Revised European Guideline on PK and Clinical Evaluation of Modified Release Dosage Forms
|
|
- Charlotte Fisher
- 6 years ago
- Views:
Transcription
1 1st MENA Regulatory Conference on Bioequivalence, Biowaivers, Bioanalysis and Dissolution Jordan September 23 24, 2013 Revised European Guideline on PK and Clinical Evaluation of Modified Release Dosage Forms José A. Guimarães Morais Faculdade de Farmácia, Universidade de Lisboa INFARMED Portuguese Medicines agency EMA European Medicines Agency 1
2 Guideline on the Pharmacokinetic and Clinical Evaluation of Modified Release Dosage Forms (EMA/CPMP/EWP/280/96 Corr1) Draft XXIII Draft Agreed by Pharmacokinetics Working Party October 2012 Adoption by CHMP for release for consultation 21 February 2013 End of consultation (deadline for comments) 31 August 2013 This guideline replaces Guideline on Modified Release Oral and Transdermal Dosage Forms Section II (Pharmacokinetic and Clinical Evaluation (EMA/CPMP/EWP/280/96 Corr1) Comments should be provided using this template. The completed comments form should be sent to Keywords Modified release, prolonged release, delayed release, transdermal drug delivery systems (TDDS), bioequivalence, pharmacokinetics, biowaiver, in vitro dissolution, generics 2
3 3 Outline Modified Release Dosage Forms (MRDF) covered in the Guideline: Which are they? Structure of the Modified Release Dosage Forms Guideline (PK and Clinical evaluation) 1. Introduction (background) 1.1. Types of Modified release and dosage forms 1.2. Rationale for Development 2. Scope The clinical rationale Considerations for use and posology 3. Legal basis and relevant guidelines 4. Applications for modified release dosage forms of new chemical entities 5. Applications for a modified release formulation of a substance that is authorized as an immediate release formulation 6. Abridged application for modified release forms referring to a marketed modified release form Definitions Appendix I (sensitization and irritation test for transdermal products) Appendix II (In vitro in vivo correlation): Appendix III: Summary of study recommendations for abridged applications:
4 Modified Release Dosage Forms Modified release dosage forms are formulations where the rate and/or site of release of the active ingredient(s) is different from that of the immediate release dosage form administered by the same route. This deliberate modification is achieved by special formulation design and/or manufacturing methods. Modified release dosage forms covered by this guideline include orally, intramuscularly, subcutaneously administered modified release and transdermal dosage forms. 4
5 Modified Release Dosage Forms Modified release dosage forms covered by this guideline include Prolonged release Delayed release Multiphasic release Multiple/single unit Intramuscular/subcutaneous Depot formulations Transdermal drug delivery systems (TDDS) 5
6 Prolonged Release Dosage Forms Prolonged release dosage forms are modified release dosage forms showing a slower release than that of an immediate release dosage form administered by the same route. 6
7 Prolonged Release Dosage Forms These drug products allow (1) reduction in dosing frequency and (2) reduce fluctuations in plasma concentrations. They can be in the form of capsules, tablets, granules, pellets and suspensions 7
8 Delayed Release Dosage Forms The release of the active substance from such dosage forms is delayed for a certain period after administration or application of the dosage. The subsequent release is similar to that of an immediate release dosage form Typically gastro-resistant coatings are intended to delay the release of the drug substance either to 8 protect the stomach from drug local undesired action or to protect the drug from the acidic medium in the stomach, or to achieve targeted release in a defined segment of the intestine
9 Multiphasic Release Dosage Forms Biphasic Release: The first phase of drug release is determined by the immediate release dose fraction providing a therapeutic drug level shortly after administration. The second extended release phase provides the dose fraction required to maintain an effective therapeutic level for a prolonged period. Pulsatile Release: Pulsatile drug release is intended to deliver a burst of drug release at specific time interval 9
10 Modified Release Dosage Forms Multiple-unit: A multiple unit dosage form contains a plurality of units e.g. pellets or beads each containing release controlling excipients, e.g. in a gelatin capsule or compressed in a tablet Single-unit: The single-unit dosage forms consist of only one unit, e.g. matrix or osmotic tablet 10
11 Modified Release Dosage Forms Intramuscular/subcutaneous Depot formulations: A depot injection is usually a subcutaneous or intramuscular product which releases its active compound continuously over a certain period of time. Subcutaneous depot formulations include implants. Transdermal drug delivery systems (TDDS): A TDDS or transdermal patch is a flexible pharmaceutical preparation of varying size containing one or more active substance(s) to be applied on the intact skin for systemic availability. 11
12 Transdermal Drug Delivery Systems (TDDS) and Intramuscular/subcutaneous Depot formulations (ISDF) Pharmacokinetic Studies required for TDDS and ISDF of a new chemical entity (it applies to a substance already in an IR form as well sections 4 & 5) Besides clinical trials, studies should be conducted to evaluate drug transport characteristics and the rate limiting step that determines systemic availability i.e. drug release and/or other formulation related particularities. Pharmacokinetic investigations should comprise single-dose and multiple-dose investigations application site-dependent absorption fluctuation lag-times. IVIVC is advisable. In case of several dose strengths, dose proportionality issues should be adequately addressed. for Transdermal Drug Delivery Systems skin irritation, sensitization (see also appendix 1), phototoxicity, patch adhesion 12
13 Transdermal Drug Delivery Systems (TDDS) and Intramuscular/subcutaneous Depot formulations (ISDF) Pharmacokinetic Studies required for TDDS referring to a marketed modified release form (generic section 6) A generic TDDS is defined by having the same amount of active substance released per unit time as compared to the reference TDDS skin irritation, sensitization, phototoxicity, patch adhesion non-inferiority trial prior to BE In case of several dose strengths, dose proportionality issues should be adequately addressed., including bracketing approach Pharmacokinetic Studies required for ISDF referring to a marketed modified release form (generic section 6) Single dose comparison test multiple-dose comparison test, unless low extent of accumulation: cut-off AUC single dose covers 90% of AUC multiple dose 13
