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
United State Pharmacopoeia (USP)The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA) definitionIVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
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".
It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentration–time curve (AUC)
Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
Acute pharmacological response.
Therapeutic response.
1.3. In-vitro dissolution studies
Closed compartment apparatus
Open compartment apparatus
Dialysis systems.
1.4. Clinical observations
Well-controlled clinical trials
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
This PPT includes what role does Dosage form impart on absorption. Why it is important in absorption. what should be its nature and type of dosage form.
United State Pharmacopoeia (USP)The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA) definitionIVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
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".
It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentration–time curve (AUC)
Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
Acute pharmacological response.
Therapeutic response.
1.3. In-vitro dissolution studies
Closed compartment apparatus
Open compartment apparatus
Dialysis systems.
1.4. Clinical observations
Well-controlled clinical trials
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
This PPT includes what role does Dosage form impart on absorption. Why it is important in absorption. what should be its nature and type of dosage form.
Pulmonary route used to treat different respiratory diseases from last decade.
The inhalation therapies involved the use of leaves from plants, vapours from aromatic plants, balsams, and myhrr.
Pulmonary drug delivery is primarily used to treat conditions of the airways, delivering locally acting drugs directly to their site of action.
Delivery of drugs directly to their site of action reduces the dose needed to produce a pharmacological effect.
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
BIOPHARMACEUTIC CONSIDERATIONS IN DRUG PRODUCT DESIGNN Anusha
BIOPHARMACEUTICS studies the in vitro impact of physicochemical properties of drugs and drug products on delivery to body under normal or pathologic conditions.
Biopharmaceutics links the physical and chemical properties of drug and drug product to their performance, in vivo.
The aim of biopharmaceutics is to adjust the delivery of drug from drug products in such a manner as to provide: optimal therapeutic activity and safety for the patient.
Biowaiver Based on BCS Classification System: Criteria and Requirements Accor...Tareq ✅
Bioavailability (BA)/bioequivalence (BE) parameters are generally required for approval of new and generic drugs. Bioequivalence based on plasma drug concentration has become the most frequently used and successful biomarker of safety and efficacy of a drug. According to the FDA’s regulations BA is defined as the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action and BE can be defined as the absence of a significant difference in the rate and extent to which the active ingredient in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administrated at the same molar dose under similar conditions in a properly designed study. Two oral dosage forms are considered to be bioequivalent if both rate and extent of absorption are the same.
A Biowaiver means that in vivo bioavailability and/or bioequivalence studies may be waived (not considered necessary for product approval). Instead of conducting expensive and time consuming in vivo studies, a dissolution test could be adopted as the surrogate basis for the decision as to whether the two pharmaceutical products are equivalent.
biopharmaceuticals classification system and biowaiverRavish Yadav
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Pulmonary route used to treat different respiratory diseases from last decade.
The inhalation therapies involved the use of leaves from plants, vapours from aromatic plants, balsams, and myhrr.
Pulmonary drug delivery is primarily used to treat conditions of the airways, delivering locally acting drugs directly to their site of action.
Delivery of drugs directly to their site of action reduces the dose needed to produce a pharmacological effect.
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
BIOPHARMACEUTIC CONSIDERATIONS IN DRUG PRODUCT DESIGNN Anusha
BIOPHARMACEUTICS studies the in vitro impact of physicochemical properties of drugs and drug products on delivery to body under normal or pathologic conditions.
Biopharmaceutics links the physical and chemical properties of drug and drug product to their performance, in vivo.
The aim of biopharmaceutics is to adjust the delivery of drug from drug products in such a manner as to provide: optimal therapeutic activity and safety for the patient.
Biowaiver Based on BCS Classification System: Criteria and Requirements Accor...Tareq ✅
Bioavailability (BA)/bioequivalence (BE) parameters are generally required for approval of new and generic drugs. Bioequivalence based on plasma drug concentration has become the most frequently used and successful biomarker of safety and efficacy of a drug. According to the FDA’s regulations BA is defined as the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action and BE can be defined as the absence of a significant difference in the rate and extent to which the active ingredient in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administrated at the same molar dose under similar conditions in a properly designed study. Two oral dosage forms are considered to be bioequivalent if both rate and extent of absorption are the same.
