The document discusses the process of drug development from discovery through clinical trials and regulatory approval. It begins with an overview of the iterative process involving biology, animal testing, and medicinal chemistry. It then outlines the typical 5 steps in drug development according to the FDA: discovery/screening, pre-clinical research including in vitro and in vivo testing, clinical research consisting of Phase I-III trials, FDA review, and post-marketing monitoring. The document provides details on each stage of development including pre-clinical and clinical research requirements and processes.
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
The safety monitoring in a clinical trail accompanies by common practices in safety monitoring, communicating safety information among stakeholders in a clinical trail.
Clinical study on human subjects according to all guidelines to form a ideal protocol and requirement to conduct clinical trial with very efficient way mainly considering to India and ICH associated countries
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
The safety monitoring in a clinical trail accompanies by common practices in safety monitoring, communicating safety information among stakeholders in a clinical trail.
Clinical study on human subjects according to all guidelines to form a ideal protocol and requirement to conduct clinical trial with very efficient way mainly considering to India and ICH associated countries
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.
Setting up of new pharmacovigilance centresPriti Gupta
this is just an overview of the setting up of pharamcovigilance with fake name of company and product. budget is also an imagination. there is not exact representation of the actual situation.
clinical and preclinical approaches to drug discovery.Here we mainly deals with preclinical approaches, ie. Pharmacological approach and toxicological approach
The Investigator's Brochure (IB) is a comprehensive document summarizing the body of information about an investigational product (IB) obtained during a drug trial.
Requirements And Guidelines For Permission To Import / or Manufacture of New Drugs For Sale or To Undertake Clinical Trials
Schedule Y was introduced under the Drugs and Cosmetics Act 1940, to
introduce requirements for countries to get permission for:
Importing
Manufacturing new drugs
Conducting Clinical Trials.
Application for permission
Clinical Trial
Studies in specific population
Post marketing surveillance
Special studies: BA/BE studies
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.
Setting up of new pharmacovigilance centresPriti Gupta
this is just an overview of the setting up of pharamcovigilance with fake name of company and product. budget is also an imagination. there is not exact representation of the actual situation.
clinical and preclinical approaches to drug discovery.Here we mainly deals with preclinical approaches, ie. Pharmacological approach and toxicological approach
The Investigator's Brochure (IB) is a comprehensive document summarizing the body of information about an investigational product (IB) obtained during a drug trial.
Requirements And Guidelines For Permission To Import / or Manufacture of New Drugs For Sale or To Undertake Clinical Trials
Schedule Y was introduced under the Drugs and Cosmetics Act 1940, to
introduce requirements for countries to get permission for:
Importing
Manufacturing new drugs
Conducting Clinical Trials.
Application for permission
Clinical Trial
Studies in specific population
Post marketing surveillance
Special studies: BA/BE studies
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.
Overview of Pharmacovigilance by Yash Dhikale | Zumbar Pote | Santosh Ghuge |...ijtsrd
Clinical research is an essential component of medical advancement, focusing on understanding health and disease to enhance healthcare practices. This exploration encompasses clinical trials, classified into interventional studies and observational studies. Interventional studies, or clinical trials, involve assigning participants interventions to evaluate their effects on health outcomes. These interventions can range from drugs to surgical procedures or preventive care. Clinical trials progress through four phases, ensuring safety and efficacy before widespread implementation. The International Clinical Trials Registry Platform ICTRP , a global initiative by WHO, facilitates comprehensive and accessible information on human clinical trials. ICTRP strives to enhance data accuracy, raise awareness about trial registration, and promote data utilization. This collaborative effort fosters transparency, benefiting not only researchers but also patients, families, and the broader healthcare community. Yash Dhikale | Zumbar Pote | Santosh Ghuge | Shital B. Thakre | Dipali S. Shegar "Overview of Pharmacovigilance" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63464.pdf Paper Url: https://www.ijtsrd.com/pharmacy/other/63464/overview-of-pharmacovigilance/yash-dhikale
process of discovery of a new drug
what are clinical trials
why clinical trials are conducted
overview of phases in a clinical trial
details about every phase
focus and purpose of conducting clinical trial
Similar to Drug Development and Clinical Studies (20)
Pharmacovigilance (PV) is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. Information received from patients and healthcare providers via pharmacovigilance reporting form as well as other sources such as the medical literature, plays a critical role in providing the data necessary for pharmacovigilance to take place.
