Impact of Modeling and Simulation on Generic Drug Development and Review
|
|
- Conrad Wilcox
- 7 years ago
- Views:
Transcription
1 Impact of Modeling and Simulation on Generic Drug Development and Review Robert Lionberger, Ph.D. Director Office of Research and Standards Office of Generic Drugs Center for Drug Evaluation and Research, FDA OrBiTo OPEN Science Day Beyond BCS based biowaivers July 1, 2015
2 2 Disclaimer The views expressed in this presentation are those of the speaker and not necessarily those of the Food and Drug Administration (FDA).
3 Impact of Generic Drugs 3
4 4 What is the Science of Equivalence? Science of bridging product A works as well as product B Generic drugs are affordable because we usually do not repeat clinical studies in patients Generic drugs are intended to be used by patients The science of therapeutic equivalence is to combine In vivo and in vitro performance data Product design Patient characteristics and product use To ensure successful generic substitution
5 5 New Office of Research and Standards within OGD Division of Therapeutic Performance (DTP) Facilitates pre-anda development of generic drugs Conducts and promotes regulatory science research to establish standards to ensure therapeutic equivalence of generic versions of drug products. Evaluates post-approval safety, product use and bioequivalence issues with approved generic drugs. Division of Quantitative Methods And Modeling (DQMM) Establishes predictive and physiological models of drug product performance, drug absorption, drug pharmacology, and other quantitative methods to ensure generic drug equivalence. Develops new tools to analyze in vitro, pharmacokinetic, pharmacodynamics and clinical bioequivalence studies.
6 6 Core DQMM Tool Set Oral Drug Release/Absorption/PBPK Models Non-Oral Drug Release/Absorption/PBPK Models Pharmacometrics PK/PD, population models Big Data Analytics for complex mixtures, systems pharmacology, risk models, business process models, medical records, generic drug utilization Goal: Support generic drug research, policy development and regulatory decisions
7 7 Generic Drug Priority Areas Post-market Evaluation of Generic Drugs Equivalence of Complex Products Equivalence of Locally Acting Products Therapeutic Equivalence Evaluation and Standards Oral PBPK Non-oral PBPK PK/PD Big Data X X X X X X X X X X X
8 M&S in Generic Drug Evaluation Use for generics is to assess the risk that differences from a reference impact therapeutic substitutability BE guidance development pauc, e.g. zopidem,. (all consideration of pauc include simulation evaluation) Narrow Therapeutic Index drugs (NTID) classification nonlinear PK properties ANDA Review BE study design or control of critical attributes Post-marketing efficacy & safety evaluation of generic drugs Evaluate risks of potential failure mechanisms Methylphenidate, Warfarin, Nifidipine
9 ORAL ABSORPTION 9
10 10 Oral Absorption Models The context for biopharmaceutics modeling and simulations in the generic drug framework is different than from modeling and simulation in drug discovery and development Much more knowledge about drug and human PK data often available Goal: Predict Bioequivalence for Oral Formulations Applications to generic drug review BE standards for MR products (different mechanism between brand and generic) Partial AUC for multiphasic MR products Waivers of lower strength products Risk of formulation changes (particle size, polymorphic form) Locally acting GI drug bioequivalence Linkage from healthy subjects to patients
11 Factors Affecting Oral Absorption 11
12 Inputs and Outputs Drug substance and product information: Dose and dose volume Solubility vs. ph profiles logp, pka Dissolution: MR: dissolution profiles; IR: particle size and density Diffusion coefficient Permeability Metabolic kinetics PK parameters Clearance, Vd Tissue/organ parameters for physiologically based distribution and elimination models Fh, BA PK profiles Metabolite Info Physiological parameters GI transit time GI geometry GI fluid properties Enzymes/transporters distribution Blood flow Fa, Fg In vivo dissolution Drug in each cmpt Parent and metabolite PK 12
13 Example Use in Formulation Evaluation 13
14 Gaps for Oral Absorption There is a linkage between challenges in absorption modeling and simulation and IVP dissolution. Both need more data about in vivo physiology You want IVP dissolution to be the input that closes gaps in the models Gap: Improving the modeling and simulation for colon absorption to fully account for the performance of modified release dosage forms. Gap: Improving knowledge of in vivo hydrodynamics is needed to improve the models and IVP dissolution
15 Gaps for Oral Absorption Variability: For the generic drug program, simulation of a cross-over bioequivalence study is an important modeling and simulation application but current data sets and models of within subject variability for GI parameters lag the understanding of between subject variability. Formulation: The interaction of formulation variables with physiological factors is important to the design of bioequivalent formulations. This includes improved prediction of food effect, prediction of bioavailability for complex formulations and solid dispersions, and prediction of bioavailability for nano-size formulations.