A Biowaiver means that in vivo bioavailability and/or bioequivalence studies may be waived (not considered necessary for product approval). Instead of conducting expensive and time consuming in vivo studies, a dissolution test could be adopted as the surrogate basis for the decision as to whether the two pharmaceutical products are equivalent.
biopharmaceuticals classification system and biowaiverRavish Yadav
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
2.Sagar Goda Biological classification system (BCS); its significance on diss...Sagar Goda
This presentation provides a detailed information about Biopharmaceutics classification system(BCS) and its significance on dissolution study as well as its application in dosage form development.
Bioavailability and bioequivalence studyMcpl Moshi
BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability.
It is a drug development tool that allows estimation of solubility, dissolution and intestinal permeability affect that oral drug absorption.
Kashikar V S
PES Modern College of Pharmacy ( for ladies), Moshi Pune
Bioavailability and Bioequivalence studyMcpl Moshi
Bioavailability and Bioequivalence study, BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability.
It is a drug development tool that allows estimation of solubility, dissolution and intestinal permeability affect that oral drug absorption.
BCS Guideline for solubility and Dissolution.pptxImdad H. Mukeri
Briefly explanation of The Biopharmaceutics Classification System (BCS) of drug substance
and its solubility in the pH range of 1–7.5, absorption or intestinal membrane permeability
A review on waiving in vivo bioequivalence tests or Biovaiwer, with a case review on the biowaiver monograph on Ibuprofen by H. POTTHAST, J.B. DRESSMAN, H.E. JUNGINGER, K.K. MIDHA, H. OESER, V.P. SHAH,
H. VOGELPOEL, D.M. BARENDS
in J Pharm Sci 94:2121–2131, 2005
Explaining different approaches to waive different BCS class medicines based on their solubility and permeability, as is described by FDA and WHO
Bio pharmaceutical classification System [BCS]Sagar Savale
The Biopharmaceutical Classification System was first developed by in 1995, by Amidon et al & his colleagues.
Definition:
“The Biopharmaceutical Classification System is a scientific framework for classifying a drug substance based on its aqueous solubility & intestinal permeability & dissolution rate”.
To saved time fast screening is required so drug substances are classified on basis of solubility and permeability. This classification is called Biopharmaceutical Classification System
In this presentation I have mentioned whatever the possible relevant content required for the title.
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
In this presentation I have mentioned whatever the possible relevant content required for the title.
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
In this presentation I have mentioned whatever the possible relevant content required for the title.
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
In this presentation I have mentioned whatever the possible relevant content required for the Mucoadhesive drug delivery system.
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
THIS PRESENTATION CONTENT WILL GIVE YOU BRIEF KNOWLEDGE ABOUT HOW YOU CAN IMPROVE THE PROCESS OUTPUT WITH A PROPER PRE-DESIGNED STRUCTURE FOR THAT PARTICULAR.
ISO 9000, Lean manufacturing, and Six Sigma Works on the principle of total quality management or we can say that they overshadowed the TQM due to their efficient output in comparison to it.
In this presentation I have mentioned whatever the possible relevant content is required for this method
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
In this presentation I have mentioned whatever the possible relevant content required for the aptamer based drug delivery.
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
Almost Exact Procedure is provided in each & every slide ..
Thanks & Best Regards
Anurag Pandey (B.Pharm)
Contact :- anurag.dmk05@gmail.com (Facebook & Gmail)
Easy & to the point Topics are clearly given in this presentation..
Thanks & Best Regard
(Anurag Pandey) B.Pharm
Contact :- anurag.dmk05@gmail.com (Facebook & Gmail both)
More from Institute of Pharmacy, Nirma University (9)
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
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5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
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effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
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Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
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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 .
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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.
