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.
Prescription Drug Advertising: Manufacturer to Consumer (DTC) (2 of 2)
For DTC print advertising, what does the FDA encourage manufacturers to do
what is exempt from the requirements
what did the GAO report note
what did the FDAAA provide the FDA with
For DTC print advertising, FDA encourages manufacturers to present key risk information in user-friendly ways.
Reminder and help-seeking ads are exempt from requirements.
The GAO report noted FDA weaknesses in regulating DTC ads.
The FDAAA has provided FDA with the authority to require prereview of ads.
Promoting Prescription Drugs and Devices Through Social Media
what does the FDA have guidance documents for
where can communication occur
FDA guidance documents relating standards for:
Communications through interactive promotional media
Communications through social media platforms with space limitations
Correcting third-party misinformation through the internet or social media
Promoting Prescription Drugs for Off-Label Uses
Manufacturers providing off-label use information is very controversial; FDAMA allowed with restrictions
The 2009 compliance guide reinstituted most of FDAMA off-label use provisions, clarified by 2014 compliance guide.
The U.S. v. Caronia decision may limit FDA’s authority to regulate off-label use communications.
Amarin Pharma, Inc. v. FDA ruled against the FDA to allow the company to engage in truthful and non-misleading “promotion” of off-label use information to healthcare professionals.
Due to confusion, the FDA responded with two draft guidance documents in January 2017.
Nonprescription Drug Advertising by Manufacturers
The FTC under the FTC Act regulates deceptive ads.
Ads are deceptive when they are likely to mislead reasonable consumers; ad claims must have a reasonable basis.
The FTC need only prove consumers are “likely” to be misled, not that they actually are misled.
The FTC has authority to require corrective advertising.
Lanham Trademark Act
Prohibits use of any false description or representation
Allows for private cause of action and recovery of monetary damages
Durham-Humphrey Amendment(1 of 2)
Establishes criteria for distinguishing prescription drugs from OTC drugs
Legally establishes oral prescriptions and refills
Although the amendment did not contemplate electronic prescriptions, other federal and state laws permit them.
Durham-Humphrey Amendment (2 of 2)
what does it exempt from regarding pharmacy labels?
what does it specificity of a label
what is required on dispensed Rx labels
Exempts the pharmacy label on dispensed drugs from Section502, except for certain provisions
Specifies the minimum information that a dispensed Rx label must contain
Expiration or beyond-use dating on dispensed Rx labels is required pursuant to state laws
Switching Prescription Drugs to OTC
Three methods:
SNDA: product-specific switch
Petition: product-specific switch
Adding or amending an OTC drug monograph: affects all products in the class
Third Class of Drugs/Behind-the-Counter/Nonprescription Under Conditions of Safe Use
Refers to creating a class of drugs that can only be sold from the pharmacy department
Rationale based on the fact that more dangerous drugs are being switched and would allow even more to be switched
Historic opposition of the FDA appears to be shifting
Professional Practice Considerations Related to D-H
Prescription refill authorization issues
Distinguish authorization of refill from transmittal authority
Prescriptive authority issues
Federal law leaves it up to the states to determine who may prescribe independently or in collaborative practice.
Scope of authority as determined by the state for prescribers who are not MDs or DOs is important for pharmacists to know.
Emergency Contraception:Historical Journey of Plan B(1 of 2)
Plan B approved in 1999 as Rx only
Citizen Petition in 2001 requesting switch to OTC status without age restriction followed by SNDA requesting the same in 2003
After initial rejection of Barr’s SNDA, the FDA finally approved the drug in 2006 as OTC in women 18 and older and only sold behind the counter of pharmacies.
FDA denied Citizen Petition in 2006 prompting Tummino lawsuit, where judge found FDA abused its discretion
Judge ordered age reduced to 17 and FDA to reconsider petition
Emergency Contraception:Historical Journey of Plan B (2 of 2)
In 2011, Teva submitted SNDA for drug as OTC without age or point-of-sale restriction.
FDA Commissioner approved SNDA to eliminate age restriction in 2011; overturned by secretary of DHHS
The FDA again denied the Citizen Petition leading to another Tummino decision in 2013 where the court reversed the FDA’s decision and ordered the FDA to make Plan B OTC without restrictions.
The FDA ultimately declined to appeal and approved Plan B One-Step as an OTC drug without restriction.
Conscientious Objection
Refers to whether a pharmacist has a right to refuse to dispense prescriptions when a moral or religious objection exists
States have passed laws or regulations addressing this issue.
Courts have held that a pharmacist cannot obstruct a patient’s legal right to receive medications. State regulations requiring pharmacists to dispense except in certain situations have been upheld.
Other D-H Related Practice Considerations
Collaborative practice agreements
Authority granted to pharmacists in most states
Authority to dispense
Depends on state law
The FDA does not believe D-H dispensing standards apply to prescribers; however, most states regulate prescriber dispensing in some manner.
Prescription Drug Labeling Information for the Patient(1 of 3)
Patient package inserts (PPIs)
Although the FDA originally had wanted PPIs required for most drugs, it applies to very few, including estrogen-containing drugs, DES, and oral contraceptives.
Duty of manufacturers and pharmacists to distribute to patients
Law applies to institutional pharmacy as well as community.
Prescription Drug Labeling Information for the Patient (2 of 3)
what did the FDA originally want to require for what
how did congress intervene
a 2008 study shows what
what is the manufacturer and dispenser responsible for
Consumer medication information (CMI)
Originally, the FDA wanted to require MedGuides for drugs posing a serious and significant concern to public health and CMI for all other drugs.
Congress intervened to prevent the FDA from implementing CMI rules and allowed private sector to develop standards for CMI.
A 2008 study shows private sector has not yet met the 95% “useful information” standard required by Congress.
Responsibility of manufacturer and dispenser to dispense MedGuides to patients for drugs requiring MedGuides
Prescription Drug Labeling Information for the Patient (3 of 3)
Medication guides (MedGuides)
Required for drugs FDA has determined as posing “serious and significant concerns”
Required for new and refill prescriptions
Generally required for outpatients not under direct supervision of healthcare professional with some exceptions
Content of MedGuide must be approved by FDA
Every new MedGuide approved since 2007 has been in conjunction with a REMS.
FDA proposing a single page information document
Prescribing and Dispensing Approved Drugs for Off-Label Indications
where is Off-label prescribing and dispensing legal
what does Off-label prescribing and dispensing require
how does the court look at labeling
Drug products commonly prescribed for off-label uses
Off-label prescribing and dispensing is legal under FDCA.
Off-label prescribing and dispensing require a professional evaluation of risk vs. benefit.
Courts generally regard labeling as evidence toward the standard of care and not as prima facie establishing the standard of care.
Pharmacy Compounding(1 of 2)
Pharmacies compounding for their patients pursuant to prescription are exempt from FDCA manufacturing provisions.
FDA 1992 compliance guide
Published by FDA over concern that some pharmacies were crossing the line from compounding to manufacturing and were not compounding properly
FDAMA (Section503A) 1997
Defined compounding and delineated nine activities that might cross the line from compounding to manufacturing; added other requirements regarding compounding
Stripped FDA of authority to consider compounded drugs as “new drugs”
Pharmacy Compounding (2 of 2)
The U.S. Supreme Court ruled that advertising restrictions in Section503A were unconstitutional, but failed to consider if all of the compounding law was invalid as ruled by the Ninth Circuit or whether the unconstitutional provisions were severable.