16 16 GDUFA Research Studies Prediction of In Vivo Performance for Oral Solid Dosage Forms Awarded to the University of Michigan (HHSF C) The purpose of this contract is to improve prediction of in vivo performance of oral solid dosage forms. The scope includes modeling of GI fluid hydrodynamics, sampling of GI tract fluids composition and ph, novel dissolution methods and in vivo PK studies to validate model predictions. Pharmacokinetic Study of Bupropion Hydrochloride Products with Different Release Patterns Awarded to University of Michigan (HHSF C) The objectives of this contract are to conduct healthy subject pharmacokinetic studies of bupropion HCl modified release products with different release patterns and different doses. This will help FDA understand how the release pattern of bupropion HCl products and the genotype of metabolic enzyme may affect the bioequivalence conclusions across different dose strengths within one product line due to the saturation of intestinal metabolism.
17 17 GDUFA Research Studies Bioequivalence and Characterization of Generic Drugs Awarded to Vince & Associates Clinical Research, Inc. (#HHSF I). As part of the continuous monitoring of approved generics, this contract will support bioequivalence studies of approved generic drugs including bioequivalence between: (1) generic and brand methylphenidate hydrochloride extended release (ER) tablets and (2) a reference listed drug and generic warfarin sodium products from different suppliers and stored under different conditions, including real world use conditions. Research outcomes will include evaluating the use of replicate design bioequivalence studies for generic methylphenidate hydrochloride ER products and developing clinically relevant quality standards for warfarin sodium products.
18 18 GDUFA Research Studies Effect of Different Preparation Methods on the In Vitro and In Vivo Performance of Solid Dispersion Formulations Awarded to Purdue University, West Lafayette (1U01FD ). The study goal is to investigate the in vitro and in vivo performance of solid dispersion drug products originating from different manufacturing processes or polymer carriers and to assess performance consistency among batches and during storage. Study outcomes will identify critical process parameters and critical quality attributes for solid dispersion drug products originating from various preparation methods and will develop discriminating analytical methods for these drug products.
19 NON-ORAL ABSORPTION 19
20 Physiologically based absorption and PK models Drug substance Formulations In vitro performance Model In vivo performance 20 Jiang W, Kim S, Zhang X, Lionberger RA, Davit BM, Conner DP, Yu LX. Int J Pharm Oct 14;418(2):
21 21 Non-Oral Absorption Models The lack of efficient bioequivalence methods for locally acting drugs has limited the availability of generic drugs in this category. Research is focused on new bioequivalence approaches Inhalation Topical dermatological Nasal GI acting Ophthalmic Role of Models Planned project outcomes are simulation tools that capture the current understanding of the complex interplay between product attributes and human physiology and that help to develop new bioequivalence approaches for locally-acting drugs. Models that embody mechanistic absorption modeling and physiologically-based pharmacokinetics (PBPK) can be useful tools for both industry scientists and regulators to reduce the time and expense involved in determining whether a new formulation will be bioequivalent to an approved dosage form.
22 22 Funded Studies Topical and dermal absorption modeling University of South Australia, and Simcyp, LTD Ocular dosage forms PBPK modeling Simulations Plus, Inc., and CFD Research Corporation Intranasal CFD-PBPK modeling Applied Research Associates, Inc. Lung CFD-PBPK absorption modeling CFD Research Corporation PBPK modeling for complex parenteral injectables State University of New York at Buffalo
23 23 Highlights of Work in Progress Topical Dermatological Products Six coordinated grants (international: US, Europe, Australia) that include New in vivo data Manufacturing of semi-solid formulations Characterization of semi-solid formulations New PBPK modeling approaches Inhalation Products Role of dissolution, particle size and PK studies CFD modeling of deposition Ophthalmic Products Nine coordinated grants on in vitro characterization, drug release, and drug delivery modeling Nasal Products Use of PK studies alone for BE: in vitro, in vivo and modeling projects
24 24 GDUFA Research Studies Pulmonary Delivery Awarded to CFD Research Corporation (1U01FD ). A hybrid CFD model will be developed to predict particle deposition throughout the human airway. The hybrid model will be linked to PBPK and PD models to predict in vivo performance for orally-inhaled drug products. This computational tool will serve as a virtual platform to simulate drug PK/PD, optimize pulmonary drug delivery, and facilitate generic pulmonary drug development. Nasal Delivery Awarded to Applied Research Associates, Inc. (1 U01 FD ). In this proposal, PBPK absorption models will be linked to computational fluid dynamics models to simulate the delivery of sprayed droplets to the nose, the absorption of the drug through the nasal mucosa, and the systemic bioavailability of intranasal corticosteroids. Model simulations will improve our understanding of the absorption of intranasal corticosteroids under different dosing scenarios and will support and facilitate generic drug guidance and product development for nasal suspensions.
25 25 GDUFA Research Studies: Dermal Dermal absorption PBPK Models Awarded to the University of South Australia (1 U01 FD ) and Simcyp, Ltd. (1 U01 FD ). The University of South Australia project aims to develop a framework of physiologically-based absorption and pharmacokinetic models that define the interactions between the product and the skin and seek to predict drug and drug plasma/blood concentrations at the site of action. The Simcyp, Ltd. project goal is to develop a physiologically-based dermal absorption and disposition model supported by a clinical trials simulator platform model that accounts for variability and gender effects in healthy Caucasian volunteers. This model will be mechanistically enhanced and validated with reference to other races and special populations including pediatric, geriatric, and those populations with diseases, such as rheumatoid arthritis. The performance of the PBPK model and associated databases will be validated against clinical pharmacokinetics data for dermal products.
