The document discusses Investigational New Drug Applications (INDs), New Drug Applications (NDAs), and Abbreviated New Drug Applications (ANDAs). It provides information on the purpose and requirements for submitting each type of application to regulatory agencies like the FDA.
An IND is required to get approval to conduct clinical trials of an investigational drug in humans. It must contain preclinical and manufacturing data as well as details on the proposed clinical trial protocol. An NDA is submitted to seek marketing approval for a new drug after Phase III trials. It contains extensive data from nonclinical studies, clinical trials, and information on manufacturing. An ANDA can be submitted for a generic drug to demonstrate equivalence to an approved brand name
Investigational medical product dossierSachinFartade
Investigational medical product dossier is document made to apply for clinical trial application in European Union. European Medical Agency is regulatory body for drug approval in European Union.
CMC, post approval regulatory affairs, etcJayeshRajput7
this document covers points such as CMC, post approval regulatory affairs, regulation for combination products, and medical devices, common technical document (CTD) and electronic common technical document (eCTD) format, industry and FDA liasion, ICH guidelines of ICH Q,S,E,M, regulatory requirements of EU, MHRA, TGA and ROW countries.
M.pharm (Pharmaceutics) modern pharmacy unit-5 Study of consolidation parameters; Diffusion parameters, Dissolution
parameters and Pharmacokinetic parameters, Heckel plots, Similarity factors – f2
and f1, Higuchi and Peppas plot, Linearity Concept of significance, Standard
deviation , Chi square test, students T-test , ANOVA test
GLOBAL SUBMISSION OF IND, NDA, ANDA.pdfLokeshThakre6
It's important to note that the specific requirements and processes for INDs, NDAs, and ANDAs may vary between regulatory authorities in different countries. The descriptions provided here are general and based on the common practices in the United States.
Investigational medical product dossierSachinFartade
Investigational medical product dossier is document made to apply for clinical trial application in European Union. European Medical Agency is regulatory body for drug approval in European Union.
CMC, post approval regulatory affairs, etcJayeshRajput7
this document covers points such as CMC, post approval regulatory affairs, regulation for combination products, and medical devices, common technical document (CTD) and electronic common technical document (eCTD) format, industry and FDA liasion, ICH guidelines of ICH Q,S,E,M, regulatory requirements of EU, MHRA, TGA and ROW countries.
M.pharm (Pharmaceutics) modern pharmacy unit-5 Study of consolidation parameters; Diffusion parameters, Dissolution
parameters and Pharmacokinetic parameters, Heckel plots, Similarity factors – f2
and f1, Higuchi and Peppas plot, Linearity Concept of significance, Standard
deviation , Chi square test, students T-test , ANOVA test
GLOBAL SUBMISSION OF IND, NDA, ANDA.pdfLokeshThakre6
It's important to note that the specific requirements and processes for INDs, NDAs, and ANDAs may vary between regulatory authorities in different countries. The descriptions provided here are general and based on the common practices in the United States.
For better understanding of students. This will give you a detailed explanation of IND APPLICATION. Contact me through comment section if you need any assistance in understating this topic.
INTRODUCTION
IND TYPES
IND CATEGORIES
THE IND APPLICATION MUST CONTAIN INFORMATION IN THREE BROAD AREA
THE REGULATORY ENVIRONMENT AND FDA ROLE
LIST OF IMPORTANT SECTIONS
GENERAL PRINCIPLES
INVESTIGATIONAL NEW DRUG GUIDANCE AND PLANNING
FDA FORM 1571
FDA FORM 1572
FDA FORM 3674
SUBMITTING AN IND
FOLLOWING RECEIPT OF IND BY THE FDA
RESPONDING TO A CLINICAL HOLD
REGULATORY REQUIREMENTS FOR AN IND DURING STUDY AND AT COMPLETION
PROTOCOL AMENDMENTS (21 CFR 312.30)
INFORMATION AMENDMENTS (21 CFR 312.31)
SAFETY REPORTS (21 CFR 312.32)
ANNUAL REPORTS (21 CFR 312.33)
WITHDRAWAL, TERMINATION, AND INACTIVATION
MONITORING RESPONSIBILITIES FOR SPONSOR-INVESTIGATORS
This Slide explains US-FDA requirements for IND. It will answer; What is an IND ?What are the IND Phases ?What is the IND Content?When FDA Terminates an IND ?Are cGMP Required for IND ?What Studies are exempt from IND?