FDA 2002 compliance guide
The FDA adopted the Ninth Circuit’s position that Section503A was not valid, but reinstituted most of its requirements in the 2002 compliance guide.
Reestablished position that pharmacy-compounded drugs are new drugs
Pharmacy Compounding: New Drug Issue
The Fifth Circuit disagreed with the Ninth Circuit and found that the unconstitutional advertising provisions of Section503A are severable. It further found that compounded drugs are thus exempt from the new drug provisions, provided the pharmacy meets all the conditions established in Section503A.
Franck’s Lab decision regarding compounding for animals
Compounding Quality Act of 2013passed as part of the issue regarding the NE Compounding center tragedy (1 of 2)
Passed as part of Drug Quality and Security Act in response to New England Compounding Center tragedy
Reinstated Section503A, minus unconstitutional provisions, thus stripped FDA of its perceived new drug authority
It allows compounders of sterile products to voluntarily register as “outsourcing facilities”- 503 B Products are exempt from misbranding provisions but must meet certain CGMP requirements.
Compounding Quality Act of 2013 (2 of 2)
Outsourcing facilities:
May compound non-sterile drugs
May dispense to individual patients
Cannot have a separate area functioning as a Section503A pharmacy
State Compounding Laws
The NECC event and DQSA prompted many states to enhance compounding laws and regulations.
Many state laws and regulations follow USP standards.
Repackaging Rx Drugs
Section503A and Section503B do not exempt repackaged drugs from the act.
Compliance guidance, however, provides conditions under which the FDA will not take enforcement action.
Compounding Essentially Copies
Compounding “regularly or in inordinate amounts” products that are “essentially copies” of “commercially available products” prohibited unless change for an identified patient produces a significant difference
Guidance provides definitions of terms for Section503A pharmacy and Section503B outsourcing facility.
Mixing, Diluting, Repackaging Biologicals
The FDCA does not permit this under Section 503A or Section503B.
Compliance guidance, however, provides conditions under which the FDA will not take enforcement action.
Compounding by Hospitals and Health Systems
Unless an outsourcing facility must comply with Section503A
Compliance guidance, however, permits hospital pharmacy to compound without receiving prescriptions or orders, provided certain conditions are met.
Insanitary Conditions
Both Sections503A and 503B facilities subject to Section501(a)(2)(A) adulteration provisions
Compliance guidance describes insanitary conditions, procedures and actions facilities should employ, and potential regulatory actions.
Compounding Using Bulk Drug Substances
Section503A requires that bulk drug substances used in compounding must appear on a list as developed by the FDA pursuant to regulation.
Section503B requires that bulk drug substances used in compounding must appear on a list established by the FDA based upon clinical need or an FDA list of drug shortages.
Radiopharmaceuticals
Compounding of radiopharmaceuticals specifically excluded from the exemptions of Section503A
The guidance document, however, provides conditions under which the FDA will not take action when nuclear pharmacies compound or repackage to meet patient needs.
Section503B applies to the compounding of radiopharmaceuticals.
MOU
what is required (between what) to distribute how much of what
what does draft MOU require states to do
MOU required between state and FDA in order to allow a compounder to distribute more than 5% of total prescriptions dispensed or distributed
Draft MOU guidance requires states to determine if compounder’s interstate distributions are “inordinate” and defines “inordinate.”
Rx Requirement for Section503A Pharmacies’
what does it prohibit
how does the guidance interpret limited quantity
Guidance prohibits supplying compounded drugs for “office use;” the drug product is compounded must be for an identified individual patient based on the receipt of a valid prescription order.
The guidance interprets “limited quantity” as applied to anticipatory compounding.
Other Compounding Issues
Dietary supplements
OTC drugs
Manufacturer patent issues
USP 800
what does it establish for healthcare entities?
Establishes standards for all healthcare entities that handle hazardous drugs (HDs)
Compliance required by December 1, 2019
HDs are defined and identified by the National Institute for Occupational Safety and Health (NIOSH); the Institute maintains a list of these drugs (to be updated in 2018).
Allows entities to make an assessment of risk and to determine alternative strategies
Orange Book and Generic Substitution
State generic substitution laws
Every state permits pharmacists to substitute generically in some manner.
State laws differ considerably.
Labeling must accurately differentiate generic product from brand.
Orange Book
Evaluates pharmaceutically equivalent products on the basis of bioequivalence
Pharmaceutical equivalence—products contain same active ingredients and are identical in strength and dosage form
Bioequivalent pharmaceutical equivalents are generally presumed therapeutically equivalent—having the same clinical safety and efficacy.
The Orange Book uses a two-letter rating system; some products use two letters and a number.
Pharmacists must comply with state law when substituting and exercise professional judgment substituting B-rated products.
Narrow Therapeutic Index (NTI) Drugs
Drugs with less than a two-fold difference between median lethal dose and median effective dose or two-fold difference between minimum toxic concentrations and minimum effective concentrations
Controversy exists as to whether the FDA’s statistical parameters for bioequivalence are accurate enough for certain NTI drugs; the FDA drafted new guidelines.
Pharmacists should exercise particular professional judgment when called upon to substitute B-rated NTI drugs.
Substitution of Biosimilar Biologics
to be interchangeable to a reference product, what must a bio similar have
what does the purple book provide
Interchangeable biosimilars may be substituted without what if state allows it
Under the BPCIA, to be “interchangeable” a biosimilar must not only be “highly similar” but also produce the same clinical result as the reference product without greater risk.
The Purple Book provides a guide to health care professionals.
Interchangeable biosimilars may be substituted without intervention of a prescriber (state law allowing).
Drug Supply Chain Security
Numerous opportunities for diversion and introduction of counterfeit drug products
Federal efforts to protect the security of the drug supply chain include the Prescription Drug Marketing Act of 1987 and the Drug Supply Chain Security Act of 2013.
Prescription Drug Marketing Act(1 of 4)
Requires state licensing of wholesalers
Bans reimportation of Rx drugs except by manufacturer
Bans sale, trade, or purchase of Rx drug samples
Mandates requirements for Rx drug samples
Prohibits resale of Rx drugs purchased by hospitals or healthcare facilities
Prescription Drug Marketing Act (2 of 4)
Drug samples
Establishes restrictions to limit misbranding and adulteration situations
Defined as a unit of drug not intended to be sold and intended to promote the sale of the drug
Establishes requirements for distribution to prescribers
Prohibits community pharmacies from receiving samples
Prescription Drug Marketing Act (3 of 4)
Purchase and resale
Enacted to prevent hospitals and similar entities from reselling, purchasing, trading, or offering to do any of these activities; differentially priced drugs to community pharmacies and others so as to prevent adulteration and misbranding opportunities
Important exceptions exist, most notably selling or dispensing Rx drugs pursuant to prescription.
Prescription Drug Marketing Act (4 of 4)
Product returns permitted
Wholesaler regulation intensified
Pedigrees Under PDMA
The FDA granted authority to require secondary wholesalers to maintain pedigrees of drugs.