26 26 GDUFA Research Studies: Ocular Ocular delivery PBPK Models Awarded to Simulations Plus, Inc. (1U01FD ) and CFD Research Corporation (1U01FD ). The Simulations Plus award will advance the state of the art for ocular PBPK and mechanistic absorption modeling (MAM) software through a combination of expanding the existing knowledge base for ocular drug absorption and pharmacokinetics and implementing enhanced physiological models for human and animal eyes in the well-established Ocular Compartmental Absorption and Transit (OCAT ) MAM/PBPK model within the GastroPlus software program. The CFD Research grant will support high-fidelity models in the form of a parametric 2D/3D eye mesh model (human and animal), enabling simulation of various modes of delivery. The novel computational tool will simulate ocular drug delivery and its interaction locally and systemically within the whole body, thereby providing an accurate and efficient computational platform to virtually test, design, and develop generic ocular drug products.
27 M&S Impact in OGD Type N Examples ANDA Reviews CP, CC, and Other Consult Response PD modeling and simulation for budesonide nasal spray to support the selected dose for BE study. Development of BE criteria for zolpidem tartrate ER tablets Steady state simulations for risperidone long acting injection Simulation of in vivo alcohol dose dumping studies BE Guidances Regulatory Research Study Simulations for the development of BE criteria for complex drugs, HVDs and NTI drugs PK/PD modeling and simulation to determine the appropriate study design and evaluate BE between generic anti-epilepsy drugs and immunosuppressant drugs in patients. 27
28 28 M&S (PBPK) Submissions NDA PBPK ANDA Little attempt to use in submission Use in development? Two dispute resolution requests Nasal GI locally acting
29 Innovation Model for Future ANDA 29
30 30 GDUFA Regulatory Science Leap FDA is engaging with leading pharmaceutical and clinical scientists from across the world to ensure that the regulatory review of generic drugs is based on the best available science. Over 100 GDUFA related proposals were submitted and reviewed last summer Contracts/Grants ($$) And ORISE New Contracts/Grants FY2014 $22.8M 35 FY2013 $20.9M 28 FY2012 $3.6M 4 FY2011 $2.2M 3 FY2010 $3.1M 5
31 31 GDUFA Regulatory Science Impact Both FDA and Generic Industry Have a Common Customer Patients who want high quality generic products in all product categories Research leads to generic availability in all product categories Standards and post-approval monitoring build confidence in generic drug substitution Advance the science of equivalence: Prioritize tools and science that make equivalence evaluation clear and development easier Product design for human use
GDUFA Regulatory Science Update
GDUFA Regulatory Science Update Robert Lionberger, Ph.D. Director Office of Research and Standards Office of Generic Drugs Center for Drug Evaluation and Research, FDA GPhA Annual Meeting Feb 9, 2015 Goals
More informationGuidance for Industry
Guidance for Industry Food-Effect Bioavailability and Fed Bioequivalence Studies U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER)
More informationOverview of Dissolution for BA/BE
Biopharmaceutics Classification System based on Solubility/Permeability Biowaivers for BCS I Drugs Discussion of BCS III Drugs Models establishing in vivo-in vitro Correlations (IVIVC Levels A-C) 1 Biopharmaceutics
More informationGuidance for Industry
Guidance for Industry Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs General Considerations DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments
More informationGuidance for Industry
Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products General Considerations U.S. Department of Health and Human Services Food and Drug Administration Center
More informationANDA CHECKLIST FOR CTD or ectd FORMAT FOR COMPLETENESS and ACCEPTABILITY of an APPLICATION FOR FILING
ANDA CHECKLIST FOR CTD or ectd FORMAT FOR COMPLETENESS and ACCEPTABILITY of an APPLICATION FOR FILING For More Information on Submission of an ANDA in Electronic Common Technical Document (ectd) Format
More informationDRAFT GUIDANCE. This guidance document is being distributed for comment purposes only.
Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System Guidance for Industry DRAFT GUIDANCE This guidance
More informationEXIGENCIA DE ESTUDIOS DE BIOEQUIVALENCIA A TRAVÉS DE METODOS IN VITRO
EXIGENCIA DE ESTUDIOS DE BIOEQUIVALENCIA A TRAVÉS DE METODOS IN VITRO Q.F. ALEXIS ACEITUNO, PhD Jefe Subdepto. Biofarmacia & Bioequivalencia Agencia Nacional de Medicamentos Instituto de Salud Pública
More informationBundesinstitut für Arzneimittel und Medizinprodukte. Dissolution Testing. Analytik,Methodenentwicklung, Bioäquivalenz SAQ. Olten, 25.
