FDA Regulations and Drug Development

FDA Regulations

Overview

• The Food and Drug Administration (FDA) is responsible for regulating drugs in the United States.
• The FDA ensures that drugs are safe and effective for human use.

Key Regulations

• Federal Food, Drug, and Cosmetic Act (FD&C Act): The primary law governing FDA regulations.
• Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act): Allows for the approval of generic drugs.

Drug Development and Approval Process

• Investigational New Drug (IND) Application: Required for conducting clinical trials in the US.
• New Drug Application (NDA): Submitted to the FDA for drug approval.
• Abbreviated New Drug Application (ANDA): Submitted for generic drug approval.

FDA Drug Classification

• Schedule I: High potential for abuse, no currently accepted medical use (e.g., heroin).
• Schedule II: High potential for abuse, currently accepted medical use (e.g., cocaine).
• Schedule III: Moderate to low potential for abuse, currently accepted medical use (e.g., anabolic steroids).
• Schedule IV: Low potential for abuse, currently accepted medical use (e.g., benzodiazepines).
• Schedule V: Low potential for abuse, currently accepted medical use (e.g., cough suppressants).

Labeling and Packaging

• Labeling: Information on the drug's packaging, including ingredients, dosage, and warnings.
• Prescription Drug Labeling: Includes information on dosage, administration, and warnings.
• Over-the-Counter (OTC) Drug Labeling: Includes information on dosage, administration, and warnings for non-prescription drugs.

Post-Marketing Surveillance

• Adverse Event Reporting: Manufacturers and healthcare professionals report adverse events to the FDA.
• Post-Marketing Studies: Conducted to gather additional safety and efficacy data after drug approval.

Enforcement and Compliance

• FDA Inspections: Regular inspections of drug manufacturing facilities to ensure compliance with regulations.
• Warning Letters: Issued to companies that violate FDA regulations.
• Recalls: Voluntary or mandatory removal of a drug from the market due to safety concerns.

FDA Regulations

Overview

• The FDA ensures drugs are safe and effective for human use in the United States.

Key Regulations

• The Federal Food, Drug, and Cosmetic Act (FD&C Act) is the primary law governing FDA regulations.
• The Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act) allows for the approval of generic drugs.

Drug Development and Approval Process

• An Investigational New Drug (IND) Application is required for conducting clinical trials in the US.
• A New Drug Application (NDA) is submitted to the FDA for drug approval.
• An Abbreviated New Drug Application (ANDA) is submitted for generic drug approval.

FDA Drug Classification

• Schedule I drugs have high potential for abuse and no currently accepted medical use (e.g., heroin).
• Schedule II drugs have high potential for abuse and currently accepted medical use (e.g., cocaine).
• Schedule III drugs have moderate to low potential for abuse and currently accepted medical use (e.g., anabolic steroids).
• Schedule IV drugs have low potential for abuse and currently accepted medical use (e.g., benzodiazepines).
• Schedule V drugs have low potential for abuse and currently accepted medical use (e.g., cough suppressants).

Labeling and Packaging

• Labeling includes information on the drug's packaging, including ingredients, dosage, and warnings.
• Prescription Drug Labeling includes information on dosage, administration, and warnings.
• Over-the-Counter (OTC) Drug Labeling includes information on dosage, administration, and warnings for non-prescription drugs.

Post-Marketing Surveillance

• Adverse Event Reporting involves manufacturers and healthcare professionals reporting adverse events to the FDA.
• Post-Marketing Studies are conducted to gather additional safety and efficacy data after drug approval.

Enforcement and Compliance

• FDA Inspections are regular inspections of drug manufacturing facilities to ensure compliance with regulations.
• Warning Letters are issued to companies that violate FDA regulations.
• Recalls involve the voluntary or mandatory removal of a drug from the market due to safety concerns.