The United States Food and Drug Administration's Investigational New Drug (IND) program is the means by which a pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug across state lines (usually to clinical investigators) before a marketing application for the drug has been approved. Regulations are primarily at 21 C.F.R. 312. Similar procedures are followed in the European Union, Japan, and Canada
An Investigational New Drug Application (IND) is a request from a clinical study sponsor to obtain authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans
This powerpoint presentation includes all the details regarding the topic Drug approval process with special procedure of Drug approval process in India.
Preformulation Studies: Introduction to preformulation, goals and objectives, study of
physicochemical characteristics of drug substances.
a. Physical properties: Physical form (crystal & amorphous), particle size, shape, flow
properties, solubility profile (pKa, pH, partition coefficient), polymorphism.
b. Chemical Properties: Hydrolysis, oxidation, reduction, racemisation, polymerization
BCS classification of drugs & its significant
Application of preformulation considerations in the development of solid, liquid oral and
parenteral dosage forms and its impact on stability of dosage forms.
Extraction, isolation and structure elucidation of lignans(podophyllotoxin)Mohammad Khalid
Extraction, isolation and structure elucidation of- Lignans(Podophyllotoxin)
Introduction
Extraction and Isolation
Identification test
Sructure elucidation of Podophyllotoxin
Adverse Effects
Extraction, isolation and structure elucidation of flavonoids: QuercetinMohammad Khalid
Extraction, isolation and structure elucidation of- Flavonoids Quercetin
Introduction
FLAVONOIDS & THEIR EXAMPLES
Quercetin
general isolation method
Extraction and isolation
Extraction from neem leaves
Isolation of Quercetin Methanolic Extract of Azadirachta indica leaves
Structure elucidation of Quercetin
Health benefits
Side Effects of Quercetin
Brief introduction to Agmark, BIS and FSSAI
Introduction (AGMARK)
Objectives of Agmark Scheme
Requirement of Agmark Application Proceedings
Advantages of agmark
Bureau of Indian Standards (B.I.S)
Structure of BIS/ Members of BIS
OBJECTIVES and FUNCTIOS OF BIS
Food Safety and Standards Authority of India (FSSAI)
NEED OF FSSAI
Functions of fssai
FSSAI Structure
Landmark cases with FSSAI
Differences between agmark and fssai
Extraction , Isolation and Structure Elucidation of DigoxinMohammad Khalid
Introduction
Mechanism of Action
Pharmacokinetics
Indication
Administration
Contraindication and Precaution
Use cautiously in
Adverse Effects
Extraction and Isolation of Digoxin
CHEMICAL TESTS
Structure Elucidation
Testing of neutraceuticals and food products
Introduction
Testing of microbial load
Bioburden Test
Total Aerobic Microbial Count
Total combined yeast and molds count
Testing of nutritional value
Laboratory based nutraceutical Analysis
Testing of heavy metals
Calorific Value
Nutraceutical label claim testing
Packaging, Label claims. Regulatory aspects of nutraceutical products in India.Mohammad Khalid
Packaging,
label claims.
regulatory aspects of nutraceutical products in India.