The 1999 regulation to implement was enjoined on the grounds it would likely cause irreparable harm to secondary wholesalers and violate the equal protection clause.
The FDAAA in 2007 mandated that the FDA develop track and trace standards and SNIs, but fell short of developing a true federal pedigree program until the DSCSA of 2013.
Drug Supply Chain Security Act(DSCSA 2013)
Established timeline for trading partners toward implementation of a track and trace system
A full system electronic track and trace system must be in place by November 2023.
Applies to transactions where prescription drugs change ownership with some important exceptions
Establishes uniform national licensing standards for wholesalers and 3PL providers
Trading Partners
Trading partners include:
Manufacturers
Wholesalers
Repackagers
3PLs
Pharmacies
Suspect and Illegitimate Products
Trading partners must have a system to quarantine, investigate, and notify the FDA and other partners of “suspect” and “illegitimate” prescription drug products.
Product Tracing Information
Includes transaction information, history, and statement
Must be passed, received, and maintained for six years by each trading partner
Any method (paper or electronic) of passing the information is permissible until November 2023, at which time only electronic is permissible.
Important exceptions for pharmacies
Unique Product Identifier (UPI)
Manufacturers are required to affix UPI to each individual package and homogenous case by November 2018.
Importation for Personal Use
PDMA generally prohibits reimportation of Rx drugs
Many stakeholders wish to obtain Rx drugs from Canada and other countries because of lower costs.
The FDA has instituted a “compassionate use policy.”
The CSA also allows for limited personal importation.
The MMA allows wholesale importation of Rx medications from Canada, provided the secretary of DHHS would approve.
The Homeland Security Act permits limited personal importation from Canada.
The FDA will enforce the no importation law against businesses (Rx Depot case).
FDA Inspection of Pharmacies
The FDA can inspect a pharmacy to determine if the pharmacy is compounding or manufacturing.
It can extend the search if probable cause exists that the pharmacy is manufacturing.
The FDA may search without a warrant.
Use of Alcohol in Pharmacy Practice
Tax-paid alcohol
Used in compounding in community pharmacies
Obtainable from outlets that sell liquor at retail
Tax-free alcohol (190 proof ethyl alcohol)
Available to hospitals for medicinal, mechanical, and scientific purposes and in treatment of patients. May be used only for inpatients.
Charity clinics may use for medicines for outpatients if they do not charge.
Poison Prevention Packaging Act(1 of 2)
Intent of act to protect children from accidental poisonings due to “household substances”
Administered by the Consumer Product Safety Commission
The law establishes the standards for child-resistant containers.
Container may not be reused unless glass or threaded plastic and then only with new closure.
Poison Prevention Packaging Act (2 of 2)
Exemptions
Prescriber requests- only good for that prescription
Patient requests- good for all the drugs that the patient requests for, does not have to be in writing
Institutionalized patients
Certain drug products such as SL nitroglycerin and SL and chewable isosorbide dinitrate
For manufacturer: may market one size in noncompliant package with appropriate statement
Drug Advertising by Pharmacies
Price advertising
Considered reminder advertising and thus exempt from Section502(n), provided that certain conditions are met
Product advertising
Subject to strict liability standard
Constitutionality of State Pharmacy Advertising Laws
what had failed
The Virginia decision established that what
what does the Virginia decision not bar states of doing
Challenges to state laws that prevented advertising based on the reasonableness of the laws had failed
The Virginia decision established that the First Amendment applies to commercial speech and to recipients of the speech.
The Virginia decision does not bar states from prohibiting false or misleading advertising, advertising professional superiority, or making it illegal for pharmacies to offer discounts or rebates.
Federal Controlled Substances Act
Creates a closed system via registration
Establishes national uniformity
Enforced by DEA
State vs. Federal Authority
State law must be stricter than federal law to not conflict.
Pharmacists should follow stricter law.
The DEA generally has a close relationship with state pharmacy boards.
Presumption of interstate commerce in the federal regulation of controlled substances
Definition of Narcotic
Narcotic: natural or synthetic opium or opiates or derivatives including cocaine, which is not an opiate derivative
Classification of Controlled Substances
Placement into one of five schedules depending on abuse potential and degree to which drug may cause physical or psychological dependence
C-I Drugs
No accepted medical use, as opposed to drugs in the other schedules
High potential for abuse and lack accepted information on safety of use
Includes hallucinogenics, some opiates, methaqualone, and unapproved GHB
Medical and Recreational Use of Marijuana
Marijuana for medical purposes: legal in many states and in a few states for recreational use, as well
Marijuana remains a C-I drug under federal law.
Federal courts have held that there is no constitutional right of patients to obtain marijuana.
The U.S. Supreme Court held that federal agents can seize medical marijuana because of a presumption of interstate commerce.
The U.S. Supreme Court held that marijuana buying cooperatives violate the CSA.
Federal court held that government could not take action against physicians who recommend medical marijuana
C-II Drugs
what level abuse does it have what may it lead to
what does it include
AGSPMAO
High potential for abuse and abuse may lead to severe physical or psychological dependence
Includes
opium and many other opiates (including products containing hydrocodone); cocaine;
stimulants such as amphetamine methamphetamine; depressants such as amobarbital, glutethimide, secobarbital, and pentobarbital
C-III Drugs
Lesser potential for abuse than C-II drugs, and abuse may lead to moderate or low physical dependence or high psychological dependence
Includes many C-II drugs in combination with a noncontrolled ingredient, or in smaller dosages, or in a less abusable dosage form
Also includes certain stimulants, anabolic steroids, dronabinol, ketamine, paregoric, and GHB approved by the FDA
Strength limit of 1.8 g of codeine per 100 ml. Also strength limits for dihydrocodeinone, opium, morphine, and other drugs
C-IV Drugs
Lower potential for abuse than C-III drugs, and abuse may lead to limited physical or psychological dependence
Includes narcotic drugs such as dextropropoxyphene; depressants such as alprazolam, chloral hydrate, barbital, benzodiazepines; stimulants such as diethylpropion, phentermine; tramadol
C-V Drugsv
Low potential for abuse relative to C-IV drug, and abuse may lead to limited physical or psychological dependence relative to C-IV drugs
Includes antitussives containing codeine and antidiarrheals containing an opiate
Strength limits of 200 mg of codeine per 100 ml; 100 mg of dihydrocodeine or opium per 100 ml; 1.5 mg of diphenoxylate; and not more than 25 mcg atropine per dosage unit
Authority for Scheduling
Scheduling authority is vested in the attorney general who must request a scientific and medical evaluation of the drug and recommendation from the secretary of DHHS.
The recommendation of the secretary regarding scientific and medical issues is binding on AG, except when AG finds the drug must be placed in C-I to avoid an imminent hazard to public safety.
The scheduling decision must be based on several factors.
Manufacturer Labeling and Packaging
Labels and labeling of commercial containers of controlled substances must contain the identification symbol of the schedule.
The symbol must be prominently located.
Registration
Anyone who manufactures, distributes, or dispenses controlled substances (among others) must register with the DEA.
Manufacturers and distributors must register annually; dispensers must register every 3 years.