Pharmacokinetics

• Study of the movement of drugs through the body, focusing on:
• Absorption: how a drug enters the bloodstream
• Distribution: how the drug moves throughout the body
• Metabolism: how the body breaks down the drug
• Excretion: how the body eliminates the drug
• Factors affecting pharmacokinetics include:
  • Patient-related factors: age, weight, liver/kidney function
  • Drug-related factors: dosage, route of administration, formulation

Medication Safety

• Importance of medication safety:
  • Prevents medication errors and adverse reactions
  • Ensures optimal therapeutic outcomes
• Strategies for medication safety:
  • Medication reconciliation: verifying patient medication lists
  • Barcode medication administration: verifying medication administration via barcode scanning
  • Medication therapy management: monitoring patients for medication-related issues
• Medication safety risks:
  • Medication errors: wrong drug, dose, or route
  • Adverse drug reactions: allergic reactions, side effects
  • Drug interactions: interactions with other medications or foods

Controlled Substances

• Definition: drugs with potential for abuse and addiction, regulated by the DEA
• Schedules of controlled substances:
  • Schedule I: high potential for abuse, no accepted medical use (e.g., heroin)
  • Schedule II: high potential for abuse, accepted medical use (e.g., opioids)
  • Schedule III: moderate potential for abuse, accepted medical use (e.g., anabolic steroids)
  • Schedule IV: low potential for abuse, accepted medical use (e.g., benzodiazepines)
  • Schedule V: low potential for abuse, accepted medical use (e.g., cough suppressants)
• Prescribing and dispensing controlled substances:
  • Requirements for prescription and dispensing
  • Record-keeping and reporting requirements

Drug Metabolism

• Definition: process by which the body breaks down drugs into inactive or active metabolites
• Types of drug metabolism:
  • Phase I metabolism: oxidation, reduction, and hydrolysis reactions
  • Phase II metabolism: conjugation reactions (e.g., glucuronidation, sulfation)
• Factors affecting drug metabolism:
  • Genetic factors: genetic variations in metabolizing enzymes
  • Environmental factors: diet, liver function
  • Drug interactions: inhibition or induction of metabolizing enzymes
• Importance of drug metabolism:
  • Affects drug efficacy and toxicity
  • Influences dosing and dosing intervals

Controlled Substances

• DEA schedules controlled substances into 5 categories based on potential for abuse, currently accepted medical use, and safety under medical supervision
• Schedule I: High potential for abuse, no accepted medical use (e.g., heroin, LSD)
• Schedule II: High potential for abuse, currently accepted medical use (e.g., cocaine, methamphetamine)
• Schedule III: Moderate to low potential for abuse, currently accepted medical use (e.g., anabolic steroids, ketamine)
• Schedule IV: Low potential for abuse, currently accepted medical use (e.g., benzodiazepines, modafinil)
• Schedule V: Low potential for abuse, currently accepted medical use (e.g., cough suppressants, anticonvulsants)
• Prescribers must register with the DEA and obtain a unique identifier (DEA number)
• Prescriptions for controlled substances must include the prescriber's DEA number, patient's name and address, and the quantity and strength of the medication

Drug Metabolism

Phase I and II Reactions

• Phase I Reactions: Oxidation, reduction, and hydrolysis reactions that convert the parent drug into a more polar metabolite
• Phase II Reactions: Conjugation reactions that attach a polar group to the metabolite, increasing water solubility and facilitating excretion

CYP450 Enzymes

• A family of enzymes responsible for Phase I reactions
• CYP3A4 is the most common isoenzyme involved in drug metabolism

Enzyme Induction and Inhibition

• Certain drugs can induce (increase) or inhibit (decrease) CYP450 enzyme activity, leading to drug interactions and altered metabolism

Medication Safety

Adverse Drug Reactions

• Harmful and unintended consequences of medication use
• Type A: Augmented effects (dose-dependent)
• Type B: Bizarre effects (idiosyncratic)

Medication Errors

• Preventable events that can occur during any stage of the medication use process
• Includes prescribing, transcribing, dispensing, and administering

High-Alert Medications

• Medications that can cause significant harm if used incorrectly
• Examples: anticoagulants, opioids, and insulin