14 5. Application for a prolonged release formulation of a substance that is authorized as an immediate release formulation 5.1. Pharmacokinetic studies Rate and extent of absorption, fluctuation Variability Dose proportionality Factors affecting the performance of a modified drug formulation Food GI function: interaction with e.g. opioids, ph and motility modifiers Dose dumping Effect of alcohol: in vitro, in vivo 5.2. Therapeutic studies Waiving of therapeutic studies mimicking of immediate release (pulsatile, delayed release) BE for C max, C min and AUC at steady state (different shape, no clinical effect) C max, C min below therapeutic interval with IR How to design clinical studies 14 Clinical benefit throughout 24 hours
15 6. Abridged application for modified release forms referring to a marketed modified release form Prolonged release formulations for oral administration Strength(s) to be evaluated 6.2. Delayed release formulations Strength(s) to be evaluated Prolonged residence time in the stomach 6.3. Multiphasic modified release products 6.4. Intramuscular/Subcutaneous Depot Formulations Strength to be evaluated 6.5. Transdermal Drug Delivery Systems (TDDS) Strength to be evaluated 6.6. Bracketing approach 6.7. New strength for an already approved MR product 6.8. Evaluation Parameters to be analysed Acceptance criteria 6.9. Effects of alcohol Further points to consider for bioequivalence studies
16 Multiphasic modified release products This Guideline also applies to the assessment of bioequivalence for biphasic- / pulsatile-release designed to achieve sequential release combining immediate and modified characteristics If one of the release phases is prolonged, the type of studies required are those described in section 6.1. For multiphasic modified release products additional parameters to be determined include partial AUC, C max and t max in all phases. The time point for truncating the partial AUC (cut-off) should be based on the PK profile for the IR and the MR parts respectively and should be justified and pre-specified in the study protocol based on PD 16 considerations as well.
17 5. Application for a modified release formulation of a substance that is authorized as an immediate release formulation Next few slides condense requirements on MRDF for Multiple or single unit Dosage Forms concerning Single dose & multiple dose Different strengths Fed and fasting studies 17
18 Prolonged release single unit formulation study requirements Current requirement Strength Single dose fasting Single dose fed Steady-state high yes yes yes middle yes * waiver low yes * waiver * Fed study to be conducted at the same strength as pivotal BE study SmPC recommends intake under fasting or fasting and fed conditions Strength Single dose fasting* Single dose fed Multiple dose high yes yes yes SmPC recommends intake under fed conditions Strength Single dose fasting Single dose fed* Multiple dose high yes yes yes middle yes waiver waiver middle waiver yes waiver low yes waiver waiver low waiver yes waiver * bracketing approach possible if criteria are met 18
19 Prolonged release multiple unit formulation study requirements Current requirement Strength fasting fed Steady-state* high yes yes yes middle waiver waiver waiver low waiver waiver waiver SmPC recommends intake under fasting or fasting and fed conditions Strength Single dose fasting Single dose fed Multiple dose * high yes yes yes middle waiver waiver waiver low waiver waiver waiver SmPC recommends intake under fed conditions Strength Single dose fasting Single dose fed Multiple dose * high yes yes yes middle waiver waiver waiver low waiver waiver waiver 19 * see criteria for necessity in section 6.1
20 Delayed release single unit formulation study requirements Only Single Dose Studies required Current requirement Strength fasting fed Steady-state high yes yes waiver middle waiver waiver waiver low waiver waiver waiver SmPC recommends intake under fasting or fasting and fed conditions Strength Fasting* Fed high yes yes middle yes waiver low Yes waiver SmPC recommends intake under fed conditions Strength Fasting Fed * high Yes yes middle waiver yes low waiver yes 20 * bracketing approach possible if criteria are met
21 Delayed release multiple unit formulation Single dose Only Single Dose Studies required Current requirement Strength fasting fed Steady-state high yes yes waiver middle waiver waiver waiver low waiver waiver waiver SmPC recommends intake under fasting or fasting and fed conditions Strength Fasting Fed high yes yes middle waiver waiver low waiver waiver SmPC recommends intake under fed conditions Strength Fasting Fed high yes yes middle waiver waiver low waiver waiver 21
22 Safety concerns prevent the Company from conducting single dose studies of higher strengths in healthy volunteers and that ethical constraints prevent the Company from conducting single dose studies in patients. Strength (mg) Single Dose Fasting Single Dose Fed Steady State 0.26 / x 0.52 / 0.75 x 1.05 / 1.5 x 1.57 / 2.25 x 2.1 / 3.0 x 2.62 / 3.75 x 3.15 / 4.5 x x x Strength (mg) Single Dose Fasting Single Dose Fed Steady State 0.26 / x 0.52 / 0.75 x 1.05 / 1.5 x 1.57 / 2.25 x 2.1 / 3.0 x 2.62 / 3.75 x 3.15 / 4.5 x* * fasted and fed Strength (mg) Single Dose Fasting Single Dose Fed Steady State 0.26 / x x 0.52 / / / / 3.0 x 2.62 / / 4.5 x* 22
23 Further points to consider for bioequivalence studies Same as in BE GL Test and reference product Subjects Study conduct Statistical evaluation of primary endpoints Parent compound or metabolites Enantiomers Endogenous substances Narrow therapeutic index drugs (in addition narrowing of the acceptance criteria of C might be necessary) Highly variable drugs or drug products Linearity 23
24 IS THERE A NEED FOR MULTIPLE DOSE STUDIES IN MODIFIED RELEASE DOSAGE FORMS? FDA Because single dose studies are considered more sensitive in addressing the primary question of BE (i.e., release of the drug substance from the drug product into the systemic circulation), steadystate studies are not generally recommended, even in instances where nonlinear kinetics are present. Health Canada EMA For formulations that are likely to accumulate (i.e., AUCx/AUCinf < 0.8) safety requires that steady-state studies be performed in addition to single-dose studies Multiple-dose comparison test required unless low extent of accumulation: cut-off AUC single dose covers 90% of AUC Under discussion
25 IS THERE A NEED FOR MULTIPLE DOSE STUDIES IN MODIFIED RELEASE DOSAGE FORMS? C = C min
26 IS THERE A NEED FOR MULTIPLE DOSE STUDIES IN MODIFIED RELEASE DOSAGE FORMS? Multiple dose plots: C C C min
27 IS THERE A NEED FOR MULTIPLE DOSE STUDIES IN MODIFIED RELEASE DOSAGE FORMS? The EMA MR GL states A multiple dose study is needed unless a single dose study has been performed with the highest strength which has demonstrated that the mean AUC 0- after the first dose covers more than 90% of mean AUC 0- for both test and reference, and consequently a low extent of accumulation is expected