INTRODUCTION (Packaging)
TYPES OF PACKAGING
Objective of Packaging
Consideration for packaging
FUNCTIONS OF PACKAGING
Factors for package design in international market
Introduction (Labelling)
Function of labels
Objective of labeling
Which Information Is Mandatory
Contents in a Nutraceutical label
Definition of Nutrition Claim/s
Definition of Health Claim/s
New FDA Labeling Requirements
Regulation of Nutraceuticals in India
Food Safety and Standards Authority of India (fssai)
Regulatory Requirements in India
Registration Process in India
Functional food & Phytonutrients
Definition
Examples of some functional food worldwide
Functional Food Components
Concept of functional foods
Cereals as functional food
Legumes as functional foods
Vegetables as functional food
Fruits as functional foods
Probiotics as functional food
Functional food and fortification
Phytonutrients
General functions of phytonutrients
Various Phytochemicals
Mechanisms of action of Phytonutrients
Fortified Food
Introduction
enriched food
Who will benefit from fortified foods
Purpose of food fortification
Iodine deficiency disorders
Fortification of flour
Main methods of food fortification
Fortification prevents and treats iron deficiency and nutritional anaemia
Criticism (Side Effect)
Future Challenges of Food Fortification
Reserpine(Structure Elucidation, Extraction and Isolation)Mohammad Khalid
Reserpine(Structure Elucidation, Extraction and Isolation)
Introduction
Constitution of reserpine
Structure of Reserpic acid
Structure of Yobyrine
Synthesis of Yobyrine
Structure of Reserpine
Synthesis of Reserpine
Classification
Extraction
Isolation:
Identification test
Mode of Action
dietary supplements
Overview on supplements
Definition
Facts about Supplements
Should you be taking supplements?
What about protein powders?
Regulation of dietary Supplements
Dietary Supplement and Health Education Act
ICH STABILITY TESTING GUIDELINES, Drug Stability, Stability studies are preformed on Drug Stability (DS)
Drug product (DP), TYPE SIZE, NUMBER OF BATCHES (ICH/WHO GUIDELINES), LONG TERM STABILITY STUDIES, ACCELERATED STABILITY STUDIES, PROTECTION AGAINST HYDROLYSIS, PROTECTION AGAINST OXIDATION, Testing scope for solid dosages, Testing scope for liquid form, Testing scope for oral liquid form
Good Laboratory Practices, Protocol, Contents of protocol, Conduct of a non-clinical laboratory study, Reporting of non-clinical laboratory study results,
Schedule T – Good Manufacturing Practice of Indian systems of medicine
Components of GMP (Schedule – T) and its objectives
Infrastructural requirements, working space, storage area, machinery and equipments,
standard operating procedures, health and hygiene, documentation and records.
INTRODUCTION
Components of GMP
GMP Provisions: Under Schedule-T are grouped
Location and surroundings
Factory Premises
Buildings
Water supply
Containers cleaning
Disposal of Waste
Requirements for the sterile products
store
Working space:
Space requirement for manufacturing of Unani medicine
Health & Hygiene
Machinery and Equipments
Machinery and equipments for maufacturing of ayurveda and siddha medicine
Documentation and Records
Herbs, Herbal Drugs
Present Scope of Herbal Drug Industry
Scope of Herbal Drug Medicine and Industry
Indian Herbal Industry
International Scope of Herbal Medicines
World Wide Herbal Trade
Overview on plant based industries and research institutions in India
List of few herbal drug industries in India
List of few herbal research institution/ centres in India
General Introduction to Herbal Industry
Herbal drugs industry: Present scope and future prospects.
A brief account of plant based industries and institutions involved in work on medicinal and
aromatic plants in India.
Regulations in India (ASU DTAB, ASU DCC), Regulation of
manufacture of ASU drugs - Schedule Z of Drugs & Cosmetics Act for ASU drugs.
Introduction
Regulatory Requirements
Key function of regulatory agencies
Regulation in India
DRUG TECHNICAL ADVISORY BOARD
Drugs Consultative committee-DCC
Schedule Z of Drugs & Cosmetics Act for ASU drugs.
Patenting aspects of traditional knowledge and natural products(curcuma & neem)Mohammad Khalid
Patenting aspects of Traditional Knowledge and Natural Products. Case study of Curcuma
& Neem.
