Grade Statistics without Bonus with Bonus Average = 86 Median = 87 Average = 88 Median = 89 Undergraduates Average=88 MS Average=92.

Slides:



Advertisements
Similar presentations
Design of Bioequivalence Studies Alfredo García – Arieta, PhD
Advertisements

Regulation documentation requirements
Bioequivalence Studies Anoop Agarwal
Henning H. Blume, PhD SocraTec R&D, Oberursel/Germany
III. Drug Metabolism  The aim of drug metabolism is to convert lipid soluble (non polar) drugs to polar metabolites easily excreted in urine.  The liver.
1 Endogenous Substance Bioavailability and Bioequivalence: Levothyroxine Sodium Tablets Steven B. Johnson, Pharm.D. Division of Pharmaceutical Evaluation.
Overview of the Clinical Development EMBEDA™ (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules for oral use. ASENT 12 th Annual.
Pharmacokinetics as a Tool
Kyiv, TRAINING WORKSHOP ON PHARMACEUTICAL QUALITY, GOOD MANUFACTURING PRACTICE & BIOEQUIVALENCE Introduction to the Discussion of Bioequivalence.
Dale P. Conner, Pharm.D. Division of Bioequivalence OGD, CDER, FDA
Federal Institute for Drugs and Medical Devices The BfArM is a Federal Institute within the portfolio of the Federal Ministry of Health 1 Regulatory Requirements.
Bioavailability and Bioequivalence
Clinical Pharmacology Overview From the Antiviral Perspective Kellie Schoolar Reynolds, Pharm.D. Pharmacokinetics Team Leader Office of Clinical Pharmacology.
Hanoi, WORKSHOP ON PREQUALIFICATION OF ARV: BIOEQUIVALENCE Introduction to the Discussion of Bioequivalence Study Design and Conduct Presented.
Artemisinin combined medicines, Kampala, February |1 | Training workshop on regulatory requirements for registration of Artemisinin based combined.
Evaluation of quality and interchangeability of medicinal products - EAC/EC/WHO Training workshop / September |1 | Prequalification programme:
Interchangeability and study design Drs. Jan Welink Training workshop: Training of BE assessors, Kiev, October 2009.
FDA Nasal BA/BE Guidance Overview
Venkata Ramana S. Uppoor, M.Pharm., Ph.D., R.Ph.
Tanzania, August, 2006 Dr. Barbara Sterzik, BfArM, Bonn 1 Guidelines and Tools available TRS 937 and BTIF (Bioequivalence Trial Information Form)
Documentation of bioequivalence Drs. J. Welink Workshop on WHO prequalification requirements for reproductive health medicines, Jakarta, October 2009.
Bioequivalence Studies Dr Sanet Aspinall, PhD Managing Director AddClin Research Pretoria 20 March 2009.
Gokaraju Rangaraju College of Pharmacy
OVERVIEW OF DACA BIOEQUIVALENCE REPORT EVALUATION Presented by Solomon Shiferaw 31Augst 2010.
Week 6- Bioavailability and Bioequivalence
Case studies Saila Antila, PhD WHO consultant Training workshop on Pharmaceutical Quality, Good Manufacturing Practice & Bioequivalence, Kiev
Regulatory requirements Drs. Jan Welink Training workshop: Assessment of Interchangeable Multisource Medicines, Kenya, August 2009.
1 Axcan Public Presentation for the FDA Pharmaceutical Science and Clinical Pharmacology Advisory Committee Meeting July 23, 2008.
1 QT Evaluation Studies: Pharmacometric Considerations Leslie Kenna, Peter Lee and Yaning Wang Office of Clinical Pharmacology and Biopharmaceutics CDER/FDA.
Bioavailability  The in- vitro methods of evaluating dosage forms provide only indirect evidence of the therapeutic utility of the drug in a given dosage.
SYSTEMIC ABSORPTION AS THE MOST ACCURATE AND SENSITIVE METHOD OF DETERMINING BIOEQUIVALENCE OF GENERIC TOPICAL PRODUCTS Chris Hendy Ph.D. Novum Pharmaceutical.
Bioavailability Dr Mohammad Issa.
