CLINICAL SIGNIFICANCE OF BIOEQUIVALENCE STUDIES, BIOEQUIVALENCE, REASONS TO PERFORM BIOEQUIVALENCE STUDIES , NEED FOR BIOEQUIVALENCE STUDIES, IMPORTANCE OF BIOEQUIVALANCE STUDIES, DETERMINATION OF BIOEQUIVALENCE OF A DRUG PRODUCT, CLINICAL SIGNIFICANCE.
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.
In this presentation I have mentioned whatever the possible relevant content/guidelines require for biowaiver application.
Citation Is done at the end of slide.
Content is up to date & true to my belief.
Thanks & Best Regards.
Anurag Pandey
B.Pharm (FACULTY OF PHARMACY, INVERTIS UNIVERSITY)
M.Pharm (INSTITUTE OF PHARMACY, NIRMA UNIVERSITY)
Email :- anurag.dmk05@gmail.com
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
Introduction, biopharmaceutic factors affecting drug bioavailability, rate–limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance
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.
In this presentation I have mentioned whatever the possible relevant content/guidelines require for biowaiver application.
Citation Is done at the end of slide.
Content is up to date & true to my belief.
Thanks & Best Regards.
Anurag Pandey
B.Pharm (FACULTY OF PHARMACY, INVERTIS UNIVERSITY)
M.Pharm (INSTITUTE OF PHARMACY, NIRMA UNIVERSITY)
Email :- anurag.dmk05@gmail.com
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
Introduction, biopharmaceutic factors affecting drug bioavailability, rate–limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
Dissolution : Official and Non official methods, Alternative methods of dissolution testing and transport models, Drug release testing, Invitro drug release testing
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
Dissolution : Official and Non official methods, Alternative methods of dissolution testing and transport models, Drug release testing, Invitro drug release testing
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
National Accreditation Board for Testing and Calibration Laboratories (NABL)....Durgadevi Ganesan
National Accreditation Board for Testing and Calibration Laboratories (NABL):
NABL has been established with the objective of providing Government, Industry Associations and Industry in general with a scheme of Conformity Assessment Body’s accreditation which involves third-party assessment of the technical competence of testing including medical and calibration laboratories, proficiency testing providers and reference material producers. Accreditation process details are provided in NABL 100B- Accreditation Process & Procedure.
NABL is self-financing and charges fees to Conformity Assessment Bodies to cover operational costs and other expenditure.
NABL offers accreditation services in a non-discriminatory manner. These services are accessible to all testing including medical and calibration laboratories, proficiency testing providers and reference material producers in India and other countries in the region, regardless of the size of the applicant CAB or its membership of any association or group or number of CABs already accredited by NABL. Applicable fees details are provided in NABL 100A- General Information Brochure.
SERVICES PROVIDED BY NABL:
Testing laboratories in accordance with ISO/ IEC 17025 ‘General Requirements for the Competence of Testing and Calibration Laboratories’
Calibration laboratories in accordance with ISO/ IEC 17025 ‘General Requirements for the Competence of Testing and Calibration Laboratories’
Medical testing laboratories in accordance with ISO 15189 ‘Medical laboratories -Requirements for quality and competence’
Proficiency Testing Providers (PTP) in accordance with ISO/IEC 17043 “Conformity assessment — General requirements for proficiency testing” and
Reference material producers (RMP) in accordance with ISO 17034 “General requirements for the competence of reference material producers”.
BENEFITS OF NABL CERTIFICATION:
Increased trust in Testing/ Calibration Reports issued by the research facility.
Better control of research facility activities and criticism to labs concerning whether they have a sound Quality Assurance System and are actually skilled.
Potential expansion in business because of improved client certainty and fulfillment.
Customers can look and recognize the research centers licensed by NABL for their particular prerequisites from the NABL Web - webpage or Directory of Accredited Laboratories.
Users of certified research facilities appreciate more noteworthy access for their items, in both domestic and international markets.
Savings in terms of time and money due to reduction or elimination of the need for retesting of products.
Increased trust in Testing/ Calibration Reports issued by the research facility.