Introduction
Meaning Of Traditional Knowledge
Patents And Traditional Knowledge In India
Traditional Knowledge In Danger
Turmeric Patent
Neem Patent
WHAT INDIA NEEDS TO DO?
Introduction
Concept of Bioprospecting
Why is it needed
Process of Bioprospecting
Who does bioprospecting
Added potential environmental impacts of Bioprospecting
Key issues & challenges
Lack of legal clarity
Greater sector involvement:
A comprehensive bioprospecting policy
Definition of biopiracy
History of biopiracy
Types of Biopiracy
How does it happens?
Famous Cases of biopiracy
Why is There a Need to Stop Biopiracy ?
Actions Taken Against Biopiracy
Conclusion
Good Laboratory Practices: General Provisions, Organization and Personnel, Facilities,
Equipment, Testing Facilities Operation, Test and Control Articles, Protocol for Conduct
of a Nonclinical Laboratory Study, Records and Reports, Disqualification of Testing
Facilities
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
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
- 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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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!
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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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.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
Global submission of ind, nda, anda
1. Global Submission of IND, NDA, ANDA
Mohammad Khalid
Associate Professor
Krishna Pharmacy College, Bijnor
2. INTRODUCTION
An Investigational New Drug Application (IND) is a
submission to the Food and Drug Administration
requesting permission to initiate a clinical study of a
new drug product.
The IND application allows a company to initiate and
conduct clinical studies of their new drug product.
The IND application provides the FDA with the data
necessary to decide whether the new drug and the
proposed clinical trial pose a reasonable risk to the
human subjects participating in the study.
3 February 2022 MOHAMMAD KHALID
3. Investigational New Drug is defined under 21
CFR 312.3(b) as ‘a new drug or biological drug
that is used in clinical investigation’.
The term also includes a biological product used
in vitro for diagnostic purposes.
After pre-clinical investigations when the new
molecule has been screened for pharmacological
activity and acute toxicity potential in animals the
sponsor requires permission from FDA for its
clinical trials in humans.
3 February 2022 MOHAMMAD KHALID
4. The sponsor submits the application for conduct of
human clinical trials called Investigational New
Drug (IND) application to FDA or DCGI.
Once IND application is submitted, the sponsor must
wait for 30 days before initiating any clinical trial.
Clinical trials in humans can begin only after IND is
reviewed by the FDA and a local institutional review
board (IRB).
IRBs approve clinical trial protocol, informed
consent of all participants and appropriate steps to
prevent subjects from harm.
3 February 2022 MOHAMMAD KHALID
5. If the FDA accepts the IND request within 30 days
of submission, clinical testing of the new molecule
on human may begin by the investigator.
At this point, the molecule under the legal status of
FDA becomes a new drug subject to specific
requirements of drug regulatory system.
If at any time during clinical testing, the data
furnished to FDA indicate the IP to be toxic under
the criterion of FDA’s Benefit/Risk ratio, FDA can
terminate clinical trial and its actions are not subject
to any judicial review.
3 February 2022 MOHAMMAD KHALID
6. WHEN DO I NEED AN IND?
An IND is required any time you want to
conduct a clinical trial of an unapproved
drug.
The Act further defines a new drug, in part,
as “any drug the composition of which is
such that such drug is not generally
recognized as safe and effective for use
under the conditions prescribed,
recommended, or suggested in the labeling.
3 February 2022 MOHAMMAD KHALID
7. WHEN YOU DON’T NEED
AN IND?
An IND is not required to conduct a study if
the drug:
Is not intended for human subjects, but is
intended for in vivo testing or laboratory
research animals (non clinical studies)
Is an approved drug and the study is within
its approved indication for use.
3 February 2022 MOHAMMAD KHALID
8. Types of INDs:
A. COMMERCIAL INDs
These are applications that are submitted primarily by the
companies to obtain marketing approval for a new product.
B. NONCOMMERCIAL (Research) INDs
These INDs are filed for noncommercial research. These are:
Investigator’s IND- It is submitted by a physician who both
initiates and conducts an investigation and who also
administers and dispenses the IP. A physician might submit a
research IND to propose studying an unapproved drug or an
approved drug for new indications or in new patient
population.