GMP is the part of Quality Management which ensures that the products are consistently produced and controlled to the quality standard appropriate to their intended use as required by the marketing authorization and product specification.
(Ref. WHO)
The pharmaceutical quality system “assures that the desired product quality is routinely met, suitable process performance is achieved, the set of controls are appropriate, improvement opportunities are identified and evaluated, and the body of knowledge is continually expanded...
Good Manufacturing Practice for Pharmaceutical Products.pdfMd. Zakaria Faruki
According to the WHO-
"GMP is the part of Quality Management which ensures that the products are consistently produced and controlled to the quality standard appropriate to their intended use as required by the marketing authorization and product specification".
CAREER OPPORTUNITIES OF PHARMACY GRADUATES IN THE PHARMACEUTICAL INDUSTRIES.pdfMd. Zakaria Faruki
Pharmacy is a very important profession, which deals with the manufacturing, handing, proper utilization, dispensing, and administration of life saving drugs.
Training means the process of increasing the knowledge and skills of an employee for doing a particular job. It seeks to improve the job performance and work behaviour of those trained.
Process validation is defined as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products.
The U.S. Food and Drug Administration (FDA) has proposed guidelines with the following definition for process validation: – “PROCESS VALIDATION” is establishing documented evidence which provides a high degree of assurance that a specific process consistently produces a product meeting its predetermined specifications and quality attributes.
Workshop on General Accident Prevention at The workplaces.pdfMd. Zakaria Faruki
Providing a safe environment for employees is one of the most important responsibilities of a management team. In industries with inherent risks, like construction and mining, it's crucial that employees understand and follow the proper safety protocols.
In addition, preventing job accidents call for various strategies. The organization should have a comprehensive education of the workers, proper risk management, introducing safety alerts in the establishments, security leaders, and ensuring that the workers are in a stable psychological and mental state.
Moreover, developing and enforcing safety plans in the organization can provide greater peace of mind for employees and help prevent accidents and injuries. In this Workshop, we discussed what accident prevention in the workplace is and provide tips for maintaining a safe workplace.
Therefore, please follow the safety guidelines accordingly to prevent the accident in the workplace.
The personnel is the most important asset of a company, and the easiest to neglect. The establishment and maintenance of a satisfactory system of quality assurance and GMP relies upon people who develop the system, the people who use the system and the people who examine the system to see if it has worked.
The technical people must have a knowledge and understanding of GMP to enable them to carry out their duties in accordance with GMP. These people must have the level of training and experience that will enable them to do their professional works respectively.
According to US FDA it is illustrated here that,
A recall is a method of removing or correcting products that are in violation of laws administered by the Drug Regulatory Authority.
Recall is a voluntary action that takes place because manufacturers and distributors carry out their responsibility to protect the public health and well-being from products that present a risk of injury or gross deception or are otherwise defective.
21 CFR 7 provides guidance so that responsible firms may conduct an effective recall.
Market or Customer complaint is “an expression of dis-satisfaction on a customer’s behalf to a responsible party” when their expectations have not been met! However, Complaint handling is a Good Manufacturing Practice (GMP) requirement, since all complaints concerning potentially defective products must be carefully reviewed according to a written procedure.
Good Documentation Practice (GDocP) is an essential part of the quality assurance and such, related to all aspects of GMP” this definition is based on WHO. It is a systematic procedure of preparation, reviewing, approving, issuing, recording, storing and archival of document.
GMP is the part of Quality Management which ensures that the products are consistently produced and controlled to the quality standard appropriate to their intended use as required by the marketing authorization and product specification. (Reference: WHO)
In contrast, cGMP i.e. ‘c’ before the GMP is indicative of the constantly changing technologies and systems which are up-to-date in order to comply with the regulations. These the dynamic changes in Good Manufacturing Practice to make Pharmaceuticals manufacture foul proof; assuring a high level of confidence in the safety and efficacy of the product.
Bioequivalence is a term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug. If two products are said to be bioequivalent it means that they would be expected to be, for all intents and purposes, the same.
The first generation of biological drugs, which
have introduced many revolutionary treatments to life threatening and rare illnesses, is currently facing patent expiration. As a result, research-based and generics pharmaceutical companies alike are pursuing the opportunity to develop “generic” substitutes to original biologics, which are also known as biosimilars.
GCP: An international ethical and scientific quality standard for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects.
PV: The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.