Exemptions from registration include agents or employees of registrants, common carriers, ultimate users, prescribers, and dispensers in the service of the U.S. government, and law enforcement officers.
Individual Practitioners (IPs)
Individual practitioners include physicians, dentists, veterinarians, or others licensed to dispense by the state.
IPs who are agents or employees of another IP (other than a mid-level) may administer or dispense controlled substances, but not prescribe.
IPs who are agents or employees of a hospital or other institution may administer, dispense, and prescribe controlled substances provided all requirements are met, including that the institution has assigned a specific internal code number to the IP as a suffix to the institution’s DEA number.
Activities Requiring Registration*
Manufacturing, distributing, reverse distributing, dispensing, conducting research, conducting narcotic treatment programs, conducting chemical analysis, importing, and exporting
Dispensing
Definition of dispense includes to deliver a CS pursuant to the lawful order of a practitioner; includes prescribing, administering, and dispensing
Definition of practitioner includes physician, dentist, veterinarian, scientific investigator, pharmacy, pharmacist, hospital, or others licensed by their jurisdiction to be involved with controlled substances
Definition of institutional practitioner includes hospitals, but not pharmacies
Mid-level practitioners (including pharmacists) may register as dispensers, provided that state law authorizes independent or collaborative prescriptive authority.- PA’s, NP’s, not midwives
Manufacturing
production, preparation, compounding, or processing of a drug; also, packaging, repackaging, labeling or relabeling
Excludes activities of practitioners incidental to dispensing
Manufacturer coincidental activities include: distributing its own products, chemical analysis, and preclinical research
Pharmacies are exempt if engaged in the ordinary course of pharmacy practice.
A pharmacy may manufacture and distribute to other practitioners aqueous or oleaginous solution or solid dosage form of a narcotic not exceeding 20% narcotic concentration.
Distributing
what does it mean
what must wholesalers register a
who is exempt
what are distributors required to do and who should they inform
Distributing: to deliver a CS
Wholesalers must register as distributors.
Practitioners registered to dispense are exempt, provided they comply with all conditions.
Stocking of Automated Dispensing Systems in LTCF and return of CSs to suppliers by practitioners are exempt, provided recordkeeping requirements are met.
Distributors are required to design and operate a system able to detect suspicious orders of CSs and inform the DEA upon discovery
Controversy about whether delivery to the patient’s prescriber is distributing or dispensing
Conducting Research
Coincidental activity of dispensers to________ with schedule II–V CSs if ________
what does research with C-I require
Coincidental activity of dispensers to conduct research with schedule II–V CSs if authorized
Research with C-I drugs requires submission of protocols with application.
Separate Registrations Required
when is separate registration required
Each principal place of business where CSs are administered, dispensed, or stored requires separate registration.
Application for Registration and Reregistration
to engage in an activity requiring registration, what must be done
when should current registrants receive registration
what will be sent if required
what form should a dispenser use to register
May not engage in an activity where registration is required until registration is granted and a certificate of registration issued
Current registrants should receive a registration form approximately 65 days before expiration.
A second notice will be sent electronically if required.
The dispenser registration form is DEA Form 224 (used to register with the DEA), which is available online.
Modification, Transfer, or Termination of Registration with the DEA
who must approve any modifications?
what if the registrant passes away or ceases legal existence, who must be notifed, and what happens to the registration
Any modifications must be approved by the DEA.
If the registrant dies or ceases legal existence, the DEA must be notified, and the registration terminated.
Registrations cannot be assigned or terminated without DEA approval.
Distribution of Controlled Substances on Discontinuance of Business
On discontinuance of business without transfer of business, the registrant must return a certificate of registration to the DEA for____ together with any unexecuted Form ____.
how must C-II be recorded?
Who completes the 222 forms, followed by who and sent to who
to register as a pharmacy, what form must be completed
On discontinuance of business without transfer of business, the registrant must return a certificate of registration to the DEA for cancellation together with any unexecuted Form 222s.
Controlled substances must be disposed of pursuant to regulations.
If the registrant wishes to transfer business, a proposal must be submitted to the DEA at least 14 days prior to the transfer with the required information.
The transfer may occur unless the DEA notifies otherwise.
A complete inventory of CSs must be taken on the date of transfer.
C-II products (like methylphenidate ) must be recorded via Form 222.
Who completes the 222 forms: pharmacy, purchaser begins by completing the 222 forms, supplier completes the form and sends a copy to the DEA
Pharmacy A acquiring B
Turn in registration to the DEA
To register as a new pharmacy, theDEA Form 224must be completed.
Denial, Revocation, or Suspension of Registration
what can an attorney general deny a practitioner of
after an applicant materially falsifies an application, what can an AG do?
The attorney general may deny a practitioner applicant a registration if it is determined not to be in the public interest, which requires the consideration of five factors.
The AG may suspend or revoke a registration to manufacture, distribute, or dispense upon finding that the applicant materially falsified an application; has been convicted of a felony; or has had a state license or registration suspended, revoked, or denied.
Security Requirements
what must all applicants and registrants do?
where must IPs keep CSs
where must pharmacies and institutional practitioners keep CSs (think of clean sweep)
who must not be employed
All applicants and registrants must provide effective controls and procedures to guard against theft and diversion.
The DEA considers several factors when evaluating the overall security system of a registrant or applicant.
Individual practitioners must securely lock CSs in a substantially constructed cabinet.
Pharmacies and institutional practitioners may do the same or disperse them throughout the stock of noncontrolled substances.
May not employ any person whose application for registration has been denied or revoked
Penalties
what section has penalties for drug traffickers who is it applied and under what
what section establishes for practitioners not conforming to the requirements of the CSA and what kinds of things are held against them
how much is a person fined for violating form 222 and how many years in prison
Knowingly or intentionally possessing a _______ other than by a valid _____ could result in up to _______ in prison and a fine of up to $______.
Section841 establishes penalties for drug traffickers and is applicable to practitioners who prescribe and/or dispense outside of the ordinary course of professional practice.
Section842 establishes penalties for practitioners for not conforming to the requirements of the CSA, such as recordkeeping. The standard was changed from strict liability to negligence.
Form 222 violations are subject to fines of up to tens of thousands of dollars and up to four years in prison.
Knowingly or intentionally possessing a CS other than by a valid Rx could result in up to one year in prison and a fine of up to $1,000.
Pharmacy Inspections
what does the 4th amendment protect individuals from
what does it require the issuance of and based on what
The exclusionary rule _____ that any ____ obtained in ____ of the Fourth Amendment will not be ____.
Constitutional issues
The Fourth Amendment protects individuals from unreasonable searches and seizures.
Requires the issuance of a search warrant based on probable cause
The exclusionary rule provides that any evidence obtained in violation of the Fourth Amendment will not be admissible.
DEA Inspections
where can the DEA inspect
what can they examine and copy
without consent, what can the inspector not do?
what does the audit procedure involve
before the inspection what is the inspector required to do
The DEA has the authority to inspect any place where CS records are kept or persons are registered.
Allowed to examine and copy all records and reports (222 forms etc), inspect within reasonable limits, and take an inventory of CSs
Without the consent of the owner or PIC (pharmacist in charge or manager record), the inspector is not allowed to inspect financial, sales (other than shipping), or pricing data
The audit procedure involves inspecting records of drugs received less drugs dispersed and comparing them with inventory.
