QUIZ 2 LEC: Investigational Drugs and Drug Approval Process

Comprehensive set of 110 vocabulary flashcards covering the drug discovery and approval process, clinical trial phases, regulatory legislation, ethics codes, IND filing components, expedited pathways, and investigational pharmacy practice.

Import Drug Act of 1848

Federal legislation that provided for the inspection and detention of imported drug shipments that failed to meet prescribed standards of purity and identity.

Pure Food and Drugs Act of 1906

United States legislation that mandated that drugs must not be mislabeled or adulterated in interstate commerce.

Food, Drug, and Cosmetic Act (FD&C Act) of 1938

Legislation that required the safety of new drugs to be demonstrated and proven through testing before marketing.

Durham-Humphrey Amendment of 1951

An amendment to the FD&C Act that formally divided pharmaceuticals into two distinct classes: over-the-counter (OTC) and prescription (Rx) drugs.

Kefauver-Harris Drug Amendment of 1962

An amendment that specified that drug manufacturers must demonstrate proof of efficacy as well as safety prior to commercial marketing.

Standard Drug Review Target

The FDA regulatory target timeframe to complete the review of standard new drug applications within $10\text{ months}$.

Priority Drug Review Target

The expedited FDA regulatory target timeframe to complete the review of priority new drug applications within $6\text{ months}$.

ClinicalTrials.gov

A web-based registry and database developed by the National Institutes of Health (NIH) that offers comprehensive information about ongoing clinical trials.

International Conference on Harmonization (ICH)

An international initiative whose goal is to provide a unified method to ensure simultaneous submission and rapid regulatory approval of pharmaceuticals worldwide.

Nuremberg Code

A foundational ethical code established after WWII that stated the voluntary consent of the human subject is absolutely essential in medical research.

Declaration of Helsinki (1964)

An international ethical document that re-emphasized the protection of human research subjects and specified that participants must be free from coercion.

Belmont Report (1978)

A landmark ethical report that delineated the basic ethical principles underlying medical research on human subjects.

Bureau of Food and Drugs (BFAD)

The historical name of the Food and Drug Administration (FDA) in the Philippines.

Pre-clinical Testing Subjects

Animals or in-vitro laboratory models primarily utilized during early drug discovery and development prior to testing in humans.

Commercial IND

An Investigational New Drug application submitted to the FDA by a corporate entity sponsor, such as a pharmaceutical company, aiming for eventual drug commercialization.

Investigator IND

An Investigational New Drug application filed directly by an individual clinical researcher who initiates and directs the investigation.

FDA Form 1571

The mandatory cover sheet for an Investigational New Drug (IND) application that identifies the study sponsor and contract research organization (CRO).

IND Introductory Statement

The introductory portion of an IND application that describes the scientific rationale, clinical indications, and types of trials to be conducted.

Investigator's Brochure (IB)

A comprehensive document provided to clinical investigators containing all available data on the investigational drug's formula, pharmacokinetics, and safety.

Patient Selection (Clinical Protocol)

The protocol section that defines the precise inclusion characteristics of eligible patients as well as specific exclusion criteria.

Chemistry, Manufacturing, and Control (CMC) Data

The technical section of an IND that details the chemical synthesis, drug preparation, and analytical methods used to ensure purity and stability.

Placebo Similarity Requirement

The FDA guideline providing that while placebos do not have to be completely identical to the investigational drug, any differences must not jeopardize the trial's integrity or blinding.

IND Safety Report

An expedited regulatory report submitted by a trial sponsor to notify the FDA of serious and unexpected suspected adverse reactions.

15-Day Expedited Safety Reporting Rule

The regulatory timeline requiring a sponsor to report a serious and unexpected suspected adverse reaction to the FDA in writing within $15\text{ calendar days}$.

IND Annual Report

A formal annual progress report that must be submitted to the FDA within $60\text{ days}$ of the IND's effective anniversary date.

Phase I Clinical Trial

The earliest phase of clinical testing involving the initial administration of an investigational agent to humans to establish safety and tolerance.

Phase I Trial Subject Population

A small cohort typically consisting of $20\text{ to }80$ normal healthy human volunteers used to assess initial safety.

Phase II Clinical Trial

A clinical trial phase designed primarily to evaluate the preliminary efficacy and optimal dosing of an investigational agent in patients with the targeted condition.

Phase III Trial Subject Population

A large patient cohort, usually ranging from several hundred to $3{,}000\text{ patients}$, evaluated in multicenter clinical studies.

Pivotal Trial

A definitive Phase III clinical trial that provides primary evidence of safety and efficacy and serves as the legal foundation for a New Drug Application (NDA).

Pharmacogenomics

The scientific study of variations in DNA and RNA characteristics that correlate with individual clinical drug response and adverse events.

Fast Track Review

An expedited FDA development and review process designed to facilitate drugs that treat serious conditions and fill unmet medical needs through frequent sponsor-FDA communication.

