP to notify FDA)

How can pharmacists comply with FDC act labeling requirements when dispensing? - What act allows for this?

Durham-Humphrey Amendments (section 503(b)2) - relieves dispensing pharmacist of complying with all of labeling requirements if: 1) Label not false nor misleading 2) Not an imitation (not adulterated) 3) Not sold under name of another drug 4) Packaging + labeling conform to Compendia standards; to minimize deterioriation 5) Conformance to Poison Prevention Packaging act *^these are the federal, baseline requirements

The head of the NC BOP is a _______ (elected, appointed) position - Pros/cons

Elected by pharmacists in NC - Pros: subject matter experts; familiarity + stake in matters - Cons: may look inward at sub-atomic level, or owe allegiance to pharmacists (rather than public)

Medical Device Amendments of 1976 - Device classification - Approval process (alternatives?)

Establishes medical device approval process - Devices marketed prior to '76 get to stay on the market - Manufacturers can use 510(k) submission for "substantially equivalent" to pre-76 device Classification of devices Class 1: low harm potential; registration + notification system (toothbrush) Class 2: higher risk; specific performance standard, but no premarket safety/efficacy approval Class 3: life-supporting or sustaining, or serious risk of harm (ventricular pump; insulin pump); requires premarket approval (like drugs) ---- most examples in class are Class 3

The head of the FDA is a __________ (elected, appointed) position - Pros/cons?

Executive appointment (by the President) - Pros: easier to navigate procedures/political landscape; may have broader vision (less in the weeds than topic expert) - Cons: likely not subject expert or not competent; bad for science (won't promote scientific risk or innovation)

Law tends to step in when the ___________ become so large that intervention is required

Externalities - Policy making is essentially deciding at what point do externalities become significant enough that we need to step in to help steer decisions one way or another

TRUE/FALSE The US loves monopolies

FALSE!! US law hates monopolies; we have very specific legislation to prevent the natural monopolies when FDA approves a new drug (ANDA created by Waxman-Hatch Act for generic approval)

TRUE/FALSE Both manufacturers and HCPs are required to report ADRs to the FDA

FALSE!!! - Manufacturers are required to report ADRs that they know of (includes supplements) - HCPs are never required to report ADRs (but they should!)

TRUE/FALSE FDA cannot compel manufacturers to submit direct-to-consumer advertisements for approval prior to release

FALSE!!! FDAAA 2007 authorizes "pre-review" of DTC advertisements -- can only provide recommendations about ads, but may require changes to address serious risk of drug

TRUE/FALSE PAs and NPs can dispense drugs (within their prescribing authority) under the supervision of a dispensing physician

FALSE!!! MUST dispense in a place with a pharmacy permit, under consulting pharmacist

TRUE/FALSE Generic drugs need to have the same exact PK properties as innovator drugs

FALSE!!! FDA accepts up to 20% variation from innovator drug (important implications for narrow therapeutic index drugs) - "Bioidentical" would require identical profile

TRUE/FALSE If you run out of brand Viagra, you can substitute the tabs for generic sildenafil since the tabs are identical and from the same manufacturer

FALSE!!!! Fraud + misbranding if you label a generic as being brand (even if literally exactly the same, even from same manufacturer; aka authorized generic)

TRUE/FALSE Generic vancomycin tablets can use an ANDA and prove therapeutic equivalence (pharmaceutical + bio-equivalent) to vancomycin capsules since both are PO dosage forms

FALSE!!!! Tab to cap or reverse requires entirely new NDA (new dosage form!)

TRUE/FALSE Specialists may only prescribe drugs for the treatment of conditions within their area (ex: nephrologist may not prescribe anti-convulsant for epileptic patient; obstetrician can't prescribe a triptan for migraines)

FALSE!!!!! Specialists are still full physicians and can prescribe Rx's for ANY condition - Draw the line at dentists (not MDs!): cannot prescribe outside scope of practice (can't prescribe Latisse, an eyelash grower) - States may still investigate specialists + send to Board of Medicine if prescribing patterns are sketchy (ex: all C2s) *determined at STATE level

TRUE/FALSE Only the legislative branch makes law

FALSE!!!!!! Executive branch makes (too much) law, so does judicial through its decisions - Administrative agencies certainly make law through their "promulgation" of rules (after going through notice + comment period)

TRUE/FALSE In NC, drug wholesalers are regulated by the BOP

FALSE; NC is one of few states where wholesaling is regulated by Department of Agriculture

TRUE/FALSE The law is always black-and-white and 100% clear

FALSE; never perfectly effective nor clear; lots of gray area

TRUE/FALSE The US government is built for speed!