Prior to the inspection, the inspector is required to state the purpose of the inspection and present the owner or PIC with credentials and written notice of inspection.
Notice of Inspection (NOI)
whose name must it have along with other information?
what must the inspector obtain and from who
what can be said about consent?
what can the PIC or owner grant the inspector?
The NOI must contain the name of the owner or PIC, the name and address of the business, the date and time of inspection, and a statement that the NOI was given.
The inspector must obtain a written statement of informed consent signed by the PIC or owner.
Consent must be voluntary and not coerced and may be withdrawn at any time during the inspection.
The PIC or owner can grant the inspector limited consent.
Administrative Inspection Warrant (AIW)
is consent required
who created the AIW as an alternative to SW?
When can AIW be served?
what exists for warrants
No consent required
Probable cause requirement
Valid public interest
Contrast to probable cause for a search warrant (SW, which requires probable cause that you are doing something illegal)
AIW was created by the Supreme Court as an alternative to SW
AIW may only be served during regular business hours.
Several exceptions exist as to when a warrant is not required.
State Pharmacy Board Inspections
what do some states allow for searches?
State ______ search statutes may be ______, provided certain ____are met.
Some states allow warrantless searches of pharmacies.– take a look at state laws!
State warrantless search statutes may be constitutional, provided certain requirements are met.
Opioid Treatment Programs (OTPs)
when was OTPs authorized
what drugs are treatments for opioid addictions (LMB)
practitioners must be registered with who to do what
Congress first authorized narcotic treatment programs (now OTPs) in 1974.
Only LAAM, methadone (CII- a retail pharmacy can hold this for severe pain, cannot use for cough), buprenorphine, and buprenorphine containing products are authorized drugs for treatment of opioid addiction.
Practitioners wanting to conduct maintenance or detox treatment must be registered by the DEA.
Methadone
Used for severe pain outside of narcotic treatment programs
Not legal to prescribe or dispense as an antitussive
The APhA lawsuit established that the FDA could not restrict the distribution of methadone.
Manufacturers voluntarily restricted 40 mg methadone tablets to OTPs. So, retail pharmacist usually have 5 or 10mgs
Controlled Substance Registrant Protection Act
what is made a federal crime
what are the penalties; how much jail time can result and how much is the fine? if a weapon is used or death results what happens to the fine
The purpose of the law is to make it a federal crime if robbery results in $500 or greater replacement cost of CSs, or a person suffers “significant” injury, or interstate commerce is involved in the planning or execution of the crime.
Penalties can result in up to 20 years of imprisonment, $25,000 fine, or both. If a weapon is used, the penalties are higher. If death results, the penalty is higher yet.
Anabolic Steroids (CIII) Act of 2004
why was this enacted
what is anabolic steroids maintained as
what is added to the act
what does it provide automatic scheduling of what without what
what can physicians and prescribers not do
Amends prior anabolic steroid (Testosterone etc) legislation enacted to prevent misuse in order to enhance athletic performance
Maintains anabolic steroids as schedule III
Adds several steroids to the act
Provides for automatic scheduling of certain salts, esters, and ethers of anabolic steroids without need to prove muscle growth
Physicians and prescribers cannot give for athletic performance
Combat Methamphetamine Epidemic Act of 2005 and Methamphetamine Prevention Act of 2008
what restrictions did it place on OTC
the law limits the sale of how much ephedrine, PSE, or PPA base to who for what duration of time
no consumer could purchase how much and within how many days or how much within how many days for Mail order
where must the products be stored
how must the sales be recorded
what is the age limit of pseudoephedrine and what does each employee go through
what is the strength of pseudoephedrine
you need to know how to do/process through the math to know how many tablets you must dispense! how much grams can a person take of pseudoephedrine in a day, what is that grams in mgs, divide that mg by the strength of pseudoephedrine, what did you get baby girl!?!?!?!
he asks about pseudoephedrine base not _________
Places restrictions on OTC drugs used to manufacture methamphetamine including pseudoephedrine
The law limits sale to no more than 3.6 g of ephedrine, PSE, or PPA base to a single purchaser per day.
No consumer may purchase more than 9 g within a 30-day period or 7.5 g within a 30-day period by mail order.
The products must be stored behind the counter or in a locked cabinet where customers do not have direct access.
Sales must be recorded with required information.
Many states have stricter laws.
Limits pseudoephedrine age: no age requirement, each employee undergoes training that is certified to attorney general
pseudoephedrine is 30mgs
Know basic info: 3.6g per day
3.6 grams is 3600 mg
3600/30mg is 120 tablets
Ask about pseudoephedrine base not hydrochloride or sulfate
Methamphetamine Production Prevention Act of 2008
Although electronic logbooks are not required, it is hoped that they will become the standard and that pharmacies will participate in common electronic logbooks.
Sellers can now capture information by barcode reader.
The seller or purchaser may enter the purchaser’s name, address, and date and time of sale.
The seller may collect the purchaser’s signature by any of three means.
Sellers must annually engage in self-certification.
U.S. Postal Laws’’
can CSs be mailed?
Can you mail drugs:
If you were not able to mail, there would not be what
what must the Label not say
CSs may be mailed, provided they meet the packaging standards established by the U.S. Postal Service.
Can you mail drugs: yes
Can mail CII-CV drug
If you were not able to mail, there would be things as mail order pharmacy
Label must not say that there are drugs inside
Controlled Substance (CS) Prescriptions
Defined as an order for medication dispensed to or for an ultimate user
The Rx does not include orders for medication dispensed for immediate administration (i.e., hospital chart orders).
Prohibition against prescriptions for office use
Those Allowed to Prescribe CSs
Individual practitioners (IPs) authorized to prescribe (or issue medication orders) in their state and registered by DEA or exempt from registration
Employees or agents of IP may communicate prescriptions to a pharmacist or prepare the Rx for signature of IP
Delegation of prescriptive authority not legal unless agent also has prescriptive authority
When suspicious, might check the validity of a DEA number by performing the calculations or searching national database
Those Allowed to Dispense Controlled Substances
Only a pharmacist acting in usual course of professional practice and who is registered individually or employed by a registered pharmacy or institutional practitioner
Ancillary personnel may engage in CS dispensing activities if permitted by state law.
IPs may dispense if permitted by state law.
A prescription for a controlled substance may only be issued by an individual practitioner who:
Is authorized to prescribe controlled substances in the state in which he/she is licensed to practice; and
Is registered or exempt from registration under 21 CFR 1306.03
- Who is exempt from registration:
a resident (new physician) will use the hospital’s DEA registration
DEA Registration numbers
how many digits and composed of what
what does it initially start with
Nine digits composed of letters and numbers
two alphabet letters followed by seven numbers
Initially, the registration number started with a letter A.
All registration numbers starting with A have been assigned
DEA started with B now F, started G
DEA registration number
Mid-level practitioners (and pharmacist) begin with M.
Distributors begin with either P or R
The second letter is usually, but not always, the first letter of the registrant’s last name
The next six positions are a computer-generated number unique to registrant
The last and 9th position is a computer calculated check digit.
