1) The process of bringing a new medicine from initial discovery to patient use (molecule to medicine) is a long, complex, and expensive process involving target identification, preclinical testing, clinical trials, and regulatory review and approval.
2) Preclinical testing involves evaluating a molecule's pharmacokinetics, pharmacodynamics, safety, and toxicity in cell and animal studies. Positive preclinical results allow filing an Investigational New Drug (IND) application to begin human clinical trials.
3) Clinical trials are conducted in four phases to evaluate a drug's safety, efficacy, side effects, and optimal dosing in humans. The entire development process from discovery to approval takes 8-12 years and costs over $1
Presented By :- Raghav Sharma
Class :- M.Pharm, 1st sem.
Department :- Pharmaceutics
Institute :- Parul Institute of Pharmacy
Content :-
Introduction to Clinical trials
Importance of Clinical Trials
Phase-I of Clinical Trials
Phase-II of Clinical Trials
Phase-III of Clinical Trials
Phase-IV of Clinical Trials
Conclusion
References
LINK FOR VIDEO LECTURE
https://youtu.be/TnIlNoxbpXg
THIS SLIDE SHARE IS ALL ABOUT CLINICAL TRIALS AND ITS DIFFERENT PHASES .
IT HELPS PHARMACY AS WELL AS OTHER MEDICAL AND RESEARCH STUDENTS .
Clinical Pharmacology in Orphan Drug DevelopmentE. Dennis Bashaw
This is the fourth talk that I gave in Asia back in May. It was presented at the Konect (Korea National Enterprise for Clinical Trials) 3rd symposia that was held in Seoul at Seoul National University.
Presented By :- Raghav Sharma
Class :- M.Pharm, 1st sem.
Department :- Pharmaceutics
Institute :- Parul Institute of Pharmacy
Content :-
Introduction to Clinical trials
Importance of Clinical Trials
Phase-I of Clinical Trials
Phase-II of Clinical Trials
Phase-III of Clinical Trials
Phase-IV of Clinical Trials
Conclusion
References
LINK FOR VIDEO LECTURE
https://youtu.be/TnIlNoxbpXg
THIS SLIDE SHARE IS ALL ABOUT CLINICAL TRIALS AND ITS DIFFERENT PHASES .
IT HELPS PHARMACY AS WELL AS OTHER MEDICAL AND RESEARCH STUDENTS .
Clinical Pharmacology in Orphan Drug DevelopmentE. Dennis Bashaw
This is the fourth talk that I gave in Asia back in May. It was presented at the Konect (Korea National Enterprise for Clinical Trials) 3rd symposia that was held in Seoul at Seoul National University.
The slide provides a basic understanding about Clinical Research process and the various Phases of Drug Discovery and Development. It also explains about the various trial designs and techniques in research such as blinding and randomization. It may be useful for giving a basic class for Fourth Year B.Pharm Students.
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2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
The simplified electron and muon model, Oscillating Spacetime: The Foundation...RitikBhardwaj56
Discover the Simplified Electron and Muon Model: A New Wave-Based Approach to Understanding Particles delves into a groundbreaking theory that presents electrons and muons as rotating soliton waves within oscillating spacetime. Geared towards students, researchers, and science buffs, this book breaks down complex ideas into simple explanations. It covers topics such as electron waves, temporal dynamics, and the implications of this model on particle physics. With clear illustrations and easy-to-follow explanations, readers will gain a new outlook on the universe's fundamental nature.
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
Delivering Micro-Credentials in Technical and Vocational Education and TrainingAG2 Design
Explore how micro-credentials are transforming Technical and Vocational Education and Training (TVET) with this comprehensive slide deck. Discover what micro-credentials are, their importance in TVET, the advantages they offer, and the insights from industry experts. Additionally, learn about the top software applications available for creating and managing micro-credentials. This presentation also includes valuable resources and a discussion on the future of these specialised certifications.
For more detailed information on delivering micro-credentials in TVET, visit this https://tvettrainer.com/delivering-micro-credentials-in-tvet/
Delivering Micro-Credentials in Technical and Vocational Education and Training
Molecule to medicine
1. Molecule to medicine
Dr.Meharban , MSc, Ph.D.