FARMAKOKINETIKA. INTRODUCTION Historically, pharmaceutical scientists have evaluated the relative drug availability to the body in vivo after giving a.
Evaluation of quality and interchangeability of medicinal products - WHO Training workshop / 5-9 November |1 | Prequalification programme: Priority.
Drug Administration Pharmacokinetic Phase (Time course of ADME processes) Absorption Distribution Pharmaceutical Phase Disintegration of the Dosage Form.
Bioequivalence of Locally Acting Gastrointestinal Drugs: An Overview
CHEE 4401 Definitions drug - any substance that affects the structure or functioning of an organism pharmaceutics - the area of study concerned with the.
Dr. Muslim Suardi, MSi., Apt. Faculty of Pharmacy University of Andalas.
Bioequivalence Dr Mohammad Issa Saleh.
1 Single-dose kinetics Plasma [Drug] curve Upon administration [drug] plasma reaches a max Then begins to decline as the Drug is eliminated Cp max = max.
Drug Release Specification: In Vivo Relevance Ajaz S. Hussain, Ph.D. Deputy Director, OPS/CDER/FDA.
WHO Prequalification Programme June 2007 Training Workshop on Dissolution, Pharmaceutical Product Interchangeability and Biopharmaceutical Classification.
Bioavailability Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics Faculty of Pharmacy Omer Al-Mukhtar University Tobruk, Libya.
Using Product Development Information to Address the Bioequivalence Challenges of Highly-variable Drugs Lawrence X. Yu, Ph. D. Director for Science Office.
Introduction What is a Biowaiver?
Bioavailability and Bioequivalence General concepts and overview
Malaysia, EVALUTION OF DOSSIERS IN WHO- PREQUALIFICATION PROJECT MULTISOURCE TB-DRUGS Evaluation of bioavailability/bioequivalence data Based,
Bioavailability and Bioequivalence L 10,11.  Bioavailability is a measurement of the rate and extent (amount) to which the active ingredient or active.
Exact PK Equivalence for a bridging study Steven Novick, Harry Yang (MedImmune) and Xiang Zhang (NC State) NCB, October 2015.
Evaluation of quality and interchangeability of medicinal products - WHO Training workshop / 5-9 November |1 | Prequalification programme: Priority.
Interchangeability and study design Drs. Jan Welink Training workshop: Assessment of Interchangeable Multisource Medicines, Kenya, August 2009.
PHT 415 BASIC PHARMACOKINETICS
Topic #2: Quality by Design and Pharmaceutical Equivalence Ajaz S. Hussain, Ph.D. Office of Pharmaceutical Science Center for Drug Evaluation and Research.
Test Undergraduate – 24 Questions: Multiple Choice, Fill-in and T/F – 3 Problems MS – 3 Questions: Multiple Choice, Fill-in and T/F – MS grade: Undergrad.
In vitro - In vivo Correlation
The First Conference for Medicines Regulatory Authorities In Sudan and Neighboring Countries Khartoum December 2014 Alain PRAT, Technical Officer,
Definitions and Concepts
BIOAVAILABILITY AND BIOEQUIVALENCE TESTING Department of Pharmaceutics.
Chapter 8 BIOAVAILABILITY & BIOEQUIVALENCE
Controls and Functions
Dissolution testing and in vitro in vivo correlation of conventional and SR preparations Formulation development and optimization is an ongoing process.
Chapter 1 Introduction to Biopharmaceutics & Pharmacokinetics
Quantitative Pharmacokinetics
Clinical Pharmacokinetics
Selected Bioavailability and Pharmacokinetic Calculations
1 Concentration-time curve
Basic Biopharmaceutics
Bioequivalence trials: design, evaluation, regulatory requirements
Therapeutic Drug Monitoring chapter 1 part 1
Introduction to Research Methods in Psychology
Presentation transcript:

