pharmacy law exam 1 Flashcards
what is law
what factors do courts apply when making decisions?
Requirements for human conduct applying to all persons within their jurisdiction
Fundamental notions of fairness
– Custom or history involved
– Command of a political entity
– Best balance between conflicting societal interests
reasons to regulate drugs
what are the four reasons to regulate drugs?
Marketfailures:
– Public goods
– Externalities
– Natural monopolies
– Information asymmetry
public goods
Necessary and beneficial commodities that private entities will not supply because there is no incentive
– Examples: orphan drugs; vaccines
externality
When theproductionorconsumptionofagood affects someone who does not fully consent to the effect
* Whenthecostsofthegoodarenotfullyincorporated in the price of the good
– Example: indiscriminate use of antibiotics
Monopoly
Whenthefixedcostsofprovidingagoodarehigh, relative to the variable costs of producing the good
– Example: patents and market exclusivity for new drugs
Information Asymmetry
When the consumer is uninformed about the true value of a good
Examples: prescription only drugs; written consumer information for certain drugs
Limits of the Law
Certain human relationships
De minimis violations
Protecting individual freedoms while preventing harm to others
what are the Sources of Law
U.S. Constitution
No federal or state law may conflict
Legislatures
Administrative agencies
Courts
Legislatures: Statutory Law
who makes these laws
U.S. Congress (federal laws)
State constitutions
State legislatures (state laws)
Political subdivisions (ordinances)
Law Made by Administrative Agencies
Administrative agencies are created by legislatures to administer a body of substantive law.
Law Made by Administrative Agencies:Legislative Function
what are the validity tests of a regulation?
Promulgate regulations
Regulations interpret, define, and add detail to statutes.
Regulations enacted via notice and comment rulemaking
Validity tests of a regulation:
Within the scope of the board’s authority
Based on statutory authority
Reasonable relationship to public health, safety, and welfare
Law Made by Administrative Agencies: Judicial Function
render decisions pursuant to what and what are decisions subject to
what will the court review to determine what
what does de novo entail
Render decisions pursuant to “hearings” resembling court proceedings
Decisions subject to judicial review
The court will review record to determine if decision was based on substantial evidence.
De novo: If substantial evidence is lacking, court will conduct an entirely new trial.
Federal Agencies
what is CFR
What is federal register
Regulations published in Federal Register (Fed. Reg.) and Code of Federal Regulations (CFR)
Federal Register: daily publication of proposed and final regulations and notices
CFR: compilation of final regulations divided and indexed by subject matter
Law Made by Courts: Common Law
what does common law refer to
what are judicial opions
Common law refers to judicial opinions; adopted from the English judicial system
Judicial opinions: decisions of the court
Enforceable as law
Binding on lower courts in the same jurisdiction
Stare decisis
Opinions are binding on lower courts in the same jurisdiction and serve as precedent.
Reasons for deviating from precedent include factual distinctions and changing times or circumstances.
Relationship of Common Law to Statutory Law
Courts often must interpret the meaning and application of statutes.
Principles of interpretation include:
Determining legislative intent, if possible
Ordinary meaning of words
Due process rights of the individual
Distinguishing Criminal, Civil, and Administrative Actions
what entails a criminal action? what is it based on
what is a civil crime? what can it be based on
what is an administrative crime? what can it be based on
Criminal: government v. private party
Charged with a crime as prohibited by a statute and subject to penalties specified by statute
Objectives: deter, punish, rehabilitate
Civil: private party v. private party
May be based upon statute or common law legal rights
Objective: compensation to the injured party
Administrative: agency v. private party
Disciplinary determination which may include warning, fines, licensure revocation or suspension, probation
Legislative Process:Federal Level (1 of 2)
what structures are at the federal level
Congress
Senate
House of Representatives
The sponsor of a bill must be a legislator.
The bill is sent to appropriate congressional committee.
