The document summarizes drug regulation in India. Key points:
1. The Drugs and Cosmetics Act of 1940 and Rules of 1945 regulate drug import, manufacture, distribution and sale in India through agencies like the Central Drugs Standard Control Organization.
2. Drugs are categorized into schedules based on their use and availability (e.g. Schedule X for narcotics). Manufacturing, clinical trials, and new drug development are regulated through various schedules.
3. Permission is required from licensing authorities and ethics committees to conduct clinical trials of new drugs in India. Sponsors must ensure trials are properly conducted and serious adverse events reported.
Origin and principles of international conference on harmonization- Good clin...AbhishekJoshi312
The ppt gives a basic information about ICH-GCP, how it originated , what led to the formation of ICH-GCP guidelines and what are the principles of the guidelines.
This presentation enlists all the studies which are required before submission of IND. It include IND introduction , time period of study ,flowchart showing preclinical studies...
Safety pharmacology is a branch of pharmacology with its aim to predict the potential clinical risk profile of new chemical entities (NCEs).
It has the ability to predict the potential off-target drug effects on major organ systems which are associated with exposure in the therapeutic range and above.
As an essential part of the spectrum of drug discovery and development, safety pharmacology studies are generally conducted to determine the relative drug effect on main organs, including respiratory system, central nervous system, and cardiovascular system.Safety pharmacology is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials.
SP studies are described in the international conference on harmonization (ICH) S7A and S7B Guidelines.
Origin and principles of international conference on harmonization- Good clin...AbhishekJoshi312
The ppt gives a basic information about ICH-GCP, how it originated , what led to the formation of ICH-GCP guidelines and what are the principles of the guidelines.
This presentation enlists all the studies which are required before submission of IND. It include IND introduction , time period of study ,flowchart showing preclinical studies...
Safety pharmacology is a branch of pharmacology with its aim to predict the potential clinical risk profile of new chemical entities (NCEs).
It has the ability to predict the potential off-target drug effects on major organ systems which are associated with exposure in the therapeutic range and above.
As an essential part of the spectrum of drug discovery and development, safety pharmacology studies are generally conducted to determine the relative drug effect on main organs, including respiratory system, central nervous system, and cardiovascular system.Safety pharmacology is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials.
SP studies are described in the international conference on harmonization (ICH) S7A and S7B Guidelines.
Assignment on Regulatory Prespectives of Clinical TrialsDeepak Kumar
Assignment on Origin and Principles of International Conference on Harmonization - Good Clinical Practice, (ICH-GCP) guidelines Ethical Committee- Institutional Review Board, Ethical Guidelines for Biomedical Research and Human Participant-Schedule Y, ICMR
IND (Investigational New Drug) industrial perspectiveAYESHA NAZEER
Describing the Industry's/sponsor's/drug manufacturers' perspective of the Investigational New Drug Application (IND) program based on the survey conducted by the Office Of Inspector General (OIG).
Roles and Responsibilities in Clinical Trials of Investigator, Study Coordinator, Sponsor, Monitor, a Contract research organization.
The clinical trial, definition, description, Different types of clinical trials, phases of clinical trial.
The clinical trial study team.
Requirements of the clinical trial study team.
Clinical research team role.
GCP- Good clinical practices.
Guidelines for Preparation of Documents, Clinical Study Report Clinical Trial...Dinesh Gangoda
Contents
Guidelines for Preparation of Documentation
Clinical Study Reports
Clinical Trial Monitoring
Safety Monitoring in clinical trials
Introduction
Proper documentation is critical to the success of a clinical study.
Every aspect of the study must be documented in order to obtain useful data and demonstrate compliance with Good Clinical Practice (GCP) guidelines and with all applicable regulations.
Investigator’s Brochure (IB)
List of Abbreviations
Contents & Summary
Introduction provides the chemical name (and generic and trade names, if approved) of the investigational product.
Physical, chemical and pharmaceutical properties and formulation of the medicinal product. Non-clinical studies & Clinical Studies and their results.
The Investigator's Brochure should be reviewed at least annually and revised as necessary in compliance with a standard procedures established by drug development company.
Dermal Irritation and Dermal Toxicity Studies Dinesh Gangoda
Dermal irritation and Corrosion test guidelines 204.
Dermal irritation is the production of reversible damage of the skin following the application of a test chemical for up to 4 hours.
Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions. [1]
Dermal corrosion is the production of irreversible damage of the skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test chemical for up to four hours.[2]
REFERENCES
OECD/OCDE, Test No. 404: ‘‘Acute Dermal Irritation/Corrosion’’, 28 July 2015 OECD Publishing, peris, Page no, 1- 8.
Robert A., Turner., Screening Methods in Pharmacology; 1st edition; Academic press an imprint of Elsevier, pp, 279- 281.
OECD Guideline for testing of chemicals (1981). ‘‘Repeated Dose Dermal Toxicity’’, 21/28- day Study.
animal toxicity tests are useful in finding the right dose for drugs to be used in humans. this ppt contains the method of toxicity studies and different types of toxicity studies.
Assignment on Regulatory Prespectives of Clinical TrialsDeepak Kumar
Assignment on Origin and Principles of International Conference on Harmonization - Good Clinical Practice, (ICH-GCP) guidelines Ethical Committee- Institutional Review Board, Ethical Guidelines for Biomedical Research and Human Participant-Schedule Y, ICMR
IND (Investigational New Drug) industrial perspectiveAYESHA NAZEER
Describing the Industry's/sponsor's/drug manufacturers' perspective of the Investigational New Drug Application (IND) program based on the survey conducted by the Office Of Inspector General (OIG).
Roles and Responsibilities in Clinical Trials of Investigator, Study Coordinator, Sponsor, Monitor, a Contract research organization.
The clinical trial, definition, description, Different types of clinical trials, phases of clinical trial.
The clinical trial study team.
Requirements of the clinical trial study team.
Clinical research team role.
GCP- Good clinical practices.
Guidelines for Preparation of Documents, Clinical Study Report Clinical Trial...Dinesh Gangoda
Contents
Guidelines for Preparation of Documentation
Clinical Study Reports
Clinical Trial Monitoring
Safety Monitoring in clinical trials
Introduction
Proper documentation is critical to the success of a clinical study.
Every aspect of the study must be documented in order to obtain useful data and demonstrate compliance with Good Clinical Practice (GCP) guidelines and with all applicable regulations.
Investigator’s Brochure (IB)
List of Abbreviations
Contents & Summary
Introduction provides the chemical name (and generic and trade names, if approved) of the investigational product.
Physical, chemical and pharmaceutical properties and formulation of the medicinal product. Non-clinical studies & Clinical Studies and their results.
The Investigator's Brochure should be reviewed at least annually and revised as necessary in compliance with a standard procedures established by drug development company.
Dermal Irritation and Dermal Toxicity Studies Dinesh Gangoda
Dermal irritation and Corrosion test guidelines 204.
Dermal irritation is the production of reversible damage of the skin following the application of a test chemical for up to 4 hours.
Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions. [1]
Dermal corrosion is the production of irreversible damage of the skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test chemical for up to four hours.[2]
REFERENCES
OECD/OCDE, Test No. 404: ‘‘Acute Dermal Irritation/Corrosion’’, 28 July 2015 OECD Publishing, peris, Page no, 1- 8.
Robert A., Turner., Screening Methods in Pharmacology; 1st edition; Academic press an imprint of Elsevier, pp, 279- 281.
OECD Guideline for testing of chemicals (1981). ‘‘Repeated Dose Dermal Toxicity’’, 21/28- day Study.
animal toxicity tests are useful in finding the right dose for drugs to be used in humans. this ppt contains the method of toxicity studies and different types of toxicity studies.
A review on stages of drug development and alternative methods for animal stu...Frinto Francis
Various Stages of drug development, anaesthesia ,euthanasia, animals used for preclinical analysis, clinical trials, alternative methods for animal testing, blood withdrawal methods, ethical guidelines
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.
introduction to practical pharmacology, various experimental animal uses, CPCSEA guidelines, different phases of clinical trial, pre-clinical trial, important pharmacological definition
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micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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.
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
2. • Directorate General of Health Services
Ministry of Health and Family
Welfare
• Drugs Controller General of India.