Assistant Professor, Department of Pharmacology
Vydehi Institute of Medical Sciences & Research Centre
PHARMAQUEST-2021
3. Introduction
• The drug discovery and development process (i.e
molecule to medicine)
– Discovery research
– Preclinical testing
– Investigational new drug (IND) applications
– Completed clinical testing before marketing approval from
the FDA.
4. Introduction
• The overarching goal
– More efficient
– Safer treatments to the patients
– Quickly as possible after a thorough medical evaluation
• Very lengthy, long duration, involves multi discipline
people to bring a medicine from molecules discovery
• Very expensive with lot of uncertainty and failures
5. Site
Selection
Molecules to medicine: Process
Target identification:
Choose a molecule in the body to
target with a drug; often a protein
or receptor
Target validation:
Test the target and confirm its role
in the disease pathology
Lead generation:
Find lead compound that could
become a drug through medicinal
chemistry optimization
Early safety testing:
Initial tests on lead compounds,
including pharmacokinetics, by
experiment and/or computer
modelling assess the safety risk
Lead optimisation:
Alter the structure of lead
candidates to improve properties;
this may include formulation,
delivery mechanism and scale-up.
Discovery research Preclinical research Clinical research Regulatory review
& approval
Pharmacokinetic study:
Asses the exposure across preclinical species
and derive the pharmacokinetic parameters
Pharmacodynamic study:
Confirm the efficacy in relevant disease
model in preclinical species
Chemistry, manufacturing and
control( CMC):
Robust chemical synthesis in place to supply
large qty of drug substance
Identified suitable formulation to convert
drug substance into drug product for IND
enabling studies and clinical testing
Safety and toxicology evaluation: To
assess the safety of preclinical candidate in
rodents and non rodents to build body
evidence to take compound for human
testing
Clinical trial exceptions (CTX)
applications
File CTX with appropriate authorities before
clinical testing can begin.
Phase 1 clinical trial
Initial human testing in a small group of
healthy volunteers.
Phase 2 clinical trial
Test in a small group of patients.
Phase 3 clinical trial
Test in a large group of patients to show
safety and efficacy.
Marketing authorisation
application
Apply to appropriate authorities
for approval.
Manufacturing
Begin full-scale production.
On-going studies and
Phase 4 trials
Continuing monitoring and
checking of the drug in use.
6. The essence of Drug Discovery
6
Safe
Effective
Affordable
Profitable
Globally
relevant
Sustainable
Cost
effective
Potent
Safe
Patentable
Hospital Bed
Lab Bench
De-risk
Increase
Probability
of
Success
7. Drug Discovery : timelines
1 Drug
Approve
d
Lead Opt
1000 – 5000
compounds
Pre-Clinical
5-20 compounds Clinical Trials
2-3 compounds
FDA Review
Expenses
~8-12 years
1-3 years
6-10 years
8. Molecule generation
– Random Screening
• HTS - using large compound collection in high throughput mode
– Molecular Manipulation
• Modification existing drug or leads natural product
– Molecular Designing
• Structure based design using crystal bound ligand structure or using enzyme
substrate or natural agonist of receptor or modification natural
neurotransmitter
– Drug Metabolites
• Knowledge based modification metabolites
– Serendipity
• Identification lead by accident, e.g. Viagra
10. Lead optimization- fine tuning of properties
• Optimizing chemical lead for clinical trial is commonly referred
to as lead optimization
• The refinement in structure is necessary in order to improve
• Potency
• Oral Availability
• Selectivity
• pharmacokinetic properties
• safety
11. Hameed P., et al. Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate. Nat Commun 6, 6715 (2015)
MMV253: Optimized lead from HTS hits
MMV253 is completed phase-1 study and entering phase-2 trial
12. In-vitro studies
• Drug affinity: Ability of drug to bind to its biological target (receptor,
enzyme, transport system, etc.)