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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.
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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.
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How to Give Better Lectures: Some Tips for Doctors
Biowaivers
1. PRESENTED BY :- ANURAG PANDEY
M.PHARM (PHARMACEUTICS)
INSTITUTE OF PHARMACY, NIRMA UNIVERSITY
BIOWAIVERS &
IT’S GUIDELINES
UNDER THE GUIDANCE OF:- DR. MAYUR PATEL
ASSOCIATE PROFESSOR AT DEPT. OF PHARMACEUTICS
INSTITUTE OF PHARMACY, NIRMA UNIVERSITY
Wednesday,April 11, 20181
2. HISTORY OF BIOWAIVER
Wednesday,April 11, 20182
1. The term “biowaiver” is applied to a regulatory drug approval process
when the dossier (application) is approved based on evidence of
equivalence other than through In-vivo equivalence testing.
2. In 1995, the American Department of Health and Human Services, US
Food and Drug Administration (HHS-FDA) instigated the
Biopharmaceutics Classification System (BCS), with the aim of
granting so-called biowaivers for SUPACs.
3. At that time the biowaiver was only considered for SUPAC to
pharmaceutical products.
4. More recently, the application of the biowaiver concept has been
extended to approval of certain orally administered generic products
3. INTRODUCTION
Wednesday,April 11, 20183
A Biowaiver means that in vivo bioavailability and/or bioequivalence
studies may be waived (not considered necessary for product
approval). In short, In-vitro instead of In-vivo “Bioequivalence” testing.
Instead of conducting expensive and time consuming in vivo
studies, a dissolution test could be adopted as the surrogate basis for
the decision as to whether the two pharmaceutical products are
equivalent.
Only APIs with high solubility and high permeability and which are
formulated in solid, immediate release (IR) oral formulations can be
approved on the basis of the Biowaiver procedure.
A major advantage of the Biowaiver procedure is the simplification
and reduction of time required for product approval, thus reducing
the cost of bringing new products to market.
4. CONT…
Wednesday,April 11, 20184
The risk of therapeutic inequivalence of two immediate release
products can never be reduced to zero, even if a full clinical study is
performed.
The conclusion of comparative clinical studies, in vivo bioequivalence
studies, in vitro equivalence tests and biowaivers is based on statistics
and scientific data that are assumed to be representative for the products
at issue.
The aim of biowaiver guidance is to reduce the risk of bioinequivalence
to an acceptable level.
Pharmaceutical development work aims at reducing the probability of
manufacturing inequivalent formulations taking into account the critical
aspects of the product at issue.
In this context, the absorption phase is regarded as the critical process
determining the equivalence of the pharmacokinetic profiles and
thereby the therapeutic equivalence of the test and reference product
5. BIOWAIVERS TYPE OF PRODUCTS
Wednesday,April 11, 20185
1. SOLUTIONS
2. IV PRODUCTS
3. IMMEDIATE RELEASE PRODUCTS
LOWER STRENGTH
BCS CLASS I
BCS CLASS II?
BCS CLASS III?
4. EXTENDED RELEASE PROCDUCTS
LOWER STRENGTH
5. TOPICAL DOSAGE FORMS
SOLUTIONS
AEROSOLS
ANTIFUNGALS
6. INHALATION & NASAL DOSAGE FORMS (AERSOLS)
SOLUTIONS
6. SCOPE & ADVANTAGES OF BIOWAIVER
Wednesday,April 11, 20186
SCOPE
Inside a product:
• Scale up processes
• Line extensions
• Variation after marketing authorization
Between different products:
• Application of generics without clinical data
ADVANTAGE’S
Circumvent expensive and sometimes unethically questionable human
testing.
Reducing time in bringing product to the market.
Reduce product cost
Fig. Source: INTERNET
7. LIMITATION/EXCEPTION OF
BCS-BASED BIOWAIVER
Wednesday,April 11, 20187
BCS based biowaiver are not applicable for the following:
1. Narrow therapeutic range drug products. (It’s definition is not
mentioned in the guidelines acc. To EMA it must be decided case by
case.)