FALSE; very intentionally inefficient + deliberate - Checks/balances to prevent tyranny

Guidance Documents - Who makes them? Who cares?

FDA publishes many guidance documents (sort of like BOP FAQs) to inform reader of current agency thinking - Kinda like a super informal rule, but does not hold the effect of law and is not violable - Most manufacturers tend to follow very closely (bc FDA is the only agency that can approve new drugs); others may do so for safety reasons

Would a manufacturer prefer to have a product be classified as a drug or a food?

FOOD - approval process for drugs is super expensive + lengthy.... however it does allow for therapeutic claims

Case: Stenger Horse Farms asks to buy a mare from Franklin horse farms. He does, but is unhappy when the mare doesn't produce any ponies. Stenger argues he was disadvantaged by information asymmetry and wronged as Franklin knew about his mare being sterile, and needs restitution. - What do ya say?

Franklin Farms wins via caveat emptor ("buyer beware") - While there was information asymmetry, Stenger should've done his due diligence and specified he wanted a fertile mare - Contrast with: counseling about AE (information asymmetry is so great and potential detriment is so significant with serious AE; layperson shouldn't need to know they need to ask about specific AE...... Drew knew better!); medication information asymmetry is different than everyday asymmetry

Educational programs - Frequently used for... - Requirements - Benefits, risks

Frequently used to increase awareness about product's off-label uses - Must be: independent, non-promotional; can not present info gathered in study sponsored by manufacturer (must simply present info already out there), nor false info - Benefits: increase sales (more clinicians prescribe off-label if educated); illegal to advertise off-label, so this provides alternative - Risks: manufacturers can push their luck and try to advertise, then be prosecuted by FDA

What's the order of events for new drug approval? (not generics)

IND status → Phase I, II, III studies → NDA submission → FDA approval (5yr patent protection) → post-market surveillance (mandated by FDAAA)

Historically, have drugs been marketed towards physicians or patients? Is this good or bad?

In the past, advertising was directed at physicians - Today: much more money spent on direct consumer advertising (highly effective for manufacturers) - Good: helps to inform consumers, starts conversation with MD - Bad: may mislead consumer layperson

Labeling is designed to correct what market failure?

Information asymmetry - Pharmacists are key in conveying important parts to pts

___________ ______________ is the most common market failure that laws in pharmacy try to correct

Information asymmetry!

Medical device definition

Instrument, apparatus, implement, machine, contrivance, implant, in vivo reagent or anything similarly related intended for dx, cure, mitigation, tx, prevention of disease OR to affect structure/fcn that can't be achieved through chemical action and not dependent on metabolism for purposes

Dietary supplement definition

Intended for ingestion to supplement diet containing at least one of: vitamin, mineral, herb/botanical, amino acid, any other supplement; not regulated as a drug - FDA can remove dietary supplement from market

IND status - What is it meant for? - What's required?

Investigational New Drug status - necessary for clinical testing (otherwise couldn't ship across state lines) - Informed consent required for participation in IND clinical studies

"I'm just a Bill" journey

It's a long one... - Bill introduced in House → at least 1 committee, debate, lobbying, pass committee vote → House floor vote (new debates, amendments), pass House vote → Senate committees (vote), then Senate floor (vote) (→ conference committee only if senate version doesn't match house version) → Trump vetoes it → Congress can overturn with 2/3 majority in BOTH houses

How much power does the interstate commerce clause give Congress?

LOTS - everything affects interstate commerce d/t nature of global economy - Ex: Swansboro CBD company claims all product made w/in Swansboro so not subject to Congressional oversight --> FALSE; very likely some building blocks (seeds, soil, equipment) came from out of state; or if highly popular, people may from out of state to buy or bring it over state lines - Confers power to regulate drugs, approval, marketing, pharmacy practice (though state legislation governs most day-to-day practice)

Label vs labeling

Labels: label physically attached to product - Labeling: all published info about product (package insert, MedGuide, advertisements, commercials)

Common law

Law based on previous judicial decisions-precedent; non-codified law; still enforceable - Ex: malpractice in pharmacy - Meant to guide private disputes

Administrative agencies - Describe their legislative, executive, and judicial functions

Legislative: notice & comment period (publish proposed rule + rationale on NC/Federal Registry and Agency website w/ instructions how to comment; 90d comment period) - Judicial: board rulings become de-facto law - Executive: board prosecutes violations

Strict liability - Is it fair? - Exception - How often is it applied?