CDSCO-Central Drugs Standard
Control Organization
Retail and
Distribution
Manufacturing
Practice
Clinical Trials and
new drug
development
DRUG REGULATION IN INDIA
3. • 1. Schedule X – Narcotics
2. Schedule H – Prescription drugs
3. Schedule C and C1- Biological Products (Serums and
Vaccines)
Retail and Distribution
• 1. Schedule N
List of the equipment for the efficient running of manufacturing
wing, Qualified personnel
2. Schedule M-GMP
Manufacturing Practice
• Schedule Y
Clinical Trials and new drug development
4. MINISTRY OF HEALTH AND FAMILY
WELFARE Introduced THE DRUGS AND
COSMETICS ACT (1940) AND RULES (1945)
An Act to regulate the import, manufacture,
distribution and sale of drugs and cosmetics in
India.
The drugs and cosmetics act and rules
5. SCHEDULE Y
Rules 122 A, 122 B, 122 D, 122 DA, 122 DAA, 122 DAB, 122 E, 122 DD.
REQUIREMENTS AND GUIDELINES FOR
PERMISSION TO IMPORT AND / OR
MANUFACTURE OF NEW DRUGS FOR SALE OR
TO UNDERTAKE CLINICAL TRIALS
Includes
•Responsibilities
•Applications
•Appendices
•Refinements
6. Appendices in Schedule Y
I. Data required for import/manufacture/ conduct CT of new drugs
IA. Drugs approved in other country
II. Format for clinical study reports(ICH E6)
III. Animal toxicology
IV. Animal pharmacology
V. Informed consent
VI. FDC
VII. Undertaking by the investigator
VIII. Ethics committee
IX. Stability testing
X. Proposed protocol
XI. SAE Reporting
7. • 122-A Application for permission to import
new drug.
• 122-B Application for approval to manufacture
new drug.
• 122-D Permission to import or manufacture
FDC.
8. 1. APPLICATION FOR PERMISSION:
Application for permission to import or manufacture new
drugs shall be made in the form along with following data:
Introduction
Chemical and pharmaceutical information
Animal Pharmacology
Animal toxicology
Human / Clinical pharmacology (Phase I)
Therapeutic exploratory trials (Phase II)
Therapeutic confirmatory trials (Phase III)
Special studies
Regulatory status in other countries
Prescribing information
9. Chemical and pharmaceutical information
• Information on active ingredients
– Drug information (Generic Name, Chemical Name)
• Physical and chemical properties of drug
• Analytical Data
• Complete monograph specification including
• Validations
• Stability Studies
• Data on Formulation
– Dosage form
– Composition
– Excipient compatibility study
– Packing specifications
– Process validation
10. Animal Pharmacology
General Principles
• Specific and general pharmacological studies
should be conducted to support use of
therapeutics in humans.
• Safety pharmacology studies are studies that
investigate potential undesirable
pharmacodynamic effects of a substance on
physiological functions in relation to exposure
within the therapeutic range or above.
11. • Summary
• Specific pharmacological actions
• General pharmacological actions
• Follow-up and Supplemental Safety
Pharmacology Studies
• Pharmacokinetics: absorption, distribution;
metabolism; excretion
Includes
12. SPECIFIC PHARMACOLOGICAL ACTONS
Actions which demonstrate the therapeutic potential for
humans.
Scientifically validated methods should be used.
The use of new technologies and methodologies in accordance
with sound scientific principles should be preferred.
GENERAL PHARMACOLOGICAL ACTIONS
Essential Safety Pharmacology
Safety pharmacology studies need to be conducted to
investigate the potential undesirable pharmacodynamic effects
of a substance on physiological functions in relation to exposure
within the therapeutic range and above.
Effects on different organs
13. ANIMAL TOXICOLOGY
• Toxicity studies should comply with the norms
of Good Laboratory Practice (GLP).
• Toxicokinetic studies should be conducted to
assess the systemic exposure achieved in
animals and its relationship to dose level and
the time course of the toxicity study.
14. Animal toxicology
• Systemic Toxicity studies
– Single dose toxicity studies
– Repeated dose toxicity studies
• Male fertility studies
• Female Reproduction and Developmental Toxicity
Studies
• Local toxicity
• Allergy/Hypersensitivity
• Genotoxicity
• Carcinogenicity
15. Single-dose Toxicity Studies
• These studies should be carried out in 2 rodent
species (mice and rats)
• Each group should contain at least 5 animals of
either sex.
• At least four graded doses should be given.
• Animals should be exposed to the test substance in
a single bolus or by continuous infusion.
• Animals should be observed for 14 days after the
drug administration
• Minimum lethal dose (MLD) and Maximum
tolerated dose (MTD) should be established.
• If possible, the target organ of toxicity should be
determined.