Holds hearings, conducts investigations
Determines whether bill will go to Senate or House floor
Legislative Process:Federal Level (2 of 2)
before passing to another chamber, what must be done to a bill
what is the role of a president? what can Congress do?
After the bill leaves the committee, majority leadership places the bill on a calendar.
The bill must be debated and passed in one chamber before being sent to another chamber for debate and passage.
The conference committee must rectify differences.
Role of the president:
Approve or veto the bill
Congress can override the veto with a two-thirds vote.
Legislative Process:State Level
what is state legislature generally modeled after
why is legislative history generally harder to determine
State legislatures generally modeled after Congress
Legislative history is generally harder to determine because fewer written records of committee hearings and reports
The Judicial Process: Federal Court System
U.S. Supreme Court
it is the highest what with how many justices, how long the appointment
how many judicial circuits does it have
U.S. Supreme Court
Highest U.S. court. Nine justices; lifetime appointment
Original jurisdiction only in cases involving ambassadors, other public ministers, consuls, and when a state is a party
Other cases heard by writ of certiorari
Court of appeals
12 judicial circuits and courts; primarily hear appeals
District courts
Jurisdiction is primarily based on whether there is a federal law or constitutional issue; diversity citizenship; or if a state or the U.S. is a party
Specialty courts
State Court System- State supreme court
does each state have one
what is it also called
Each state has one
Intermediate appellate courts
In more populated states
Trial courts
Often called county courts, superior courts, district courts, or circuit courts
Nearly unlimited jurisdiction
Limited jurisdiction courts: i.e., probate, family, juvenile
Very limited jurisdiction courts: i.e., traffic, small claims
Federal Versus State Law
when federal and state law conflicts, what happens
when does conflict exist
Federal authority to regulate drugs arises from what
what is derived from the tenth amendment
what must state law have a relationship with
When federal and state law conflict, federal law will preempt state law under the Supremacy Clause of the U.S. Constitution.
Conflicts generally exist when state law is less strict than federal law.
Federal authority to regulate drugs generally arises from the Interstate Commerce Clause of the U.S. Constitution.
State authority to regulate generally derives from the Tenth Amendment to the U.S. Constitution and under its inherent police powers.
State laws must bear a reasonable relationship to the public health, safety, and welfare.
Civil Court Procedures:Selection of Court– State court likely unless:
when is a state court likely
State court likely unless:
Federal issue is involved
Parties are from different states
Civil Court Procedures: Parties
what is a plantiff
defendant
order to title of case
what must the plaintiff prove
Plaintiff: person bringing the action
Defendant: person action is brought against
Plaintiff’s name appears first in title of case
Plaintiff must prove “standing”
The challenged conduct has caused the plaintiff injury.
There is a legally protectable interest.
Civil Court Procedures:Statute of Limitations
what does it limit
Limits the period of time in which a case can be filed
Civil Court Procedures:Summons, Complaints, and Answers
what is summons
what does a complain contain
Summons: issued by the court notifying the defendant of the suit and commanding the defendant to file an answer
Complaint: contains all material facts of the case and remedy requested
Answer: admitting to or denying allegations
Default judgment if answer not filed
Civil Court Procedures:Discovery
what happens during a pretrial process
A pretrial process in which each side must give the other all facts, evidence, and names of witnesses upon which it will rely
Deposition: out-of-court testimony by a witness under oath
Civil Court Procedures: Jury Selection
Voir dire examination: the questioning by each side of potential jurors
The jury’s role is to determine questions of fact.
The judge must determine questions of law.
Civil Court Procedures:Witnesses
Witnesses
May be subject to subpoena, an order to appear in court
Failure to appear may result in contempt of court.
Expert witnesses
Called when the factual subject matter is beyond the scope of jurors
Civil Court Procedures:The Trial
Motion for summary judgment: one party attempts to convince the judge that the claims of the other side have no merit, even if correct.
Motion for directed verdict: after the introduction of evidence, one party alleges that the other lacks sufficient evidence.
