This presentation enlists all the studies which are required before submission of IND. It include IND introduction , time period of study ,flowchart showing preclinical studies...
This presentation enlists all the studies which are required before submission of IND. It include IND introduction , time period of study ,flowchart showing preclinical studies...
Safety pharmacology is a branch of pharmacology with its aim to predict the potential clinical risk profile of new chemical entities (NCEs).
It has the ability to predict the potential off-target drug effects on major organ systems which are associated with exposure in the therapeutic range and above.
As an essential part of the spectrum of drug discovery and development, safety pharmacology studies are generally conducted to determine the relative drug effect on main organs, including respiratory system, central nervous system, and cardiovascular system.Safety pharmacology is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials.
SP studies are described in the international conference on harmonization (ICH) S7A and S7B Guidelines.
OECD principles of Good laboratory practice. this ppt include the basic and necessary information required for OECD GLP guideline . Content is taken from official site
Dermal Irritation and Dermal Toxicity Studies Dinesh Gangoda
Dermal irritation and Corrosion test guidelines 204.
Dermal irritation is the production of reversible damage of the skin following the application of a test chemical for up to 4 hours.
Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions. [1]
Dermal corrosion is the production of irreversible damage of the skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test chemical for up to four hours.[2]
REFERENCES
OECD/OCDE, Test No. 404: ‘‘Acute Dermal Irritation/Corrosion’’, 28 July 2015 OECD Publishing, peris, Page no, 1- 8.
Robert A., Turner., Screening Methods in Pharmacology; 1st edition; Academic press an imprint of Elsevier, pp, 279- 281.
OECD Guideline for testing of chemicals (1981). ‘‘Repeated Dose Dermal Toxicity’’, 21/28- day Study.
Role Of Transgenic Animal In Target Validation-1.pptxNikitaBankoti2
A Transgenic animal is one that carries a foreign gene that has been deliberately inserted into its genome.
The foreign gene are inserted into the germ line of the animal, so it can be transmitted to the progeny.
Transgenic animals are animals that are genetically altered to have traits that mimic symptoms of specific human pathologies.
They provide genetic model of various human disease which are important in understanding disease and development of new target.
Regulatory guidelines for conducting toxicity studies by ichAnimatedWorld
ICH is the “International Conference on Harmonization of
Technical Requirements for Registration of Pharmaceuticals for
Human Use”
ICH is a joint initiative involving both regulators and research based industry representatives of the EU, Japan and the US in
scientific and technical discussions of the testing procedures required
to assess and ensure the safety, quality and efficacy of medicines
Safety pharmacology is a branch of pharmacology with its aim to predict the potential clinical risk profile of new chemical entities (NCEs).
It has the ability to predict the potential off-target drug effects on major organ systems which are associated with exposure in the therapeutic range and above.
As an essential part of the spectrum of drug discovery and development, safety pharmacology studies are generally conducted to determine the relative drug effect on main organs, including respiratory system, central nervous system, and cardiovascular system.Safety pharmacology is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials.
SP studies are described in the international conference on harmonization (ICH) S7A and S7B Guidelines.
OECD principles of Good laboratory practice. this ppt include the basic and necessary information required for OECD GLP guideline . Content is taken from official site
Dermal Irritation and Dermal Toxicity Studies Dinesh Gangoda
Dermal irritation and Corrosion test guidelines 204.
Dermal irritation is the production of reversible damage of the skin following the application of a test chemical for up to 4 hours.
Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions. [1]
Dermal corrosion is the production of irreversible damage of the skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test chemical for up to four hours.[2]
REFERENCES
OECD/OCDE, Test No. 404: ‘‘Acute Dermal Irritation/Corrosion’’, 28 July 2015 OECD Publishing, peris, Page no, 1- 8.
Robert A., Turner., Screening Methods in Pharmacology; 1st edition; Academic press an imprint of Elsevier, pp, 279- 281.
OECD Guideline for testing of chemicals (1981). ‘‘Repeated Dose Dermal Toxicity’’, 21/28- day Study.
Role Of Transgenic Animal In Target Validation-1.pptxNikitaBankoti2
A Transgenic animal is one that carries a foreign gene that has been deliberately inserted into its genome.