16. Repeated-dose Systemic Toxicity Studies
• Should be carried out in 1 non rodent and 1
rodent species.
• Dose ranging studies should precede the 14-, 28-,
90- or 180- day toxicity studies.
• 5 animals in each group and at least 4 graded
doses should be given.
• Highest dose should be the maximun tolerated
dose of the single dose toxicity study.
• It is given consequently for 10 days
• Organ specific toxicity is established.
17. Male Fertility Study
• Each group should consist of 6 adult male
animals.
• Animals should be treated with the test
substance for minimum 28 days and maximum
70 days before they are paired with female
animals of proven fertility in a ratio of 1:2 for
mating.
• Pairing should be continued till the detection
of vaginal plug or 10 days, whichever is earlier.
18. • Females getting thus pregnant should be
examined for their fertility index after day 13
of gestation.
• All the male animals should be sacrificed at
the end of the study and organs for
reproduction are examined.
19. Female Reproduction and Developmental
Toxicity Studies
• These studies need to be carried out for all
drugs proposed to be studied or used in
women of child bearing age.
• 3 segments
SEGMENT I Albino mice or rat Female Fertility Study
SEGMENT II Albino mice or rat
+
Albino rabbits
Teratogenicity Study
SEGMENT III Albino mice or rat Perinatal Study
20. • Dose selection: administered to both males and
females, beginning a sufficient number of days before
mating
• Groups: 15 males and 15 females per dose. Control
and the treated groups should be of similar size.
• Dosing interval: Three graded doses. The route of
administration should be the same as intended for
therapeutic use. Drug treatment should continue
during mating and, subsequently, during the gestation
period.
• Dams should be allowed to litter and their medication
should be continued till the weaning of pups.
21. Observations should be carried out for
• Mating behavior
• Survival
• Growth parameter
• Length of gestation
• Parturition
• Post-partum health & gross pathology of affected organ
• Progress of gestation/ parturition periods
• Signs of intoxication
• Body weight
• Food intake
22. Local toxicity
These studies are required when the new drug is proposed
to be used by some special route (other than oral) in
humans:
It includes:
• Dermal toxicity
• Photo-allergy or dermal photo-toxicity:
• Vaginal toxicity
• Rectal tolerance test
• Parenteral toxicity: injection site toxicity
• Ocular and inhalational toxicity studies
23. Allergenicity / Hypersensitivity
Any one of the standard tests:
• Guinea pig :
– Maximization test (GPMT)
• Mouse :
– Local lymph node assay (LLNA)
24. Genotoxicity Studies
• Genotoxicity tests are in vitro and in vivo tests
conducted to detect compounds which induce
genetic damage directly or indirectly.
• These tests should enable a hazard identification
with respect to damage to DNA and its fixation.
• Genotoxicity data are not required before Phase I and
II trials. But these studies should be completed before
applying for Phase III trials.
25. The following standard test battery is generally
expected to be conducted:
• (i) A test for gene mutation in bacteria.
• (ii) An in vitro test with cytogenetic evaluation of
chromosomal damage with mammalian cells or an in vitro
mouse lymphoma tk assay.
• (iii) An in vivo test for chromosomal damage using rodent
hematopoietic cells.
26. For expected clinical use more than 6 months
For drugs used frequently in an intermittent manner
If concern about the carcinogenic potential due to :
Previous demonstration in the product class
Structure-activity relationship suggests carcinogenic risk
Preneoplastic lesions in repeated dose toxicity studies
Long-term tissue retention results in reactions
Carcinogenicity
27. • 122-DA Permission to conduct clinical trials
for new drug / investigational new drug.
– 122 - DAA Definition of CLINICAL TRIAL.
– 122- DAB Reports of Serious Adverse Events
(SAEs) including deaths.
– 122- E New Drug
28. Clinical Trial
• “Clinical trial” means a systematic study of
new drug(s) in human subject(s) to generate
data for discovering and / or verifying the
clinical, pharmacological (including
pharmacodynamic and pharmacokinetic) and
/or adverse effects with the objective of
determining safety and / or efficacy of the
new drug.
122 - DAA
29. New Drug
A new substance of chemical, biological or
biotechnological origin, in bulk or prepared dosage
form; used for prevention, diagnosis, or treatment of
disease in man or animal; which except during local
clinical, trials, has not been used in the country to any
significant extent and which except during local clinical
trials, has not been recognised in the country as
effective and safe for the proposed claims.
