Chapter 2 New Drug Development and Approval Process

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Section 1

Question Answer
New chemical entitysmall-molecule drugs that is approved by the FDA (NME)
Preformulationstudies are initiated to define the physical and chemical properties of the agent
Investigational New Drug (IND) ApplicationReviews the preclinical studies demonstrate adequate safety and the new agent shows promise as a useful drug will the drug’s sponsor file/to provide the data showing that it is reasonable to begin tests of a new drug on humans.
New Drug Application3 phases of clinical testing provides sufficient safety and therapeutic effectiveness the sponsor may file and NDA with the FDA.
PharmacogeneticsUncovered the differences among races and ethnic groups.
Termination or withdrawal of INDThe sponsor of the IND may withdraw an IND anytime.
Phase 1progressive human trials
Phases 2 and 3 assess safety and efficacy.
lead compound prototype chemical compound that has a fundamental desired biologic or pharmacologic activity.
Prodrugterm used to describe a com- pound that requires metabolic biotransformation after administration to produce the desired pharmacologically active compound.
New Molecular Entity (NME)is defined by the FDA as an active ingredient that has never before been marketed in the United States in any form
Pharmacologyscience concerned with drugs, their sources, appearance, chemistry, actions, and uses.
Toxicologyadverse or undesired effects of drugs.
clinical protocolsubmitted to ensure the appropriate design and conduct of the investigation.
Content of the INDprescribed in the CFR and is submitted under a cover sheet (Form FDA-1571)
clinical hold order issued by the FDA to delay the start of a clinical investigation or to suspend an ongoing study.
Orphan Drug Act of 1983rare disease or condition that affects fewer than 200,000 people in the United States and for which there is no reasonable expectation that costs of R&D for the indication can be recovered by sales of the product in the United States.
Phase 1 studiesdesigned to determine the human pharmacology of the drug, structure–activity relationships, side effects asso- ciated with increasing doses, and, if possible, early evidence of effectiveness.
Phase 2 trialsare controlled clinical studies to evaluate the effectiveness of a drug in patients with the condition for which the drug is intended and to assess side effects and risks that may be revealed
Phase 3 studiesinclude several hundred to several thousand patients in con- trolled and uncontrolled trials. determine the usefulness of the drug in an expanded patient base.
Drug MetabolismA series of animal studies of a proposed drug’s ADME are undertaken
Drug Delivery Systemdetermines therapeutic Indication and route of administration
Obtained during pre formulationphysical/solubility/chemical analytical
Physicaldescribe drugs’ particle size and shape, crystallinity, polymorphism, density, surface area, hygroscopicity (ability to take up and retain moisture).
Solubilityincludes intrinsic dissolution, pH solubility profile, and general solubility characteristics in various solvents.
Chemicalincludes surface energy, pH stability profile, pKa, temperature stability (dry or under various humidity conditions), and excipient interaction.
Analytical method development, including development of a stability indicating method (for both API and related substances) and cleaning methods.
DOSAGE FORM DESIGNBiopharmaceutical/physical and chemical/Marketing/Regulatory/Processing


Question Answer
3 way process of bioavailability in the bodyDisintegration/dissolution/absorption
Pharmacokineticsstudy of characterization of the time course of drug ADME and the relationship of these process to intensity and time course of therapeutic and toxicology effect of drug.
Pharmacodynamicshow a drug behaves
Absorptiondrug gets into bloodstream
Distributiongets to site of action
Metabolismbiotransformation so that it can be excreted.
Eliminationleaves the body
Biologic responseThe response is due to an alteration of biologic processes
Determines the extent of biological activityLipid Solubility /Degree of Ionization/Molecular size

Section 2

Question Answer
Types of INDTreatment IND, Emergency use IND, Investigator IND
Investigator INDsubmitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed.
Emergency Use INDallows the FDA to authorize use of an experimental drug in an emergency situation/used for patients who do not meet the criteria of an existing study protocol,
Treatment IND/Treatment Protocol/Orphan Drugsubmitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place.

Section 3

Question Answer
broad areas of INDAnimal Pharmacology and Toxicology Studies/Manufacturing Information/Clinical Protocols and Investigator Information
Animal Pharmacology and Toxicology Studies Preclinical data to permit an assessment as to whether the product is reasonably safe for initial testing in humans
Manufacturing InformationInformation pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product.
Clinical Protocols and Investigator InformationDetailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks. Also, information on the qualifications of clinical investigators--professionals