Stability study of Pharmaceutical Products and Regulatory Requirements Md. Zakaria Faruki
A marketed product stability program fulfills registration
commitments and ensures that marketed product is
stable until expiry date stamped on product
label....
Stability studies should be planned on the
basis of pharmaceutical R&D and regulatory
requirements...
Post-marketing drug safety surveillance refers to the monitoring of drugs once they reach the market after clinical trials through a process which evaluates drugs taken by individuals under a wide range of circumstances over an extended period.
Pharmacovigilance is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems.
Quality must be built into the product, it cannot be inspected into it. The Pharmaceutical industries are experiencing a “knowledge and experience deficit” regarding the use of QbD concepts.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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.
- 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
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
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
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
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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!
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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
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
1. Trainer: Md. Zakaria Faruki
Orion Pharma Limited
Dhaka, Bangladesh
Training on
Drug Development &
Clinical Studies
OPL
Slide 1 of 25
2. Overview
Drug discovery is an iterative process. It goes back and forth between
theoretical biology; the necessary, appropriate, and humane use of
animal assays to determine a compound’s biological activity in the
body; and medicinal chemistry to optimize the compound. Then in
human studies, clinical observations test hypotheses about how a
candidate drug may target cancer cells; determine its safety and
effective doses; and compare its ability to shrink tumors or stop cancer
progression relative to standard therapy. The NIH generally helps fund
all stages of research up through phase II clinical trials, as indicated by
the red borders of some panels of the flowchart. While NIH also
supports some phase III clinical trials, this portion of the drug
development process is usually funded by industry and other private
organizations and is distinguished by blue borders. Because this process
is so rigorous, only four to seven percent of candidate drugs receive
approval from the Food and Drug Administration (FDA).
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
OPL
Slide 2 of 25
3. Drug Development Lifecycle
According to FDA 5 steps are involved in the drug
development which are-
Discovery / Screening
Pre-clinical Research
In-vivo,
in-vitro
Clinical Research
Phase I
Phase II
Phase III
Phase IV*
FDA Review
Post Marketing Monitoring*
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
OPL
Slide 3 of 25
5. Drug Discovery
Typically, researchers discover new drugs through:
New insights into a disease process that allow researchers to
design a product to stop or reverse the effects of the disease.
Many tests of molecular compounds to find possible beneficial
effects against any of a large number of diseases.
Existing treatments that have unanticipated effects.
New technologies, such as those that provide new ways to target
medical products to specific sites within the body or to
manipulate genetic material.
At this stage in the process, thousands of compounds may be
potential candidates for development as a medical treatment.
After early testing, however, only a small number of compounds
look promising and call for further study.
OPL
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki Slide 5 of 25
6. Development
Once researchers identify a promising compound for
development, they conduct experiments to gather
information on:
How it is absorbed, distributed, metabolized, and excreted.
Its potential benefits and mechanisms of action.
The best dosage.
The best way to give the drug (such as by mouth or
injection).
Side effects or adverse events that can often be referred to
as toxicity.
How it affects different groups of people (such as by
gender, race, or ethnicity) differently.
How it interacts with other drugs and treatments.
Its effectiveness as compared with similar drugs.
OPL
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki Slide 6 of 25
7. Pre-Clinical Research
In-Vitro In-Vivo
OPL
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki Slide 7 of 25
8. Pre-Clinical Research Contd..
Before testing a drug in people, researchers must find out whether it has the
potential to cause serious harm, also called toxicity. The two types of preclinical
research are In Vitro & In Vivo tests. FDA requires researchers to use good
laboratory practices (GLP), defined in medical product development
regulations, for preclinical laboratory studies. These regulations set the
minimum basic requirements for:
study conduct
personnel
facilities
equipment
written protocols
operating procedures
study reports and
a system of quality assurance oversight for each study to help assure the safety
of FDA-regulated product
Usually, preclinical studies are not very large. However, these studies must provide
detailed information on dosing and toxicity levels. After preclinical testing,
researchers review their findings and decide whether the drug should be tested
in people.
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
OPL
Slide 8 of 25
9. Investigational New Drug
(IND)
Drug developers, or sponsors, must submit an Investigational New Drug (IND)
application to FDA before beginning clinical research. In the IND
application, developers must include:
Animal Pharmacology and Toxicology Studies (side effects that cause great
harm) data
Manufacturing information
Clinical protocols (study plans) for studies to be conducted
Data from any prior human research
Information about the investigator
Then developers need to-
Asking for FDAAssistance
FDA IND Review Team: Project Manager, Medical Officer, Statistician,
Pharmacologist, Pharmakineticist, Chemist, Microbiologist
FDA Approval: The FDA review team has 30 days to review the original
IND submission. The process protects volunteers who participate in clinical
trials from unreasonable and significant risk in clinical trials.