Pharmacokinetics

Absorption, Distribution, Elimination

• Absorption: The process by which a drug enters the bloodstream
• Influenced by factors such as route of administration, dosage form, and patient factors
• Distribution: The movement of a drug throughout the body
• Influenced by factors such as blood flow, protein binding, and tissue permeability
• Elimination: The removal of a drug from the body
• Primarily through metabolism and excretion

Half-Life

• The time required for the concentration of a drug in the body to decrease by 50%
• Influences dosing intervals and duration of action

Controlled Substances

• Classification of controlled substances into five schedules (I to V) based on potential for abuse, currently accepted medical use, and safety under medical supervision
• Schedule I substances have high potential for abuse and no currently accepted medical use
• Examples of Schedule I substances include heroin and LSD
• Schedule II substances have high potential for abuse, but with currently accepted medical use with severe restrictions
• Examples of Schedule II substances include cocaine and methamphetamine
• Schedule III substances have moderate to low potential for abuse, with currently accepted medical use
• Examples of Schedule III substances include anabolic steroids and ketamine
• Schedule IV substances have low potential for abuse, with currently accepted medical use
• Examples of Schedule IV substances include Xanax and Soma
• Schedule V substances have low potential for abuse, with currently accepted medical use
• Examples of Schedule V substances include cough suppressants with codeine

Pharmacokinetics

• ADME stands for absorption, distribution, metabolism, and excretion of drugs in the body
• Absorption is the process by which a drug enters the bloodstream
• Examples of routes of absorption include oral, IV, and topical
• Distribution is the movement of a drug throughout the body
• Factors affecting distribution include blood flow and tissue binding
• Metabolism is the biotransformation of a drug into active or inactive metabolites
• The liver plays a key role in metabolism through enzyme activity
• Excretion is the elimination of a drug from the body
• Examples of routes of excretion include kidneys, liver, and lungs

Drug Metabolism

• Phase I reactions involve oxidation, reduction, and hydrolysis
• Cytochrome P450 enzymes play a key role in Phase I reactions
• Phase II reactions involve conjugation
• Examples of Phase II reactions include glucuronidation and sulfation
• Induction occurs when a substance increases the activity of an enzyme
• Inhibition occurs when a substance decreases the activity of an enzyme
• Genetic variations can affect drug metabolism
• Examples of genetic polymorphisms affecting drug metabolism include CYP2D6 and CYP2C19

Medication Safety

• Adverse Drug Reactions (ADRs) are harmful or unintended effects of drugs
• Allergic reactions are immune-mediated responses to drugs
• Drug interactions occur when the effect of one drug is altered by another drug
• Examples of drug interactions include pharmacokinetic and pharmacodynamic interactions
• Medication errors are preventable mistakes in medication use
• Examples of medication errors include overdose and wrong medication
• Risk management strategies are used to minimize medication-related harm
• Examples of risk management strategies include monitoring and patient education

Controlled Substances

• DEA schedules controlled substances into 5 categories based on potential for abuse, currently accepted medical use, and safety under medical supervision
• Schedule I: High potential for abuse, no accepted medical use (e.g. heroin, LSD)
• Schedule II: High potential for abuse, currently accepted medical use with severe restrictions (e.g. cocaine, methamphetamine)
• Schedule III: Moderate to low potential for abuse, currently accepted medical use (e.g. anabolic steroids)
• Schedule IV: Low potential for abuse, currently accepted medical use (e.g. benzodiazepines)
• Schedule V: Low potential for abuse, currently accepted medical use (e.g. cough suppressants)
• Prescribers must register with the DEA to prescribe controlled substances
• Prescriptions must be written in accordance with state and federal laws

Drug Metabolism

• Phase I metabolism involves oxidation, reduction, and hydrolysis reactions (e.g. CYP450 enzymes)
• Phase II metabolism involves conjugation reactions (e.g. glucuronidation, sulfation)
• Enzyme induction or inhibition can alter drug metabolism and lead to interactions
• Genetic variations in metabolism can affect individual responses to drugs

Pharmacokinetics

• ADME: Absorption, Distribution, Metabolism, Excretion of drugs
• Bioavailability is the proportion of an administered dose that reaches the systemic circulation
• Peak and trough levels are used to determine dosing regimens
• Peak levels are the maximum drug concentrations
• Trough levels are the minimum drug concentrations

Medication Safety

• Adverse drug reactions (ADRs) are harmful and unintended effects of medications
• Medication errors are preventable events that can cause harm, such as dosing errors or allergic reactions
• Medication reconciliation is the process of verifying medication lists to ensure accuracy and reduce errors
• Patient education is crucial for medication safety, including educating patients on proper medication use, side effects, and interactions

Controlled Substances

Definition

• Controlled substances are drugs or chemicals regulated by the government due to their potential for abuse or addiction.

