IPS1: Drug Discovery and Development Part 2

Drug development

drug molecule to drug product

Drug Development

0. Pre-clinical studies

1. Submission of an Investigational New Drug Application (INDA)

2. Clinical Trials

3. Submission of New Drug Application (NDA) to regulatory body

4. Clinical Trial Phase IV: Post Marketing Surveillance (PMS)

0. Pre-clinical studies

decides whether a drug is ready for clinical trials involves extensive studies (e.g. animal models) that yield preliminary information on: efficacy, toxicity, pharmacokinetic, safety

Approaches of pre-clinical studies

General pharmacology

Toxicology

1. Submission of an Investigational New Drug Application (INDA)

requests permission to move a clinical candidate into human study

provides regulatory agencies with detailed preclinical data and detailed clinical protocols that describe how the compounds will be studied in human populations

2. Clinical research or Clinical trials

Purpose:

1. Selection criteria for participants

2. Number of people take part of the study

3. Duration of study

4. Dose and route of administration of dosage form

5. Assessment of parameters

6. Data collection and analysis

2.0 Clinical trial: Phase 0

investigative FIH trials

follows US FDA guidelines

2.0 Clinical trial: Phase 0

include human micro dose studies; 10 to 15 healthy volunteers

2.1 Clinical trial: Phase I

Safety and tolerability of an IND are examined in a small number of healthy, typically 20 to 100 people

2.2 Clinical trial: Phase II

Safety and efficacy of IND are determined in around 100 to 300 patients

2.3 Clinical trial: Phase III

Efficacy of IND in larger population including comparison with standard therapies

3. Submission of New Drug Application (NDA) to regulatory body

NDA typically contains comprehensive details of both animal and human studies

New Drug Application (NDA)

include safety findings, manufacturing procedures, dosing methods, and storage conditions

FDA Review

Once FDA obtains a complete NDA then FDA team review may require 6 to 10 months to tale a pronouncement on whether to approve an NDA

Once FDA obtains an incomplete NDA then FDA team of review refuse the NDA

4. Clinical Trial: Phase IV - Post Marketing Surveillance (PMS)

detects rare and long-term adverse effects across much larger population of patients than could be supported in Phase III

Impacts of PMS

alterations to labeling based on safety results

contraindication for use of the new drug in combination with other medications, or withdrawal of marketing approval if the findings are severe enough

Data in PMS

used to identify competitive advantages, new markets, and new indication for the products

Ethnopharmacology

the interdisciplinary scientific exploration of biologically active agents traditionally employed or observed by man

Anti-infectives and Antineoplastics

Most of these therapeutic agents originate from natural products rather than synthetic molecules

Antibiotics

derived from fungal metabolites

Paclitaxel

anticancer from Yew tree

Vinca alkaloids

anticancer drugs produced by plants of the periwinkle family

Opiates

analgesic compounds from poppies

Artemether

antimalarial drug, semisynthetic derivative of artemisinin, produced by Chinese herb

Advantage of ethnopharmacology in drug discovery and development

Such ready-ready made, highly evolved biomolecules stand a better chance of interacting with selected drug targets than do random synthetic molecules and the pool from which they come is huge and largely untapped

Disdvantage of ethnopharmacology in drug discovery and development

1. Accessibility due to geographical, cultural, and political reasons

2. Continuing availability of the active compound may be uncertain

3. Purification and structure determination of natural products is often difficult and time-consuming

True

Exploiting such a ready-made compound library from natural products is seen as an attractive strategy for important therapeutic breakthroughs

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