Pre-clinical trials involve testing new drugs, procedures, or medical treatments in animals before beginning clinical trials in humans. They aim to determine safety and efficacy. The document outlines the stages of pre-clinical trials including in vitro and in vivo testing, pharmacokinetic studies, toxicity tests, and FDA review requirements. The goals are to identify safe starting doses in humans, target organs for toxicity, and safety parameters for clinical monitoring before human trials.
In the slideshare i have discussed about principal of preclinical studies
various approaches towards preclinical studies
a route map of preclinical trials and its various methods
Preclinical Development, Introduction
Definition, Stages of development of a new drug, Objectives of Preclinical studies, Several steps in preclinical trials, Types of studies in Preclinical trials, Importance of preclinical trials
By
Ms. I. Sai Reddemma.
Department of Pharmacology
In the slideshare i have discussed about principal of preclinical studies
various approaches towards preclinical studies
a route map of preclinical trials and its various methods
Preclinical Development, Introduction
Definition, Stages of development of a new drug, Objectives of Preclinical studies, Several steps in preclinical trials, Types of studies in Preclinical trials, Importance of preclinical trials
By
Ms. I. Sai Reddemma.
Department of Pharmacology
Pre-discovery
Understand the disease
Target Identification
Choose a molecule to target with a drug
Target Validation
Test the target and confirm its role in the disease
Drug Discovery
Find a promising molecule (a “lead compound”)
that could become a drug
An overview of ICH-GCP guidelines of clinical trials.
Good clinical practice (GCP): a standard for the design , conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate and that the rights, integrity, and confidentiality of trial subjects are protected.
ICH-GCP is an International Conference on Harmonization Good Clinical Practice.
The guideline was developed with consideration of the current good clinical practices of the European union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the world health organization
Pharmacological Approach to Drug DiscoverySuhas Reddy C
For better understanding of students. This will give you a detailed explanation of Pharmacological approach. Contact me through comment section if you need any assistance in understating
clinical and preclinical approaches to drug discovery.Here we mainly deals with preclinical approaches, ie. Pharmacological approach and toxicological approach
Pre-discovery
Understand the disease
Target Identification
Choose a molecule to target with a drug
Target Validation
Test the target and confirm its role in the disease
Drug Discovery
Find a promising molecule (a “lead compound”)
that could become a drug
An overview of ICH-GCP guidelines of clinical trials.
Good clinical practice (GCP): a standard for the design , conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate and that the rights, integrity, and confidentiality of trial subjects are protected.
ICH-GCP is an International Conference on Harmonization Good Clinical Practice.
The guideline was developed with consideration of the current good clinical practices of the European union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the world health organization
Pharmacological Approach to Drug DiscoverySuhas Reddy C
For better understanding of students. This will give you a detailed explanation of Pharmacological approach. Contact me through comment section if you need any assistance in understating
clinical and preclinical approaches to drug discovery.Here we mainly deals with preclinical approaches, ie. Pharmacological approach and toxicological approach
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.
Target identification, target validation, lead identification and lead
Optimization.
• Economics of drug discovery.
• Target Discovery and validation-Role of Genomics, Proteomics and
Bioinformatics.
• Role of Nucleic acid microarrays, Protein microarrays, Antisense
technologies, siRNAs, antisense oligonucleotides, Zinc finger proteins.
• Role of transgenic animals in target validation.
Drug discovery is a
process which aims
at identifying a
compound
therapeutically useful
in curing and treating
disease
Target identification is process of
identifying the direct molecular
target(protein, nucleic acid, or
small molecule).
Identifying the biological of the
disease and the potential targets
for involvement ,is the first step in
the discovery of a medicine
Clinical trials are divided into several phases to ensure the safety and effectiveness of new medical interventions, such as drugs, treatments, or medical devices, before they are approved for widespread use. Here are the typical phases of clinical trials:
Phase 0: Exploratory Study
Phase 0 trials are relatively new and not always a part of the clinical trial process. They involve a small number of participants and aim to gather initial data on how the drug or treatment behaves in the human body. These trials help researchers decide whether to move forward with larger Phase 1 trials.
Phase 1: Safety and Dosage Study
Phase 1 trials involve a small number of healthy volunteers or patients and focus on assessing the safety of the intervention and determining the appropriate dosage range. Researchers closely monitor participants for any adverse effects, evaluate how the intervention is metabolized, and gather initial data on its efficacy.