Accelerated Approval Pathway

An expedited approval mechanism that allows early approval of a drug for a serious condition based on a surrogate endpoint reasonably likely to predict clinical benefit.

Expanded Access

A regulated pathway allowing investigational drugs to be used outside clinical trials for treatment in patients facing serious or immediately life-threatening diseases with no comparable options.

IND Cost Recovery Rule

The FDA regulation permitting manufacturers to charge for an investigational drug solely to recover direct costs attributable to making the IND, with commercial profit strictly prohibited.

Phase IV Clinical Trials

Post-marketing surveillance studies conducted after regulatory drug approval to evaluate long-term outcomes, broader patient populations, and rare adverse events.

Risk Evaluation and Mitigation Strategies (REMS)

Required drug safety programs mandated by the FDA beyond standard product labeling to guarantee that a drug's therapeutic benefits outweigh its documented risks.

Elements to Assure Safe Use (ETASU)

Specialized, highly restrictive risk mitigation components within a REMS program designed to ensure safe drug access and reduce severe toxicity.

Orphan Drug Population Limit

The legal threshold defining an orphan disease in the US as a rare disorder affecting fewer than $200{,}000\text{ individuals}$.

Orphan Drug Marketing Exclusivity

A $7\text{-year}$ period of exclusive commercial marketing rights awarded by the FDA to the first sponsor approved for a designated orphan drug indication.

Unaffiliated IRB Member Requirement

The regulatory requirement that an Institutional Review Board (IRB) must include at least one voting member who is not affiliated with the research institution.

Principal Investigator (PI) Liaison Role

The lead researcher who maintains direct clinical contact with trial subjects and serves as the official liaison between the IRB and the study sponsor.

Minimal Risk Standard

The core regulatory principle requiring clinical research protocols to minimize participant risks and ensure that the risk/benefit ratio remains reasonable.

Research Misconduct

The intentional fabrication, falsification, or plagiarism in proposing, performing, reviewing, or reporting scientific research.

Investigational Agent Preparation Guidelines

Detailed protocol instructions that pharmacists must review, including reconstitution procedures, stability limits, and vehicle compatibility information.

Investigational Pharmacy Economic Review

A formal cost assessment conducted by clinical research pharmacists to minimize drug-related trial expenses, such as converting inpatient therapies to outpatient administration.

Drug Accountability Records

Official pharmacy inventory documentation that tracks the receipt, dispensing, disposition, and lot numbers of investigational drug supplies.

Triple Blinding

A clinical study design in which the subjects, the treating investigators/clinicians, and the data analysts are all kept unaware of treatment assignments.

Investigational Pharmacy Monthly Fee

A recurring pharmacy charge that covers standard drug storage space and regular inventory management throughout the trial.

Investigational Pharmacy Professional Fee

A service fee charged by a research pharmacy when providing clinical or technical tasks that exceed standard services covered under the base fee.

Import Drug Act (Historical Mandate)

A legislative act that provided for the inspection and rejection of imported drug shipments that failed to meet established standards.

Pure Food and Drugs Act (Adulteration Standard)

Legislation establishing that pharmaceutical drugs sold across state lines must not be mislabeled or adulterated.

FD&C Act of 1938 (Pre-market Mandate)

Federal legislation requiring proven pre-market proof of drug safety before commercial distribution can occur.

Durham-Humphrey (1951 Division)

Statutory amendment that divided pharmaceuticals into over-the-counter (OTC) and prescription (Rx) categories.

Kefauver-Harris (1962 Efficacy Standard)

Federal statute that specified mandatory proof of drug efficacy and safety prior to marketing authorization.

Nuremberg Code (Consent Principle)

Ethical research principle establishing that voluntary human subject consent is absolutely essential in all clinical experimentation.

Declaration of Helsinki (Coercion Rule)

Ethical declaration re-emphasizing human subject protections and dictating that subjects must be entirely free from coercion.

Belmont Report (Ethical Framework)

Historical report that delineated the basic ethical principles (respect for persons, beneficence, justice) underlying human research.

CFR Title 45 Part 46

Federal regulatory policy designed to make the protection of human research subjects uniform across federal agencies.

ICH (Harmonization Objective)

Global regulatory process ensuring simultaneous regulatory submissions and rapid drug approvals internationally.

Form 1571 (Cover Sheet)

The official IND cover sheet that formally identifies the study sponsor and contract research organization (CRO).

Investigator's Brochure (Safety & PK)

The foundational clinical trial document compiling all available data on drug chemical formula, pharmacokinetics, and safety.

IND Introductory Statement (Rationale)

The IND document section that outlines the rationale, targeted therapeutic indications, and types of clinical trials planned.

General Investigational Plan (Approach)

The IND component that projects the expected number of patients and outlines the general investigational clinical approach.

Clinical Protocol (Operational Plan)

The detailed experimental plan describing clinical study objectives, patient selection criteria, and dosing parameters.