• Selectivity- Drug should bind to specific receptor site on the cell (eg.
Atenolol)
• Solubility and permeability: Helps to assess the drug absorption
• Metabolism and transporter studies: Asses the metabolic stability and
elimination characteristic of molecules
• Off –target selectivity testing : Screening of molecules against various
secondary pharmacology targets ( Cardiac ion channels, enzymes,
receptor and kinases) to build selectivity and reduce safety risk
13. In vivo studies
• Its experimentation using a whole, living organism.
• Gives information about,
• Pharmacokinetic profile (rodents and non rodents)
Magnitude of pharmacological effect depends
on drug concentration at its site of action.
• Pharmacodynamic profile
Establishes effectiveness of drug in preclinical animal disease model to
demonstrate proof concept
e.g SCID mice for malaria,
NOD mice- Diabetes,
Syngeneic mice tumor model for Cancer
PMID: 30131376
14. Safety and toxicity: IND package
Readout and risk assessment
Cardiovascular safety
• Conscious dog telemetry to assess the effect candidate drug on ECG changes, proarrhythmic
and QT prolongation risk
Genetic toxicity
• Ames test to assess and rule out mutagenic potential drug candidate
• in vitro micronucleus to rule out genetic toxicity in vitro under GLP conditions
• in vivo micronucleus and comet test to rule in vivo genotoxic potential drug candidate if it is
found to be positive under in-vitro conditions
General and Organ
toxicity in rodents and
non rodent species
• 14/28-day repeat dosing of compounds in rats and dog to determinate the no observed adverse
effect level(NOAEL) using clinical observations and histopathological findings
• Helps to study toxicokinetic and calculate therapeutic margins for human clinical trials
• Identification monitorable safety risk( Reversible elevation of liver enzymes)
Respiratory toxicity
• To assess the effect of drug candidate on respiration rates and volumes
Central nervous system
toxicity
• To assess the impact of drug candidate on behaviour, sensory / motor responses and body
temperature and associated risk
15. Investigational new drug application
Preparing for an IND Submission
Proof-of-concept scientific
data
• Should include considerations of product activity, ability to replicate results and a reasonable
explanation how the product will prevent, diagnose, treat or cure disease
A target clinical Indication • Disease indication for which the intended drug developed for the treatment
Animal toxicology data
• Usually obtained in two species that supports the dose, dosing schedule, administration,
and study duration proposed in the clinical protocol
Manufacturing process
• Provides evidence that product is manufactured according to GMP, including analytical
tests results confirming the quality of the product several batches of the product
Stability Information
• Data demonstrating the stability of the drug, under defined storage conditions, or the period of use
for the clinical trial
Clinical plan/ protocol • Clinical trial design to assess the safety and tolerability of clinical candidate in human
Request submitted to the FDA to allow human exposure limit to the experimental drug
16. 16
Phases clinical trials
FDA Phases ICH Types Objectives
Phase I Human
Pharmacology
•Assess tolerance
•Drug metabolism and drug interaction
•Estimate drug activity
Phase II Therapeutic
Exploratory
•Assess use for target indication
•Estimate dosage for subsequent studies
Phase III Therapeutic
Confirmatory
•Confirm efficacy
•Collect information for assessing risk /benefit
relationship to support licensing
•Monitor side effects
Phase IV Therapeutic Use Identify less common adverse effects
Refine dosing recommendations
Refine risk benefit relationship in
general or special populations
Approved for
testing in
human
Submitted for
review and
approval
Approved for
human use
Post Marketing
Surveillance
Pharmacovigilance
17. Pre-IND meeting
IND submission
Pre NDA meeting
NDA Submission
Approval
Stages of FDA Review
Engage regulatory authority (FDA) to seek
opinion on preclinical data package to incorporate into IND
Submission of NDA application post phas-3 outcome
for review and approval for human use
Involve regulatory agency for data review post phase-2b/III to elicit
the response and suggestion for NDA application
Submission of IND package for review, allow human exposure limit
and approval for testing in human
Committee reviews and majority opinion decides approval for
human use
30 day