Objections: attempt to restrict the introduction of evidence or testimony; might constitute issues of law for appeal
After all evidence is presented, the judge instructs the jury as to the applicable law.
Civil Court Procedures:Verdict and Appeal
what does the judgment notwithstanding the verdict allow the judge to do
when can a mistrial be granted
when can a party appeal the final verdict based on what
for an appeal what does an attorney submit and is it on it and why the lower court erred
Judgment notwithstanding the verdict (NOV): the judge may rule contrary to the jury if the jury clearly reached the wrong verdict.
A mistrial may be granted if a major error or violation of law or procedure occurred during the trial.
Either party may appeal the final verdict based on an error of law.
For an appeal, attorneys submit a “brief” to the court, citing the legal principles and precedent involved and why the lower court erred.
Criminal Court Procedures
A defendant can either be what or what
what is an indictment
if the defendant is arrested, what must the judge determine, if so what must the defendant enter
what may the parties agree to and what it mean for a defendant
what is in a civil trial
A defendant can be either indicted or arrested.
Indictments are issued by a grand jury when it determines that enough evidence exists for an arrest and trial.
If arrested, the judge must determine at a preliminary hearing if there is enough probable cause for an arrest; if so, the defendant must enter a plea at an arraignment.
The parties may agree to a “plea bargain,” in which the defendant agrees to a lesser charge rather than face a trial.
Burden of proof is “beyond a reasonable doubt,” rather than a “preponderance of the evidence” as in a civil trial.
Case Citations
State and federal appellate court decisions are often reported and have citations.
From the citation, one can tell the names of the parties, which court decided the case, and the volume and page number where the case can be found.
Chapter 2
Federal Regulation of Medications: Development, Production, and Marketing
Rationale for Federal Drug Regulation
Protection of the public against adulterated and misbranded drug products
Necessity of balancing “direct regulation” and “indirect regulation”
Federal Food and Drug Administration (FDA)
where is it housed?
who is the FDA secretary appointed by and who confirms it
Housed under the Department of Health and Human Services (DHHS)
Authority for administering the FDCA
FDA secretary appointed by president with confirmation of Senate
Structure of FDA
what are the 5 offices under commissioner
National headquarters and extensive field force
Five offices under commissioner:
Office of Foods and Veterinary Medicine
Office of Global Regulatory Operations and Policy
Office of Medical Products and Tobacco
Office of Operations
Office of Policy, Planning, Legislation and Analysis
Office of Medical Products and Tobacco
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research
Center for Devices and Radiological Health
Center for Tobacco Products
Oncology Center of Excellence
Office of Special Medical Programs
Patient Affairs Staff
Functions of FDA
Rulemaking
Issue guidance documents
Incorporate advice from standing advisory committees of outside experts
What Is a Drug?
Articles recognized in the USP or homeopathic pharmacopeia
Articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease (Part B)
Articles other than food intended to affect the structure or function of the body (Part C)
The definition is intentionally broad to include almost anything with an intended therapeutic purpose or purpose of altering the structure or function of the body
Evidence a Product Is a Drug
Labeling
Advertising
Nature of product
Food or Drug?
what does it usually depend on
what definition is usually not very helpful
Generally depends upon the intended use
Food definition is not very helpful in itself
Congress likely intended the meaning of food in the exclusion from part C of the drug definition to apply to food used for its ordinary purpose and in an ordinary manner.
Special Food Categories
Legal categories
Special dietary foods
Medical foods
Publicly conceived categories
Nutraceuticals and functional foods
Health or Disease Claims for Foods
a health claim could result in what
what did the Nutrition Labeling and Education Act of 1990 and FDAMA allow foods to contain
A health claim for a food made by a manufacturer could result in the product being considered a drug.
The Nutrition Labeling and Education Act of 1990 and subsequently FDAMA allow foods to contain health claims if approved by the FDA by regulation or by the “significant scientific agreement” test.
Manufacturers must submit considerable evidence to support the claim to obtain FDA approval.