2. BCS based biowaivers have limited application for the class II drugs
and not applicable for class III.
3. Dosage form meant for absorption in the oral cavity e.g. sublingual or
buccal tablets.
4. Effects of food, absorptive transporters, efflux transporters, and
routes of elimination (renal/biliary) were important determinants of
overall drug absorption and bioavailability for immediate release oral
dosage forms, which are not considered in BCS.
8. BCS-BASED BIOWAIVER
Wednesday,April 11, 20188
According to the HHS-FDA definitions,
the four possible categories for an API according to the BCS:
HIGH
SOLUBILITY
HIGH PERMEABILITY LOW PERMEABILITY
LOW
SOLUBILITY
Source: INTERNET
9. BRIEF ABOUT BCS CLASS
Wednesday,April 11, 20189
BCS CLASS-1
Compound are well absorption & high absorption rate as compared to excretion.
Drugs exhibit High Abs. number & High dissolution number.
RLS – Dissolution
If, dissolution is rapid then gastric emptying rate will be RLS.
Examples: Metoprolol, Diltiazem, Verapamil, Propranolol
BCS CLASS-2
Bioavailability of these products is limited by their solvation rate.
Drugs have a high absorption number but a low dissolution number.
The absorption for class II drugs is usually slower than class I and occurs over a
longer period of time.
10. Wednesday,April 11, 201810
BCS CLASS-3
The absorption is limited by the permeation rate but the drug is solvated very fast..
If the formulation does not change the permeability or gastro-intestinal duration
time then class I criteria can be applied.
High variation in the rate and extent of drug absorption.
Since the dissolution is rapid, the variation is an aspect to alteration of physiology
and membrane permeability rather than the dosage form factors.
Examples: Cimetidine, Acyclovir, Neomycin B and Captopril.
BCS CLASS-4
These compounds have a poor bioavailability and not good absorbed over the
intestinal mucosa properly
Lot of problems for effective oral administration.
Examples : Hydrochlorothiazide and Taxol.
11. BCS CLASS BOUNDARIES: OBJECTIVES
Wednesday,April 11, 201811
DISSOLUTION
(PRODUCT)
SOLUBILITY
(DRUG)
PERMEABILITY
(DRUG)
Thisinformationistakenfromthe:WHOworkshopon
pre-qualificationofmedicinesprogramme,
Abudhabi,11-13october,2010presentedbyDr,JANWELINK
Very rapid/rapid dissolution - ensure
that in vivo dissolution is not likely to
be the “rate determining” step
High solubility- ensure that solubility
is not likely to limit dissolution and,
therefore, absorption
High permeability - ensure that drug
is completely absorbed during the
limited transit time through the small
intestine
12. DATA TO SUPPORT REQUEST FOR
BIOWAIVERS
Wednesday,April 11, 201812
HIGH SOLUBILITY DEFINITION:
The highest single unit dose is completely soluble in 250 ml or less of aqueous
solution at pH 1 – 7.5 (37°C)
250 ml: derived from typical BE study protocols that prescribe the administration
of a drug product to fasting human volunteers with a glass (approx. 250 ml) water
HIGH PERMEABILITY DEFINITION:
According to HHS-FDA, when 90 % or more of the orally administered dose is
absorbed in the small intestine.
Permeability can be assessed by pharmacokinetic studies (for example, mass
balance studies), or intestinal permeability methods, e.g. intestinal perfusion in
humans, animal models, Caco2 cell lines or other suitable, validated cell lines.
13. Wednesday,April 11, 201813
Dissolution:
In three different media: pH 1.2 HCl, pH 4.5 Acetate buffer and pH 6.8 Phosphate
buffer, composition in a paddle (50 rpm) or basket (100 rpm) apparatus at 37 °C
and a volume of 900 ml.
A. Very Rapid Dissolution:
An IR drug product is considered VERY RAPIDLY DISSOLVING when >85%
of the labeled amount of drug substance dissolves within 15 minutes.