OPL
Slide 9 of 25Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
10. Clinical Research
Human Testing: But unlike with animals; the sponsor cannot just go
ahead and run testing in humans without supervision
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
OPL
Slide 10 of 25
11. Clinical Research Contd…
OPL
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
While preclinical research answers basic questions about a drug’s safety, it is not
a substitute for studies of ways the drug will interact with the human body.
“Clinical research” refers to studies, or trials, that are done in people. As the
developers design the clinical study, they will consider what they want to
accomplish for each of the different Clinical Research Phases and begin the
Investigational New Drug Process (IND), a process they must go through before
clinical research begins. It is involved with following terms-
Designing Clinical Trials
Clinical Research Phase Studies
The Investigational New Drug Process
Asking for FDAAssistance
FDA IND Review Team
Approval
Slide 11 of 25
12. Clinical Trials
Researchers design clinical trials to answer specific research questions
related to a medical product. These trials follow a specific study
plan, called a protocol that is developed by the researcher or
manufacturer. Before a clinical trial begins, researchers review prior
information about the drug to develop research questions and
objectives. The clinical trails are-
Highly regulated
A panel of scientists, ethicists, and non scientists oversees each
clinical medical center
A protocol document must be presented and approved by the FDA,
the protocol is very detailed specifies everything about the study…
There are mainly four Clinical trails which are- Phase I, Phase II,
Phase III & Phase IV Studies.
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13. Case Report Form (CRF)
The collection of forms where all the clinical data is going
to be collected for a patient
Designed according to the protocol
A blank CRF is always submitted to the FDA for approval
before the trial must be run
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14. Phase I Clinical Trials
Phase I studies are primarily concerned with the drug's safety. These studies
are typically done in a small number of healthy volunteers (20-100), usually
in a hospital setting where they can be closely watched and treated should
there be any side effects. These volunteers are usually paid for their
participation and for the most part tend to be men (approximately 30 years
of age on average). The purpose of these studies is to determine how the
experimental drug is absorbed, metabolized, and excreted in humans.
Additionally, they seek to determine what types of side effects occur as the
dosage of the drug is increased. Any beneficial effects of the drug are also
noted.
Small number of healthy volunteers or patients
Assess the most common acute adverse effects
Examine the size of doses that patients can take safely without a
high incidence of side effects.
Begin to clarify what happens to a drug in the human body
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15. Phase II Clinical Trials
If phase I studies do no reveal any major problems, such as unacceptable toxicity, the next step is
to conduct a clinical study in which the drug is given to patients who have the condition it’s
intended to treat. Researchers then assess whether the drug has a favorable effect on the condition.
Once an experimental drug has been proven to be safe and well tolerated in healthy volunteers, it
must be tested in the patients that have the disease or condition that the experimental drug is
expected to improve/cure.
In addition to ensuring that the experimental drug is safe and effective in the patient population of
interest, Phase II studies are also designed to evaluate the effectiveness of the drug. The second
phase of testing may last from several months to a few years and may involve up to several
hundred patients. Most Phase II studies are well controlled, randomized trials.
In general, the purpose of Phase II studies is to provide the pharmaceutical company and the FDA
with comparative information about the relative safety of the experimental drug, the proper
dosage needed to treat the condition, and the drug's effectiveness. Only about one-third of
experimental drugs successfully complete both Phase I and Phase II testing.
