The Food and Drug Administration (FDA or USFDA) is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments.
The FDA is responsible for protecting and promoting public health through the regulation and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), veterinary products, and cosmetics.
The FDA also enforces other laws, notably Section 361 of the Public Health Service Act and associated regulations, many of which are not directly related to food or drugs.
These include sanitation requirements on interstate travel and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction.
Regulatory authorities (US-FDA, WHO and ICH)Sagar Savale
To promote the public health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely manner.
With respect to such products, protect the public health by ensuring that the food are safe, Wholesome, sanitary, and properly labelled; human and veterinary drugs are safe and effective; there is reasonable assurance of the safety and effectiveness of devices intended for human use; cosmetics are safe and properly labelled, and public health and safety are protected from the electronic product radiation.
Participates through appropriate process with representatives of other countries to reduce the burden of regulation, harmonize regulatory requirements, and achieve appropriate reciprocal arrangements.
The Food and Drug Administration (FDA or USFDA) is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments.
The FDA is responsible for protecting and promoting public health through the regulation and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), veterinary products, and cosmetics.
The FDA also enforces other laws, notably Section 361 of the Public Health Service Act and associated regulations, many of which are not directly related to food or drugs.
These include sanitation requirements on interstate travel and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction.
Regulatory authorities (US-FDA, WHO and ICH)Sagar Savale
To promote the public health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely manner.
With respect to such products, protect the public health by ensuring that the food are safe, Wholesome, sanitary, and properly labelled; human and veterinary drugs are safe and effective; there is reasonable assurance of the safety and effectiveness of devices intended for human use; cosmetics are safe and properly labelled, and public health and safety are protected from the electronic product radiation.
Participates through appropriate process with representatives of other countries to reduce the burden of regulation, harmonize regulatory requirements, and achieve appropriate reciprocal arrangements.
ICH: Introduction, objectives & guidelines: A brief insight.RxVichuZ
This is my 44th powerpoint........deals with ICH guidelines.....
Deals with brief introduction, precise objectives, organization(in short) & guidelines (in precise), based on SAFETY, EFFICACY, QUALITY & MULTIDISCIPLINARY guidelines.
Happy reading!!
:)
The NDA application is the vehicle through which drug sponsors, such as biotech and pharmaceutical companies, formally propose that the FDA approve a new pharmaceutical for sale and marketing
An overview of ICH-GCP guidelines of clinical trials.
Good clinical practice (GCP): a standard for the design , conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate and that the rights, integrity, and confidentiality of trial subjects are protected.
ICH-GCP is an International Conference on Harmonization Good Clinical Practice.
The guideline was developed with consideration of the current good clinical practices of the European union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the world health organization
Regulatory affairs in Pharmaceutical IndustryRama Shukla
Regulatory affairs is a profession developed from the desire of governments to protect public health by controlling the safety and efficacy of products in areas including pharmaceuticals, veterinary medicines, medical devices, pesticides, agrochemicals, cosmetics and complementary medicines.
Regulations for drug approval in USA, E.U & India
Pharmaceutical industry is the most regulated of all the industries. Regulations are put in order to develop the most efficient and safe pharmaceutical products. It takes more than 8 to 15 years to develop a new drug product & costs more than $ 800 million.
MARKETING AUTHORISATION, LICENSING AND QUALITY ASSESSMENT OF VACCINES IN INDI...Swapnil Fernandes
- European pharmaceutical legislation provides a comprehensive framework for the marketing authorisation of vaccines.
- In contrast to the European scenario, the Indian scenario for vaccines is relatively less regulated and follows the same process of approval as other biologics in spite of having a National Handbook for Vaccine Policy.
- Vaccine authorisation in the US, as is the case in EU, is a more straightforward process than in most other markets as the USFDA has provided vaccines with a distinct set of regulations in concerned areas of safety and quality.
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
How to access and process FDA drug approval packages for use in researchErick Turner
FDA reviews on new drugs can be used to learn the results of unpublished studies. Unfortunately, the FDA website (Drugs@FDA) is not user-friendly, nor are these review documents. These slides explain how to navigate Drugs@FDA, and they provide tips on how to make documents easier to use.