To check the validity of a DEA registration number:
A pharmacist:
adds the first, third and fifth digits
adds the sum of the second, fourth and sixth digits, multiplied by 2, to the first sum
determines whether the right most digit of this sum corresponds with the ninth check digit
HYPOTHETICAL
Jane the pharmacist receives a prescription from Dr. William Nash. The DEA number on the prescription is AN1257218.
Could this be a valid DEA number?
A: physician
N: first initial of last name
Math:
- 1 +2 + 5 = 8
- 2 + 7 + 1 = 10
AN1257218
1+5+2= 8
(2+7+1) x 2= 20
8+20 = 28
The 8 in 28 corresponds to the 8 in 18
This number could be valid
- will need to make up your own DEA number and test if it could be valid*
Disclaimer
In reality, many forgers are familiar with the procedure to verify a DEA registration number and can invent a number that would be plausible.
Therefore, pharmacists cannot rely solely on this check to determine the validity of a controlled substance prescription.
Information Requirements of CS Prescriptions
Date of issuance required: no predating or postdating
Must contain full name and address of patient; drug name, strength, dosage form, and quantity prescribed; directions for use; and name, address, and registration number of practitioner & DEA #
Before filing, must contain written or typed name or initials of dispensing pharmacist, the date dispensed, and the units or volume dispensed
The date is the date that they write a prescription
Other Requirements of Written CS Rxs
Must be signed on day of issuance
Written in ink, indelible pencil (cannot erase), or typed and manually signed
Corresponding responsibility of pharmacist and prescriber that a CS Rx complies with all requirements
IPs Exempt from Registration
Must include registration number of institution and special internal code number
Must include name of prescriber stamped, typed, or hand printed, as well as signature of prescriber
IPs in armed services or public health must include on the Rx the service ID number in place of the registration number.
Correcting Errors and Omissions
For C-III, C-IV, and C-V Rxs, state law component: the pharmacist may add or change any information after consultation with practitioner and documentation, except for the patient’s name, name of CS (except generic substitution), or prescriber’s signature.—whatever the state allows
For C-II Rxs: the DEA had traditionally maintained that additions or changes could be made the same as with other CS Rxs. That position has flip-flopped in recent years, but it appears corrections can be made if state law or policy permits.
Purpose of CS Prescription
A CS Rx must be for a legitimate medical purpose in the usual course of professional practice.
Corresponding responsibility upon the pharmacist
Knowingly prescribing or dispensing a CS Rx not for a legitimate medical purpose violates the law.
“Knowingly” standard is one of a conscious disregard for the obvious.
When suspicions should exist, a pharmacist is expected to exercise professional judgment and investigate.
Legitimate medical purpose in the usual course of professional practice generally means acting in accordance with accepted standards of medical practice.
Legitimate Medical Purpose and Usual Course of Professional Practice
Examples of invalid prescriptions include:
Narcotic Rxs written for the purpose of maintaining or detoxifying an addict
Rxs written for fictitious patients
Rxs written without a good-faith medical examination
Rxs written when there is no medical reason
A facially valid Rx is not necessarily a valid Rx.
Pharmacists will more likely face enforcement action in situations where there is blatant or glaring misconduct as opposed to isolated prescriptions.
DEA has published examples of situations that might be suspicious
Exercise of Clinical Judgment and Pain Treatment- providing drugs for legitimate pain– not on exam
Treatment of pain is a legitimate medical purpose.
Drug tolerance and physical dependence as a consequence of opioid use is normal and natural.
The quantity of drugs prescribed and frequency of Rxs alone are not indicators of improper prescribing.
The pharmacists’ role under CSA is determining the legitimacy of Rx for pain rather than therapeutic appropriateness of using opioids.
Differentiating Treatment of Pain from Treatment of Addiction – not on exam
Important to determine whether the purpose of opioid treatment is legally for pain or illegally for addiction
Important to ascertain whether taper-down dosages are for detoxification of addiction or withdrawal due to physical dependence
Important to distinguish addiction from dependence
Exceptions allowing for treatment of addicts outside of licensed addiction programs or DATA
Ascertaining the Legitimacy of Opioid Rxs in Pain Treatment – not on exam
Alleged pain clinics create special concerns for pharmacists.
Pharmacists should familiarize themselves with the medical standards of practice for diagnosing and treating pain.
Pharmacists should seek a collaborative practice relationship with pain physicians.
When necessary and appropriate, pharmacists should interview both the patient and prescriber regarding the pain and the treatment.
Federal/State Efforts to Balance Pain Treatment with the Opioid Epidemic
Overdose deaths in the U.S. continue to rise.
Various federal and state efforts have been implemented to help address the epidemic, including prevention, treatment, and enforcement efforts.
Examples of various efforts: prescribing guidances and laws, PDMPs, naloxone access, FDA REMS, medication disposal, expansion of partial fills, mandated electronic prescribing
Dispensing C-II Drugs
General rule: C-II prescriptions must be written and signed by a prescriber.
Some states have stricter laws, e.g., quantity limits, time limits, security Rx forms.
Exceptions:
Emergency situations
Narcotic compounded drug for direct administration by infusion: faxed Rx serves as original
Long-term care facility patients: faxed Rx serves as original
Hospice patients for narcotic C-II drugs: faxed Rx serves as original
Electronic (pursuant to requirements discussed later)
Emergency Situations in Which Controlled Substances in Schedule II May be Dispensed Upon Orally or Electronically Transmitted Prescription
“Emergency situations”, for the purpose of permitting the dispensing of any controlled substance in Schedule II upon orally or electronically transmitted prescription, means those situations in which the practitioner who intends to prescribe a controlled substance in Schedule II determines:
(a)That the immediate administration of the controlled substance is necessary for the proper treatment of the intended ultimate user;
(b)that no appropriate alternative treatment is available, including administration of a controlled substance which is not in Schedule II; and
(c)that it is not reasonably possible for the prescribing practitioner to provide a written prescription to be presented to the person dispensing the controlled substance prior to the dispensing.
Emergency Situations in Which Controlled Substances in Schedule II May be Dispensed Upon Orally or Electronically Transmitted Prescription
In case of an emergency situation, a pharmacist may dispense a controlled substance in Schedule II upon receiving the orally or electronically transmitted authorization of a prescribing practitioner, provided that:
(a)The quantity prescribed and dispensed is limited to the amount adequate to treat the patient during the emergency period.
(b)the prescription contains all information required by state lawexcept for the actual signature of the prescribing practitioner, and in the case of an oral prescription, or prescription transmitted electronically by computer modem or other similar electronic device, the prescription is immediately reduced to writing by the dispensing pharmacist; and
(c)the dispensing pharmacist makes a reasonable good faith effort to determine that the orally or electronically transmitted authorization was issued by an authorized practitioner, which effort may include a callback to the prescribing practitioner or other good faith efforts to ensure the prescribing practitioner’s identity.
Partial Filling of C-II Drugs
The 2016 CARA law allows pharmacies to provide partial fills of a C-II medication up to 30 days from the date of the prescription if state law does not prohibit.
CARA also allows partial fills of schedule II controlled substances when a pharmacist receives a verbal emergency prescription, with any remainder being provided within 72 hours.