Dietary Supplement and/or Drug?
who created a new category of food
does this new class require premarket approval
what are examples of DSs
DSHEA
Created a new special category of food called “dietary supplements” (DSs)
DSs do not require premarket approval
DS is defined as a vitamin, mineral, herb, or other botanical, amino acid, or substance used to supplement the diet by increasing total dietary intake
Nutritional or Structure/Function Claims
what are the four types of nutritional support claims the the DSHEA permits
what should the claims be
what must the label contain
DSHEA permits four types of nutritional support claims:
Benefiting a classical nutrient deficiency disease
Describing the role of the DS in affecting the structure/function of the body
Characterizing the mechanism by which a DS acts to maintain the structure or function
Statements of general well-being
Claims must be substantiated as truthful and not misleading.
The label must contain a disclaimer.
Health or Disease Claims
when can DS manufacturers make health claims?
what did Pearson v. Shalala case do
DSHEA only permits DS manufacturers to make health claims if either the FDA approves the claim by regulation or by the significant scientific agreement test.
Pearson v. Shalala, however, held that DS manufacturers could make health claims not approved by the FDA, provided they are not false or misleading and accompanied by a disclaimer.
The FDA now allows qualified and unqualified health claims.
Dietary Supplements Containing Drugs
when does DSHEA excludes an article as a DS
DSHEA excludes an article as a DS if it was approved as a drug prior to being marketed as a DS.
The Pharmanex case establishes that DSs cannot be specially manufactured to concentrate the natural drug ingredient.
Safety Issues
when can FDA remove DS
what is an example
The FDA can only remove a DS on the basis of the product being adulterated, defined as presenting a “significant or unreasonable risk of illness or injury under the conditions of use recommended or suggested in the labeling.”
Example: ephedrine alkaloid DS
The Dietary Supplement and Nonprescription Drug Consumer Protection Act requires manufacturers to report serious adverse events.
Implications of DSHEA for Pharmacists
Product selection
Education of patients as opposed to promotion of products
Restrictions regarding the display of DS publications
Drug and/or Device?
The historical approach of the FDA prior to the Medical Device Amendments was to declare devices as drugs when necessary.
The definition of a device excludes articles that achieve their purpose through chemical action and metabolism.
Whether a device containing drugs is a drug or device is dependent on various factors.
Drug and/or Cosmetic?
what is the definition of a cosmetic?
when can a cosmetic become a drug?
what standard is likely applied
some products can be both what
The definition of cosmetic generally includes topical articles intended for cleansing, beautifying, or altering appearance.
A cosmetic can become a drug if the seller makes a health or structure/function claim.
“Ignorant, unthinking consumer” standard likely applied
Some products can be both cosmetics and drugs.
Labels and Labeling
what does the term labeling include
what is the definition of labeling
what is considered advertising
The term labeling includes labels.
Labeling is defined as written or printed or graphic matter “accompanying” the article.
Courts have defined accompanying.
If the written, printed, or graphic matter is not labeling, it is advertising.
Official Compendia
what is USP & HPUS
USP
Published by the USPC
Sets uniform standards
USPC works closely with the FDA, but is private.
HPUS
Publishes standards for homeopathy products by the HPCUS, a private organization
Role and legal authority of HPUS
Pursuant to FDCA, if a drug is recognized in USP or HPUS, the drug product must meet all standards of the compendia.
Prohibited Acts
what do most prohibited acts involved
violation of what is subject to what
what is good faith excuse applicable to
what are examples of prohibited acts
Most prohibited acts involve misbranding or adulteration.
Violation of FDCA is subject to strict liability
Good faith excuse applicable
to pharmacies
1 - receipt and subsequent delivery of an adulterated or misbranded drug (Section 301(c))
2 - The doing of any act which causes a drug to be counterfeit (Section 301(i)(3))
The alteration, mutilation, etc. of the labeling (Section 301(k))
FDA Enforcement Authority
what is the punishment through enforcement authority?