The foreign gene are inserted into the germ line of the animal, so it can be transmitted to the progeny.
Transgenic animals are animals that are genetically altered to have traits that mimic symptoms of specific human pathologies.
They provide genetic model of various human disease which are important in understanding disease and development of new target.
Regulatory guidelines for conducting toxicity studies by ichAnimatedWorld
ICH is the “International Conference on Harmonization of
Technical Requirements for Registration of Pharmaceuticals for
Human Use”
ICH is a joint initiative involving both regulators and research based industry representatives of the EU, Japan and the US in
scientific and technical discussions of the testing procedures required
to assess and ensure the safety, quality and efficacy of medicines
Good Laboratory Practices form a part of Good Manufacturing Practices.
• It is very difficult to separate Good Laboratory Practices from Good Manufacturing
Practices.
• In a manufacturing unit , if the production department strictly follows Good Laboratory
Practices and does not make shortcuts, product failures are minimum.
NOIDA INSTITUTE OF ENGINEERING AND TECHNOLOGY (PHARMACY INSTITUTE) Test item characterization Presented by: Arbaz Khan M.Pharm 2nd semester Submitted to: Dr. Saumya Das Associate Professor NIET(Pharmacy Institute).
Background
Definitions
Roles and responsibilities
Transport and receipt
Identification, labelling and sampling
Characterisation
Handling and disposal
References
GOOD LABORATORY PRACTICES - A DETAILED STUDYTeny Thomas
A detailed study of the rules, regulations and guidelines of Good Laboratory Practices that should be practiced while conducting a Non Clinical Laboratory Study in Animals.
The Principles of Good Laboratory Practice (GLP) are a managerial quality control system covering the organisational process and the conditions under which non-clinical health and environmental studies are planned, performed, monitored, recorded, reported and retained (or archived). The OECD Principles of GLP are followed by test facilities carrying out studies to be submitted to receiving authorities for the purposes of assessing the health and environmental safety of chemicals and chemical products which may also be of natural or biological origin and, in some circumstances, may be living organisms.
The Principles of GLP define the responsibilities of test facility management, study director, study personnel and quality assurance personnel that are operating within a GLP system, and minimum standards concerning the suitability of facilities and equipment to perform studies, the need for standard operating procedures, documentation of raw data, study reports, the archiving of records, etc.
Asia Pesticide Residue Mitigation through the Promotion of Biopesticides and ...apaari
Asia Pesticide Residue Mitigation through the Promotion of Biopesticides and Enhancement of Trade Opportunities (APRMP), Virtual lab meeting
10 August 2020
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
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.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
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.
In silico drugs analogue design: novobiocin analogues.pptx
Kk Test item characterization
1. TEST ITEM CHARACTERIZATION IN
REGULATORY TOXICOLOGY
STUDIES
(ACCORDING TO OECD - GLP
ADVISORY GUIDELINES
DOCUMENT NO.19)
PREPARED BY
KESHARI KUMAR SRIWASTAWA
M.PHARM (PHARMACOLOGY),1ST YEAR
2. OBJECTIVE OF THE GUIDELINES
• This guidance provides clarity for test facilities on
the expectations of national Good Laboratory
Practice (GLP) compliance monitoring authorities on
how test items are transported, received, identified,
labelled, sampled, handled, stored, characterised,
archived and disposed.
• The document consolidates existing OECD guidance
on test items that are used in studies conducted in
compliance with the Principles of GLP.
• It also aims to promote a consistent approach that is
appropriate to the objective of the study and the
nature of the test item.
3. • This document is designed to provide guidance on
– The transportation, receipt, identification, labelling, sampling,
handling, storage, characterisation, archiving and disposal of
all test items used in GLP studies.
– The expectations on the characterisation of different types of
test items that are used in the conduct of a broad range of non-
clinical studies carried out in compliance with the Principles of
GLP.
– Test items could be from different origins such as chemical,
biological, synthetic, natural, living organisms, transgenic
organisms, items from complex industrial or biological
processes, complex mixtures or part of them. The final use of
test items includes but is not limited to agrochemicals,
industrial chemicals, pharmaceuticals (human and veterinary),
cosmetics products, food/feed additives and medical devices.