In LTCFs or for terminally ill patients, may partially fill for up to 60 days from date of issuance, provided recordkeeping requirements are met
Multiple C-II Rxs for Same Drug and Patient on Same Day
Permitted provided:
Each Rx must be on a separate blank.
The total quantity prescribed does not exceed 90-day supply.
The practitioner determines a legitimate medical purpose to do this.
The practitioner writes instructions on each Rx (other than first) as to earliest date each Rx may be dispensed.
Multiple Rxs do not create undue risk of diversion.
Permissible under state law
Dispensing C-III, C-IV, and C-V Drugs
May be dispensed pursuant to written, faxed (considered original), electronic, or oral order (need to be reduced to writing)
Oral orders must be promptly reduced to writing.
IPs may administer or dispense without a prescription.
Refilling C-III and C-IV Rxs
For C-III and C-IV drugs: limit of 6 months after date of issuance or five times, whichever comes first
The practitioner may orally authorize additional refills if original was written for less than five and authorization is recorded on hard copy or in automated system.
The refill quantity cannot exceed quantity originally authorized.
Recording Refills of C-III and C-IV Rxs
If nonautomated system, must record required information on back of Rx or other readily retrievable document
If automated system, must provide online retrieval either by display or hard copy printout of the original Rx information and up-to-date refill history
Hard copy printout requirements
In lieu of printout, may maintain bound logbook or separate refill file
Records must be maintained for two years. Keep invoices for 2 years. Exceptions: Medicare Rx which is 10 years
Pharmacies must have an auxiliary system for documenting refills if computerized system suffers downtime.
Partial Filling of C-III, C-IV, and C-V Rxs
Permitted provided:
Recorded in same manner as refill
The total quantity dispensed does not exceed total prescribed.
No dispensing after 6 months from date of issuance
Important to differentiate partial fills from refills
Labeling
The label must include date of filling if a C-II drug and date of initial filling if in another schedule.
Refills should be labeled with both date of initial filling and date of dispensing.
Labels must include all required information plus a cautionary statement prohibiting the ultimate user from transferring the drug.
Labeling requirements are not applicable if prescribed for administration to an institutionalized patient, provided that restrictions and requirements are met.
Electronic Transmission Rxs(1 of 3)
Prescribers must:
Undergo identity proofing
Digitally sign using two of three possible factors for authentication
An agent can enter Rx information but cannot have access to authentication factors and sign.
Electronic Transmission Rxs (2 of 3)
Pharmacy requirements:
The pharmacy or ASP must digitally sign, and the pharmacy must archive the Rx.
If Rx transmission fails, regulation establishes that certain requirements must be followed.
May make changes to Rx after receipt
Must back up daily and keep records for two years
Electronic Transmission Rxs (3 of 3)
All application systems must be approved by a third-party audit or certified by a DEA-approved entity.
Transferring Prescription Information
CS Rx information (except C-II) may be transferred one time between pharmacies if state law allows and requirements are followed by both the transferring pharmacy and receiving pharmacy.
Rx information sharing among pharmacies participating in common-electronic record systems is not subject to the transfer Rx requirements (CS Rxs may be transferred up to the maximum number of refills permitted).
Return of CSs (controlled substances) to Pharmacy for Disposal
Historically, the DEA forbade that CSs be returned by a patient or LTCF to a pharmacy for disposal.
The Secure and Responsible Drug Disposal Act of 2010 allows an ultimate user to deliver to another person for disposal.
DEA regulations in 2014 allow authorized entities, including pharmacies, to collect CSs from ultimate users, provided they register as a “collector.”
Party doing destruction fill form 41
Central Filling of Rxs
Pharmacies that fill Rxs for other retail pharmacies pursuant to contractual arrangement
May fill both new and refill Rxs
Any Rx dispensed for another pharmacy must be transported to that pharmacy for furnishing to patient.
The label of the dispensed drug must indicate at which pharmacy the drug was dispensed.
Cannot accept Rxs directly from patient or practitioner or deliver Rx directly to patient or practitioner
Corresponding responsibility doctrine applies to pharmacists at both facilities.
Internet Prescriptions
what do rogue internet pharmacies sell
what is a valid Rx – what act is this under to act establishes several requirements with which online pharmacies must complies
what do most states consider an invalid Rx
Rogue internet pharmacy businesses are those that sell Rx medications to customers either without requiring Rxs or by issuing Rxs pursuant to online surveys.
The Ryan Haight Act law defines a valid Rx as one that has been issued for a legitimate medical purpose by a practitioner who has conducted at least one in-person medical evaluation of the patient.
The act establishes several requirements with which online pharmacies must comply.
Although the act only applies to CS Rxs, most states consider any Rx not dispensed pursuant to a legitimate physician–patient relationship as invalid
State Electronic Drug Rx Monitoring Programs (PDMPs)
All states have a PDMP.
A state PDMP requires a pharmacy to electronically transmit to the state a record of the CS Rx dispensed.
Enables states to determine possible diversion and abuse situations
Most PMPs allow or mandate practitioners to request patient-specific information.
Many states share data between PDMPs.
Long-Term Care (LTC) Pharmacy
LTC facilities (LTCFs) not registered with DEA
DEA concerned about excess supplies of CSs and thus permits automated dispensing systems, partial filling, and voluntary collection receptacles by registered “collectors”
Automated Dispensing Systems (ADS) in LTCFs
is a mechanical system that does what
what is the goal?
do the distributions that the pharmacy makes to ADSs count to the pharmacy’s 5%
ADS is a mechanical system that stores, packages, counts, labels, and dispenses medications and maintains transaction information.
The purpose is to reduce stocks of excess CSs in LTCFs.
A pharmacy that installs ADS must maintain separate DEA registration at the LTCF location.
Distributions that a pharmacy makes to ADSs do not count towards the pharmacy’s 5% limit which would require a separate registration as a distributor.
LTCF Nurses as Agents of the Prescriber
what has the DEA changed
what does The latest Federal Register notice permit
what can an agent do
The DEA has changed positions as to whether LTCF nurses can be an agent of the prescriber.
The latest Federal Register notice permits an agency relationship, provided there is a formal written, witnessed agreement.
An agent may only perform certain acts.
Dispensing from LTCF Emergency Kits
LTCF emergency kits permitted
The pharmacy is responsible for the kits.
The DEA does not consider a nurse as an agent of the prescriber for this purpose.
The prescriber must issue the prescription to the pharmacy and the pharmacist must authorize nurse to dispense from the kit.
Recordkeeping
Every registrant must keep a complete and accurate record of all CSs.
Three types of records involved:
Inventory
Drugs received
Drugs dispersed
Negligent recordkeeping is a violation of the CSA.
General Recordkeeping Requirements
how long are records kept?
if DEA requests how long should records get to registered location
how should C-I & C-II records be kept
Records generally must be kept for two years.
Certain records may be kept at a central location with notification to the DEA.
Centralized records require that the DEA be notified.
Records must be able to be delivered to a registered location within two business days per DEA request.
C-I and C-II records must be maintained separately unless readily retrievable.
Inventory Records
how often is inventory taken?
what must it contain?
what does on hand mean
when can inventory take place?
how must records be transcribed?
when should newly scheduled drugs be inventoried?
an exact amount of what must be made
The ____ count is ____ for other schedules unless the ____ holds more than ____ units.