Injunction
Criminal action
Seizure of products
Warning letters
Corporate Officer Liability:“Park Doctrine”
Affirmative duty of corporate officers to be aware of and correct violations
Product Recalls
The FDA established the ___ authority to order ____ for certain products, but ______.
how many classes
what are Manufacturers responsible for doing; sellers are responsible for doing what
what is Pharmacists responsible for
The FDA established the FDA authority to order drug recalls for certain products, but not drugs.
Three classes of recalls
Manufacturers are responsible for notifying sellers; sellers are responsible for notifying consumers, if necessary
Pharmacists responsible for knowing of product recalls
Adulteration(1 of 2)
what does it focus on
when is a drug adulterated
Adulteration provisions focus on both the facility and the product. A pure drug may be considered adulterated on the basis of the facility.
A drug is adulterated if its strength, quality, or purity differs from compendia standards unless plainly stated on the label.
A drug is adulterated if its strength, quality, or purity differs from the label.
Adulteration (2 of 2)
a product is adulterated unless what
what is the cGMP
What is an example of adulteration and also misbranding
A product is adulterated unless manufacturer complies to CGMP.
CGMP is an exhaustive set of standards directed at manufacturers.
The failure to manufacture a product in a tamper-resistant container when required by law is adulteration and also misbranding.
Misbranding
labeling must not be what
labeling must include what
labeling must contain what
is it misbranding if a drug imitates another drug
Labeling must not be false or misleading, including healthcare economic information.
Labeling must include a listing of active ingredients and quantity and a listing of inactive ingredients in alpha order.
Labeling must contain “adequate directions for use” and “adequate warnings against use” by children and others for whom use might be dangerous.
If a drug cannot be labeled with “adequate directions for use,” it must contain “adequate information for use.”
It is misbranding if a drug imitates another drug.
Nonprescription Drug Labeling
what must be included on the label PC&WDF
pharmacies that relabel must do what
professional OTC labeling may do what
when can both OTC and Rx exist
User-friendly format including pharmacological category or principal intended use, cautions and warnings, adequate directions for use, and “Drug Facts” panel
Pharmacies that relabel or repackage must conform to the same labeling requirements as manufacturers.
Professional OTC labeling may be published by manufacturers for indications not appropriate for lay diagnosis or treatment.
Drugs that are both OTC and prescription exist when some indications can be labeled with adequate directions for use and some cannot.
Prescription Drug Labels and Labeling
what do Newer package insert require
Regulations specify information requirements of commercial labels.
Unit dose labeling is subject to different information requirements.
Newer package insert requirements include a “Highlights” section at the beginning, a table of contents, “Full Prescribing Information” organized to give prominence to the most important information, and a “Patient Counseling Information” section.
Black Box Warnings
when is a black box warning required and for many what?
Required in labeling when use of a drug may lead to death or serious injury
Required for many prescription drugs
Pregnancy Warnings
after 6/30/15, what is required on labels
what 3 categories must be on there
The labeling system prior to June 30, 2015, required that drugs potentially risky during pregnancy be placed into one of five categories: A, B, C, D, and X.
A 2014 regulation replaces the above system. For drugs approved after June 30, 2015, labeling will require the inclusion of three subsections to describe risks: “Pregnancy,” “Lactation,” and “Females and Males of Reproductive Potential.”
Drugs approved prior to June 30, 2015, will be gradually phased into the new labeling standards.
National Drug Code Number
how many digits
what is the 1st, 2nd and 3rd segemnts identify
how many digits do billings and claims submissions require
10-digit three segment code (4-4-2, 5-3-2, or 5-4-1)
The first segment identifies the manufacturer or distributor; the second identifies strength, dosage form, and formulation; and the third identifies package size and type of drug.
Billings and claims submissions require an 11-digit NDC number.
New Drug Approval
No person may introduce a “new drug” into interstate commerce unless ____.
“New drug” is defined as a drug that is not generally recognized by qualified experts as ____and ____(GRASE) for use under the _____ recommended in the drug’s labeling and has been used for a ____extent and time for conditions recommended in the labeling.