28 IS THERE A NEED FOR MULTIPLE DOSE STUDIES IN MODIFIED RELEASE DOSAGE FORMS?
29 IS THERE A NEED FOR MULTIPLE DOSE STUDIES IN MODIFIED RELEASE DOSAGE FORMS?
30 IS THERE A NEED FOR MULTIPLE DOSE STUDIES IN MODIFIED RELEASE DOSAGE FORMS? The simulations presented in this paper show that the inclusion of additional steady-state PK parameters increases the ability to identify differences between formulations. The extra benefit over single dose PK parameters does not compensate the extra effort expended. However the benefit obtained from performing multiple-dose studies is too small to compensate the extra effort expended. By using C max, AUC 0 t and additionally C, the evaluation of bioequivalence between two ER formulations can be made simply by using single dose data, with similar discriminatory characteristics of the current EMA requirements without the need of a multiple-dose study Reduction in the number of studies and volunteers is possible without loss of discriminative power
31 IS THERE A NEED FOR MULTIPLE DOSE STUDIES IN MODIFIED RELEASE DOSAGE FORMS?
32 IS THERE A NEED FOR MULTIPLE DOSE STUDIES IN MODIFIED RELEASE DOSAGE FORMS? As a result of this discussion the following note was added The discussion of the opportunity of using equivalence in C in single dose studies as basis for waiving the multiple dose study has been recognized. However, there is not considered to be sufficient scientific evidence at the moment to encourage this approach
33 33
EMA/EGA. Session 1: orally administered Modified Release Products European Regulatory Requirements London 30 April 2015 Dr.
EMA/EGA Session 1: orally administered Modified Release Products European Regulatory Requirements London 30 April 2015 Dr. Henrike Potthast Disclaimer The presentation reflects the personal opinion of
More informationDraft Agreed by Pharmacokinetics Working Party February Adoption by CHMP for release for consultation 1 April 2016
15 December 2016 Committee for Medicinal Products for Human Use (CHMP) Everolimus tablets 0.25 mg, 0.5 mg, 0.75 mg and 1 mg; 2.5 mg, 5 mg and 10 mg, dispersible tablets 0.1 mg and 0.25 mg; 2 mg, 3 mg and
More informationPrasugrel hydrochloride film-coated tablets 5 mg and 10 mg product-specific bioequivalence guidance
31 May 2018 EMA/CHMP/158772/2016/Rev.1 Committee for Medicinal Products for Human Use (CHMP) Prasugrel hydrochloride film-coated tablets 5 mg and 10 mg Draft Agreed by Pharmacokinetics Working Party April
More informationMR dosage forms with special release characteristics
MR dosage forms with special release characteristics Henning H. Blume, PhD DSc SocraTec C&S, Oberursel Concepts and Strategies in Clinical Drug Development www.socratec.eu AGAH Workshop "The new European
More informationInterested parties (organisations or individuals) that commented on the draft document as released for consultation.
23 February 2017 EMA/CHMP/810545/2016 Committee for Medicinal Products for Human Use (CHMP) Overview of comments received on Paliperidone palmitate depot suspension for injection 25 mg, 50 mg, 75 mg, 100
More informationBioequivalence of MR Products. AGAH Conference on the New European Modified Release Guideline Bonn, June 15 th, 2015
Bioequivalence of MR Products AGAH Conference on the New European Modified Release Guideline Bonn, June 15 th, 2015 Disclaimer This presentation represents the personal interpretation and opinion of the
More informationPatch adhesion and local tolerability of Transdermal Delivery Systems Requirements according to the new draft EMA Guidelines
Patch adhesion and local tolerability of Transdermal Delivery Systems Requirements according to the new draft EMA Guidelines Dr. Janet Schriever Federal Institute for Drugs (BfArM), Germany Transdermal
More informationInterested parties (organisations or individuals) that commented on the draft document as released for consultation.