Phase 2: Expanded Safety and Efficacy Study
Phase 2 trials involve a larger number of patients who have the condition the intervention is intended to treat. These trials continue to assess safety, evaluate dosage regimens, and gather more data on the intervention's efficacy. Researchers may also explore different patient populations, dosages, or combinations with other treatments.
Phase 3: Confirmatory Study
Phase 3 trials are large-scale studies involving a significant number of patients to confirm the intervention's safety, effectiveness, and monitor any side effects. These trials often include a randomized and controlled design, comparing the new intervention against existing standard treatments or placebos. Phase 3 trials provide critical data for regulatory agencies to evaluate whether the intervention should be approved for widespread use.
Phase 4: Post-Marketing Surveillance Study
Phase 4 trials take place after the intervention has received regulatory approval and is available to the general public. They aim to monitor the intervention's long-term safety, effectiveness, and identify any rare or long-term side effects. Phase 4 trials may involve a larger and more diverse population than earlier phases.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
2. Overview
• Drug Development Review
• Introduction
• Review By FDA
• Objectives
• Importance
• Goals
• Types
• Stages Of Preclinical Trials
Introduction to Pre-
Clinical Trials
2
3. Drug Development Review
Post Market Safety Monitoring
Supplemental Application IND Application Manufacturer Inspection Drug Advertising Reporting Problems Active Surveillance
FDA Approval
NDA FDA Review FDA Approval
Clinical studies
Phase I Phase II Phase III
Preclinical Studies
In-Vitro In-Vivo
Discovery and Development
Discovery of new treatment and development of new formula
Introduction to Pre-
Clinical Trials
3
4. Introduction
• Pre-Clinical Trials is a study to test a drug, a procedure, or another
medical treatment in animals.
• In drug development, pre-clinical development, also
named preclinical studies and nonclinical studies, is a stage of
research that begins before clinical trials (testing in humans) can
begin, and during which important feasibility, iterative testing and
drug safety data is collected.
• It also means in vivo or in vitro experiments in which test articles
are studied prospectively in test systems under laboratory
conditions to determine their safety.
Introduction to Pre-
Clinical Trials
4
5. Introduction (Contd.)
• We assume that
▫ In vitro assays predict in vivo effects
▫ The effects of chemicals in laboratory animals apply to humans
▫ The use of high doses in animals is valid for predicting possible toxicity
in humans.
• These assumptions are broadly true, but despite this, we cannot be
certain that a chemical will show no toxic effects in humans.
Introduction to Pre-
Clinical Trials
5
6. Preclinical Review by FDA
• Under FDA requirements, a sponsor must first submit data showing
that the drug is reasonably safe for use in initial, small-scale clinical
studies. Depending on whether the compound has been studied or
marketed previously, the sponsor may have several options for
fulfilling this requirement:
▫ Compiling existing nonclinical data from past in vitro laboratory or
animal studies on the compound
▫ Compiling data from previous clinical testing or marketing of the drug
▫ Undertaking new preclinical studies designed to provide the evidence
necessary to support the safety of administering the compound to
humans.
Introduction to Pre-
Clinical Trials
6
7. Preclinical Review By FDA (Contd.)
• At the preclinical stage, the FDA will generally ask,
▫ Develop a pharmacological profile of the drug
▫ Determine the acute toxicity of the drug in at least two species of animals
▫ Conduct short-term toxicity studies ranging from 2 weeks to 3 months,
depending on the proposed duration of use of the substance in the
proposed clinical studies.
Introduction to Pre-
Clinical Trials
7
8. Objectives of Preclinical Trial
• Objective is to develop adequate data to decide that it is reasonably
safe to proceed with human trials of the drug, means, a laboratory
test of a new drug or a new medical device, usually done on animal
subjects, to see if the treatment really works and if it is safe to test
on humans.
Introduction to Pre-
Clinical Trials
8
9. Importance of Preclinical Trials
Determination of dose, toxic
dose, pharmacological action,
etc.
Requirement of regulatory body
Necessary to check safety of
drug on animals before starting
to check on human being.
Check for kinetic profile of drug
and on this basis, selection of
route of administration
Importance
Introduction to Pre-
Clinical Trials
9
10. Goals Of Preclinical Studies
Identify initial safe dose and dose escalation
schemes in humans
Identify target organs for toxicity
Study of such toxicity whether reversible
Identify safety parameters for clinical
monitoring
Introduction to Pre-
Clinical Trials
10
12. Types of Trials
In Vitro Preclinical
Trials
Pharmacokinetics
Pharmacodynamics
In Vivo Preclinical Trials
Screening
Isolated Organ
Bacteria Culture
Animal Models
General Observation
Confirmatory
Mechanism of Action
Systemic Pharmacology
Quantitative Test
Toxicity Tests
Introduction to Pre-
Clinical Trials
12
13. In Vitro Preclinical Trials
• Needed for better characterisation by providing evidence for the
desired biological effect of a drug.
