UNIT 1 (PRE-CLINICAL RESEARCHㅡFDA REVIEW)

Question 1

The following are determined by the researchers about the drug:

Answer 1

● Absorption, distribution, metabolization and excretion information

● Potential benefits and mechanisms of action

● Best dosage, and administration route

● Side effects/adverse events

● Effects on gender, race, or ethnicity groups

● Interaction with other treatments

● Effectiveness compared to similar drugs

Question 2

● Is a pharmacokinetic process of measuring the ways the new drug affects the body

Answer 2

ABSORPTION, DISTRIBUTION, DISPOSITION, METABOLISM, & EXCRETION

Question 3

● Are an early stage of clinal drug development when a compound has shown potential in animal models and early safety testing

● Are designed to detect a signal that the drug is active on a pathophysiologically relevant mechanism, as well as preliminary evidence of efficacy in a clinically relevant endpoint.

Answer 3

PROOF PRINCIPLE / PROOF OF CONCEPT

Question 4

●_________ use these studies to estimate whether their compound might have clinically significant efficacy in other disease

Answer 4

sponsors

Question 5

● “within the living” – performed in a whole, living organism – mice rat, and dog models.

Answer 5

In Vivo

Question 6

● “within the glass” – performed outside a living organism but inside a laboratory glassware i.e. test tube, petri dish, etc.

Answer 6

In Vitro

Question 7

● “out of the living” – done in or on tissue in an artificial environment outside the organism with the minimum alteration of natural conditions

Answer 7

Ex Vitro

Question 8

● test systems or biological experiments performed on a computer or via computer simulation

Answer 8

In Silico Assay

Question 9

● are used for target delivery or controlled release of new drugs

• Oral
• Tropical
• Parental (IM, SC)
• Parental (Intravenous)
• Parental (Inhalation)

Answer 9

Drug Delivery Systems

Question 10

● chose the suitable formulation for the active ingredient or lead compound

Answer 10

Formulation Optimization

Question 11

● as the rate and extent to which the active constituent of a drug is absorb from a drug product and reaches the circulation

Answer 11

Bioavailability

Question 12

● is a request for Food and Drug Administration (FDA) authorization to administer an investigational drug to humans.

Answer 12

INVESTIGATIONAL NEW DRUG APPLICATION

Question 13

● as defined by the TheFreeDictionary.com, it is a progressive increase in the strength of any treatment (drug), to improve its tolerability or maximize its effect.

Answer 13

Dose Escalation

Question 14

● a small group of subjects/healthy volunteers receive a single dose of study drug while being observed and tested for a period of time to confirm safety and characterize the PK of the study drug.

• Perform first in order to obtain a rough understanding of the single dose pharmacokinetics.

Answer 14

Single Ascending Dose (SAD)

Question 15

● a group of healthy volunteer/patients receive multiple low doses of the drug, while samples (of blood and other fluids) are collected at various time points and analyzed to acquire information on how the drug is processed within the body.

• investigate the pharmacokinetics and pharmacodynamics (PK and PD) of multiple doses of the drug, looking at safety and tolerability.

Answer 15

Multiple Ascending Dose (MAD)

Question 16

● This phase is the first time the drug is tested on human primarily for the purpose of assessing safety.

● Less than 100 volunteers (20-100)

● The human subjects are usually healthy volunteers

● designed to determine:

• the human pharmacology of the drug
• structure–activity relationships
• side effects associated with increasing doses
• (if possible) early evidence of effectiveness

● Among the basic that are being collected in Phase I are the rate of absorption, concentration of the drug in the blood overtime, rate and mechanism of drug metabolism and elimination, toxic effect in the body tissue and major organ, and change in physiological processes from the baseline

Answer 16

PHASE I

Question 17

● it is tested in much larger population

● controlled clinical studies to evaluate –

• the effectiveness of a drug in patients with the condition for which the drug is intended
• assess side effects and risks that may be revealed

Answer 17

PHASE II

Question 18

● additional data are collected on the drug’s pharmacokinetics and studies undertaken to determine dose-response and dose ranging

Answer 18

Phase IIa Studies

Question 19

● dose determination studies results in the specific doses and the dose range to be used in Phase 3 studies.

Answer 19

Phase IIb Studies

Question 20

● Include several hundred to several thousand patients in controlled and uncontrolled trails.

● Determine the usefulness of the drug in expanded patient base

● Sufficient information on the drug’s effectiveness and safety during Phase 3 to evaluate the overall benefit-risk relationship of the drug and to file a complete NDA

Answer 20

PHASE III

Question 21

● studies that are sufficient for a New Drug Application

Answer 21

PHASE IIIa

Question 22

● studies used to gather supplemental information that may:

• Support certain labelling requests
• Provide information on patients’ quality of life issues
• reveal product advantages over already marketed competing drugs
• provide evidence in support of possible additional drug indications
• provide other clues for prospective post marketing studies (Phase 4)

Answer 22

Phase IIIb

Question 23

● A ______________ is used to show that a biological response has occurred in an individual who has been exposed to a medical product or an environmental agent.

Answer 23

biomarker

Question 24

● – is a biomarker whose level changes in response to an exposure to a medical product or an environmental agent.

• Can be used to measure the level of response to the intervention, and to guide clinical close-response studies

Answer 24

PHARMACODYNAMIC/RESPONSE BIOMARKER

Question 25

● is an experimental trial that determines the theory of how a new drug behaves in the human body

Answer 25

PHARMACOKINETIC ANALYSIS

Question 26

● created as per sec 12 of the Philippine National Health Research System Act of 2013 (RA 10532) adopted from DOST Special Order No. s 2006

Answer 26

Philippine Health Research Ethics Board (PHREB)

Question 27

● A ____________________________ is a body that make independent decisions regarding the review, approval, and implementation of research protocols/proposals, in order to ensure the protection of the rights, safety, and well-being of human participants and promotes integrity of research data. It shall be constituted by a duly recognized authority and shall adhere to national and international research ethics guidelines.

Answer 27

Research Ethics Committee (REC)

Question 28

● This application may be filed to the FDA after the completion of the carefully designed preclinical and clinical studies for the purpose of seeking approval to market the new product.

● However, some drug products that have been granted NDA Approvals were later removed from the market, for safety reasons.

Answer 28

NEW DRUG APPLICATION (NDA)

Question 29

● used to gain approval to market a generic equivalent of a product that is already approved and being marketed by the pioneer, or the original sponsor, of the drug.

_____ provides documentation on the chemistry, manufacturing, controls (CMCs), and bioavailability of the proposed product to demonstrate biologic equivalency to the original product

Answer 29

ABBREVIATED NEW DRUG APPLICATION (ANDA)

Question 30

⮚ Drug that is put out by the company that spends billions of dollars on research to discover a molecule of a substance.

Answer 30

PATENTED DRUG/INNOVATOR DRUG PRODUCT/BRANDED ORIGINAL

Question 31

⮚ Drugs that have the same active pharmaceutical ingredient as the innovator drugs but costs less and are not covered by patent protection.

• are available once the patent protections afforded to the original developer have expired.

Answer 31

GENERIC DRUGS

Question 32

● are submitted to the FDA for the manufacture of biologics such as blood products, vaccines, and toxins.

Answer 32

BIOLOGICS LICENSE APPLICATION (BLA)

Question 33

● refers to any drug or medicine used to treat or alleviate the symptoms of persons afflicted with a rare disease and declared as such by the DOH upon recommendation of the National Institutes of Health (NIH)

Answer 33

Orphan drugs