3 February 2022 MOHAMMAD KHALID
9. Emergency Use IND-This IND allows FDA to
allow the use of an experimental drug in an
emergency situation that does not allow submission
of an IND in accordance with 21 CFR Sec312.23 or
Sec 312.34. It can also be used for patients who do
not meet the criteria of an existing study protocol or
if an approved study protocol does not exist.
Treatment IND- Also called Expanded Access
IND this IND may be submitted for experimental
drugs showing promise in clinical testing of serious
and immediately life threatening conditions while
the final clinical work is conducted and the FDA
review takes place (21 CFR 312.34).
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11. The IND application must contain
information in 3 broad areas:
Animal Pharmacology and toxicology studies-
Preclinical data to assess if the product is
reasonably safe for initial testing in humans. Also ,
included are any previous with drug in humans.
Manufacturing information- Information
pertaining to composition, manufacturer, stability
and controls used for manufacturing drug product
to ensure that the company can adequately
produce and supply consistent batches of the drug.
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12. Clinical Protocol and Investigator information
Detailed protocols for proposed clinical studies to
make sure subjects are not exposed to undue risks.
Also, information on the qualifications of the
investigators (chiefly physicians) if they fulfill
their clinical duties.
Finally, commitments to obtain informed consent
from all research subjects, to obtain review of the
study by an IRB and to adhere to the
investigational new drug regulations.
An IND must also include The Investigator’s
brochure.
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13. Guidance Documents for INDs:
1. Guidance for Industry: CGMP's for Phase 1 Investigational
Drugs
2. Guidance for Industry: Exploratory IND Studies
3. Content and Format of Investigational New Drug Applications
(INDs) for Phase 1 Studies of Drugs Including Well
Characterized, Therapeutic, Biotechnology- Derived Products.
4. Q & A - Content and Format of INDs for Phase 1 Studies of
Drugs, Including Well-Characterized, Therapeutic,
Biotechnology-Derived Products. This guidance is intended to
clarify when sponsors should submit final, quality-assured
toxicology reports and/or update the Agency on any changes
in findings since submission of non-quality-assured reports or
reports based on non-quality-assured data.
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14. 5.Bioavailability and Bioequivalence Studies for
Orally Administered Drug Products –
6.IND Exemptions for Studies of Lawfully Marketed
Drug or Biological Products for the Treatment of
Cancer.
7.Drug Master Files: A Drug Master File (DMF) is a
submission to the Food and Drug Administration
(FDA) that may be used to provide confidential
detailed information about facilities, processes, or
articles used in the manufacturing, processing,
packaging, and storing of one or more human
drugs.
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15. Criteria for IND application
A clinical study is required for an IND if it is
intended to support :
A new indication
Change in the approved route of administration or
dosage level.
Change in the approved patient population
(vulnerable subjects e.g. pediatrics, elderly, HIV
+ve, immunocompromised)
Significant change in the promotion of an
approved drug.
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17. Format and content of IND
1. Cover sheet (Form FDA 1571).
2. A table of contents.
3. Introductory statement and General Investigational
Plan.
4. Investigator’s Brochure.
5. Protocols.
6. Chemistry, Manufacturing and Control information.
7. Pharmacology and Toxicology Information.
8. Previous human experience with IP.
9. Additional Information.
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18. WITHDRAWAL OF an IND
At any time a sponsor can withdraw an
effective IND . In such a case, FDA and
IRB shall be so notified with reasons for
withdrawal, all clinical studies ended, all
current investigators and subjects notified,
all stocks of drug returned to the sponsor or
otherwise disposed off on request of
sponsor in accordance with 312.59.
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19. IND PROCESS IN INDIA:
IND has been defined under Rule 122-DA (3) of
Drugs and Cosmetics Rules 1945 as a chemical entity
having therapeutic indication but which have never
been earlier tested on humans.