25 January 2018 EMA/CHMP/729976/2017 Committee for Medicinal Products for Human Use (CHMP) Overview of comments received on 'Paracetamol oral use, immediate release formulations product-specific bioequivalence
More informationSession 1 : Orally Administered Modified Release Products
Session 1 : Orally Administered Modified Release Products Gerald Beuerle Head of Clinical Development/Biopharmaceutics European Scientific Operations, Teva / ratiopharm 1 Disclaimer This presentation and
More informationInterchangeable Drug Products - Additional Criteria
Interchangeable Drug Products - Additional Criteria Principle: Decisions respecting interchangeability and drug lists remain in the domain of the institution responsible for the costs of the product which
More informationBASIC PHARMACOKINETICS
BASIC PHARMACOKINETICS MOHSEN A. HEDAYA CRC Press Taylor & Francis Croup Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business Table of Contents Chapter
More informationDRAFT GUIDANCE DOCUMENT Comparative Bioavailability Standards: Formulations Used for Systemic Effects
1 2 3 DRAFT GUIDANCE DOCUMENT Comparative Bioavailability Standards: Formulations Used for Systemic Effects 4 This guidance document is being distributed for comment purposes only. 5 6 Published by authority
More informationHelmut Schütz. The Global Bioequivalence Harmonisation Initiative. 12 April 2018 [Session II: Necessity of multiple dose studies in BE testing] 1
Primary and secondary PK metrics for evaluation of steady state studies, C min vs.c τ, relevance of C min /C τ or fluctuation for bioequivalence assessment Helmut Schütz 12 April 2018 [Session II: Necessity
More informationGuidance Document. Comparative Bioavailability Standards: Formulations Used for System Effects
Guidance Document Comparative Bioavailability Standards: Formulations Used for System Effects Date Adopted: 2012/12/08 Revised Date: 2018/06/08 Effective Date: 2018/07/01 (for submissions filed on or after
More informationModified Release: C min C τ. Modified Release
Wikimedia Commons 2007 Sokoljan Creative Commons Attribution-ShareAlike 3.0 Unported Modified Release: C min C τ Modified Release C C min C τ Helmut Schütz BEBAC 1 24 Another Reminder Rose is a rose is
More informationFDB FOOD AND DRUGS BOARD G H A N A GUIDELINES FOR CONDUCTING BIOEQUIVALENCE STUDIES
FDB FOOD AND DRUGS BOARD G H A N A GUIDELINES FOR CONDUCTING BIOEQUIVALENCE STUDIES 1 SCOPE In pursuance of section 47 of the Food and Drugs Law 1992, P.N.D.C.L 305B, as amended by Act 523, 1996, these
More informationBCS: Dissolution Testing as a Surrogate for BE Studies
BCS: Dissolution Testing as a Surrogate for BE Studies Dirk M Barends National Institute of Public Health and the Environment The Netherlands APV / IKEV Seminar on Bioavailability and Bioequivalence, Istanbul,
More informationExcipient Interactions Relevant For BCS Biowaivers Peter Langguth
Excipient Interactions Relevant For BCS Biowaivers Peter Langguth Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University Mainz, Germany 3rd Symposium on Harmonization
More informationCOMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP)
The European Agency for the Evaluation of Medicinal Products Evaluation of Medicines for Human Use plondon, 20 February 2003 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) APPENDIX TO THE NOTE FOR
More informationPublic Assessment Report Scientific discussion. Ibuprofen 400 mg/100 ml solution for infusion & Ibuprofen 600 mg/100 ml solution for infusion
Public Assessment Report Scientific discussion Ibuprofen 400 mg/100 ml solution for infusion & Ibuprofen 600 mg/100 ml solution for infusion Ibuprofen arginine ES/H/0390/001/DC ES/H/0392/001/DC Applicant:
More informationApplication of IVIVCs in Formulation Development Douglas F Smith
Application of IVIVCs in Formulation Development Douglas F Smith PQRI Workshop on Application of IVIVC in Formulation Development September 5-6, 2012 Bethesda, Maryland In Vitro/In Vivo Correlations -
More informationDE/H/0763/01-04 / MR DE/H/0764/01-04 / MR DE/H/0765/01-05 / MR
PUBLIC ASSESSMENT REPORT Mutual Recognition Procedure Module 5 Scientific discussion during the initial procedure Fenta Regiomedica Matrix 25 / 50 / 75 and 100 µg/h transdermal patch Fentapatch Matrix
More informationPublic Assessment Report Scientific discussion. Ivabradine Grindeks 5 mg and 7.5 mg and filmcoated. Ivabradine hydrochloride ES/H/0375/ /DC
Public Assessment Report Scientific discussion Ivabradine Grindeks 5 mg and 7.5 mg and filmcoated tablets Ivabradine hydrochloride ES/H/0375/001-002/DC Registration number in Spain: 81.898, 81.899 This
More informationSCIENTIFIC DISCUSSION. Antimycobacterial (J04AC01).