Drug is given to Designed to test effectiveness patients who have the condition it’s intended
to treat/cure
Often dose-ranging
Control, randomized trials
It’s Blinded
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16. Phase III Clinical Trials
In a Phase III study, an experimental drug is tested in several hundred to
several thousand patients with the disease/condition of interest. Most
Phase III studies continue to be randomized and blinded. The large-scale
testing provides the pharmaceutical company as well as the FDA with a
more thorough understanding of the drug's effectiveness, benefits/risks,
and range/severity of possible adverse side effects. Phase III studies
typically last several years. Seventy to 90 percent of drugs that enter
Phase III studies successfully complete this phase of testing. There are-
Large-scale testing
Several hundred to several thousand patients
Typically last several years
Most continue to be randomized and it is double-blinded
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17. Pre-approval Clinical Trials OPL
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18. New Drug Application
(NDA)
A New Drug Application (NDA) tells the full story of a drug. Its purpose is to
demonstrate that a drug is safe and effective for its intended use in the
population studied. A drug developer must include everything about a drug from
preclinical data to Phase 3 trial data in an NDA. Developers must include
reports on all studies, data, and analyses. Along with clinical results, developers
must include:
Proposed labeling
Safety updates
Drug abuse information
Any data from studies that may have been conducted outside the United States
Patent information
Institutional review board compliance information
Directions for use
An IND is filed with the FDA to begin human trials
An NDA is filed with the FDA to obtain approval to market drug
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19. FDA Review
Once FDA receives an NDA, the review team decides if it is complete. If it is
not complete, the review team can refuse to file the NDA. If it is complete,
the review team has 6 to 10 months to make a decision on whether to
approve the drug. The process includes the following:
FDA inspectors travel to clinical study sites to conduct a routine inspection.
The Agency looks for evidence of fabrication, manipulation, or withholding
of data.
The project manager assembles all individual reviews and other documents,
such as the inspection report, into an “action package.” This document
becomes the record for FDA review. The review team issues a
recommendation, and a senior FDA official makes a decision.
Each member of the review team conducts a full
review of his or her section of the application. For
example, the medical officer and the statistician
review clinical data, while a pharmacologist reviews
the data from animal studies. Within each technical
discipline represented on the team, there is also a
supervisory review.
Slide 19 of 25Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
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20. FDA Approval
In cases where FDA determines that a drug has been shown to be safe
and effective for its intended use, it is then necessary to work with
the applicant to develop and refine prescribing information. This is
referred to as “labeling.” Labeling accurately and objectively
describes the basis for approval and how best to use the drug. Often,
though, remaining issues need to be resolved before the drug can be
approved for marketing. Sometimes FDA requires the developer to
address questions based on existing data. In other cases, FDA
requires additional studies. At this point, the developer can decide
whether or not to continue further development. If a developer
disagrees with an FDA decision, there are mechanisms for formal
appeal.
Slide 20 of 25Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
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21. Timeline 3
Regulatory Operations Training 21
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Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
Slide 21 of 25
22. Post Approval Clinical Research
Phase IV Trials
compare a drug with other drugs already in the market
monitor a drug's long-term effectiveness and impact on a
patient's quality of life
designed to determine the cost-effectiveness of a drug therapy
relative to other traditional and new therapies
Marketing
OPL
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
Key Points of Phase 4:
Study Participants: Several thousand volunteers who have the
disease/condition
Purpose: Safety and efficacy
Slide 22 of 25
23. FDA Post-Market Safety
Monitoring
Even though clinical trials provide important information on a drug’s efficacy and
safety, it is impossible to have complete information about the safety of a drug at
the time of approval. Despite the rigorous steps in the process of drug
development, limitations exist. Therefore, the true picture of a product’s safety
actually evolves over the months and even years that make up a product’s
lifetime in the marketplace. FDA reviews reports of problems with prescription
and over-the-counter drugs, and can decide to add cautions to the dosage or usage
information, as well as other measures for more serious issues. It is involved with
following terms-
Supplemental Applications
INDs for Marketed Drugs
Manufacturer Inspections
Drug Advertising
Generic Drugs
Reporting Problems
Active Surveillance
Slide 23 of 25Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
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24. Summary of Drug Dev. Phases
Phase
I
Phase
II
Phase
III
Why?
Assess
safety,
toxicity, and
efficacy
Determine
safety and
dosage
Evaluate
efficacy,
assess
side
effects
Evaluate
efficacy,
monitor
adverse
reactions
from long
term use
Who /
What is
Tested?
Laboratory
and animal
studies
20-80
healthy
volunteers
100 to 300
patient
volunteers
w/ disease
1000 to
3000
patient
volunteers
w/ disease
How
long?
6-7 years ~1 year ~2 years ~3 years .5 - 2 years
Results
5,000
compounds
evaluated
1 drug
approved
Preclinical
Phase
FDA
Review
Phase
IV
File
IND
with
FDA
30d
5
evaluated in trials
File
NDA
at
FDA
Review NDA
for drug
approval or
disapproval
Annual
reporting
on
product
Additional
long term
testing
required
by FDA
Clinical Trials
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