Better control of research facility activities and criticism to labs concerning whether they have a sound Quality Assurance System and are actually skilled.
Potential expansion in business because of improved client certainty and fulfillment.
NABL ACCREDITATION PROCESS
DEFINITION,PRINCIPLE, OBJECTIVES, ELEMENTS AND TOOLS OF QUALITY BY DESIGN (Qb...Durgadevi Ganesan
Quality by Design is a concept first outlined by Joseph M. Juran in various publications. He supposed that quality could be planned. The concept of QBD was mention in ICH Q8 guidelines, which states that, “To identify quality can not be tested in products, i.e. Quality should be built in to product by design.”
What is Quality by Design (QbD)?
Quality by Design (QbD) is a strategic approach employed in various industries, including pharmaceuticals, manufacturing, and product development, to ensure the consistent delivery of high-quality products.
Why QbD?
Principle of QbD
Objectives of QbD
ELEMENTS OF PHARMACEUTICAL QUALITY BY DESIGN:
- Quality Target Product Profile
- Critical Quality Attributes
- Product Design and Understanding
- Process Design and Understanding
- Process Design and Understanding
- Design space
- Control Strategy
- Continual Improvement
DESIGN TOOLS
- Prior Knowledge
- Risk Assessment
- Mechanistic Model, Design of Experiments, and Data Analysis
- Process Analytical Technology
OVERVIEW, BENEFITS, ELEMENTS AND STEPS FOR REGISTRATION OF ISO 9000 & ISO 140...Durgadevi Ganesan
INTERNATIONAL STANDARDS ORGANIZATION: ISO 9000 & ISO 14000.
- DEFINITIONS OF ISO 9000 & ISO 14000.
- OVERVIEW OF ISO 9000 & ISO 14000.
- BENEFITS OF ISO 9000 & ISO 14000.
- ELEMENTS OF ISO 9000 & ISO 14000.
- STEPS FOR REGISTRATION AND CERTIFICATION OF ISO 9000 & ISO 14000.
- ISO AUDITS OF ISO 9000 & ISO 14000.
- ISO 9000 STANDARDS:- 9000, 9001, 9004 AND 19011.
- ISO 14000 STANDARDS:- 14001, 14002, 14004, 14015, 14016, 14017, 14020, 14021, 14024, 14030, 14031, 14040 AND 14043.
- DIFFERENCE BETWEEN ISO 9000 AND 14000.
ICH STABILITY TESTING GUIDELINES (ICH Q1A-Q1F).pptxDurgadevi Ganesan
ICH Stability Testing Guidelines: ICH Q1A-Q1F (Q1 series)
Q1A(R2): STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS
Q1B: PHOTOSTABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS
Q1C: STABILITY TESTING FOR NEW DOSAGE FORMS
Q1D: BRACKETING AND MATRIXING DESIGNS FOR STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS
Q1E: EVALUATION OF STABILITY DATA
Q1F: STABILITY DATA PACKAGE FOR REGISTRATION APPLICATIONS IN CLIMATIC ZONES III & IV
Contents:
Vitamins: Definition
Classification of vitamins.
Fat soluble vitamins: Vitamin A, Vitamin D, Vitamin E and Vitamin K. Chemical nature, Dietary sources, Coenzyme forms, Biochemical functions, recommended dietary allowances and deficiency diseases of fat soluble vitamins.
CROSSOVER STUDY DESIGN, DESIGN OF PHARMACOKINETIC STUDIES, FACTORS INFLUENCING BIOAVAILABILITY STUDIES, STUDY DESIGN, PARALLEL DESIGN, CROSS-OVER STUDIES, LATIN SQUARE DESIN, TWO-PERIOD CROSSOVER STUDY DESIGN, BALANCED INCOMPLETE BLOCK DESIGN (BIBD), REPLICATE CROSSOVER STUDY DESIGN , DIFFERENCE BETWEEN PARALLEL AND CROSSOVER STUDY DESIGN.