SCIENTIFIC DISCUSSION Name of the Finished Pharmaceutical Product: Manufacturer of Prequalified Product: Active Pharmaceutical Ingredients (APIs): International Nonproprietary Name: Pharmaco-therapeutic
More informationBIOPHARMACEUTICS and CLINICAL PHARMACY
11 years papers covered BIOPHARMACEUTICS and CLINICAL PHARMACY IV B.Pharm II Semester, Andhra University Topics: Absorption Distribution Protein binding Metabolism Excretion Bioavailability Drug Interactions
More informationAnnex I. List of the names, pharmaceutical form, strengths of the medicinal product, route of administration, applicants in the Member States
Annex I List of the names, pharmaceutical form, strengths of the medicinal product, route of administration, applicants in the Member States 1 Member State EU/EEA Applicant (Invented) Name Strength Pharmaceutical
More informationDraft Agreed by Biosimilar Working Party (BMWP) October Adoption by CHMP for release for consultation 17 November 2011
1 2 3 17 November 2011 EMA/CHMP/BMWP/671292/2010 Committee for Medicinal Products for Human Use (CHMP) 4 5 6 7 Guideline on non-clinical and clinical development of similar biological medicinal products
More informationBioequivalence Requirements: USA and EU
Bioequivalence Requirements: USA and EU Dr. Nicholas Cappuccino Chair, IGPA Science Committee Global Head of Quality, Dr. Reddy s Laboratories Ltd. 15 th Annual IGPA Conference Kyoto, Japan December 6,
More informationPublic Assessment Report. Scientific discussion. Diliban Retard Tramadol/Paracetamol IS/H/0168/001/DC. Date:
CMDh/223/2005 February 2014 Public Assessment Report Scientific discussion Diliban Retard Tramadol/Paracetamol IS/H/0168/001/DC Date: 12.10.2015 This module reflects the scientific discussion for the approval
More informationNOTE FOR GUIDANCE ON TOXICOKINETICS: THE ASSESSMENT OF SYSTEMIC EXPOSURE IN TOXICITY STUDIES S3A
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE NOTE FOR GUIDANCE ON TOXICOKINETICS: THE ASSESSMENT
More informationGuideline on the demonstration of palatability of veterinary medicinal products
10 July 2014 EMA/CVMP/EWP/206024/2011 Committee for Medicinal Products for Veterinary Use (CVMP) Guideline on the demonstration of palatability of veterinary medicinal products Draft agreed by Efficacy
More informationCONTROLLED-RELEASE & SUSTAINED-RELEASE DOSAGE FORMS. Pharmaceutical Manufacturing-4
CONTROLLED-RELEASE & SUSTAINED-RELEASE DOSAGE FORMS Pharmaceutical Manufacturing-4 The improvement in drug therapy is a consequence of not only the development of new chemical entities but also the combination
More informationVICH GL58 Stability Testing of New Veterinary Drug Substances and Medicinal Products in Climatic Zones III and IV
1 2 3 19 July 2018 EMA/CVMP/VICH/335918/2016 Committee for Medicinal Products for Veterinary Use (CVMP) 4 5 6 7 VICH GL58 Stability Testing of New Veterinary Drug Substances and Medicinal Products in Climatic
More informationDocuments Regarding Drug Abuse Assessments
Overview of the FDA Guidance Documents Regarding Drug Abuse Assessments ABUSE DETERRENT FORMULATION SCIENCE MEETING DISCUSSION OF THE FDA DRAFT GUIDANCE FOR INDUSTRY: ABUSE DETERRENT OPIOIDS EVALUATION
More information(Invented) name Strength. Leflunomide Apotex 10 mg Tablet Oral use. Leflunomide Apotex 20 mg Tablet Oral use
Annex I List of the names, pharmaceutical form, strengths of the medicinal products, route of administration, marketing authorisation holders in the member states 1 Member State EU/EEA Marketing authorisation
More informationInterested parties (organisations or individuals) that commented on the draft document as released for consultation.
31 May 2018 EMA/CHMP/258276/2017 Committee for Medicinal Products for Human Use (CHMP) Overview of comments received on 'Dabigatran etexilate, hard capsules, 75 mg, 110 mg and 150 mg productspecific bioequivalence
More informationReport from the CMD(h) meeting held on 17 th, 18 th and 19 th September 2007
Report from the CMD(h) meeting held on 17 th, 18 th and 19 th September 2007 CMD(h)/EMEA Sub-Group on Paediatric Regulation The CMD(h) and the EMEA have agreed on a procedural guidance to facilitate the
More informationFORMULATION DEVELOPMENT - A QbD Approach to Develop Extended Release Softgels
Seite 1 von 8 Share this story: Issue: April 2015, Posted Date: 3/30/2015 FORMULATION DEVELOPMENT - A QbD Approach to Develop Extended Release Softgels INTRODUCTION Soft gelatin capsules (softgels) continue
More informationCurrent Challenges and Opportunities in Demonstrating Bioequivalence
Current Challenges and Opportunities in Demonstrating Bioequivalence Gur Jai Pal Singh, Ph.D. Watson Laboratories, Inc. Corona, California, USA Demonstrating Bioequivalence of Locally Acting Orally Inhaled
More informationDecentralised Procedure. Public Assessment Report. Memantin AbZ 10 mg/20 mg Filmtabletten ; Starterpack
Decentralised Procedure Public Assessment Report Memantin AbZ 10 mg/20 mg Filmtabletten ; Starterpack Memantin-ratiopharm Starterpackung 5 mg /10 mg /15 mg /20 mg Filmtabletten ;10 mg/20 mg Filmtabletten
More informationSCIENTIFIC DISCUSSION
This part reflects the scientific knowledge and the information about this product available at the time of prequalification. Thereafter, updates may have become necessary which are included in parts 1
More informationBiowaiver and Dissolution Profile Comparison
Biowaiver and Dissolution Profile Comparison Triporn Wattananat Bureau of Drug and Narcotic Department of Medical Sciences June 14, 2011 Biowaiver Outline: 1. Introduction 2. Biopharmaceutics Classification
More informationICH Topic S1C(R2) Dose Selection for Carcinogenicity Studies of Pharmaceuticals. Step 5
European Medicines Agency October 2008 EMEA/CHMP/ICH/383/1995 ICH Topic S1C(R2) Dose Selection for Carcinogenicity Studies of Pharmaceuticals Step 5 NOTE FOR GUIDANCE ON DOSE SELECTION FOR CARCINOGENICITY
More informationPublic Assessment Report. Scientific discussion. Bloxazoc 25 mg, 50 mg, 100 mg and 200 mg prolonged-release tablets Metoprolol succinate
CMDh/223/2005 February 2014 Public Assessment Report Scientific discussion Bloxazoc 25 mg, 50 mg, 100 mg and 200 mg prolonged-release tablets Metoprolol succinate HR/H/0103/001-004/DC Date: 16.2.2016 This
More informationClinical Studies in BE Evaluation of Generic Products. Brenda S. Gierhart, M.D. Medical Officer, Division of Clinical Review, Office of Generic Drugs
Clinical Studies in BE Evaluation of Generic Products Brenda S. Gierhart, M.D. Medical Officer, Division of Clinical Review, Office of Generic Drugs 1 Disclaimer The opinions and information in this presentation
More informationChapter 2 Rationale and Objective