No clinical trial for new drug for any purpose be
conducted without permission, in writing, of the
Licensing Authority (DCGI).
Application for conducting clinical trials in India
require submission by the sponsor on Form 44 along
with requisite fee (Rs 50k) and documents as provided
under Schedule Y to Drugs and Cosmetics Act 1940
3 February 2022 MOHAMMAD KHALID
20. Data to be submitted along with the application on
Form44 to conduct clinical trials (2 hard copies and 2 soft
copies i.e., CDs in PDF format)
1. Application on Form 44
2. Introduction of the drug
3. Fee Rs 50K through challan form
4. Chemical and Pharmaceutical information as per
Appendix I of Schedule Y
5. Animal Pharmacology as per Appendix IV
6. Animal Toxicology as per Appendix III
7. Human/Clinical Pharmacology data as per Appendix I
8. Regulatory status in other countries as per Appendix I.
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21. After receiving the
application, the Central drug
standard control organization
(CDSCO) Headquarters in
New Delhi refers it to
The New Drug division where it
is reviewed by IND committee.
The Committee submits its
report to
To DCGI along with its
recommendations. If the report
by Committee is favorable,
DCGI approves the INDA.
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22. It takes 4-6 months for the approval but it is
not documented. The Ethical Committee
also requires 1-3 months time. Thus, it
almost takes 7-9 months for approval of
INDA from DCGI.
For international applicants, import license
to import IP samples and permission from
Director General Foreign Trade to export
blood samples is also needed.
3 February 2022 MOHAMMAD KHALID
24. NEW DRUG APPLICATION (NDA)
The New Drug Application is the vehicle through
which the drug sponsors formally propose FDA or
DCGI to approve a new investigational drug for sale
and marketing after Phase IIIA Pivot trials.
The official definition of New Drug is in Sec 201(p)
of Federal Drug, Food and Cosmetics Act as;
Any new drug , the composition of which is such that
it is not recognized among experts qualified by
scientific training as safe and effective for use under
prescribed, recommended or suggested conditions.
OR
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25. Any drug the composition of which is such that it
as a result of investigations to determine safety
and efficacy for use has become recognized, but
which has not, otherwise in such investigations
been used to a material extent .
The following letter codes describe the review
priority of the drug;
S-Standard review: For drugs similar to currently
available drugs
P-Priority review: For drugs that represent
significant advances over existing treatments.
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26. Classification of drugs in NDA
Center of drug evaluation and Research(CDER) classifies
new drug applications according to the type of drug being
submitted and its intended use:
A. New molecular entity
B. New salt of previously approved drug
C. New formulation of previously approved drug
D. New combination of two or more drugs
E. Already marketed drug product- Duplication (i.e., new
manufacturer)
F. New indication (claim) for already marketed drug (includes
switching marketing status from prescription to OTC)
G. Already marketed drug product ( no previous approved NDA)
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27. In US following 4 types of applications are
submitted for approval of drug for marketing
depending upon the type and nature of the
drug:
A. New Drug Application (NDA)
B. Biological License Application (BLA)
C. Application u/s 505(b)(2)-Paper NDA
D. Supplemental New Drug Application (SNDA)
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28. Format and content of NDA
The application is required to be submitted in
common technical document format with the
following different sections:
i. FDA Form 356h
ii. User Fee Cover Sheet (FDA Form 3397)
iii. Cover letter (Comprehensive table of contents for
Modules 1to 5)
iv. Summary
v. Chemistry, Manufacturing and Control
vi. Samples, Method Validation Package and Labeling
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29. vii. Nonclinical Pharmacology and Toxicology
viii. Human Pharmacokinetics and Bioavailability
ix. Microbiology (For anti-microbial drugs only)
x. Statistical methods and analysis of Clinical Data
xi. Safety Update Report (typically submitted 120
days after NDA submission)
xii. Statement regarding compliance to IRB and
Informed Consent requirements
xiii.Case Report Tabulations
xiv.Case Report Forms
xv. Patent information and certification
xvi.Other information.