Liability without fault; violating FDC act does not require knowledge of law-breaking (if your employee violates FDC, you are liable) - Seems harsh, but healthcare is high stakes (externalities) - Exception: 303(c) pharmacists get "good faith" defense to adulteration/misbranding if they disclose source of misbranded product

In general, there are _______ (few, many) requirements for drug labeling

MANY - designed to benefit consumer (patients if OTC; providers if Rx)

Who might have pushed back against the Durham-Humpreys amendments? Why?

MD's! DHA permitted verbal Rx's and refills - MDs wanted more office visits to generate revenue (w/o refills, pts need to go in each time)

How is a drug's status changed from Rx to OTC? Why would they want to do this?

Manufacturer needs to demonstrate it's safe enough to be used w/o MD supervision --> FDA approves safety --> now OTC - Might preserve market share after patent protection is lost

From a consumer/manufacturer PoV, what are the pros and cons of a natural monopoly within Pharma?

Manufacturer: its great! No competition means you can charge w/e you want (price gouge) Consumer: Bad! 1) Quality + efficiency suffer (no incentive to innovate and improve) 2) High prices, lower availability

Why are cGMPs required for manufacturing and outsourcing facilities but not for patient-specific compounding?

Manufacturing/outsourcing makes large batches, where contamination would affect MANY more patients (an issue of magnitude of externalities)

Poison Prevention Packaging Act

Many OTC and most Rx dispensed in child-resistant container - Single-use containers - Patients can request non-child resistant containers (ex: arthritis and difficult to open) - Exempt: SL nitroglycerin

Market failures - Definition, examples

Market failures: individual decisions that produce an undesirable outcomes - "Public" good - needed, but w/o incentive (vaccines, orphan drugs) - Externalities - one's choices that negatively affect others (not vaccinating yourself may put others who can't vaccinate at risk - Natural monopoly - high barrier d/t high start up costs (proving safety/efficacy) - Information asymmetry - one party (manufacturer, HCP) has more info than other (consumer, patient)

MedGuide program - What drugs? - How effective? - Part of _____ Programs

Meant to require written info for drugs posting "serious and significant conern" (Accutane; fentanyl; thousands of products) - Ineffective: info overload, interference with work flow; poor distribution and availability *Key part of REMS programs (count as part of drug labeling)

_____________ is a voluntary reporting adverse event reporting system

MedWatch - HCPs (including pharmacists) voluntarily submit AE reports to FDA (no law requires AE reporting from HCPs!)

Why are adulteration prevention efforts aimed at facilities and means of production rather than the drugs themselves?

Much more feasible and practical to regulate facilities - Facilities producing a given formulation have to follow same general procedures

Administrative agencies - Where do they come from? - Where do they get off? - Why have them?

"Creatures of statute" - created by legislation; gives statutory authority (confers and limits administrative scope of authority) - Sort of tyrannical: create law (rulemaking), enforce law (board comes after violations), and interpret law (board hearings; becomes de-facto law) → no separation of powers! - Necessary: legislature doesn't have expert opinion about specialized, technical fields (like pharmacy), so they need topic experts to make framework; to translate broad statute into specific, actionable regulations

Per section 502(b), all drugs are misbranded unless all advertising to professionals include what 4 things? How does this differ for advertising to consumers?

"True statement " including: 1) Established name of drug 2) Formula of drug 3) Brief, fair balance of AE, c/i and efficacy 4) Broadcast media - may condense true statement (as long as adeuqate dissemination of approved labeling) *for consumers: adequate dissemination includes toll free number, Web page, referral to print advertisement or brochure, referral to HCP

2 general types of way law deals with issues

1) Reactive regulation - in reaction to something terrible happening (Pure Food and Drug Act 1906; DSHEA) 2) Proactive regulation - in reaction to something conceived of that would be terrible (FDCA, Kefauver-Harris)

ANDA - What's it for? - What's required? (x3) - What act codified it?

Abbreviated NDA - Meant for generic drugs Requirements: - Pharmaceutical equivalent (same API, dosage form, etc.) - Demonstrate bioequivalence in human trials (same pharmacologic effect in vivo) - Demonstrate cGMP compliance Waxman-Hatch Act made it

Stare Decisis - When is it binding? - Benefits

Abiding by rules established in prior cases - Only binding when decision made by directly superior court (but often refer to prior decision regardless anyway) - Benefits: consistency, efficiency (may resolve outside of court if expected outcome known based on precedent); helps one understand base expectations *less binding than statutes

Definition of a drug

Articles intended (by supplier) for the diagnosis, cure, mitigation, tx, or prevention of disease in any animal (including man); or intended to affect structure or function of body, except food - Articles recognized by USP, Homeopathic Pharmacopoeia of US, National Formulary - Anything to be used as a component of such articles *Broadest definition ever - includes almost anything (supplements, devices, etc.), thus extra distinction made through DSHEA, Medical Devices Act, etc.