These slides are based on, and expand upon, an article in the BMJ, available at http://www.bmj.com/content/347/bmj.f5992 .
Bioanalytical Methods and Bioequivalence Studies Journal - SciDocPublishersScidoc Publishers
International Journal of Behavioral Research & Psychology (IJBRP) ISSN 2332-3000 is a comprehensive, peer reviewed journal devoted to Behavioral Research & Psychology. IJBRP, published by SciDocPublishers is an Open Access journal that includes high quality papers, which covers all major areas of Behavioral Research & Psychology. SciDocPublishers with its Open Access publication model spreads all the day-to-day developments and research to readers around the world.
IJBRP retains its interest in evolutionary research as an international journal dedicated to the latest advancement in Behavioral Research & Psychology and publishes articles from researchers in any area of psychology, neuroscience, behavioral biology or cognitive science. It provides a platform for Scientists and Academicians all over the world to promote, share, and discuss various new issues and developments in different areas of Behavioral Research & Psychology.
For more details: http://scidoc.org/behavioral-research-and-psychology.php
ICH: Introduction, objectives & guidelines: A brief insight.RxVichuZ
This is my 44th powerpoint........deals with ICH guidelines.....
Deals with brief introduction, precise objectives, organization(in short) & guidelines (in precise), based on SAFETY, EFFICACY, QUALITY & MULTIDISCIPLINARY guidelines.
Happy reading!!
:)
The NDA application is the vehicle through which drug sponsors, such as biotech and pharmaceutical companies, formally propose that the FDA approve a new pharmaceutical for sale and marketing
An overview of ICH-GCP guidelines of clinical trials.
Good clinical practice (GCP): a standard for the design , conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate and that the rights, integrity, and confidentiality of trial subjects are protected.
ICH-GCP is an International Conference on Harmonization Good Clinical Practice.
The guideline was developed with consideration of the current good clinical practices of the European union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the world health organization
Regulatory affairs in Pharmaceutical IndustryRama Shukla
Regulatory affairs is a profession developed from the desire of governments to protect public health by controlling the safety and efficacy of products in areas including pharmaceuticals, veterinary medicines, medical devices, pesticides, agrochemicals, cosmetics and complementary medicines.
Regulations for drug approval in USA, E.U & India
Pharmaceutical industry is the most regulated of all the industries. Regulations are put in order to develop the most efficient and safe pharmaceutical products. It takes more than 8 to 15 years to develop a new drug product & costs more than $ 800 million.
MARKETING AUTHORISATION, LICENSING AND QUALITY ASSESSMENT OF VACCINES IN INDI...Swapnil Fernandes
- European pharmaceutical legislation provides a comprehensive framework for the marketing authorisation of vaccines.
- In contrast to the European scenario, the Indian scenario for vaccines is relatively less regulated and follows the same process of approval as other biologics in spite of having a National Handbook for Vaccine Policy.
- Vaccine authorisation in the US, as is the case in EU, is a more straightforward process than in most other markets as the USFDA has provided vaccines with a distinct set of regulations in concerned areas of safety and quality.
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
How to access and process FDA drug approval packages for use in researchErick Turner
FDA reviews on new drugs can be used to learn the results of unpublished studies. Unfortunately, the FDA website (Drugs@FDA) is not user-friendly, nor are these review documents. These slides explain how to navigate Drugs@FDA, and they provide tips on how to make documents easier to use.
These slides are based on, and expand upon, an article in the BMJ, available at http://www.bmj.com/content/347/bmj.f5992 .
Bioanalytical Methods and Bioequivalence Studies Journal - SciDocPublishersScidoc Publishers
International Journal of Behavioral Research & Psychology (IJBRP) ISSN 2332-3000 is a comprehensive, peer reviewed journal devoted to Behavioral Research & Psychology. IJBRP, published by SciDocPublishers is an Open Access journal that includes high quality papers, which covers all major areas of Behavioral Research & Psychology. SciDocPublishers with its Open Access publication model spreads all the day-to-day developments and research to readers around the world.
IJBRP retains its interest in evolutionary research as an international journal dedicated to the latest advancement in Behavioral Research & Psychology and publishes articles from researchers in any area of psychology, neuroscience, behavioral biology or cognitive science. It provides a platform for Scientists and Academicians all over the world to promote, share, and discuss various new issues and developments in different areas of Behavioral Research & Psychology.