4. • The amount of information required for transportation, receipt,
identification, labelling, sampling, handling, storage,
characterisation, archiving and disposal can vary from study-to-
study.
• This is due to the wide variety of test items, the objectives of the
study and the development stage of the test item.
• Because of the diverse nature of test items there is an expectation
that Test Facility Management will undertake appropriate and
proportionate risk-based assessments of the management,
characterisation and use of each test item throughout their use on
GLP studies.
• This should enable the test facility personnel to maintain a
controlled approach in assessing whether information they have
available on the test item is sufficient.
• Adoption of a risk-based approach to decision making should also
serve to ensure that the test item is what it purports to be and is
suitable to fulfil the objectives of the study.
5. Test Item Test item is defined as an article that is the subject of a
study. The conclusion of a GLP study provides
information on the properties of the test item which allows an
assessment of the risk it presents to the safety of humans,
animals or the environment. It should be noted that test item is
also referred to as "test chemical" in some of the OECD Test
Guidelines.
Batch Batch (or lot) is defined as a specific quantity of a test
item produced during a defined cycle of manufacture in such a
way that it could be expected to be of a uniform and
homogeneous character and should be designated as such.
Vehicle Vehicle is defined as any agent that serves as a carrier and is
used to mix, disperse, suspend or solubilise the test item to
facilitate the administration and/or application to the test
system.
Formulation A formulation (or mixture) is a combination of a test item and
different ingredients such as excipients that are combined and
administered and/or applied to the test system in a different
form, e.g. tablet, capsule, solution.
BASIC TERMINOLOGIES
6. Test system Test system means any biological,
chemical or physical system or a
combination thereof used in a study
Expiry Date Expiry Date (or Expiration Date) is
the designated date a test item is
expected to remain within established
shelf life specifications if stored under
defined conditions and after which it
should not be used.
Retest Date Retest Date is the date a test item
should be re-examined to ensure that
it is still suitable for use.
Characterisation Determines attributes of the test item
and provides the evidence to support
its suitability for use in GLP studies.
7. PREPARATION OF THE TEST ITEM
• Preparation of test item (or prepared test item) could be a
formulation (or mixture) containing the test item or the test item
in a vehicle, where the combination is obtained by dilution,
mixing, dispersion, suspension, solubilisation and/or another
process with the intention to be administered to the test system.
• The test facility can be supplied with the 2 Unclassified test item
or with preparation(s) of the test item to be processed again or
preparation(s) of the test item ready to be applied or
administrated to the test system (also called “ready-to-use”).
• A test item which is encapsulated or packed in some other way,
in the absence of excipients or a vehicle, for the purposes of
delivery to the test system is not regarded as a prepared test item
as per these guidelines
8. • General information
The Principles of GLP require information on identity, such as name, code, CAS
number, biological parameters, batch number, purity, composition, concentrations,
and, in case of several batches of test item, characteristics to appropriately define
each batch. Stability of the test item under storage and test conditions should also
be available.
No or inadequate information on the characterisation of the test item constitutes a
deviation from the Principles of GLP. The impact the deviation has on the validity of
the study data and the extent of compliance with the Principles of GLP should be
described by the Study Director in the GLP compliance statement of the final study
report.
Consideration should always be given to whether information on the characteristics
of the test item is needed in order to design the study and issue the study plan.
There is an expectation that test item administration or application only occurs
when sufficient information is available that confirms the identity of the test item.
The characterisation of the test item, including stability, should always be
completed by the end of the study so that information can be detailed in the final
study report.
Where multiple batches of test item are used during a GLP study, characterisation
information should be available for each batch of the test item used.
CHARACTERISATION OF THE TEST ITEM
9. SOURCES OF CHARACTERIZATION DATA
The characterisation of the test item may be carried
out by the sponsor, a supplier or the test facility.
If characterisation is performed by the sponsor or a
supplier, Test Facility Management should ensure
that documented procedures are in place to verify
the integrity and quality of the information provided.
In every case, the final study report should describe
who is responsible for test item characterisation and
who performed it.
The report may also provide other relevant
information such as the quality system under which
the characterisation was performed.