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30. General requirements for filing NDA
The new NDA regulations require the application to
be submitted in 2 copies:
A. An Archival Copy- It is a complete copy of
application submission that serves as its permanent
record.
B. A Review Copy-It is divided into 6 technical
sections:
i. Chemistry , Manufacturing and Controls (CMC)
ii. Nonclinical Pharmacology and Toxicology
iii. Human Pharmacokinetics and Bioavailability
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31. iv. Microbiology (if required)
v. Clinical data
vi. Statistical
On receipt of NDA, the CDER stamps with a receipt date
to enable FDA to forward action within 180 days called
‘Review Clock’ under Review Time Frames (21CFR
314.1OO). The FDA assigns the application for review.
The FDA has to intimate the applicant if it is incomplete
within 60 days according to Filing Time Frames (21CFR
314.101).
FDA notifies the sponsor of its completion/ incompletion
and if complete sends it for secondary review process.
FDA inspects the manufacturing facilities for the drug, It
may also inspect sample of clinical trial locations to verify
the accuracy of data submitted.
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33. Throughout the process FDA and sponsor
communicate through in person meetings,
telephone conferences, fax etc. to seek
clarification if necessary. Once all reviews are
complete; the Divisional Director evaluates the
reviews and makes FDA’s decision. The FDA
may:
Approve the drug for marketing.
Approve the drug with condition when problem
exist with the application that needs to be
addressed before approval.
Refuse to approve the drug, when it may require
additional research or reformulation of the drug
product. 3 February 2022 MOHAMMAD KHALID
34. NDA PROCESS IN INDIA
In India, New Drug is defined under Rule 122-E of
Drugs and Cosmetics Act as:
a) A drug which has not been used in the country to
any significant extent under various conditions b) A
drug already approved by DCGI for certain claims
which is now proposed to be marketed with new
claims like indications, dosage, dosage form etc.
c) A fixed dose combination of two individually
approved drug being combined for the first time in a
fixed ratio or new ratio in already marketed
combination.
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35. d) All vaccines are considered as new drugs.
e) A new drug continues to be considered as new
drug for a period of 4 years from its approval or its
inclusion in Indian Pharmacopoeia.
After successful finishing of clinical trials, the
applicant seeking for approval to manufacture a
new drug requires to submit application on Form
44 along with data as given in Appendix I to
Schedule Y of Rules 1945 to DCGI who grants its
approval in Form 46 or 46-A.
Further, the applicant is required to submit
evidence that the drug for manufacturing approval
has already been approved by DCGI
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36. In his name while applying to manufacture
a new drug to State Licensing Authority.
Thus the applicant is required to obtain
necessary approval from DCGI as well as
SLA for manufacturing a new drug for sale
purposes in India.
The approval issued is ‘manufacture for
sale’ rather than ‘marketing approval’ as per
the practice world over.
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37. PERMISSION TO MANUFACTURE
A NEW DRUG:
Brief introduction of the new drug
Chemical and pharmacological information
Animal pharmacology and Toxicology
Human/ Clinical Pharmacology (Phase I)
Exploratory Clinical Trials (Phase II)
Confirmatory Clinical Trial s(Phase III)
Bio-availability, dissolution and stability study data
Regulatory status in other countries
Application for test license
Marketing information.
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39. ABBREVIATED NEW DRUG
APPLICATION (ANDA)
Generic drug applications are referred to Abbreviated New
Drug Application.
Pharmaceutical companies must admit ANDAs and receive
FDA’s approval before marketing new generic drugs
according to 21CFR 314.105(d).
Once ANDA is approved, an applicant can manufacture
and market generic drug to provide safe, effective and low
cost alternative of innovator drug product to the public.
Generic drugs are termed ‘abbreviated’ as they are not
required to include preclinical and clinical data to establish
safety and efficacy. They must scientifically demonstrate
Bioequivalence to Innovator (brand name) drug.