Chapter 2 SPP School of Pharmacy & Technology Management, SVKM s NMIMS, Mumbai 44 2.0 Rationale Need for extended release drug delivery systems Over the past 50 years or so, substantial research in the
More informationAnnex I. Scientific conclusions and grounds for refusal presented by the European Medicines Agency
Annex I Scientific conclusions and grounds for refusal presented by the European Medicines Agency Scientific conclusions and grounds for refusal presented by the European Medicines Agency Overall summary
More informationEffect of Common Excipients on the Oral Drug Absorption of Biopharmaceutics Classification System Class 3 Drugs
Effect of Common Excipients on the Oral Drug Absorption of Biopharmaceutics Classification System Class 3 Drugs James E. Polli jpolli@rx.umaryland.edu April 26, 2016 Topics BCS Class 3 excipient study
More informationBrand and Generic Drugs. Educational Objectives. Absorption
Peter J. Rice, PharmD, PhD Associate Professor of Pharmacology East Tennessee State University Educational Objectives Pharmacokinetic Processes Distribution Metabolism Excretion Similarities Active ingredient(s)
More informationCompletion of the development of a formulation: Requirements for compliance check vs. requirements for Marketing Authorisation
Completion of the development of a formulation: Requirements for compliance check vs. requirements for Marketing Authorisation Workshop on Paediatric Formulations For Assessors in National Regulatory Agencies
More informationSection 5.2: Pharmacokinetic properties
Section 5.2: Pharmacokinetic properties SmPC training presentation Note: for full information refer to the European Commission s Guideline on summary of product characteristics (SmPC) SmPC Advisory Group
More informationCHAPTER-I DRUG CHARACTERIZATION & DOSAGE FORMS
CHAPTER-I DRUG CHARACTERIZATION & DOSAGE FORMS by: j. jayasutha lecturer department of pharmacy practice Srm college of pharmacy srm university DRUG CHARACTERIZATION: Pre-formulation studies will attempt
More informationANNEX I LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTHS OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, APPLICANTS IN THE MEMBER STATES
ANNEX I LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTHS OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, APPLICANTS IN THE MEMBER STATES 1 Member State EU/EEA Austria Denmark Finland France Germany
More informationBasic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook with Computer Simulations
Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook with Computer Simulations Rosenbaum, Sara E. ISBN-13: 9780470569061 Table of Contents 1 Introduction to Pharmacokinetics and Pharmacodynamics.
More informationANNEX II SCIENTIFIC CONCLUSIONS AND GROUNDS FOR POSITIVE OPINION
ANNEX II SCIENTIFIC CONCLUSIONS AND GROUNDS FOR POSITIVE OPINION 3 Scientific conclusions Overall summary of the scientific evaluation of Okrido and associated names (see Annex I) Okrido is an oral solution
More informationQ&A for submission of applications for prequalification of Zinc Sulfate tablets and Zinc Sulfate oral liquid (solution)
Q&A for submission of applications for prequalification of Zinc Sulfate tablets and Zinc Sulfate oral liquid (solution) This document should not be treated as a comprehensive guideline; it serves as a
More informationModeling and Simulation to Support Development and Approval of Complex Products
Modeling and Simulation to Support Development and Approval of Complex Products Mathangi Gopalakrishnan, MS, PhD Research Assistant Professor Center for Translational Medicine, School of Pharmacy, UMB
More informationDrug/Device Combination Products: Bioequivalence
Drug/Device Combination Products: Bioequivalence Three stories:. The story of Nasal and Inhalation Product BE 2. The story of the Generic Auto-Injector 3. The story of User Interface Considerations Bioequivalence
More informationDraft Guideline on Pharmaceutical Development of Medicines for Paediatric Use. C. Nopitsch-Mai London 1
Draft Guideline on Pharmaceutical Development of Medicines for Paediatric Use C. Nopitsch-Mai 08-11-2011 London 1 Content - Background - Pharmaceutical Problems - Scope - Characterisation of the Active
More informationPublic Assessment Report. Scientific discussion. Leflunomide Apotex 10 mg and 20 mg, tablets. (leflunomide) NL/H/2548/ /DC
Public Assessment Report Scientific discussion Leflunomide Apotex 10 mg and 20 mg, tablets (leflunomide) 001-002/DC Date: 3 August 2015 This module reflects the scientific discussion for the approval of
More informationYear in review. Vit Perlik Director of Regulatory Science and Clinical Development
Year in review Vit Perlik Director of Regulatory Science and Clinical Development Content Year in review Covering September 2013 to September 2014 Where the regulation goes selection of events for illustration
More informationSCIENTIFIC DISCUSSION. Efavirenz
SCIENTIFIC DISCUSSION Name of the Finished Pharmaceutical Product: Manufacturer of Prequalified Product: Active Pharmaceutical Ingredient (API): Pharmaco-therapeutic group (ATC Code): Therapeutic indication:
More informationDecentralised Procedure. Public Assessment Report. Oxycodon-ratiopharm 20, 40, 80 mg Retardtablette. Oxycodone hydrochloride DE/H/0790/01-03/DC
Decentralised Procedure Public Assessment Report Oxycodon-ratiopharm 20, 40, 80 mg Retardtablette Oxycodone hydrochloride DE/H/0790/01-03/DC Applicant: ratiopharm GmbH Reference Member State Germany The
More informationUsing Pharmacokinetics (PK) as a Tool During the Evaluation of Target Animal Safety (TAS)
Using Pharmacokinetics (PK) as a Tool During the Evaluation of Target Animal Safety (TAS) Marilyn N. Martinez, Ph.D. Senior Research Scientist CVM-FDA Traditional paradigm for the target animal safety
More informationDecentralised Procedure. Public Assessment Report. Pramipexol-neuraxpharm 0,26 / 0,52 / 1,05 / 1,57 / 2,1 / 2,62 / 3,15 mg Retardtabletten
Decentralised Procedure Public Assessment Report Pramipexol-neuraxpharm 0,26 / 0,52 / 1,05 / 1,57 / 2,1 / 2,62 / 3,15 mg Retardtabletten Pramipexole dihydrochloride monohydrate DE/H/4703/001-007/DC Applicant:
More informationThe EU PIP - a step in Pediatric Drug Development. Thomas Severin Bonn,
The EU PIP - a step in Pediatric Drug Development Thomas Severin Bonn, 13.01.2009 Agenda Implications for Industry Company Preparation Time of PIP Submission Content of the PIP The PIP Process and first
More informationBasic Concepts of TDM
TDM Lecture 1 5 th stage What is TDM? Basic Concepts of TDM Therapeutic drug monitoring (TDM) is a branch of clinical pharmacology that specializes in the measurement of medication concentrations in blood.