For more details: http://scidoc.org/behavioral-research-and-psychology.php
USFDA Approval Process For Drug Products & Biological Product i.e NDA Vs. BLA
Comparison of NDA and BLA application process in USA. IND, NDA, ANDA & BLA dossier submission procedure.
Introduction to Grey literature for Health SciencesFranklin Sayre
Slides for a short (1 hour 20 minute) workshop for graduate and post-graduate health science students and researchers on searching for grey literature.
Overview of the Patient-Centered Outcomes Research Institute (PCORI), how PCORI views Patient-Centered Outcomes Research and how this is related to PCORI’s major funding mechanisms.
Jake Williams - Navigating the FDA Recommendations on Medical Device Security...centralohioissa
In January, the FDA has draft recommendations for medical device security after the sale. Among other things, the recommendations tell manufacturers how to evaluate security risks, how to build a program for coordinated vulnerability disclosure program, and how to intake vulnerability reports from researchers. While the security of medical devices is especially important given the potential consequences, we can learn from the FDA recommendations regardless of our industry. Any recommendations adopted by the FDA for medical devices are likely to be implemented across other verticals for their IoT devices as well. Whether you manufacture, purchase, integrate, implement, or generally try to run away from IoT devices, there’s plenty to take away from this session while learning about the future of IoT device security.
FDA Compliance Programme Manual : Program 7356.002A is a manual which FDA investigators follow while inspection Sterile drug manufacturing operations This guidance for FDA Investigators covers the manufacture and testing of all sterile drug products, including Drugs that are sterilized by filtration or other means, aseptically processed, and drug products that are terminally sterilized.
The type of products covered by this program include
Sterile bulk drugs
Ophthalmic drugs
Otic dosage forms
Small volume parenteral (SVS)
Products for small molecule and licensed biological therapeutic drug products,
Large volume parenteral (LVP) products, and
Any other drug products required to be sterile or labeled as sterile.
Excluded under this Programme
Center for Biologics Evaluation and Research (CBER) regulated products
Veterinary drug product
At the end of this compliance guide 7356.002A questions have been given to help FDA investigators understand the manufacturing operations better and help in conduct of Inspections. Subsequent slides gives summary of these questions, which we feel, will help us prepare for an Inspection.
Part of the MaRS Best Practices Series - Pre-Clinical development workshop
http://www.marsdd.com/bestpractices
Speaker: Jack Jiang, VP Medicinal and Analytical Chemistry, Ricerca BioSciences
It consists the details about the pharmaceutical formulations and development as well as new drug development.
It consists the different stages in clinical trials.
It have the details about new drug application process
ANDA
NDA
FDA APPROVAL
IND APPLICATION
CLINICAL TRIALS AND RESEARCH
New drug invention
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.
Regulatory requirements for drug approval - industrial pharmacy IIJafarali Masi
Regulatory requirements for drug approval - industrial pharmacy IIDrug Development Teams, Non-Clinical Drug Development, Pharmacology, Drug Metabolism and Toxicology, General considerations of Investigational New Drug (IND) Application, Investigator’s Brochure (IB) and New Drug Application (NDA), Clinical research / BE studies, Clinical Research Protocols, Biostatistics in Pharmaceutical Product Development, Data Presentation for FDA Submissions, Management of Clinical Studies.
The release of the drug substance from the drug product leading to the bioavailability of the drug substance. The assessment of drug product performance is imp. Since bioavailability is related both to the pharmacodynamic responses and the adverse events. The performance tests relate the quality of a drug product to clinical safety and efficacy.
Bioavailability studies are drug product performance studies used to define
the effect of changes in the physicochemical properties of the drug substance, the formulation of the drug, and the manufacturing process of the drug product.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
2. Food and Drug Administration (FDA), a
federal agency of United States Department
of Health and Human Services was formed in
June 1906.
FDA is responsible for protecting and
promoting public health through the
regulation and supervision of
◦ Food safety
◦ Dietary Supplements
◦ Prescription and OTC pharmaceutical drugs
◦ Biopharmaceuticals &
◦ Medical Devices
3. Active Pharmaceutical Ingredient (API)
◦ A drug substance is the API or component that
produces pharmacological activity.