Dissolution Testing Analytik,Methodenentwicklung, Bioäquivalenz SAQ Olten, 25. Januar 2006 Dr. H. Potthast (h.potthast@bfarm.de) 1 2 Basis for Biowaiver Applications/Decisions Note for Guidance on the
More informationBIOAVAILABILITY & BIOEQUIVALENCE TRIALS
BIOAVAILABILITY & BIOEQUIVALENCE TRIALS Shubha Rani,, Ph.D. Technical Director & Head-Biometrics and Data Management Synchron Research Services Pvt. Ltd. Ahmedabad 380 054 drshubha@synchronresearch.com
More informationPost-Approval Change Management: Challenges and Opportunities An FDA Perspective
CMC Workshop From Drug Development to Global Supply to Patients April 15-17, 2013, Washington, DC Post-Approval Change Management: Challenges and Opportunities An FDA Perspective Christine M. V. Moore,
More informationGuidance for Industry
Guidance for Industry Dissolution Testing of Immediate Release Solid Oral Dosage Forms U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research
More informationLetter Date March 27, 2007 Stamp Date March 28, 2007 PDUFA Goal Date January 28, 2008
CLINICAL REVIEW Application Type NDA Submission Number 22-157 Submission Code Letter Date March 27, 2007 Stamp Date March 28, 2007 PDUFA Goal Date January 28, 2008 Reviewer Name Review Completion Date
More informationIntroduction to pharmaceutical technology
Introduction to pharmaceutical technology Marie Wahlgren Chapter 1 What is the topics of today Introduction to the course Introduction to the project assignment How to choose a new drug formulation 1 Contacts
More informationCompilation of individual product-specific guidance on demonstration of bioequivalence
17 December 2014 EMA/CHMP/736403/2014 Committee for Medicinal Products for Human Use (CHMP) Compilation of individual product-specific guidance on demonstration of bioequivalence Initial batch of individual
More informationDevelopment of the compound database
APS - Progress within the IMI OrBiTo project predictive tools for oral biopharmaceutics GSK Stevenage Kristin Lacy, Alison Margolskee, Adam Darwich, Xavier Pepin, Amin Rostami Development of the compound
More informationAbsorption of Drugs. Transport of a drug from the GI tract
Absorption of Drugs Absorption is the transfer of a drug from its site of administration to the bloodstream. The rate and efficiency of absorption depend on the route of administration. For IV delivery,
More informationCTD Dossier Preparation. Sr.Manager-Regulatory Affairs
CTD Dossier Preparation K. Srikantha Reddy Sr.Manager-Regulatory Affairs Medreich Limited Srikanth.k@medreich.com CTD Dossier Preparation CTD (Common Technical Document) contains 5 modules Module 1 Module
More informationGeneric drugs are copies of innovator drug products
dx.doi.org/10.14227/dt190412p51 In Vitro Equivalence Studies of Generic Metformin Hydrochloride Tablets and Propranolol Hydrochloride Tablets Under Biowaiver Conditions in Lagos State, Nigeria e-mail:
More informationMULTISOURCE (GENERIC) PHARMACEUTICAL PRODUCTS: GUIDELINES ON REGISTRATION REQUIREMENTS TO ESTABLISH INTERCHANGEABILITY DRAFT REVISION
RESTRICTED WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE MULTISOURCE (GENERIC) PHARMACEUTICAL PRODUCTS: GUIDELINES ON REGISTRATION REQUIREMENTS TO ESTABLISH INTERCHANGEABILITY DRAFT REVISION
More information4.1 Objectives of Clinical Trial Assessment
L1 4.1 Objectives of Clinical Trial Assessment Presentation to APEC Preliminary Workshop on Review of Drug Development in Clinical Trials Celia Lourenco, PhD, Manager, Clinical Group I Office of Clinical
More informationGuidance for Industry
Guidance for Industry Immediate Release Solid Oral Dosage Forms Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation
More informationMain Conference Agenda
Sponsored by: (Co-located with Bioequivalence: Intersection between Science & Regulatory Conference) Main Conference Agenda Day One Wednesday, November 5 th, 2014 7:30 Registration Opens & Continental
More informationLongitudinal Modeling of Lung Function in Respiratory Drug Development
Longitudinal Modeling of Lung Function in Respiratory Drug Development Fredrik Öhrn, PhD Senior Clinical Pharmacometrician Quantitative Clinical Pharmacology AstraZeneca R&D Mölndal, Sweden Outline A brief
More informationGuidance for Industry
Guidance for Industry Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product DRAFT GUIDANCE This guidance document is being distributed for comment purposes only.
More informationGuidance for Industry
#171 Guidance for Industry Waivers of In Vivo Demonstration of Bioequivalence of Animal Drugs in Soluble Powder Oral Dosage Form Products and Type A Medicated Articles (This version of the guidance replaces
More informationMULTISOURCE (GENERIC) PHARMACEUTICAL PRODUCTS: GUIDELINES ON REGISTRATION REQUIREMENTS TO ESTABLISH INTERCHANGEABILITY. REVISION (JULY 2014)
1 Working document QAS/14.583/Rev.1 July 2014 Document for comment 2 3 4 5 6 7 8 9 MULTISOURCE (GENERIC) PHARMACEUTICAL PRODUCTS: GUIDELINES ON REGISTRATION REQUIREMENTS TO ESTABLISH INTERCHANGEABILITY.