More informationDecentralised Procedure. Public Assessment Report
Decentralised Procedure Public Assessment Report Venlafaxin ratiopharm Venlafaxin AbZ-Pharma Venlafaxin CT-Arzneimittel prolonged-release capsule hard venlafaxine hydrochloride DE/H/3393-3395/01-03/DC
More informationReflection paper on assessment of cardiovascular safety profile of medicinal products
25 February 2016 EMA/CHMP/50549/2015 Committee for Medicinal Products for Human Use (CHMP) Reflection paper on assessment of cardiovascular safety profile of medicinal products Draft agreed by Cardiovascular
More informationDecentralised Procedure. Public Assessment Report. Metamizol Midas / Metamizol STADA / Mimetanal 500 mg Tabletten. Metamizole sodium monohydrate
Decentralised Procedure Public Assessment Report Metamizol Midas / Metamizol STADA / Mimetanal 500 mg Tabletten Metamizole sodium monohydrate DE/H/4091-4093/001/DC Applicant: Midas Pharma GmbH, Germany
More informationDetermination of bioavailability
Pharmaceutics 2 Bioavailability Bioavailability is the rate and extent to which an administered drug reaches the systemic circulation. For example, if 100 mg of a drug is administered orally and 70 mg
More informationDraft Agreed by Immunologicals Working Party January Adoption by CVMP for release for consultation 12 March 2009
15 March 2010 EMA/CVMP/IWP/105506/2007 Committee for medicinal products for veterinary use (CVMP) Guideline on data requirements for multi-strain dossiers for inactivated vaccines against avian influenza
More informationCOMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) GUIDELINE ON THE PHARMACEUTICAL QUALITY OF INHALATION AND NASAL PRODUCTS
European Medicines Agency Inspections London, 16 February 2005 Doc Ref.: EMEA/CHMP/QWP/49313/2005 corr. COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) GUIDELINE ON THE PHARMACEUTICAL QUALITY OF
More informationReflection paper on assessment of cardiovascular risk of medicinal products for the treatment of cardiovascular and metabolic diseases Draft
1 2 3 21 May 2015 EMA/CHMP/50549/2015 Committee for Medicinal Products for Human Use (CHMP) 4 5 6 7 Reflection paper on assessment of cardiovascular risk of medicinal products for the treatment of cardiovascular
More informationPrequalification Programme Bioequivalence Assessment Update. Dr. John Gordon
Prequalification Programme Bioequivalence Assessment Update Dr. John Gordon WHO Prequalification of Medicines Programme 3 rd Meeting with Manufacturers of FPPs and APIs Overview Review of commonly used
More informationNoncompartmental Analysis (NCA) in PK, PK-based Design
Noncompartmental Analysis (NCA) in PK, PK-based Design Helmut Schütz BEBAC Consultancy Services for Bioequivalence and Bioavailability Studies 17 Vienna, Austria helmut.schuetz@bebac.at Bioequivalence
More informationPublic Assessment Report. Scientific discussion. Metoprololsuccinat Actavis. Prolonged release tablets 25 mg, 50 mg, 100 mg and 200 mg
Public Assessment Report Scientific discussion Metoprololsuccinat Actavis Prolonged release tablets 25 mg, 50 mg, 100 mg and 200 mg Metoprolol succinate This module reflects the scientific discussion for
More informationUse of Bridging Justifications to Support the Safety of Excipients in Generic Drug Products
Use of Bridging Justifications to Support the Safety of Excipients in Generic Drug Products Sruthi King, Ph.D. Pharmacology/Toxicology Team Leader Division of Clinical Review, Office of Generic Drugs Center
More informationREGULATORY PERSPECTIVE. Dr. Raghunandan H V Associate Professor JSSCP, JSSU, Mysore
1 REGULATORY PERSPECTIVE Dr. Raghunandan H V Associate Professor JSSCP, JSSU, Mysore Contents 2 1. Role of Dissolution Testing in Generic Drug Approval 2. Dissolution Testing Recommendation for Solid Oral
More informationAnnex I. List of the names, pharmaceutical form, strengths of the medicinal products, route of administration, applicant in the Member States
Annex I List of the names, pharmaceutical form, strengths of the medicinal products, route of administration, applicant in the Member States 1 Member State EU/EEA Applicant Invented Name Strength Pharmaceutical
More informationEUROPEAN COMMISSION HEALTH AND FOOD SAFETY DIRECTORATE-GENERAL VOLUME 2C. Guidelines. Medicinal products for human use
EUROPEAN COMMISSION HEALTH AND FOOD SAFETY DIRECTORATE-GENERAL Brussels, March 2018 SANTE-2017-11668 Revision 2 NOTICE TO APPLICANTS VOLUME 2C Guidelines Medicinal products for human use Safety, environment
More informationPublic Assessment Report. Scientific discussion. Mogilarta. (Telmisartan and hydrochlorothiazide) DK/H/2306/ /DC.