The FDA will not accept a GRASE application and requires a ___
No person may introduce a “new drug” into interstate commerce unless approved by the FDA.
“New drug” is defined as a drug that is not generally recognized by qualified experts as safe and effective (GRASE) for use under the conditions recommended in the drug’s labeling and has been used for a material extent and time for conditions recommended in the labeling.
The FDA will not accept a GRASE application and requires a new drug application.
Approved Drugs as New Drugs
An approved drug can become a new drug under certain conditions:
Addition of new substance
New combination of approved drugs
Change in proportion of ingredients
New intended use
Dosage, method, or duration of administration or application is changed
New Drug Application (NDA) Process
what application must be made for before the NDA
What must a sponsor receive in order to ship a drug in interstate commerce to conduct what
what can the FDA terminate at any time
what does the FDAAA require NDA sponsors to publish regarding what on a public registry
IND Investigational New Drug Application
The sponsor must receive approved Notice of Claimed Investigational Exemption for a New Drug in order to ship drug in interstate commerce to conduct phase 1, 2, and 3 clinical studies.
The FDA may terminate testing at any time under risk–benefit criteria; the decision is not subject to appeal or judicial review.
The FDAAA requires NDA sponsors to publish summary information regarding phase 1 trials on a public registry.
Informed Consent
what is required in all three phases
what are research subjects required to know
whose approval is required
Informed consent required in all three phases
Research subjects required to know risks, possible benefits, and alternative courses of treatment
Institutional Review Board (IRB) approval required in some settings
New Drug Application (NDA)
how many days does the FDA have to act on a completed NDA, what is common
what is approval based on
an applicant can appeal what and what is very unlikely
The FDA has 180 days to act on a completed NDA, but delays are common.
Approval is based on proof of safety and efficacy, the manufacturing process, and risk–benefit ratio.
Applicant may judicially appeal a rejected NDA, but success is very unlikely.
21st Century Cures Act and New Drug Approval
when was it passed?
what was the purpose?
what does it also create or amend
Passed in 2016
Objectives include streamlining and adding flexibility to the drug development and approval process and creating a more patient-focused approach to the process.
It encourages the consideration of novel clinical trial designs and the incorporation of “real-world evidence” into the decision-making process.
The law also creates or amends four pathways or programs for drugs that treat serious or life-threatening diseases that affect smaller populations or diseases with significant public health risk
Supplemental New Drug Application (SNDA)
when is it required?
how many categories
A “change being effected (CBE)” SNDA allows the ____ to make the change before _____ approval and is important for ______ changes.
SNDA is generally required when a manufacturer makes any change in an approved drug or in its production
Three categories of SNDA
A “change being effected (CBE)” SNDA allows the sponsor to make the change before FDA approval and is important for labeling changes.
Drug Rating and Classification System
how are drugs rated?
what does it determine
what does a number designate and what a letter
A priority classification system rates new drugs by chemical type and therapeutic potential
this determines how quickly the drug will move through the IND/NDA process.
A number designates chemical type, and a letter (S, P, or O) designates therapeutic potential.
Postmarketing Surveillance
who is it required by
what must be submitted to FDA
Required of the manufacturer after NDA approval
Must submit to FDA reports of serious adverse drug reactions and any new information on safety and efficacy
Phase 4 Studies
The FDAAA empowered the FDA to require manufacturers to conduct phase 4 studies when adverse event reporting or active surveillance is inadequate.
Risk Evaluation and Mitigation Strategy (REMS)
what did the FDAAA grant the FDA to do
Under REMS authority, the FDA can ____ a variety of ____ ranging from ______to limiting the drug to specified settings for dispensing.
The FDAAA granted the FDA authority to require REMS as a condition for approval of an NDA or postmarket when the FDA believes it necessary to ensure benefits outweigh risks.
Under REMS authority, the FDA can require a variety of procedures ranging from Medication Guides to limiting the drug to specified settings for dispensing.