More informationBioequivalence Study Design Considerations. Dr. John Gordon
Bioequivalence Study Design Considerations Dr. John Gordon Key Output of Programme A list of prequalified medicinal products used for treatment of HIV/AIDS, malaria, tuberculosis, influenza, and for reproductive
More informationDMPK: Experimentation & Data
DMPK: Experimentation & Data Interpretation Mingshe Zhu, Mike S. Lee, Naidong Weng, and Mark Hayward Prerequisite: Entry-level scientists with hands on experience in LC/MS as well as advanced students
More informationGeneric Drug User Fee Act Program Performance Goals and Procedures
Generic Drug User Fee Act Program Performance Goals and Procedures The performance efficiencies, metric goals and procedures to which FDA will agree upon commencement of a generic drug user fee act (GDUFA)
More informationINTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE S1A. Current Step 4 version
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE GUIDELINE ON THE NEED FOR CARCINOGENICITY STUDIES
More informationFood, Medicine and Health Care Administration and Control Authority
Food, Medicine and Health Care Administration and Control Authority Bio equivalence Study Registration Requirements in Ethiopia (Four Countries Experience) Mengistab W.Aregay (Bpharm, MSc. in Health Monitoring
More informationPharmacology skills for drug discovery. Why is pharmacology important?
skills for drug discovery Why is pharmacology important?, the science underlying the interaction between chemicals and living systems, emerged as a distinct discipline allied to medicine in the mid-19th
More informationStudy (s) Degree Center Acad. Period. 1201 - Grado de Farmacia FACULTY OF PHARMACY 3 Annual 1211 - PDG Farmacia-Nutrición Humana y Dietética
COURSE DATA Data Subject Código 34081 Name Biopharmacy and Pharmacokinetics Cycle Grade ECTS Credits 10.5 Curso académico 2014-2015 Study (s) Degree Center Acad. Period year 1201 - Grado de Farmacia FACULTY
More informationCOMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP)
The European Agency for the Evaluation of Medicinal Products Human Medicines Evaluation Unit London, 29 July 1999 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON QUALITY OF MODIFIED
More informationIntroduction to Enteris BioPharma
Introduction to Enteris BioPharma Enteris BioPharma Intelligent Solutions for Oral Drug Delivery Privately held, New Jersey based biotech company Owned solely by Victory Park Capital, a large Chicago based
More informationM4E(R2): The CTD Efficacy
M4E(R2): The CTD Efficacy This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for
More informationICH Topic S 1 A The Need for Carcinogenicity Studies of Pharmaceuticals. Step 5
European Medicines Agency July 1996 CPMP/ICH/140/95 ICH Topic S 1 A The Need for Carcinogenicity Studies of Pharmaceuticals Step 5 NOTE FOR GUIDANCE ON THE NEED FOR CARCINOGENICITY STUDIES OF PHARMACEUTICALS
More informationGuidance for Industry
Guidance for Industry End-of-Phase 2A Meetings U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) September 2009 Procedural Guidance
More informationHybrid or Mixed Marketing Authorization Application in the European Union: Not a Trivial Decision in New Development Programs for Established Drugs
Hybrid or Mixed Marketing Authorization Application in the European Union: Not a Trivial Decision in New Development Programs for Established Drugs Drug Information Journal 00(0) 1-6 ª The Author(s) 2012
More informationGuidance for Industry
Guidance for Industry Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments
More informationEuropean Continuing Education College
Design and Development of Conventional and Modified Release Oral Drug Delivery Systems Three Day Intensive Course for Managers, Scientists and Technicians with the Emphasis on the Principles of Oral Drug
More informationImporting pharmaceutical products to China
Importing pharmaceutical products to China Imported pharmaceutical products need pre-market approval before entering the Chinese market Imported drugs for human use are required to obtain pre-market approval
More informationQuality by Design for ANDAs: An Example for Modified Release Dosage Forms
Quality by Design for ANDAs: An Example for Modified Release Dosage Forms Introduction to the Example This is an example pharmaceutical development report illustrating how ANDA applicants can move toward
More informationFor personal use only
6 July 2015 KEY ADVANCEMENT TOWARDS COMMENCEMENT OF PHASE 1 CLINICAL STUDY OF ORAL FORMULATIONS Highlights PhytoTech Medical has submitted key documents to the Institutional Review Board (IRB or Helsinki