B. Rapid Dissolution:
An IR drug product is considered RAPIDLY DISSOLVING when >85% of the
labeled amount of drug substance dissolves within 30 minutes.
CONT….
14. REQUIREMENTS FOR A
BCS-BASED BIOWAIVER
Wednesday,April 11, 201814
There have been certain requirements for a biowaiver study that include
allowance of regulatory authorities like FDA and WHO etc. The drugs
should have high solubility and high permeability according to BCS.
Requirements for a BCS-based biowaiver study include:
1. Dissolution Test in 3 different media (in 900 ml and at 37°C) which are:
Buffer pH 1.2, Or simulated gastric fluid without enzymes or 0.1N HCl.
Buffer pH 4.5.
Buffer pH 6.8 or simulated intestinal fluid without enzymes.
2. 12 samples in each media, paddle rotating at 50 rpm or basket at 100 rpm.
3. Sampling times are 10, 15, 20, 30, 45 and 60 minutes.
4. The profiles of the test and reference products must be similar in all
three media.
15. ADDITIONAL CONSIDERATIONS
FOR REQUESTING A BIOWAIVER
Wednesday,April 11, 201815
A. Excipients
BCS classification is related to API without excipients. However,
literature evidence illustrates how excipients may affect the fraction of
dose absorbed by modulating disintegration, solubilization or stabilizing a
specific polymorphic form, thereby changing the dissolution characteristics
of the API.
The effect of excipients is strictly limited by the guidance documents:
qualitative differences in excipients from which an effect on the
bioavailability could be expected are not accepted, whereas scientific
reasoning may justify larger and still safe deviations.
16. CONT..
Wednesday,April 11, 201816
Excipients used in the dosage form must have been used in a previously
approved immediate release solid oral dosage form by the FDA.
The quantity of excipients in the IR product should be consistent with
their intended function. Large quantities of certain excipients, such as
surfactants (e.g., sodium lauryl sulfate) or osmotic ingredients (e.g.,
sorbitol) may be problematic.
B. Prodrugs
Conversion site of prodrug to drug must be considered, if it occurs
before intestinal absorption then permeability study of drug must be
done otherwise permeability study of prodrug must be done.
17. To be considered bioequivalent according to the
HHS-FDA biowaiver procedure
Wednesday,April 11, 201817
Or,
Eligibility criteria for biowaiver acc. to HHS-FDA
1. BCS Class of API:- CLASS 1
2. Dissolution characteristics: Rapidly dissolving, in three different media
• First Option: Very rapidly dissolving and no further profile comparison
•Second Option: Rapidly dissolving and Proving similarity of dissolution profiles
of T and R (e.g. using f2-test).
3. Excipients:- Must not influence the absorption of the API (affecting motility or
permeability).
4. Therapeutic Index:- Not contain’s an API with a narrow T.I
5. Formulation:- Product should not be designed to be absorbed from the oral
cavity.
18. To be considered bioequivalent according to the
WHO biowaiver procedure
Wednesday,April 11, 201818
Or,
Eligibility criteria for biowaiver acc. to WHO
1. BCS Class of API:- Class II acids with D:S ratio in 250ml or lower at pH 6.8
or >85% dissolved within 30 minutes at pH (75rpm) .
Class III compounds are eligible, if they dissolved within 15 minutes in buffer
media ph 1.2-6.8 (75rpm).
2.FILLING PROCEDURE:-
MUST NOT FOLLOW FDA, SHOULD BE STICK TO WHO GUIDELINES
3. pH FOR SOLUBILTIY DETERMINATION:- 1.2 TO 6.8
4. PERMEABILITY:- MUST BE HIGH (i.e., >85%)
19. REGULATORY PROVISONS OF BIOWAIVERS :
GLOBAL PERSPECTIVE;
A COMPARATIVE APPROACH
Wednesday,April 11, 201819
PARAMETERS US EU JAPAN
ALLOWED BCS
CLASS
I I & III All
HIGHLY
PERMEABLE
>90% >85% Not relevant
RAPIDLY
DISSOLVING
>85% in 30 min,
at pH 3
(pH 1.0, 4.6 , 6.8)
>85% in 15 min,
at pH 3
(pH 1.2, 4.5 , 6.8)
No requirement
MEDIA
SURFACTANT
SUPAC allowed- if
justified.