Grade Statistics without Bonus with Bonus Average = 86 Median = 87 Average = 88 Median = 89 Undergraduates Average=88 MS Average=92

Advice for Next Test Normalized means /kg, unless otherwise specified – Normalized dose = mg/kg Don’t totally depend on the handouts – Check website for changes and updates, student questions answered, etc. Bonus Points – Rules on the (0.5 and 1.0 points)

Advice for Next Test Multiply Normalized Values by the weight. – V Normalized = 0.1 L/kg – V = 0.1 L/kg * 70 kg = 7L (Experts Only) Keep normalized values consistent.

MS Project NCA Modeling Project due today Due 9/28/15: More Comprehensive Project – Plotting – Table – NCA – Compartment Modeling (Classic) Grading?

MS Project Your Own Data to Analyze4 Excercises

BIOAVAILABILITY Lecture #14

AUC?, C MAX ?, t MAX ?, k a ?, k? Elimination “Rate” Limiting ~Slope Shallow ~Slope Steep

Bioavailability

Drug Interactions My version Book’s Cryptic Version

Relative Bioavailability Dosage Forms Different Extravascular Administration Routes Different Conditions

Relative Bioavailability (A vs. B)

Dosage Forms Tablet Capsule

Extravascular Administration Routes Oral Intramuscular (I.M.)

Conditions Without food With food

Urine Data

Bioavailability and Urine

Relative Bioavailability and Urine

Assessment of Product Performance Formulation – Biopharmaceutics – Excipients Bioequivalence (BE) Bioavailability (BA) and BE Testing

Biopharmaceutics Physical/Chemical Drug Properties Dosage Form (Tablet, Capsule) – Formulations (Industry) Route of Administration Rate/Extent of Systemic Drug Exposure

Excipients Inactive stuff that you put with the drug Natural/Synthetic Bulking up the formulation – “bulking agents”, “fillers”, “diluents” Therapeutic Enhancement – drug absorption – solubility

Bioequivalence Essentially similar – Different Dosage Forms/Same PK Generic products 0.8 to 1.25 (Test/Reference Ratio) 90% CI AUC and C MAX

On the NDA = New Drug Application IND = Investigational New Drug Application Not in Textbook

BA and BE Testing: Study Types Longitudinal Study – Same Subjects over a Period of Time – Cohort (Defined)/Panel (Cross-Section) – Retrospective Clinical Trials – Randomized – Crossover – Blind, Double blind and Triple Blind

Randomized vs. Crossover Clinical Trials Tablet Patient 1 Capsule Patient 2 Placebo Patient 3 Randomized (Treatments Random) Tablet Capsule Placebo Capsule Tablet Placebo Tablet Capsule Placebo Patient 1 Patient 2 Patient 3 Crossover (Sequence of Treatments Random)

Randomized vs. Crossover Trials Randomized – Pros Relatively simple to execute. Not susceptible to carry-over effects. – Cons Wide variation  significant error in the analysis. Crossover – Pros Compare treatments with a patient, so variation between patients is eliminated – Cons Susceptible to carry-over effects.

Blind Clinical Trials Patient Receiving the Drug Person Administering the Drug Person Overseeing the Trial Blind Double BlindBlind Triple BlindBlind

BA and BE: Considerations by the FDA Study Type Dosing Frequency What is measured? PK? Other Documentation (Lots)

Study Type Pilot Study – 8-12 Subjects Full-Scale – Subjects >18 years old and healthy Cohort or Panel – (gender?) Fasting conditions (>10 hours overnight)

Dosing Frequency Single Dose – Preferred – Easier to assess PK parameters than multiple dose (steady state) Multiple Dose – Differences absorption rate, not the extent of absorption. – Excessive variability in bioavailability (BA) – [drug] plasma too low with single dose – Extended release dosage form

Moieties to be Measured Preferred: Active Ingredient or moiety Active Metabolite – [Active ingredient or moiety] too low – Contributes to safety/efficacy

PK? Appropriate Fluid: blood, plasma, serum PK – Peak Exposure: C MAX (Directly Plasma) t max – Total Exposure AUC – Partial Exposure Partial AUC MEC = Minimum Effective Concentration MTC = Minimum Toxic Concentration

Other In vitro to human in vivo correlation (IVIVC) – in vitro dissolution/drug-release characterization PD studies – not recommended for orally administered drugs – PK measurements preferred (More accurate/sensitive/reproducible) – only if PK fails Clinical Endpoints (e.g. Cured) (Rare) In vitro (e.g. dissolution testing)

Bioavailability Example Parameters AUC ev = (mg*hr)/L A ev = 7 mg F? AUC iv = (mg*hr)/L A iv = 4 mg