Postmarket Labeling
what did the FDAAA require manufacturers to do
The FDAAA gave the FDA the authority to require manufacturers to add safety information or warnings postmarket.
Postmarket Drug Safety Information for Patients and Providers
what did the FDAAA require the FDA to develop for who
what did the sentinel initiative that. the FDAAA established detect
The FDAAA required the FDA to develop and maintain a website for patients and providers including labeling, safety information, REMS, guidance documents, etc.
The FDAAA also established “Sentinel Initiative” designed to detect early signs of a drug’s risk
Drug Efficacy Study Implementation (DESI)
what was the purpose?
what does the ADNA require
what did the U.S supreme court rule about generic drugs
Initiated to evaluate the efficacy of drugs approved between 1938 and 1962
The FDA created the ANDA for generic drugs approved between 1938 and 1962.
The ANDA only requires evidence of bioequivalence and manufacturing methods rather than proof of safety and efficacy.
The U.S. Supreme Court ruled that generic drugs are new drugs and subject to FDA approval.
Paper NDA
The FDA lacked the authority to allow ANDAs for post-1962 generics, so it created the “paper NDA.”
The paper NDA was not very effective.
Drug Price Competition and Patent Term Restoration Act (PTRA) of 1984
what did it create
concessions to innovator drug companies included what
Statutorily created the ANDA, expediting generic approval
Concessions to innovator drug companies included:
Patent extensions
Market exclusivity
Patent Considerations of ANDA
The generic manufacturer must make one of four types of patent certifications.
A paragraph IV certification contends that the parent drug’s patent is invalid or will not be infringed by the generic company. The ANDA applicant must notify the patent holder.
If the holder sues, the FDA is enjoined for 30 months, unless a court rules otherwise. The generic company receives 180 days of market exclusivity if it prevails under a paragraph IV certification.
Controversies for Healthcare Practitioners
Bioequivalence of generics to the parent and each other
Whether a drug without market exclusivity for a particular indication could be prescribed and dispensed for that indication
Drug Manufacturer Controversial Practices
Producing “authorized generics”
30-month stay from ANDA approval awarded when a patent holder sues for patent infringement
Filing of secondary patents, often for product changes and attempts to shift market share to new product
Exclusion payments (pay-for-delay agreements)
Generic Drug Labeling Controversies
Whether FDA can approve an ANDA for a generic when the labeling will not include one or more of the indications contained on the innovator drug product’s labeling
Whether generic drug manufacturers should be required to change labeling to reflect a known adverse effect
Section505(b)(2) NDAs
Similar to extinct “paper NDA”
Used to file for:
New indications for approved drugs
Generic approvals that do not qualify under ANDA
Drug Competition Action Plan
The goal is to institute new policies aimed at bringing more competition to the drug market, most notably improving the efficiency of the generic drug approval process.
Policies designed to bring complex generic drugs to market more quickly
Guidance also released to streamline the ANDA process for all generic drugs
OTC Drug Review
The OTC drug review process approves drugs on the basis of therapeutic category and conformance to a monograph rather than on a drug-by-drug basis like prescription drugs.
Marketed Unapproved Drugs
what does the FDA say about unapproved drugs?
what are the reasons they give
The FDA estimates that there are thousands of unapproved drugs on the market today.
Reasons include:
Pre-1938 drugs
The FDA has yet to remove some drugs lacking efficacy after DESI.
Lax FDA policies applied to generic approvals prior to 1984
Unscrupulous manufacturers
If a manufacturer obtains NDA approval for an unapproved marketed drug, all marketed drugs in the class must obtain NDA approval within one year.
Patient Treatment with Investigational Drugs on a Widespread Basis
An investigational drug may be used for treatment outside of phase 1, 2, or 3 clinical tests.
Only for patients with serious or life-threatening diseases for which no comparable or satisfactory alternative therapy is available
Certain conditions must be met.