Prior to beginning business and subsequently every two years, an inventory must be conducted containing a complete and accurate record of all CSs “on hand.”
“On hand” means in possession of or under the control of the registrant.
Inventory may be taken at the beginning or end of the business day; records must be written, typed, or printed.
Newly scheduled drugs must be inventoried on the date of scheduling.
The exact count must be made of C-I or C-II drugs.
The estimated count is permissible for other schedules unless the container holds more than 1,000 units.
Records of Receipt
what are acceptable records of receipt
what must a pharmacy record on the acceptable records
if the invoice has both CS & nonCS, how must the CS be identified?
what must all records of receipt inlcude
Acceptable records of receipt include invoices and Form 222.
A pharmacy must record the date of receipt on the invoice or Form 222.
If the invoice contains both CSs and nonCSs, the CSs must be identified in a manner so as to be readily retrievable.
Records of receipt must contain all required information.
Records of Dispersal
what form do you fill out
what are the acceptable records of dispersal?
what must Rx contain?
Acceptable records of dispersal include Rxs, record books, Form 222, invoices, records of disposal, theft or loss, etc.
Prescriptions may be filed in one of two ways and each Rx must contain all required information.
Nonprescription Schedule V Sales
in some states, CS can be sold without what as long as who does what
No more than ___ of an______ product or ____ of any other CS may be _____
to the ____ purchaser within a ____ period (some states have stricter requirements).
how old should the purchaser be
what does the purchaser have to provide
where must the sale be recorded
In some states, C-V products may be sold without Rx, provided:
Dispensing is done only by a pharmacist
No more than 8 oz of an opium-containing product or 4 oz of any other CS may be dispensed to the same purchaser within a 48-hour period (some states have stricter requirements).
The purchaser is at least 18 years of age.
The purchaser furnishes suitable identification.
The sale is recorded in a bound record book with all required information.
Distributions from a Pharmacy to Another Practitioner
what is required for CS III-V
what form is required for C-II
what must not exceed %5 of what
Invoice required for C-III, C-IV, and C-V products containing all required information
Form 222 is required for C-II products
The total number of dosage units distributed to another registrant must not exceed 5% of the total units of CSs distributed and dispensed in one year.
Institutional Medication Records
What are distinguished from Rxs
how much information is necessary to get an acceptable dispersal record
how long should it take to retrieve
discharge medication can only be dispersed pursuant to what
Medication or chart orders are distinguished from prescriptions and need only contain the minimum information necessary to provide an acceptable dispersal record.
Must be readily retrievable
Discharge medication orders may only be dispensed pursuant to Rx.
Disposal or Destruction
what form must you request from the DEA and where is it available through
form 41 does not apply to those who
The DEA allows destruction pursuant _______
“________________” may be allowed for hospitals.
A registrant may also transfer CSs to a ______________.
Must request via a DEA Form 41 (available online) and completed with the required information
Form 41 does not apply to CSs collected from ultimate users or LTCFs.
The DEA allows destruction pursuant to various options.
“Blanket authorization” may be allowed for hospitals.
A registrant may also transfer CSs to a reverse distributor.
Records of Theft or Loss
when should the registrant notify the DEA?
What has the DEA listed
what form should be completed?
A registrant must notify the DEA within one day of discovery of any “theft or significant loss” of any CS (should also notify police and most likely required to notify state board of pharmacy).
The DEA has listed several factors to be considered in determining whether a loss is significant.
A registrant must complete Form 106, which is available online.
Records Required of Individual Practitioners
what records must they keep and not keep
what do they need not do unless they regularly engage in dispensing or administering and charge patients?
when should a record of CSs administered be kept?
do you need an Rx to administer or dispense a CS (ARE YOU SURE…?)
Must keep records of CSs they dispense, but not of those they prescribe
Need not keep records of CSs they administer unless the IP regularly engages in dispensing or administering and charges patients
A record must be kept of CSs administered in the course of maintenance or detoxification of treatment of addiction.
May administer or dispense CS without Rx
DEA Form 222 (are you sure it is not 224?)
when is it required?
how are the forms obtained
how are the forms issued?
each form is in how many copies
how are the forms serially numbered
what can a registrant not do
Required for any distribution of C-I or C-II drugs
Forms obtained by requesting in writing from the nearest DEA office
Forms issued in mailing envelopes containing 7 or 14 forms
Each form is in triplicate titled Copy 1, Copy 2, Copy 3. just have 1 form now
Forms are serially numbered and issued with the name, address, and registration number of the registrant, authorized activity, and schedules the registrant is authorized to handle.
A registrant may not correct or change any information or errors on the forms.
Execution of Form 222
what should be executed simultaneously?
how many lines are on each form and how many items should be on each line?
what must be noted on each form?
who must be sign and date?
what must the purchaser record
what must be completed within 60 days?
what is not permitted
All three copies must be executed simultaneously.
Ten numbered lines on each form, only one item per line
The number of the last lines completed must be noted on each form
The form must contain the required information. The NDC number is optional (the supplier must enter it).
Must be signed and dated by the authorized person
The purchaser, upon receipt of the order, must record the number of containers received of each item and the date received.
Partial order fills by the supplier must be completed within 60 days.
Errors, alterations, or erasures are generally not permitted
Proposed Single Copy Form 222
books of triplicate order forms would be replaced with what
who would the purchaser send the original completed copy to and after what
the supplier would then send the original completed form to who after making and retaining what
Books of triplicate order forms would be replaced by a single-sheet tamper-resistant form.
The purchaser would send the original completed form to the supplier after making and retaining a copy.
The supplier would then send the original completed form to the DEA after making and retaining a copy.
Electronic Order System (CSOS)
can be used instead of what form
what drug can the purchaser order
what must the registrant obtain?
May be used instead of Form 222
The purchaser can order any drug.
The registrant must obtain a digital certificate for each DEA-registered location.
Power of Attorney (POA)
What does it require
Required to allow person other than one who signed registration to execute Form 222
Distributions of C-I and C-II Drugs Between Registrants
what form must be filled out when distributing a C-I or C-II
Whenever registrants distribute C-I or C-II drugs among themselves, they must execute a Form 222 following proper procedure.
Lost or Stolen Forms
If an unfilled order form is ______, the purchaser must ____ another together with a ____ noting the _____ number of the _____form, the ____of the _____form, and that the _____ were not _____.
what must be maintained together?
what must be sent with the copies 1 & 2
other than in transmission, if forms, is lost or stolen, who must be notified and what must you provide to them, if it is found, who must be notified immediately
If an unfilled order form is lost, the purchaser must execute another together with a statement noting the serial number of the lost form, the date of the lost form, and that the CSs were not received.
Must maintain together Copy 3 of the second order form and lost order form with a statement
The copy of the statement must be sent with Copies 1 and 2 to the supplier.
If forms are stolen or lost other than in transmission, must notify the DEA and provide the serial # numbers of missing forms; if found, the DEA must be notified immediately
Preservation of Forms
how must form 222 be maintained with other records and how long should they be retained
where must copy 3 be kept
Executed Form 222s must be maintained separately from all other records and retained for two years.
Copy 3 must be kept at the registered location.