More informationThe 505(b)(2) Drug Development Pathway:
The 505(b)(2) Drug Development Pathway: When and How to Take Advantage of a Unique American Regulatory Pathway By Mukesh Kumar, PhD, RAC and Hemant Jethwani, MS The 505(b)(2) regulation offers a less expensive
More informationThe Clinical Trials Process an educated patient s guide
The Clinical Trials Process an educated patient s guide Gwen L. Nichols, MD Site Head, Oncology Roche TCRC, Translational and Clinical Research Center New York DISCLAIMER I am an employee of Hoffmann-
More informationProof-of-Concept Studies and the End of Phase IIa Meeting with the FDA
Medpace Discovery Series presents Proof-of-Concept Studies and the End of Phase IIa Meeting with the FDA DR. JIM WEI: Today my topic is going to be Proof-of-Concept Studies and FDA End of Phase 2a Meetings
More informationGENERAL CONSIDERATIONS FOR CLINICAL TRIALS E8
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE GENERAL CONSIDERATIONS FOR CLINICAL TRIALS E8 Current
More informationINTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE THE COMMON TECHNICAL DOCUMENT FOR THE REGISTRATION
More informationA Peak at PK An Introduction to Pharmacokinetics
Paper IS05 A Peak at PK An Introduction to Pharmacokinetics Hannah Twitchett, Roche Products Ltd, Welwyn Garden City, UK Paul Grimsey, Roche Products Ltd, Welwyn Garden City, UK ABSTRACT The aim of this
More informationGuidance for Industry
Guidance for Industry Major, Minor, and Telephone Amendments to Abbreviated New Drug Applications Comments and suggestions regarding this document should be submitted within 90 days of publication in the
More informationPRODUCT DEVELOPMENT GUIDE
PRODUCT DEVELOPMENT GUIDE PRE-FORMULATION - TABLETS Introduction Guidelines for the development of a ANDA product for the US market, Note: some tests or procedures may be unnecessary. The order of performing
More informationRevised checklist for BA/BE NOC effective from 01 st February 2014 (Draft for comments before 25 Jan 14)
Revised checklist for BA/BE NOC effective from 01 st February 2014 (Draft for comments before 25 Jan 14) Documents to be submitted for grant of permission to conduct BA/BE studies in Human Subjects/Patients
More informationCourse Curriculum for Master Degree in Clinical Pharmacy
Course Curriculum for Master Degree in Clinical Pharmacy The Master Degree in Clinical Pharmacy is awarded by the Faculty of Graduate studies at Jordan University of Science and Technology (JUST) upon
More informationBioequivalence Testing, using the Dissolution Profile
Determining Similarity of Products- F 2 Criterion and Variability of Dissolution Test Vivian Gray V. A. Gray Consulting Dissolution Workshop December 10, 2010 Bioequivalence Testing, using the Dissolution
More informationIs a Career in the. Pharmaceutical. Check out our online Student Center to find out more: www.aaps.org/forstudents
Is a Career in the Pharmaceutical Sciences Right for Me? Check out our online Student Center to find out more: www.aaps.org/forstudents How Do I Know If a Career in the Pharmaceutical Sciences is Right
More informationJSPS. Modeling & Simulation: A Tool to Enable Efficient Clinical Drug Development. March 29, 2005
Dr. Kunihiro Sasahara, Ph.D. Dr. Russell Wada, Ph.D. Dr. Yuying Gao, M.D., Ph.D. Modeling & Simulation: A Tool to Enable Efficient Clinical Drug Development JSPS March 29, 2005 Agenda Overview of Clinical
More informationGuideline on the conduct of bioequivalence studies for veterinary medicinal products
11 April 2011 EMA/CVMP/016/00-Rev.2 Committee for Medicinal Products for Veterinary Use (CVMP) Guideline on the conduct of bioequivalence studies for veterinary medicinal products Draft revised GL agreed
More informationClinical Pharmacology 1: Phase 1 Studies and Early Drug Development. Gerlie Gieser, Ph.D. Office of Clinical Pharmacology, Div. IV
Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development Gerlie Gieser, Ph.D. Office of Clinical Pharmacology, Div. IV Objectives Outline the Phase 1 studies conducted to characterize the Clinical
More informationQUALITY BY DESIGN (QBD) : A COMPLETE REVIEW
Review Article QUALITY BY DESIGN (QBD) : A COMPLETE REVIEW Nishendu P. Nadpara*, Rakshit V. Thumar, Vidhi N. Kalola, Parula B. Patel Department of Quality Assurance, S. J. Thakkar Pharmacy College, Opp.
More informationPublic Assessment Report. Scientific discussion. Paracetamol Orifarm 500 mg film-coated tablets. (Paracetamol) DK/H/2271/001/DC.