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40. A generic drug is comparable to Innovator drug I dosage
form, strength, route of administration, quality,
performance and intended use.
One of the ways to demonstrate bioequivalence is to
measure the time taken by generic drug to reach
bloodstream in 24-36 healthy volunteers. The time and
amount of active ingredients in the bloodstream should be
comparable to those of Innovator drug.
Use of bioequivalence as base for approving generic drug
products was established in 1984, also known as
WAXMAN-HATCH ACT. It is because of this act that
generic drugs are cheaper without conducting costly and
duplicative clinical trials
3 February 2022 MOHAMMAD KHALID
41. CODE OF FEDERAL REGULATIONS
The following regulations apply to ANDA process:
21 CFR 314- Applications for FDA approval to
market a New Drug or Antibiotic Drug
21 CFR 320- Bioavailability and Bioequivalence
requirements
21 CFR 310- New Drugs.
Office of Generic Drug(OGD) strongly encourages
submission of bioequivalence, chemistry and
labeling portions of the application in electronic
format.
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42. FORMAT AND CONTENT OF ANDA
3 copies of the Abbreviated application are required
to be submitted; an archival copy, a review copy and
a field copy. An Archival copy shall contain the
following:
Application form
Table of Contents
Basis for ANDA submission
Conditions of use
Active Ingredients
Route of Administration
Dosage form and Strength
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43. Bioequivalence and Bioavailability
Labeling
Chemistry, Manufacturing and Controls
Samples
Patent Certification
Financial Certification or disclosure statement.
Other Information.
Under Sec 314.94 (a) (12), the patent certification
includes one of the following:
I. Paragraph I Certification- That the patent
information has not been submitted to FDA
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44. II. Paragraph II Certification- That the patent
has expired
III. Paragraph III Certification- That the
patent will expire (on date of marketing)
IV. Paragraph IV Certification- That the
patent is invalid, unenforceable, or will not
be infringed by manufacture, use or sale of
generic drug.
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46. Difference between submission
of NDA and ANDA
NDA requires submission of :
Well-controlled clinical studies to demonstrate effectiveness.
Preclinical and clinical data to show safety.
Details of Manufacturing and Packaging.
Proposed annotated Labeling
In contrast ANDA requires submission of :
Detailed description of components.
Manufacturing, Controls, Packaging, data to assure
bioequivalence and bioavailability and Labeling. Labeling should
be prepared in accordance with DESI (Drug efficacy study
implementation)
3 February 2022 MOHAMMAD KHALID
47. EXCLUSIVITY
Exclusivity is a statutory provision designed to
promote a balance between an Innovator and Generic
drug competitor. As long as a drug patent lasts , a
reference listed drug company enjoys a period of
market exclusivity or monopoly. Expiration of patent
removes the monopoly of the patent holder.
TERMS OF EXCLUSIVITY •
Orphan drugs---------- 7 years
New Chemical Entity----------5 years
Pediatric Exclusivity---------6 months additional
Patent Challenge----------180 days.
3 February 2022 MOHAMMAD KHALID
48. Hatch-waxman amendments
and 180 days exclusivity.
Before Hatch Waxman Amendment, generic
manufacturer could file ANDA only after
innovator’s patent expiry or cancellation. But under
Sec 505(j)(5)(B) of Hatch Waxman amendment it
permits preparation and filing of ANDA before
patent expiration, so that the effective approval date
of generic drug would be on expiration date of the
patent of Innovator Original drug.
The Act also establishes another procedure in which
the generic company can challenge patent of the
Innovator.
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49. For generic companies, the amendment provide
an inventive 180-day exclusivity period in which
no other ANDA for that drug can be approved.
This 180-day period is to encourage generic
companies to challenge validity of Orange book
listed patents or to design around these patents to
bring more quickly a generic drug to market.
For Innovator company, filing of an ANDA is an
act of patent infringement. So, if innovator
company brings suit within 45 days, the approval
of generic company’s ANDA is delayed for upto
30 months.
3 February 2022 MOHAMMAD KHALID