None “strictly
discouraged”.
Required if low
solubility
INTRA-MURAL
COMPOSITION
CHANGE
SUPAC allowed- for
all BCS classes.
Variation Type A-E, Type B, C, E
like SUPAC level 1,2,3
Type D unique
IVIVC AS DOSAGE
REGIMEN/BE
SURROGATE
Allowed for Moderate
Release SUPAC
Allowed Not permitted
Source: INTERNET
20. CURRENT PEDESTALS OF BIOWAIVERS
Wednesday,April 11, 201820
C.P :- COMPOSITION PROPORTIONALITY
SOURCE ;- INTERNET
BCS
• CONSIDER THE DOSE:SOLUBILITY RATIO,
PERMEABILITY & DISSOLUTION BEHAVIOUR.
IVIVC
• BASED ON CORRELATION BETWEEN IN-VITRO
DATA TO IN-VIVO PROFILE.
C.P
• NEW PRODUCT IS QUALITATIVELY SAME &
QUANTITATIVELY PROPORTIONAL TO BIO-BATCH.
21. APPLICATION OF BIOWAIVER
Wednesday,April 11, 201821
1 & 2
• FOR CHECKING VARIATIONS IN DRUG PRODUCTS
• FOR GENERIC DRUG APPLICATION
3
• DEVELOPING NEW DRUG PRODUCTS e.g., BRIDGING
STUDIES, PILOT BATCH v/s PRODUCTION BATCH.
4
• BIOWAIVER MEANS TO OBTAIN WAIVE OFF FOR
CARRYING OUT EXPENSIVE AND TIME-CONSUMING BA
AND BE STUDIES.
22. CONCLUSION
Wednesday,April 11, 201822
An important application of BCS in the regulatory documents is the use of
BCS in the guidance for biowaiver procedures. One of the most important
criteria for deciding whether a BCS-based biowaiver is appropriate is
the BCS class of the API.
For instance, products containing BCS class IV APIs are excluded from
the BCS-based biowaiver procedure.
Additionally, products containing class III APIs cannot, as of this
writing, be approved in the USA by the biowaiver procedure. In the
EU and countries using the WHO criteria, products containing Class
III APIs are only eligible for biowaiving if they are very rapidly
dissolving.
Class II APIs are only eligible for the biowaiver procedure in countries
using the WHO criteria and then only in the case of a weak acid that is
highly soluble at pH 6.8.
By contrast, Class I APIs are eligible for the biowaiver procedure in all
jurisdictions that apply it (Japan, notably, is a country that does not
yet allow approval of drug products using the BCS-based biowaiver
procedure).
23. REFERENCE
Wednesday,April 11, 201823
REVIEW ARTICLES
Biowaivers - an updated review By, Abilash. N*, Chandramouli. R, “Department of
Quality Assurance”, Krupanidhi College of Pharmacy, #12/1, Chikkabellandur, Carmelaram
Post, Varthur Hobli, Bangalore - 560035, KA
POWERPOINT PRESENTATION
Basis for BCS-based Biowaiver By Mohamed Abdeen, “R&D department”,
Azal pharmaceutical Co.LTD
Biowaiver monograph for Immediate release Solid oral dosage forms:
Ibuprofen by H.POTTHAST*, Federal institute for drug & medical devices,
(BfArm), kurt georg-kiesinger-Allee 3, Bonn, Germany
BIOWAIVERS: CRITERIAAND REQUIREMENTS, “Prepared by Dr. Mazen
Kurdi”, “Reviewed by Dr. Rita Karam 2015