10. DATA ON STABILITY DATA ON IDENTITY
The test facility should be provided
with information on the stability of
the test item under storage and test
conditions, or the test facility should
determine such information. The
stability of the test item can only be
assured if the material is handled and
stored appropriately, and is used
before expiration.
The Principles of GLP require that
for each study, the identity, including
batch number, purity, composition,
concentrations, or other
characteristics necessary to
appropriately define each batch of
the test item, should be known.
The available data (e.g. retest
or expiry date or any other
indicator of stability) should
be reported in as detailed a
fashion as possible in the
final study report.
The test facility may be supplied with a
certificate of analysis, which usually
provides basic information on the
physical characteristics of the test item.
In the absence of a certificate of analysis,
information needed to confirm the
identity and properties of the test item
may be supplied in alternative formats
such as a laboratory report, safety data
sheet, memorandum, letter or email from
the sponsor.
11. CHARACTERIZATION OF SPECIFIC
TEST SUBSTANCES
1. Test items in the early stage of development
2. Biochemicals
3. Living Organisms
4. Transgenic organisms
5. Medical devices
6. Test items with complex composition
7. Radiolabeled test items
12. 1.TEST ITEMS IN THE EARLY STAGE OF
DEVELOPMENT
• The extent to which a test item will be
characterised may be commensurate with the
stage of product development.
• In the earlier stages of test item development
there may be less characterisation
information available.
• However, the Study Director should always
be able to demonstrate that the test item used
in the study is what is required in the study
plan.
13. 2. BIOCHEMICALS
• If the test item is a biochemical, for example an
antibody, a peptide, a protein, a viral vector or an
enzyme, the need for information to verify biological
activity should always be considered, including the
determination method and its quantification
(potency) as part of the characterisation process.
• If no information is provided to demonstrate the
biological activity of the test item, the reasons why
the test item is still considered suitable for use in the
study should be clearly outlined in the study plan
and in the final study report.
14. 3. LIVING ORGANISMS
• If the test item is a living organism, for example a cell, a virus or
a microorganism, the characterisation may require specific
information on properties which are unique to the test item. For
example, if the test item is a cell line, it may be appropriate to
confirm passage number.
• Other biological properties that may have to be taken into
consideration because they have an impact on the viability of
the test item may include viability rate, proliferation rate,
culture conditions or infectious titer determination.
• Information required to characterise living organisms should
be considered on a case-by-case basis and the rationale for
performing the tests described in the study plan.
15. 4. TRANSGENIC ORGANISMS
• A test item may be a transgenic
organism . If a unique identifier is
available this can be included.
• If information is available on seed
certification this can be used and may
include:
– The name of the host species,
– A description of the inserted genetic material,
– The trait and the name of the developer.
16. 5. MEDICAL DEVICES
• For studies on medical devices, characterisation data can include the
description of the device, the lot number, the types of materials of
which the device is made (and method of manufacture and name of
the manufacturer of any polymers, colorants, metals), the methods of
manufacture and synthesis of the final device (e.g. injection molding)
and the location of manufacturing facilities.
• Illustrations or photos could be the best way to show the entire
configuration of the medical device.
• The date of manufacture, stability, and storage conditions should be
known and documented. Where applicable, information on the
sterilisation status of the device used as a test item should be
provided by the supplier.
• If the test item is only a component part or a representative sample of
a medical device, information of the full medical device should be
available when possible.
17. 6. TEST ITEMS WITH COMPLEX
COMPOSITION
• Substances of unknown or variable composition, or
biological materials (UVCBs), complex reaction
products or products from animal or vegetable or
natural origin cannot be sufficiently identified by
their chemical composition because the number of
their constituents is relatively large and/or the
composition is, to a significant part, unknown and/or
the variability of composition is relatively large or
poorly predictable.
• In such cases, the composition could then be
defined by the manufacturing process and/or by the
origin description.
18. 7. RADIOLABELLED TEST ITEMS
• Radiolabeled test items are generally unstable;
however, their exact stability characteristics are not
normally known so it is not possible to provide a
retest or expiry date or any other stability indicator
for them.
• Therefore, their radiopurity should be checked at the
start of the study and be reported.
• Characterisation data should also include the
amount of radioactivity per unit mass or volume –
i.e. specific activity and/or specific concentration.