Schedules of Controlled Substances

• The Controlled Substances Act categorizes controlled substances into five schedules based on their potential for abuse, medical use, and safety under medical supervision.
• Schedule I: High abuse potential, no accepted medical use, and lack of safety under medical supervision (e.g., heroin, LSD, marijuana).
• Schedule II: High abuse potential, accepted medical use with severe restrictions (e.g., cocaine, methamphetamine, opium).
• Schedule III: Moderate to low abuse potential, accepted medical use, and moderate to low dependence risk (e.g., anabolic steroids, ketamine).
• Schedule IV: Low abuse potential, accepted medical use, and low dependence risk (e.g., Xanax, Soma).
• Schedule V: Low abuse potential, accepted medical use, and low dependence risk (e.g., cough suppressants with codeine).

Regulation and Enforcement

• The Drug Enforcement Administration (DEA) enforces the Controlled Substances Act and regulates controlled substances distribution and possession.
• The DEA issues registrations to manufacturers, distributors, and practitioners handling controlled substances.
• The CSA allows for criminal and civil penalties for violating controlled substance laws.

Prescribing and Dispensing

• Practitioners must register with the DEA to prescribe controlled substances.
• Prescriptions for controlled substances must comply with CSA requirements, including written prescriptions and quantity limits.
• Pharmacists must verify prescription authenticity and ensure CSA compliance before dispensing controlled substances.

Medication Administration

• Uncontrolled medications require monitoring by the provider but do not pose a risk for misuse.

Controlled Substances

• Have a potential for misuse and dependence
• Have a schedule classification (e.g., Heroin is Schedule 1, morphine is Schedule 2, phenobarbital is Schedule 5)

FDA Regulations

• The Food and Drug Administration (FDA) tests new drugs to determine effectiveness and safety before approval

Pregnancy Schedule

• Categories medications based on safety during pregnancy (A, B, C, D, X)
• X is the most dangerous category

Types of Medication Prescriptions

• Routine or standing order
• Single or one-time order
• Stat prescription
• PRN prescription

Components of a Medication Prescription

• Client's full name
• Date and time of prescription
• Name of medication (generic or trade)
• Strength and dose of medication
• Route of administration
• Time and frequency
• Quantity to dispense
• Signature of the prescribing provider

Medication Reconciliation

• Comparing the list of the client's current medications to new prescriptions
• Process takes place during admission, transfer, and discharge

Right to Safe Medication Administration

• Right client (check client's name, assigned ID number, telephone number, ID band, check for allergies, use barcode)
• Right medication (read medication label and compare it with MAR)
• Right dose (check drug reference, have another nurse verify)
• Right time (critical: 30 minutes before, non-critical: 20-30 minutes before or after)
• Right route (oral is the most used)
• Right documentation (after administration, document immediately)
• Right client education (nurse should inform client about medication, right to refuse)
• Right evaluation (follow up with client to verify therapeutic effects and adverse effects)

Nursing Process

• Data collection (know the medication, sources include provider, nurses, physicians, pharmacists, poison control center, etc.)
• Planning (identifies client's outcomes of medication administration, set priorities)
• Implementation (avoid interruptions during medication preparation, prepare one client's medication at a time, double-check with another nurse)
• Evaluation (evaluate client's responses to medications, document and report)

Error Reporting

• Notify provider of all errors (include client's identification, name and dose of medication, time and place of incident, accurate and objective account of event)
• Do not include incident report in client's medical record
• Report all errors to facility to prepare and find ways to avoid errors