◦ API may be produced by chemical synthesis,
recovery from a natural product, recombinant DNA
technology, fermentation or combination of these
processes
New Chemical Entity (NCE)
◦ A drug substance with unknown clinical,
toxicological, physical and chemical properties.
4. Drug Product
◦ A drug product is the finished dosage form (e.g.
capsule, tablet, injectable etc) that contains API,
general in association with other excepient, or inert
ingredients.
7. Preclinical Testing
◦ Animal pharmacology & toxicology data are
obtained to determine the safety and efficacy of the
drug.
◦ No attempt is made to develop a final formulation
during this stage.
8. Phase I
◦ An Investigational New Drug (IND) application is
submitted to the FDA. Clinical testing takes place
once the IND application is submitted and
approved.
◦ Healthy volunteers in phase I clinical studies to
determine drug tolerance and toxicity.
◦ Dually signed consents from investigator and
volunteers are pre requisite at this phase.
◦ Toxicological studies- including acute, chronic in
various animal species are planned during this
phase
9. Phase II
◦ Limited number of diseased volunteers (patients)
are treated for the ailment or condition for which
drug was developed under closed supervision.
◦ Dose-response studies, bioavailability,
Pharmacokinetics are performed to determine the
optimum dosage regimen for treating the disease.
◦ Safety is measured to determine Therapeutic Index.
◦ A drug formulation having good physico-chemical
stability is developed.
◦ Chronic Toxicity studies are started in two species;
such studies normally last more than 2 years
duration.
10. Phase III
◦ A large scale, multicenter clinical studies are
performed with the final dosage form developed in
phase II.
◦ Objective of these studies are to determine safety
and efficacy of the drug product in large diseased
human sample.
◦ Side effects are monitored.
11. Submission of New Drug Application (NDA)
◦ An NDA is submitted to FDA for review and
approval after the completion of clinical trials that
show to the satisfaction of the medical community
that the drug is satisfactory by all parameters and is
safe as demonstrated by animal and human studies.
12. Phase IV
◦ After NDA submission and approval large scale
manufacturing of product starts and is marketed
◦ Improvement in product formulation in terms of
manufacturing, packing carries on
◦ Additional clinical studies in special population is
conducted such as in elderly, pediatric and renal
impaired patients etc.
◦ Additional clinical studies may be performed to
determine if the drug can be used for new or
additional labeled indications.
13. Labeled indication
◦ It is the disease area where drug has been tested in
Phase III trials and has exhibited profound clinical
outcome compared with pre marketed standard
drug and hence is approved by FDA in that
particular ailment.
Off labeled Indication
It is the area where drug has not been approved by
FDA may be due to limited amount of evidence, or lack
of effectiveness.
Promotion of drugs in off labeled indications in not
allowed in by FDA
14. Phase V
◦ Drug formulation may be modified slightly
◦ Changes in drug formulation always comply with
SUPAC guidelines.
15. ◦ Product Line Extension
Only physical form or strength is changed in the same
indication.
Developing transdermal patch when only tablets have
been available, for example:
Progesterone
Nicotine
Estradiol
Ibuprofen
Nitroglycerine
Additional Strength
Example is Ibuprofen 200mg, 400mg
As long as the new strength is in the range of total daily
dose.
16. Biological Products
◦ Biological product according to FDA is “any virus,
serum, toxin, antitoxin, vaccine, blood, blood
component or derivatives, allergenic product, or
analogous product applicable to the preventions,
treatment or cure of disease or injuries.
◦ Biologic License Application (BLA) is approved for
marketing under the provisions of the Public Health
Services (PHS) act.
17. Generic Drug Products
◦ After patent expiry of API or Branded Drug product,
generic drug product can be marketed.
◦ But the generic drug product should be
bioequivalent (I.e. having the same rate and extent
of drug absorption) to the branded product.
◦ These bioequivalence studies are normally
conducted in healthy volunteers.
18. Meanwhile, generic product may differ
physical appearance e.g. in color, shape, size
or in the amount of excepient used.
Generic product may also differ in dosage
form as well until the adequate safety studies
have been established.