Public Assessment Report Scientific discussion Mogilarta 40 mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg tablets (Telmisartan and hydrochlorothiazide) DK/H/2306/001-003/DC 17 November 2014 This module reflects
More informationReport from the CMD(h) meeting held on 19 th, 20 th and 21 st March 2007
Report from the CMD(h) meeting held on 19 th, 20 th and 21 st March 2007 Best Practice Guide EU Work Sharing Procedure in the Assessment of Paediatric Data The CMD(h) has updated the Best Practice Guide
More informationEprosartan 300 mg, 400 mg and 600 mg Film-coated Tablets. (Eprosartan mesilate) PL 37222/
Eprosartan 300 mg, 400 mg and 600 mg Film-coated Tablets (Eprosartan mesilate) PL 37222/0027-29 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 5 Steps taken for assessment Steps
More informationUnderstanding Regulatory Global Requirements for Nasal Drug Products. Julie D. Suman, Ph.D. April 8, 2016
Understanding Regulatory Global Requirements for Nasal Drug Products Julie D. Suman, Ph.D. April 8, 2016 AGENDA NDA vs ANDA Regulatory Approaches for Bioequivalence (BE) FDA Drug Specific Guidances FDA,
More informationIn Vitro Considerations for Development Abuse Deterrent Dosage Forms
In Vitro Considerations for Development Abuse Deterrent Dosage Forms Presentation to AAPS Annual Meeting Nov 3, 2014 Nagesh Bandi, Ph.D. Global CMC New Products Pfizer Inc. 1 Disclaimer The thoughts and
More informationPublic Assessment Report Scientific discussion. Trelema (lacosamide) SE/H/1648/01-07/DC
Public Assessment Report Scientific discussion Trelema (lacosamide) SE/H/1648/01-07/DC This module reflects the scientific discussion for the approval of Trelema. The procedure was finalised on 2018-03-08.
More informationAdopted by CVMP 10 March Date for coming into effect 1 July Revised draft guideline agreed by Immunologicals Working Party 22 June 2017
1 2 3 7 September 2017 EMA/CVMP/IWP/105506/2007-Rev.1 Committee for medicinal products for veterinary use (CVMP) 4 5 6 7 Guideline on data requirements for multi-strain dossiers for inactivated vaccines
More informationUSP Chewable Gels Monographs
USP Dietary Supplements Stakeholder Forum Tuesday, May 15, 2018 USP Chewable Gels Monographs Natalia Davydova, Ph.D. Scientific Liaison DS Gummies Market Value of the gummy vitamins market in the United
More informationGuideline on influenza vaccines submission and procedural requirements
1 2 3 October 2014 EMA/56793/2014 Human Medicines Research and Development Support 4 5 6 Guideline on influenza vaccines submission and procedural requirements Regulatory and procedural requirements module
More informationE11(R1) Addendum to E11: Clinical Investigation of Medicinal Products in the Pediatric Population Step4
E11(R1) Addendum to E11: Clinical Investigation of Medicinal Products in the Step4 October 2017 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 1 Legal
More informationBIOEQUIVALENCE AND THERAPEUTIC EQUIVALENCE. Soula Kyriacos, B.Pharm, PhD Head R&D, Pharmaline November 2016
BIOEQUIVALENCE AND THERAPEUTIC EQUIVALENCE Soula Kyriacos, B.Pharm, PhD Head R&D, Pharmaline November 2016 Introduction Early 1970 s FDA regulations for submission of BA data 1984 US Congress passed the
More informationBioequivalence of Oral Generic Product with An Alternate Administration
Bioequivalence of Oral Generic Product with An Alternate Administration Minglei Cui, Ph.D. CDR, U.S. Public Health Service Division of Bioequivalence 2 Office of Generic Drugs CDER/FDA 1 Disclaimer & Disclosure
More informationClinical Study Synopsis for Public Disclosure
abcd Clinical Study Synopsis 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
More informationGuide to Interchangeable Medicines
Guide to Interchangeable Medicines AUT-G0115-6 01 JUNE 2018 This guide does not purport to be an interpretation of law and/or regulations and is for guidance purposes only. CONTENTS 1 BACKGROUND 3 1.1
More informationMutual Recognition Procedure. Public Assessment Report. Valproat Orion 300 / 500 mg Retardtabletten. Sodium valproate DE/H/1910/ /MR
Mutual Recognition Procedure Public Assessment Report Valproat Orion 300 / 500 mg Retardtabletten Sodium valproate DE/H/1910/001-002/MR (former FI/H/0608/001-002/MR) Applicant: Orion Corporation Date:
More informationSchool of Pharmacy Faculty of Medicine The Chinese University of Hong Kong. Transdermal Drug Delivery System
Workshop in Celebration of 25 th Anniversary of the School of Pharmacy Biopharmaceutics of Modified Release Products and Challenging Drug Molecules Design and Regulatory Assessment of Transdermal Drug
More informationClinical Study Synopsis for Public Disclosure
abcd Clinical Study Synopsis 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
More informationDOSE SELECTION FOR CARCINOGENICITY STUDIES OF PHARMACEUTICALS *)
DOSE SELECTION FOR CARCINOGENICITY STUDIES OF PHARMACEUTICALS *) Guideline Title Dose Selection for Carcinogenicity Studies of Pharmaceuticals *) Legislative basis Directive 75/318/EEC as amended Date
More informationPublic Assessment Report. Scientific discussion. Citalopram Jubilant 10 mg, 20 mg, 30 mg and 40 mg, film-coated tablets.
Public Assessment Report Scientific discussion Citalopram Jubilant 10 mg, 20 mg, 30 mg and 40 mg, film-coated tablets (citalopram) NL/H/2919/001-004/DC Date: 28 October 2014 This module reflects the scientific
More information