Rationale for the reporting and control of degradationDurgadevi Ganesan
Rationale for the reporting and control of degradation, Reporting procedure, Identification of degradation products, Threshold for degradation products in new drug products, Analytical procedure, Reporting degradation products contents of batches.
Mass spectrometry, Categories of ion sources, Ionization techniques, Electron Impact ionization (EI), Chemical ionization, Field ionization, Fast atom bombardment (FAB), Matrix associated laser desorption ionization (MALDI), Atmospheric pressure chemical ionization (APCI), Electrospray ionization (ESI) and Atmospheric pressure photo ionization (APPI).
Mass analyzers : Quadrupole mass analyzer, time of flight mass analyzer, fourier transform ion cyclotron resonance(FT-ICR), ion trap mass analyzer(3D ion trap and 2D ion trap), orbitrap mass analyzer.
Patent and its types, rights and responsibilities of patentee, filing patent applications, patent application forms and guidelines, types of patent applications.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
2. It is a relative term which denotes that the drug substance in two or more
identical dosage forms, reaches the systemic circulation at the same relative
rate and to the same relative extent i.e. their plasma concentration-time
profiles will be identical without significant statistical differences.
When statistically significant differences are observed in the bioavailability
of two or more drug products, bio- inequivalence is indicated.
The absence of a significant difference in the rate and extent to which the
active ingredient or active moiety in pharmaceutical equivalents or
pharmaceutical alternatives becomes available at the site of drug action
when administered at the same molar dose under similar conditions in an
appropriately designed study.
3. To enable clinical trial formulations to be modified or production ‘scaled up’
throughout a drug’s development.
To compare a clinical trial formulation with the ‘to be marketed’ product
just prior to filing
To compare a generic drug product with a corresponding reference drug.
To change the dosage regimen by means of a change in formulation
Immediate release
Modified-release
4. New product is intended to be a substitute for an approved medicinal
product as a pharmaceutical equivalent or alternative
To ensure clinical performance of such drug products
Bioequivalence studies are conducted if there is:
A risk of bio-in equivalence and/or
A risk of pharmacotherapeutics failure or diminished clinical safety
In vivo bioavailability / bioequivalence studies and in vitro dissolution
testing recommended to applicants intending to submit Investigational new
drug application (INDs)New drug applications (NDAs)Abbreviated new
drug applications (ANDAs) for conventional and extended release dosage
forms administered orally.
In conditions where a suitable method for determining active drug is not
available, an indirect indication of bioavailability and bioequivalence by
comparing the pharmacodynamic responses of the formulations may be
possible
5. To evaluate the absolute bioavailability of dosage form compared with
reference dosage forms.
Dose proportionality study to determine if bioavailability parameters are
linear over proposed dosage range.
Intra/inter subject variability
Intervention study to examine effect of e.g. Food and concomitant
medication.
Dosage form proportionality study to determine if equipotent drug
treatments administered at different dose strength of the market form
produce equivalent drug bioavailability.
Bioequivalence study needed as a result of changes in the formulation or
manufacturing processes.
6. Different approaches for determination of bioequivalence of a drug product are:
An in vivo test in humans in which the concentration of the active ingredient and
when appropriate, its active metabolites, in blood, plasma, serum or other suitable
biological fluid is measured as a function of time.
An in vivo test in humans in which the urinary excretion of the active ingredient and
when appropriate, its active metabolites are measured as a function of time.
An in vitro test that has been correlated with and is predictive of human
bioavailability profile or the one acceptable to FDA (e.g. dissolution rate test) that
ensures human in vivo bioavailability.
An in vivo test in humans in which an appropriate pharmacological effect of the
active ingredient and when appropriate, its active metabolites are measured as a
function of time if this effect can be measured with adequate accuracy, sensitivity
and reproducibility
Well-controlled clinical trials that establish the efficacy and safety of the drug
product, for purpose of determining bioavailability, or comparative clinical trials, for
purpose of demonstrating bioequivalence.
7.