Public Assessment Report Scientific discussion Paracetamol Orifarm 500 mg film-coated tablets (Paracetamol) DK/H/2271/001/DC 15 October 2014 This module reflects the scientific discussion for the approval
More informationOverview of Drug Development: the Regulatory Process
Overview of Drug Development: the Regulatory Process Roger D. Nolan, PhD Director, Project Operations Calvert Research Institute November, 2006 Adapted from course taught by Cato Research Background: Roger
More informationUnderstanding Our Curriculum
Understanding Our Curriculum One question that comes up quiet frequently when talking with preceptors is what are we teaching our students and when are they exposed to certain classes. Below you will find
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure Olopatadine Zentiva 1 mg/ml eye drops, solution (olopatadine hydrochloride) Procedure No: UK Licence No: PL 17780/0568 Winthrop Pharmaceuticals UK Limited
More informationThomas Hinchliffe, Pharm.D. CDR, U.S. Public Health Service Special Assistant to the Director Office of Generic Drugs Food and Drug Administration
Thomas Hinchliffe, Pharm.D. CDR, U.S. Public Health Service Special Assistant to the Director Office of Generic Drugs Food and Drug Administration Disclaimer & Disclosure Views presented are those of the
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure TELMISARTAN DR REDDY S 20 MG TABLETS TELMISARTAN DR REDDY S 40 MG TABLETS TELMISARTAN DR REDDY S 80 MG TABLETS (telmisartan) Procedure No: UK/H/5034/001-003/DC
More informationICH Topic E 8 General Considerations for Clinical Trials. Step 5 NOTE FOR GUIDANCE ON GENERAL CONSIDERATIONS FOR CLINICAL TRIALS (CPMP/ICH/291/95)
European Medicines Agency March 1998 CPMP/ICH/291/95 ICH Topic E 8 General Considerations for Clinical Trials Step 5 NOTE FOR GUIDANCE ON GENERAL CONSIDERATIONS FOR CLINICAL TRIALS (CPMP/ICH/291/95) TRANSMISSION
More informationPharmaceutical Sciences
Is a Career in the Pharmaceutical Sciences Right for Me? Check out our online Student Center to find out more: www.aapspharmaceutica.com/students How do I know if a career in the pharmaceutical sciences
More informationHypromellose Eye Drops BP 0.3% w/v PL 23097/0006
Hypromellose Eye Drops BP 0.3% w/v PL 23097/0006 UKPAR TABLE OF CONTENTS Lay summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 9 Summary of product characteristics Page 10 Patient
More informationTeriflunomide is the active metabolite of Leflunomide, a drug employed since 1994 for the treatment of rheumatoid arthritis (Baselt, 2011).
Page 1 of 10 ANALYTE NAME AND STRUCTURE TERIFLUNOMIDE Teriflunomide TRADE NAME Aubagio CATEGORY Antimetabolite TEST CODE PURPOSE Therapeutic Drug Monitoring GENERAL RELEVANCY BACKGROUND sclerosis. The
More informationDisclosure. This presentation contains forward-looking statements.
Disclosure This presentation contains forward-looking statements. These forward-looking statements are based on management's current expectations and assumptions as of the date of this presentation, and
More informationNot All Clinical Trials Are Created Equal Understanding the Different Phases
Not All Clinical Trials Are Created Equal Understanding the Different Phases This chapter will help you understand the differences between the various clinical trial phases and how these differences impact
More informationICH Topic Q 1 A Stability Testing Guidelines: Stability Testing of New Drug Substances and Products
The European Agency for the Evaluation of Medicinal Products Human Medicines Evaluation Unit CPMP/ICH/380/95 ICH Topic Q 1 A Stability Testing Guidelines: Stability Testing of New Drug Substances and Products
More informationClinical Study Synopsis for Public Disclosure
abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of the clinical
More informationA FDA Perspective on Nanomedicine Current Initiatives in the US
A FDA Perspective on Nanomedicine Current Initiatives in the US Carlos Peña, PhD Office of the Commissioner FDA September 3, 2010 Outline Context Nanotechnology Task Force report summary Identification
More informationNIMULID MD. 1. Introduction. 2. Nimulid MD Drug delivery system
NIMULID MD 1. Introduction Nimulid MD is a flavoured dispersible Nimesulide tablet with fast mouth dissolving characteristics thereby providing immediate relief. Nimesulide is a non-steroidal antiinflammatory
More informationPOLICY AND PROCEDURES OFFICE OF NEW DRUGS. Good Review Practice: Management of Breakthrough Therapy-Designated Drugs and Biologics.
POLICY AND PROCEDURES OFFICE OF NEW DRUGS Good Review Practice: Management of Breakthrough Therapy-Designated Drugs and Biologics Table of Contents PURPOSE...1 BACKGROUND...2 POLICY...3 ROLES AND RESPONSIBILITIES...4
More informationOral Bioavailability of Creatine Supplements: Is There Room for Improvement?