122-E
30. • Clinical trial on a new drug shall be initiated only after
the permission has been granted by the
Licensing Authority
Respective ethics committee(s).
• All trial Investigator(s) should possess appropriate
qualifications, training and experience and should have
access to such investigational and treatment facilities as
are relevant to the proposed trial protocol.
Approval for clinical trial
31. Responsibilities of Sponsor
• Implementing and maintaining quality
assurance systems.
• submit a status report on the clinical trial
• in case of studies prematurely discontinued
for any reason including lack of commercial
interest in pursuing the new drug application,
a summary report should be submitted within
3 months.
• Report SAE
32. Responsibilities of the Investigator
• Conduct of the trial according to the protocol and
the GCP Guidelines
• Follow the SOP’s.
• Ensure that adequate medical care is provided to
the participant for any adverse events.
• Report SAE.
33. • 122 – DD Registration of Ethics
Committee (EC).
34. ETHICS COMMITTEE
It is the responsibility of the ethics committees that reviews
and accords its approval to a trial protocol to safeguard the
rights, safety and well being of all trial subjects.
• Care of the vulnerable group in the study: patients with
incurable diseases, unemployed or impoverished persons,
patients in emergency situation, others incapable of
personally giving consent
• Ethics Committee(s) should make, at appropriate intervals,
an ongoing review of the trials for which they review the
protocol
122 – DD
35. • The number of persons in an Ethics
Committee should have at least seven
members
Chairperson
outside the institution
Member Secretary
(a)basic medical scientists (preferably one
pharmacologist).
(b) clinicians
(c) legal expert
(d) social scientist/ representation of non-
governmental voluntary agency /
philosopher / ethicist / theologian or similar
person
(e) lay person from the community
36. INFORMED CONSENT
In all clinical trials freely given, informed written
consent is required to be obtained from each study
subject
• Verbal information of the study using a patient
information sheet
• Language that is nontechnical and understandable
by the study subject.
• Where a subject is not able to give informed
consent, the same may be obtained from a legally
acceptable representative.
37. • Where a subject is not able to give informed consent,
same may be obtained from a legally acceptable
representative .
• If the Subject or his/her legally acceptable
representative is unable to read/write – an impartial
witness should be present during the entire informed
consent process who must append his/her signatures
to the consent form.
38.
39. For new drugs approved outside India,
Phase III studies need to be carried out
primarily to generate evidence of efficacy
and safety of the drug in Indian patients.
40. Post Marketing Trials (Phase IV)
Post Marketing trials are studies (other than routine
surveillance) performed after drug approval and
related to the approved indication(s).
It is done to detect unexpected adverse effects and
drug interactions dose-response or efficacy ,safety
studies and trials designed to support use under the
approved indication(s), e.g. mortality/morbidity
studies, epidemiological studies .
41. • for new drug substances discovered in
countries other than India, Phase I data should
be submitted along with the application.
• After submission of Phase I data generated
outside India to the Licensing Authority,
• Phase 1 Phase 2
Phase 3
Phase III trials are required to be
conducted in India before
permission to market the drug in
India is granted
42. Post Marketing Surveillance
• Subsequent to approval of the product, new
drugs should be closely monitored for their
clinical safety once they are marketed.
• The report is to be submitted every six months
for the first two years after approval of the
drug is granted to the applicant. For
subsequent two years need to be submitted
annually and may be extended if necessary.
43. • The applicants shall furnish Periodic Safety
Update Reports (PSURs) in order to-
• report all the relevant new information from
appropriate sources;
• relate these data to patient exposure ;
• summarize the market authorization status in
different countries and any significant variations
related to safety;
• indicate whether changes should be made to product
information in order to optimize the use of the
product.
44. Serious Adverse Events
• Any undesirable experience associated with the
use of a medical product in a patient
• It should be reported within 14 days by the
Sponsor to the Licensing Authority and to the
other Investigator(s) participating in the study
Death Life-threatening
Hospitalization Disability or Permanent Damage
Congenital Anomaly/Birth Defect Required Intervention to Prevent
Permanent Impairment or Damage
(Devices)
Other Serious (Important Medical
Events)
122- DAB
45.
46. Geriatrics
• Geriatric patients should be included in Phase III
clinical trials (and in Phase II trials, at the Sponsor's
option)
– Geriatric patients should only if the disease intended to be
treated is characteristically a disease of aging
– The conditions to be treated should be common in the
elderly are likely to be encountered
– When the new drug is likely to alter the geriatric patient’s
response compared with that of the non-geriatric patient.