19. Before the generic product is marketed, the
manufacturer must submit an Abbreviated
New Drug Applications (ANDA) to the FDA for
approval.
Since as NDA clinical trials have already been
performed, only bioequivalence studies are
required for ANDA approval.
20.
21. A New Chemical Entity (NCE)
◦ Preformulation
◦ It is the characterization of the physical and chemical
properties of NCE.
◦ These evaluations are started in preclinical stage and
may continue up to Phase I and Phase II.
◦ Following information is usually required.
Physical- Size, Shape, crystallinity, polymorphism, Flow
properties, hygroscopicity
Solubility- Dissolution, pH solubility profile.
Chemical - excepient interaction, pH stability, pKa,
temperature stability
Analytical- Method development for quantitative analysis
22. Formulation Development
◦ When the submission of an NDA is considered the
manufacturer attempts to develop the final dosage
form.
◦ Injectable
Final injectable drug product is usually developed in
the preclinical phase.
Major concerns include, stability of the drug in
solution for and its sterility.
Acute toxicity studies are necessary in order to change
the dosage form.
23. Formulation Development
◦ Topical
Includes antibacterial, antifungal, corticosteroids and
local anesthetics.
The final dosage form for a topical drug product is
usually developed in Phase I.
Release of the drug from the matrix is measured in-
vitro with various diffusion cell models.
Following problems may be encountered and should
be kept under checked for topical formulation
Local Irritation
Skin Sensitization
System Drug absorption
24. Formulation Development
◦ Oral
Prototype dosage forms are often developed during
the preclinical phase to ensure that drug is optimally
available and dissolves in GI well.
In early stage of product development, hard gelatin
capsule, are formulated for phase I clinical trials.
Final dosage form is decided to develop before the
start of Phase III.
25. Regulatory Approvals for Product Line
Extension
◦ Analytical and manufacturing controls
◦ Stability Information
◦ Bioavailability and Bioequivalence studies
◦ Safety Studies (e.g. skin irritation studies for
transdermal patches)
26. Preapproval Inspections (PAIs)
◦ The manufacturing facility is inspected by FDA after
an NDA, abbreviated antibiotic drug application
AADA or ANDA is submitted.
◦ Pre approval Inspection may also be initiated if a
major change is reported in a supplemental
application to an NDA, AADA or ADNA.
27. Preapproval Inspections (PAIs)
During PAI, the FDA investigator:
◦ Performs a GMP inspection.
◦ Reviews the development report about the validated
product and rationale manufacturing directions.
◦ Consults the chemistry, manufacturing and control
(CMC) section of the NDA, AADA or ANDA and
determines the capability of manufacture to
produce the drug product as prescribed.
◦ Recommends approval for the manufacturing of the
drug product based
28. Scale Up and Post Approval Changes (SUPAC)
◦ Purpose. These guidelines are intended to reduce
the manufacturing changes that require pre-
approval by FDA.
◦ Function. To review slight changes in the amount of
excepient to aid in the processing of the product
during scale-up.
◦ Changing the site of manufacture.
◦ Scale up or Scale down the batch size of
formulation
◦ Changing the manufacturing process or equipment.
29. Product With drawl from market
◦ Initiation of recall may be voluntarily initiated from
company or it can be initiated
Black box Warning for serious adverse event
reported. This box warning is even
mandatory to be mentioned in leaf insert of
the product pack.
30. Pre Clinical
Testing
Phase I Phase II Phase III FDA Approval
Years 3.5 1 - 2 2 - 4 4 - 6 1.5 Total = 12 - 17
TestPopulation
Laboratory
and Animal
Studies
20 to 100 Healthy
Volunteers
100 – 300 Patient
Volunteers
1,000 to 3,000
Patient Volunteers
Review
Post Marketing
Safety Monitoring
Purpose
Assess
Safety and
Biological
Activity
Determine Safety
and Dosage
Evaluate
Effectiveness. Look
for Side Effects.
Verify Effectiveness,
Monitor Adverse
Reactions from Long-
Term Use
Process
Large Scale
Manufacturing
--------------
Distribution
--------------
Education
%ofall
newdrugs
thatpass
FILEIND
70% of INDs 30% of INDs 27% of INDs
FILENDA
20% of INDs