Oral Bioavailability of Creatine Supplements: Is There Room for Improvement? Donald W. Miller Associate Professor Department of Pharmacology and Therapeutics University of Manitoba Acknowledgements ISSN
More informationAsian Journal of Research in Biological and Pharmaceutical Sciences Journal home page: www.ajrbps.com
Research Article ISSN: 2349 4492 Asian Journal of Research in Biological and Pharmaceutical Sciences Journal home page: www.ajrbps.com IMPROVEMENT OF SOLUBILITY OF OMEPRAZOLE MAGNESIUM BY SOLID DISPERSION
More informationCATEGORY Advertising. CATEGORY Biopharmaceutics. CATEGORY Biosimilarity
CATEGORY Advertising Guidance Agenda: New & Guidances CDER is Planning to Publish During Calendar Year 2016 (See the Good Guidance Practices (GGPs) regulation on this Web page or 21 CFR 10.115 for details
More informationGuidance for Industry
#238 Guidance for Industry Modified Release Veterinary Parenteral Dosage Forms: Development, Evaluation, and Establishment of Specifications DRAFT GUIDANCE This guidance document is being distributed for
More informationFexinidazole a new oral treatment for sleeping sickness update of development
Fexinidazole a new oral treatment for sleeping sickness update of development SMe O 2 Me CH 2 O Antoine TARRAL Olaf Valverde Séverine Blesson Clélia Bardonneau Wilfried Mutumbo September 2011 Fexinidazole
More informationGuidance for Industry ANDAs: Stability Testing of Drug Substances and Products
Guidance for Industry ANDAs: Stability Testing of Drug Substances and Products Questions and Answers U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation
More informationSAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS S7A
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS
More informationAMBERLITE IRP64 Pharmaceutical Grade Cation Exchange Resin (Polacrilex Resin)
AMBERLITE IRP64 Pharmaceutical Grade Cation Exchange Resin (Polacrilex Resin) Description AMBERLITE IRP64 [1] resin is an insoluble, weakly acidic, hydrogen form, cation exchange resin supplied as a dry,
More informationOutsourcing in Drug Development From the Bench to the Market. Steven A. Kates, PhD Ischemix LLC
Outsourcing in Drug Development From the Bench to the Market Steven A. Kates, PhD Ischemix LLC Ischemix LLC 2012 Introduction Drug Development Process Ischemix LLC 2012 2 Introduction Drug Development
More informationAMBERLITE IRP69 Pharmaceutical Grade Cation Exchange Resin (Sodium Polystyrene Sulfonate USP)
AMBERLITE IRP69 Pharmaceutical Grade Cation Exchange Resin (Sodium Polystyrene Sulfonate USP) Description AMBERLITE IRP69 [1] resin is an insoluble, strongly acidic, sodium form cation exchange resin supplied
More informationGuidance for Industry
Guidance for Industry Applications Covered by Section 505(b)(2) DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document
More informationResearch needs in pharmaceutical excipients: implications of a global supply chain
Research needs in pharmaceutical excipients: implications of a global supply chain FY 2015 GDUFA Regulatory Science Initiatives Part 15 Public Meeting June 5, 2015 Silver Spring, MD Stephen W. Hoag, Ph.D.
More informationCOMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE INVESTIGATION OF BIOAVAILABILITY AND BIOEQUIVALENCE
The European Agency for the Evaluation of Medicinal Products Evaluation of Medicines for Human Use London, 14 December 2000 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE
More informationPublic Assessment Report Scientific discussion. Amitriptylin Abcur (amitriptyline hydrochloride) Asp no : 2013-0678 2013-0679 2013-0680
Public Assessment Report Scientific discussion Amitriptylin Abcur (amitriptyline hydrochloride) Asp no : 2013-0678 2013-0679 2013-0680 This module reflects the scientific discussion for the approval of
More informationStatistics and Pharmacokinetics in Clinical Pharmacology Studies
Paper ST03 Statistics and Pharmacokinetics in Clinical Pharmacology Studies ABSTRACT Amy Newlands, GlaxoSmithKline, Greenford UK The aim of this presentation is to show how we use statistics and pharmacokinetics
More informationIN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF COLUMBIA
IN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF COLUMBIA VIROPHARMA INCORPORATED, 730 Stockton Drive, Exton, PA 19341, Plaintiff, Civil Action No. v. MARGARET A. HAMBURG, M.D., in her official
More informationCareers in Biostatistics and Clinical SAS Programming An Overview for the Uninitiated Justina M. Flavin, Independent Consultant, San Diego, CA
PharmaSUG 2014 Paper CP07 Careers in Biostatistics and Clinical SAS Programming An Overview for the Uninitiated Justina M. Flavin, Independent Consultant, San Diego, CA ABSTRACT In the biopharmaceutical
More informationGuidance for Industry
Guidance for Industry Codevelopment of Two or More New Investigational Drugs for Use in Combination U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation
More informationDecentralised Procedure. Public Assessment Report
Bundesinstitut für Arzneimittel und Medizinprodukte Decentralised Procedure Public Assessment Report ben-u-ron direkt Erdbeer/Vanille 250/500 mg Granulat in Beuteln ben-u-ron direkt Cappuccino 500/1000
More informationIN VITRO BINDING BIOEQUIVALENCE STUDY SUMMARY TABLES AND SAS TRANSPORT FORMATTED TABLES FOR DATASET SUBMISSION
IN VITRO BINDING BIOEQUIVALENCE STUDY SUMMARY TABLES AND SAS TRANSPORT FORMATTED TABLES FOR DATASET SUBMISSION I. For Calcium Acetate Drug Products Table I.1 Submission Summary * Drug Product Name Strength(s)
More informationWorking with ICH Quality Guidelines - the Canadian Perspective
Working with ICH Quality Guidelines the Canadian Perspective Krishnan Tirunellai, Ph. D. Bureau of Pharmaceutical Sciences Therapeutic Products Directorate Health Canada December 3, 2008 Outline Introduction
More informationPublic Assessment Report. Scientific discussion. Paracetamol Alternova 500 mg, 650 mg, 1 g (paracetamol) Asp no: 2012-0005, 2012-0006, 2012-0007
Public Assessment Report Scientific discussion Paracetamol Alternova 500 mg, 650 mg, 1 g (paracetamol) Asp no: 2012-0005, 2012-0006, 2012-0007 Applicant: E Consult ApS, Denmark This module reflects the
More information