– the population to be treated is known to include
substantial numbers of geriatric patients
47. Pregnant or nursing women
• Pregnant or nursing women should be included in
clinical trials only when the drug is intended for use by
pregnant/nursing women or foetuses/nursing infants
and where the data generated from women who are
not pregnant or nursing, is not suitable.
• For new drugs intended for use during pregnancy,
follow-up data (pertaining to a period appropriate for
that drug) on the pregnancy, fetus and child will be
required.
48. Paediatrics
• When clinical development is to include studies in
children, it is usually appropriate to begin with
older children before extending the trial to
younger children and then infants.
• If the new drug is for diseases predominantly or
exclusively affecting paediatric patients.
• Initial safety and tolerability data should be
obtained from the adult population data before
starting trial in children.
• Written informed consent should be taken from
the legal guardians.
49. Bioavailability / Bioequivalence Studies
• For drugs approved elsewhere in the world and
absorbed systemically, bioequivalence with the
reference formulation should be carried out wherever
applicable.
• Dissolution and bioavailability data submitted with
the new drug application must provide information
that assures bioequivalence or establishes
bioavailability and dosage correlations between the
formulation(s) sought to be marketed and those used.
52. The Drugs and Cosmetics Rule made an amendment
GSR 53(E) dated 30-01- 2013 inserting a Rule 122DAB
and a new Appendix-XII in Schedule Y
It determine the quantum of compensation, if any, to
be paid by the Sponsor or his representative,
whosoever have obtained permission from the Drugs
Controller General(India) in a time bound manner.
B = Base amount (i.e. 8 lacs)
F = Factor depending on the age of the
subject (based on Workmen
Compensation Act)
R = Risk Factor
54. RISK FACTOR INDEX(R) RISK FACTORS
0.50 terminally ill patient (expected survival
not more than (NMT) 6 months)
1.0 Patient with high risk (expected
survival between 6 to 24 months)
2.0 Patient with moderate risk
3.0 Patient with mild risk
4.0 Healthy Volunteers or subject of no risk
Editor's Notes
Minister of health- Jagat prakash NADDA
DG-Jagdish Prasad
DCGI-G N Singh
Dose selection: administered to both males and females, beginning a sufficient number of days before mating
Groups: 15 males and 15 females per dose. Control and the treated groups should be of similar size.
Dosing interval: Three graded doses. The route of administration should be the same as intended for therapeutic use. Drug treatment should continue during mating and, subsequently, during the gestation period.
to ensure that the clinical trial is conducted and data generated, documented and reported in compliance with the protocol and Good Clinical Practice (GCP) Guidelines issued by the Central Drugs Standard Control Organization
to the Licensing Authority at the prescribed periodicity.
Any unexpected serious adverse event (SAE) (as defined in GCP Guidelines) occurring during a clinical trial should be communicated promptly (within 14 calendar days) by the Sponsor to the Licensing Authority and to the other Investigator(s) participating in the study
Studies conducted in Phase I, usually intended to involve one or a combination of the following objectives:-
Maximum tolerated dose
Pharmacokinetics
Pharmacodynamics
Early Measurement of Drug Activity:
Phase II studies can include evaluation of potential study endpoints, therapeutic regimens and target populations
Studies in Phase III are designed to confirm the preliminary evidence accumulated in Phase II that a drug is safe and effective for use in the intended indication and recipient population. These studies should be intended to provide an adequate basis for marketing approval.
Studies in Phase III may also further explore the doseresponse relationships
Prior to conduct of Phase III studies in Indian subjects, Licensing Authority may require pharmacokinetic studies to be undertaken to verify that the data generated in Indian population is in conformity with the data already generated abroad.
The timing of paediatric studies in the new drug development program will depend on the medicinal product, the type of disease being treated, safety considerations, and the efficacy and safety of available treatments.
However, all paediatric participants should be informed to the fullest extent possible about the study in a language and in terms that they are able to understand. Where appropriate, paediatric participants should additionally assent to enrol in the study. Mature minors and adolescents should personally sign and date a separately designed written assent form.
Rs.4 lacs to a maximum of Rs.73.60 However,
expected mortality is 90 % or more within 30 days, a fixed amount of Rs. 2 lac should be given