Individual Patient Access to Investigational Drugs
Individual patients acting through a physician may request an investigational drug for treatment purposes if the physician determines the patient has no comparable or satisfactory alternative and that the risk from the drug is no greater than the risk from the disease or condition. The FDA had restricted requests to drugs in phase 3 leading to the Abigail Alliance lawsuit.
The Abigail Alliance decision rejected the plaintiffs’ claim that they have a constitutional right to investigational drugs.
FDA’s Expanded Access Program
The FDA enacted regulations permitting greater access by patients to investigational drugs.
Permits patients to seek access to experimental drugs even in phase 1
Expands and clarifies the treatment use of experimental drugs
Clarifies and establishes the criteria for drug manufacturers to charge patients for investigational drugs
Several states have passed “right-to-try” laws
Expedited Approval Process:“Fast Track”
Expedited review is possible for drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs for the condition and have an effect on a clinical endpoint predictive of clinical efficacy.
Conditional on manufacturer agreeing to phase 4 testing
“Accelerated approval” also available for certain drugs
Biologics
Products derived from living organisms
Licensure by PHSA, but subject to FDCA and FDA requirements
The Biologics Price Competition and Innovation Act created a regulatory framework in 2010 for biosimilars or “follow-on” biologics.
The FDA Purple Book lists biological products, including any biosimiliar and interchangeable biological products.
MedWatch
Voluntary reporting system to allow healthcare professionals to report any serious adverse events, product use errors, and product quality issues
The FDA emphasizes the importance of reporting by healthcare professionals.
The FDAAA requires pharmacies to provide patients with the MedWatch number and a statement about reporting side effects.
Medical Device Amendments of 1976
Establishes criteria for classifying devices into one of three classes
The FDA has authority to reclassify devices based on new safety and efficacy information.
Medical device manufacturers and device-user facilities must report any deaths or serious injuries related to their products.
The FDA can require firms to notify healthcare professionals, repair or replace devices, or refund purchase price of devices.
The FDA can recall devices.
Cosmetics
No premarket approval, nor conformance with CGMP
Manufacturers must substantiate product safety.
The FDA may remove if misbranded, adulterated, or a health hazard.
Must be labeled with list of ingredients in descending order of predominance and appropriated warnings
Drug Advertising and Promotion
The FDA regulates Rx drug advertising, and FTC regulates OTC drug advertising.
The First Amendment restricts government regulation of commercial advertising.
Any regulation will be evaluated pursuant to the four factors established by the U.S. Supreme Court.
Prescription Drug Advertising: Manufacturer to Professionals
Section502(n) requires all advertisements to contain “true statement” and “brief summary.”
Reminder advertising is exempt.
True statement is not met if advertising is false or misleading, does not present a fair balance, and fails to reveal material facts.
Advertising includes ads in journals and other periodicals, broadcast media, and telephone communications.
Brochures, booklets, mailings, bulletins, calendars, and other information distributed to healthcare professionals by a manufacturer is labeling.
Adequate Provision Requirement
Applicable to broadcast media
The manufacturer only needs to include “major risks” as opposed to brief summary.
The manufacturer must make adequate provisions for the dissemination of the labeling.
Prescription Drug Advertising: Manufacturer to Professionals(1 of 2)
Journal advertising
Actively scrutinized by FDA after early studies showed considerable violation
Industry-supported educational programs
Concerns that programs are independent and objective
Factors distinguishing independent from promotional programs published in guidance document
The court decision requires that the guidance document be used as a “safe harbor.”
PhRMA has published self-policing guidelines.
Prescription Drug Advertising: Manufacturer to Professionals(2 of 2)
Physician Payment Sunshine Act
FDA Bad Ad Program
Prescription Drug Advertising: Manufacturer to Consumer (DTC)(1 of 2)
Significant congressional and public controversy
No specific laws and regulations, thus Section502(n) applies
Because compliance with Section502(n) is impractical, FDA allows manufacturers to apply the “adequate provision” requirement.
The consumer must be offered full labeling information from one or all of four sources.