Why is the 501(k) route available for medical device approval?

Avoids natural monopoly pre-76 device would have if competitor medical device had to go through entire safety/efficacy approval with clinical trials - Incentivizes fair pricing, promotes innovation

Misbranding of drugs - Required info?

Claim something prohibited by federal law, or omitting to say something required by federal law; comply with anti-tampering act - Required: adequate directions for use, list of inactive ingredients, no false/misleading info - Applies to labels, labeling, advertising (print, media, etc)

Tort law and advertising

Common law- legal liability when someone suffers harm - Practical source of regulating direct-to-consumer advertising-----FDA will definitely step in if people are suffering harm as a result of improper advertising

How efficacious is considered efficacious enough under Kefauver-Harris amendments?

Effective compared with placebo (not standard of care or other pdts on market)

Black box warnings - What do they warn about? - Practical benefits - Drawbacks

Emphasize serious or life-threatening risk of AE of drug (though benefit > risks) - Benefit: help identify serious ADRs quickly, esp in susceptible pts (risk v benefit can be close for select populations) - Drawbacks: may scare off pts and/or MDs from using drug, preventing clinical benefit (ex: after SSRI BBW about suicidality in young adults, prescribing decreased and suicide increased likely d/t untreated depression)

Natural monopoly

Exists due to high start-up costs or powerful economies of scale of conducting business in specific industry (classic Pharma!) - Ex: FDA approval is, by nature, a natural monopoly bc others don't want to go through R&D to prove safety/efficacy

A brief history of patient package inserts in the US

FDA believes information overload with PPI is crucial to correct info asymmetry for pts: - Began with only hormonal/contraceptive drugs - Federal law passed to require info with every dispensed prescription - Pharma, pharmacies rebelled and promised they would provide info to 95% on their own (but did not end up doing successfully) - Federal law requiring distribution no longer valid d/t Pharma promise ----- "suggested" to always include (but not enforceable)

What happens if a therapy has both drug and medical device features? (what is it treated as?)

FDA decides; can choose either or both - If it has drug component, usually just treated as a drug

Pros/cons of generic drugs

Great! Except for innovator who loses market exclusivity.... - Lower prices, increased access + innovation

What should courts consider when interpreting law?

Original intent of the legislature who passed law; may look at: - Committee reports that produced given law - Consider reason why law was proposed in first place

How can one go about compounding drugs for "office use"?

Outsourcing facilities!!!! - Not a ton of these.... mostly designed for producing sterile fluids or other drugs that go on shortage

What is the most effective way to convey information regarding drugs to patients?

PHARMACISTS!! :) MedGuides, Patient Package Inserts are rarely read or understood

OTC drugs - Review for safety and efficacy? - Who decides? - Recognized as....

Post-62, OTC drugs reviewed for safety/efficacy by therapeutic category - Advisory review panel makes OTC recs - OTC recognized as safe + effective, w/ appropriate monograph

Post-market surveillance studies - Aka... - What act made these mandatory? - Pros/cons - What can happen if something goes wrong?

Post-marketing = "Phase IV studies" - Food and Drug Administration Amendments Act of 2007 ("FDAAA") - made it mandatory (prior, most companies did actually comply w/ FDA to stay on their good side) - Higher R&D burden, but also better safety - FDA can always revoke approval if something goes terribly wrong

How can the executive branch influence pharmacy?

Presidential appointments to FDA; agenda-setting

What are the costs of setting up legal systems entirely preventative in nature? Reactive?

Preventative: lack of choice w/o consequences; inability to innovate/take risk Reactive: everyone does w/e they want; chaos! *careful balance bw pro/reactive is crucial

Federal Anti-Tampering Act 1982 - What prompted it?

Requires certain OTC products to have tamper-resistant packaging (evident if tampered with) - Prompted by Tylenol/cyanide scare

Why would agencies make FAQs on their website?

To avoid going through the trouble of rule-making, but want to inform those in field of agency thinking and encourage compliance (not legally binding) - Agency can take action against you if you don't comply, but not on grounds of FAQ (same rationale as FDA releasing Guidance Documents)

_______ standards regulate pharmacy compounding - Required by ______ (state, federal) law

USP = a private, standard-setting agency; composed of experts from around the world - USP <795>: general; non-sterile - USP <797>: sterile *required under federal law, and by some states (should ALWAYS abide b/c without = adulterated + misbranded under FDCA if it goes across state lines)