Chemistry Data (IND Specification)

IND technical data that details the chemical synthesis, drug preparation, and analytical assay methods.

Previous Human Experience (IND Data)

The IND section that summarizes drug safety and clinical data derived from prior domestic and foreign market use.

Protocol Amendment

A formal submission to an active IND used to amend study design, dosing regimens, or clinical protocol details.

IND Safety Report (Adverse Event)

An urgent regulatory report that must be submitted to the FDA within $15\text{ days}$ for serious and unexpected suspected adverse reactions.

IND Annual Report (Progress Tracking)

A mandatory periodic filing submitted within $60\text{ days}$ of the IND effective date to document ongoing trial progress.

Phase I Trial (Healthy Volunteers)

Clinical trials using normal healthy volunteers to evaluate drug tolerance, metabolic pathways, and early human safety.

Phase II Trial (Efficacy Evaluation)

Clinical trials evaluating therapeutic efficacy and side effects in a small group of patients suffering from the targeted condition.

Phase III Trial (Multicenter Studies)

Large-scale multicenter studies treating hundreds to $3{,}000\text{ patients}$ to gather definitive evidence of clinical efficacy.

Phase IV Trial (Post-Marketing)

Clinical and surveillance trials initiated after regulatory drug approval to assess real-world use and safety profiles.

Priority Review (Six-Month Target)

An expedited review category where the FDA establishes a target to review a new drug application within $6\text{ months}$.

Accelerated Approval (Surrogate Endpoint)

Regulatory approval granted based on an effect on a surrogate endpoint reasonably likely to predict meaningful clinical benefit.

Breakthrough Therapy (Substantial Improvement)

An FDA expedited designation for drugs that demonstrate substantial clinical improvement over existing available therapies in early trials.

REMS (Safety Interventions)

Enforceable risk mitigation safety measures required beyond package labeling to ensure therapeutic benefits outweigh risks.

Base Fee (Investigational Pharmacy)

A fixed clinical pharmacy charge established based on trial patient population size or study protocol complexity.

Double Blinding (Masking Method)

A trial masking methodology where neither the participating patient nor the research team knows the specific drug assignment.

Pre-clinical Model Validation

The standard research rule establishing that early drug discovery pre-clinical tests utilize animals or in-vitro models rather than human subjects.

Corporate Sponsor IND

A commercial IND filed by a corporate pharmaceutical entity, in contrast to an investigator IND initiated by an individual clinician.

Drug Development Timeline

The average duration of approximately $15\text{ years}$ required for an experimental compound to progress from initial synthesis to NDA approval.

Multicenter Phase III Structure

The organizational design of Phase III trials that treats hundreds to thousands of patients across multiple distinct clinical institutions.

ClinicalTrials.gov Ownership

The official registry infrastructure developed and maintained by the National Institutes of Health (NIH), rather than the FDA.

Nuremberg Tribunal Precedent

The landmark legal trial following WWII established to prosecute involuntary human experimentation conducted by Nazi physicians.

IND Exemption for Approved Drugs

A regulatory exemption where an IND is not required for studying a marketed US drug if used within its approved indication without increasing patient risk.

Expanded Access Profit Prohibition

The federal rule preventing manufacturers from generating commercial profits when providing investigational drugs under expanded access.

Expanded Access Indication Criteria

The statutory requirement restricting expanded access exclusively to patients with serious or immediately life-threatening conditions.

Pharmacogenomic Correlation

The biological connection between an individual patient's genotype or phenotype and their drug efficacy or adverse event susceptibility.

Rare Disease Definition

A statutory disease classification under US law defined as affecting fewer than $200{,}000\text{ individuals}$ nationwide.

Orphan Drug Act Incentives

Statutory benefits including tax incentives and $7\text{ years}$ of market exclusivity that do not directly alter the standard FDA review process timeline.

Independent Community IRB Member

The regulatory requirement mandating that every Institutional Review Board contain at least one member with no institutional affiliation.

Principal Investigator Subject Contact

The direct clinical and communication relationship maintained between the principal investigator and human research subjects.

Written Informed Consent Mandate

The legal and ethical rule requiring that clinical trial consent must always be formally executed and documented in writing.

Scientific Misconduct Triad

The three recognized categories of research misconduct: data fabrication, data falsification, and intellectual plagiarism.

Drug Storage Fee Structure

The investigational pharmacy billing framework where regular drug storage and inventory are covered by monthly fees, while specialized services incur professional fees.

Two-Year Record Retention Mandate

The federal regulation mandating that trial drug accountability records be maintained on-site for $2\text{ years}$ following NDA approval or study discontinuation.

Single-Blinded Trial Design

A clinical trial procedure where participating subjects are unaware of their treatment assignment, but the researchers are fully aware.

REMS Assessment Milestones

The mandatory statutory timeline requiring formal evaluations of REMS effectiveness at $18\text{ months}$, $3\text{ years}$, and $7\text{ years}$ post-approval.