8. Products requiring be studies are mainly
(1) drugs with narrow margin of safety,
e.g. digoxin, antiarrhythmics, anticoagulants, cytostatics, lithium, phenytoin,
cyclosporine, sulphonylureas, theo-phylline
(2) critical use drugs, i.e. drugs indicated for serious conditions requiring
assured therapeutic response,
e.g. antiinfectives, cardiovascular drugs, antiepileptics, antiasthmatics; and
(3) sustained or modified release products, due to the difficult formulation.
9. In practice, bioequivalence in drug absorption has been interpreted that the
confidence interval for the ratio of means (of drug absorption) is within
bioequivalence limits.
An alternative would be to show that the tolerance intervals (or a
distribution free model) overlap sufficiently.
Many practitioners interpret that generic drug products and the innovative
drug product can be used interchangeably because they are therapeutically
equivalent.
The FDA, however, does not indicate that approved generic drug products
and the innovative drug products can be used interchangeably.
The FDA only indicates that an approved generic drug product can be used
as a substitute to the innovative drug product.
Basically, drug interchangeability can be classified either as
drug prescribability or
drug switchability
10. Drug prescribability is defined as the physician’s choice for prescribing an
appropriate drug product for his/her new patients between a brand-name
drug product and a number of generic drug products that have been shown
to be bioequivalent to the brand-name drug product.
Drug switchability, on the other hand, is related to the switch from a drug
product (e.g., a brand-name drug product) to an alternative drug product
(e.g., a generic copy of the brand-name drug product) within the same
subject, whose concentration of the drug product has been titrated to a
steady, efficacious, and safe level.
As a result, drug switchability is considered more critical than drug
prescribability in the study of drug interchangeability for patients who have
been on medication for a while.
Drug switchability, therefore, is exchangeability within the same subject.
11. Bioequivalence (BE) study is required to show whether a generic copy product
can be interchangeable with the brand innovator product.
E.g.: BE studies of clopidogrel generics :
Clopidogrel is a prodrug that must undergo hepatic metabolism to become
the active metabolite.
The active metabolite is highly unstable and thus difficult to measure.
Therefore, the BE study of clopidogrel may be a pharmacokinetic study or a
pharmacodynamic study.
The pharmacokinetic BE study of clopidogrel is based on the measurement
of clopidogrel parent compound
The pharmacodynamic BE study of clopidogrel is based on the inhibition of
ADP binding to its platelet membrane receptors, P2Y12, which causes
platelet aggregation.
12. Bioequivalence for most of oral tablets or capsules is demonstrated in vivo
by comparing the rate and extent of absorption that is bioavailability of the
generic product with that of the innovator product.
This is done by measuring the active ingredient concentration in blood,
plasma, serum or other biological fluids over a certain period of time for
both the generic and innovator products, also called test and reference drugs
respectively.
By doing so the bioequivalence studies frequently rely on pharmacokinetic
measures such as area under the concentration-time curve (AUC) and peak
drug concentration (Cmax)
Use of Alternate routes:Drugs with high hepatic first pass metabolism
should be given by routes other than oral. ie., sublingual, transdermal eg.,
Nitroglycerine
High oral doses: Some drugs have high hepatic extraction ratio.
Less dose in hepatic Disease: In severe hepatic cirrhosis/ portal systemic
shunts, the dose of the drugs with large extraction ration and hepatic first
pass effect should be reduced otherwise toxicity
13. Bioequivalence studies are very important for the development of a
pharmaceutical preparation in the pharmaceutical industry.
Their rationale is the monitoring of pharmacokinetic and pharmacodynamic
parameters after the administration of tested drugs.
The target of such study is to evaluate the therapeutic compatibility of tested
drugs (pharmaceutical equivalents or pharmaceutical alternatives).
14. Clinical interpretation is important in evaluating the results of a
bioequivalence study.
Bioequivalence studies should be conducted for the comparison of two
medicinal products containing the same active substance.
Two products marketed by different licensees, containing same active
ingredient(s), must be shown to be therapeutically equivalent to one another
in order to be considered interchangeable.
Differences of less than 20% in AUC & Cmax between drug products are
unlikely to be clinically significant in patients.
Minimize product to product variability by different manufactures & lot to
lot variability with a single manufacture.