• Providing insight into potential toxicities to establish a human starting
dose
Pharmacodynamic Studies
• The absorption, tissue distribution, metabolism, excretion, volume of
distribution and half-life of drug are quantified.
Pharmacokinetic Studies
Introduction to Pre-
Clinical Trials
13
14. In Vivo Preclinical Trials
• Simple and rapidly performed tests to indicate presence or absence of a
particular activity.Screening
• Study of activity on isolated organs
• Eg: AntipyreticsIsolated Organs
• Study of any activity using bacterial cultures
• Eg: AntibioticsBacterial Cultures
• Animal models used
• Eg. Kindled seizures in rats, genetically hypersensitive rats, experimental
tuberculosis in mouse
Animal Models
• Drug is injected in tripling doses to small groups of mice which are observed
for overt (hidden) effects.
• Preliminary clues are drawn from the profile of effect observed.
General Observations
Introduction to Pre-
Clinical Trials
14
15. In Vivo Preclinical Trials (Contd.)
Introduction to Pre-
Clinical Trials
15
• Attempts are made to find out the mechanism of action.
• E.g. whether an anti-hypertensive is an α blocker/ β blocker/ ACE inhibitor/
calcium channel blocker, etc.
Mechanism of Action
• Irrespective of the primary action of the drug, its effect on major organ systems
such as nervous, cardio-vascular, respiratory, renal are worked out.Systemic Pharmacology
• The dose-response relationship, maximal effects and comparative efficacy with
existing drug is carried out
Quantitative Tests
• Chronic Toxicity Mutagenicity
• Teratogenicity OncogenicityToxicity Tests
• Compounds found active are taken up for detailed study by more
elaborate (Complex) tests which confirm and characterize the activity.Confirmatory Tests
17. Stages Of Preclinical Development
Lead Selection
and
Optimisation
Drug Candidate
Confirmation
Preclinical Drug
Characterisation
Introduction to Pre-
Clinical Trials
17
18. Lead Selection and Optimisation
• Structural
Characterisation
• Impurity
Identification
• Solubility
Assessment
• Prototype
formulation
• Stability Testing
Essential
Pharmaceuticals
Introduction to Pre-
Clinical Trials
18
• In vitro models
• In vivo models
• Other models
Screening
Efficacy
• In silico profiling
• Plasma Stability
• Membrane Permeability
• Develop analytical method
Early
ADME
• Off screen target
• In vitro cytotoxicity
Early
Toxicology
19. Drug Candidate Confirmation
Preliminary Chemistry,
Manufacture, Control
Formulation for GLP
Toxicology
Stability Testing of API
Physicochemical
Characterisation
Impurity Analysis
In Vivo Models
Validated Models
Models in other disease
areas
ADME Profiling
Analytical method
Development
P’cokinetics and Oral
Bioavailability
Drug Metabolism
Preliminary Toxicology
Maximum Tolerated Dose
Repeat Dose
Cardiovascular Safety
Pharmacology
Data from Lead Selection and Optimisation
Introduction to Pre-
Clinical Trials
19
20. Preclinical Drug Characteristics
Detailed Preclinical CMC
• ICH Stability Testing
• ICH Impurity Analysis
• Prototype Formulation
Comprehensive ADME
• Analytical Method Development
• P’cokinetics
• Identification of Metabolites
GLP Toxicology Package
• Acute Study
• Subchronic Repeat Dose Study
• Genotoxicity Study
• Safety Pharmacology
Detailed
Preclinical CMC
Comprehensive
ADME GLP Toxicology
Presentation to
Pharma
Introduction to Pre-
Clinical Trials
20
Data From Previous Stages
21. Considerations for trials
Selection of
Relevant
Animal Species
Age
Physiological
State
Manner of
Delivery
Stability of Test
Material
Introduction to Pre-
Clinical Trials
21
22. Reference
• www.fda.gov
• www.medicinenet.com
• ICH Guidelines
• BRITISH JOURNAL OF PHARMACOLOGY The successes
and limitations of preclinical studies in predicting the
pharmacodynamics and safety of cell-surface-
targeted biological agents in patients; Andrew G
Polson and Reina N Fuji
Introduction to Pre-
Clinical Trials
22
