PDDS (Prelim): New Drug Development Process

New drug development process

NDDP

• Plant kingdom

• Animal sources

• Microbiological world

• Biological source

Sources of New Drug (4)

Reserpine (Rauwolfia serpentina)

Plant Source:___

Tranquilizer and hypotensive agent

Vinblastine and Vincristine

Vinca rosea (Periwinkle)

Plant Source ___

Treatment of cancer

Pacific Yew Tree

Plant Source:

Taxus brevifolia

Endocrine glands of cattle, sheep and swine

Animal Source: Thyroid extract, insulin and pituitary hormone (Replacement Therapy).

Pregnant mares

Animal Source: Source of estrogens

Embryo

- vaccines

penicillin,

cephalosphorin,

tetracyclines,

aminoglycosides

Microbiological Source (4)

●Recombinant DNA

●Monoclonal Antibody production

▫ Gene therapy

Genetic engineering (2)

Goal Drug

• Produce specifically the desired effect

• Administered by the most desired route

• Minimal dosage and dosage frequency

• Have optimal onset and duration of activity

• Exhibit no side effects

• Would be eliminated completely and

without residual effect

Choosing a disease

Methods of Discovery:

- focus is on the financial return

Choosing a drug target

Methods of Discovery:

- receptor, enzymes and nucleic acid

Molecular modification

In vivo test

Bioassay:

- inducing a clinical condition and treated with the test drug

In vitro test

Bioassay:

- drugs activity is tested on isolated tissues, cells or enzymes

Lead Compound

prototype chemical compound that has a fundamental desired biologic or pharmacologic activity

*starting point of studying

Prodrugs

compound that requires metabolic biotransformation after administration to produce the desired pharmacologically active compound

*inactive drugs that can be active

●Chemical and physical characterization

●Pharmacology

●Pharmacokinetics

●Pharmacodynamics

●Analytical studies

●Toxicology

●Pharmaceutics

Preclinical Studies (7)

Pharmacology

science of the properties of the drugs and its effects in the body

Pharmacodynamics

study of the interaction of

drugs with cells

Pharmacokinetics

handling of a drug within the body, it includes the ADME processes

Toxicology

study of the ADVERSE EFFECT (A/E ) of the chemical agents or living organisms

Pharmaceutics

general area of study concerned with

the formulation, manufacturing

stability and effectiveness of a

pharmaceutical dosage form

Preformulation

characterization of the physical and chemical properties of the active drug substance in relation to the desired dosage form.

• Solubility

• Partition coefficient

• Dissolution rate

• Physical form

• Stability

Preformulation Parameters (5)

Investigational New Drug (IND)

IND means

Patent the drug

File IND Application:

exclusive rights to the use and profits of a novel pharmaceutical for limited term

Orphan drugs and Treatment IND

special consideration is given on ___

Phase I

Clinical Studies:

• 20 - 100 healthy volunteer

• Tolerance and safety

• Toxicological studies

Phase II

Clinical Studies:

• 100 - 300 first controlled studies on patients

• Efficacy and therapeutic index

Phase III

Clinical Studies:

• 1000 - 3000 extended clinical trials

• dose, efficacy, toxicity and side

effects

• Performed with the final dosage form

developed in phase II

• Side effects are monitored

FDA

Submission of a New Drug

Application:

• Submitted to the ____ for review and

approval

• Products is effective by all parameters

Scaleup

increase in batch size from the clinical batch, submission batch, or to the full-scale production batch size, using the finished, marketed product.

Phase IV

Clinical Studies:

• Post marketing studies

• Drug product may be improved

• Additional clinical studies

Modification

scale-up and validation

___ on drug formulation as obtained from manufacturing ___and ___ process may be done

ANDA - Abbreviated New Drug Application

BLA - Biologics License Application

SNDA - Supplemental New Drug Application

SNADA - Supplemental New Animal Drug Application

Medical Devices (e.g., Catheters and Cardiac Pacemakers)

5Related Terms

Controlled Studies

• The effects of the IND are compared with another agent ➡️ placebo or active drug

• Single blinded

• Double blinded

Dosage Regimen

-schedule of dosage

Usual dose

amount that may be expected to produce, in adults, the medicinal effect for which it is intended

Usual dosage range

amounts of drug that may be

prescribed within the work of usual medical practice

Pediatric dose

- dose administered to children

Initial dose/ priming or loading dose,

amount required to attain the desired concentration of the drug in the blood or tissues

Prophylactic dose

the amount administered to a patient before exposure or contraction of the

illness

Therapeutic dose

amount which is administered to a patient after the exposure or contraction of an illness

Therapeutic Index

TD50/ ED50

Toxic dose/ effective dose

relationship between the desired and

undesired effects of a drug

• Age

• Pharmacogenetics

• Body Weight

• Body Surface Area

• Sex

• Pathologic State

• Tolerance

• Concomitant Drug therapy

• Time and Condition of Administration

• Dosage Form and Route of Administration

Factors Affecting the Dose

Pharmacogenetics

- genetic polymorphism

Body Surface Area