TGN 1412 Welche Änderungen haben sich für die Erstanwendung am Menschen aus Sicht des BfArM ergeben?

Size: px
Start display at page:

Download "TGN 1412 Welche Änderungen haben sich für die Erstanwendung am Menschen aus Sicht des BfArM ergeben?"

Transcription

1 TGN 1412 Welche Änderungen haben sich für die Erstanwendung am Menschen aus Sicht des BfArM ergeben? PD Dr. med. Thomas Sudhop Bundesinstitut für Arzneimittel, Bonn Bundesinstitut für Arzneimittel

2 IMP Risk Classes Trials with High Risk IMPs Trials with Non-High Risk IMPs Intermediate risk IMPs Low risk IMPs

3 High-Risk IMPs An IMP has to be considered as high-risk IMP when there are concerns that serious ADRs may occur in first-in-man trials Case-by-case decision based on knowledge or uncertainties Mode of action Nature of Target Relevance of Non-Clinical models

4 Intermediate- / Low-Risk IMP Intermediate-Risk IMPs neither classified as high risk IMPs nor as low risk IMPs Low-Risk IMP IMP is member of a well known and well characterised class of medicinal products or is second in class and the class has well described pharmacological properties and prior clinical trials did not exert any unforeseeable risk then a clinical trial should be considered as a low risk trial.

5 Trials with High-Risk IMPs: Non-clinical Data Pharmacodynamics Primary and secondary pharmacodynamics in in vitro animal and human systems and in vivo in one or more chosen animal models including receptor binding receptor occupancy duration of effect dose-response Appropriate titration necessary to detect possible U- or bellshaped dose response curves

6 Trials with High-Risk IMPs: Non-clinical Data Pharmacokinetics Standard ADME programme for all species used for in-vivo studies Absorption, Distribution, Metabolism and Elimination Exposure data at pharmacological doses from the relevant animal models should be provided

7 Trial Population Health status Healthy volunteers or patients? Primary purpose is to assess tolerability and PK not therapeutic benefit No parallel inclusion of the same subjects in other trials Definition of healthy Patients: Effect of concomitant treatment Gender Women in first in man trials? Age range Ethnics

8 Dose Regimen First dose Route of administration Number of subjects per dose increment (cohort) Number of subjects to be dosed at the same time Time lag between dosing of the next subjects of the same dose level (within cohort) the next higher dose level (between cohorts) Dose progression factor When to stop (who and when)

9 How to obtain a safe starting Dose Classic approach: NOAEL / Safety factor (>10) Usually derived from doses rather than exposures Allometric Methods according FDA Guidance Human equivalent dose (HED) according FDA recommendations is usually calculated on animal NOAELs PAD adjustment might be necessary NOAEL-HED Approach: Combining NOAELs with HED plus Safety factor Guidance for industry and reviewers: Estimating the safe starting dose in clinical trials for therapeutics in adult healthy volunteers, July 2005,

10 Mabel Approach Recommended for first-in-man trials with high-risk IMPs MABEL: Minimal anticipated biological effect level Based on all relevant in-vitro and in-vivo PK and PD data such as Receptor binding and receptor occupancy Concentration/response data Exposures at pharmacological doses in relevant species MABEL should be calculated based on PK/PD modelling approach Starting dose = MABEL dose / Safety factor If NOAEL-HED dose is lower, use NOAEL-HED-derived dose

11 Dosing in High-risk Trials Initial sequential dose administration design within each cohort Adequate period of observation between the administration of each subject depending on estimated PK and PD data Before administration of the next cohort all results from all subjects of the subsequent cohort(s) must be reviewed PK and PD data from the previous cohorts should be compared to known non-clinical PK, PD and safety information

12 Number of subjects dosed simultaneously Trials with high risk IMPs not more than one subject sequential administration design within each cohort Trials with intermediate risk IMPs not more than two subjects per new dose level at first Staggered administration designs suitable for several cohort sizes (6+2, 8+3, 10+3 )

13 Staggered Administration Design (6+2) Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day 10 Day 11 Dose 1 2A+1P 4A+1P Dose 2 2A+1P 4A+1P Dose 3 2A+1P 4A+1P Dose 4 2A+1P 4A+1P Dose 5 2A+1P 4A+1P Dose 6 2A+1P 4A+1P Dose 7 2A+1P 4A+1P Dose 8 2A+1P 4A+1P Dose 9 2A+1P 4A+1P Dose 10 2A+1P 4A+1P A: Active medicinal product P: Placebo For the next dosing day all relevant clinical and safety data must be available and reviewed

14 Time lag between administered Doses High risk trials Individually calculated, risk based lag time Intermediate risk trials Time lag between the first two subjects of each new dose level should be based on appropriate nonclinical estimates t max -based approach Adjustment might be necessary in case of observed events with late onset

15 Conclusion BfArM changed the requirements for first-in-man trials Additional requirements enhance trial subjects safety Additional requirements shall enhance predictability of human results from non-clinical data No stand-alone approach but concept is in line with the new EMEA-SWP guideline on first-in-man trials with high-risk IMPs

16 Backup Folien Bundesinstitut für Arzneimittel

17 The Tegenero Incident Bundesinstitut für Arzneimittel

18 Trial Design Mono-centre, double-blind, randomised first-in-man trail on TGN1412 TGN1412: CD-28 super-agonist antibody Trial population: 32 healthy volunteers in 4 cohorts 0.1 mg/kg, 0.5 mg/kg, 2 mg/kg, 5 mg/kg First cohort: 8 subjects 6 TGN mg/kg, 2 Placebo Acute cytokine release syndrome in all six subjects treated with TGN1412 Life-threatening Requiring ICU treatment

19 Clinical Course Suntharalingam et al. NEJM 2006

20 Cytokine Release Suntharalingam et al. NEJM 2006

21 Lessons needed to be learned from TGN1412 Sponsors / Pharmaceutical companies CROs Ethic Committees Competent Authorities Trial subjects

22 Relevant Guidelines for Clinical Trials Non-Clinical Safety Studies For The Conduct Of Human Clinical Trials For Pharmaceuticals (ICH M3; CPMP/ICH/286/95) Preclinical safety evaluation of biotechnology-derived pharmaceuticals (ICH S6; CPMP/ICH/302/95) The Non-clinical Evaluation of the Potential for delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals (ICH S7B; CPMP/ICH/423/02) Safety pharmacology studies for human pharmaceuticals (ICH S7A; CPMP/ICH/539/00) Guideline for Good Clinical Practice (ICH E6; CPMP/ICH/135/95) General Considerations for Clinical Trials (ICH E8; CPMP/ICH/291/95) Guideline on Virus Safety Evaluation of Biotechnological Investigational Medicinal Products Draft (EMEA/CHMP/BWP/398498/2005-corr) Guideline on the Requirements to the Chemical and Pharmaceutical Quality Documentation concerning Investigational Medicinal Products in Clinical Trials (CHMP/QWP/185401/2004) EUDRALEX- Vol. 10 Clinical trials more

23 How to improve current practise? First in man trial bear multiple risks due to limited data on the IMP and the interaction of IMP and human body Unfortunately this part of clinical development had virtually no commonly accepted guidelines A Guideline on Requirements for First-in-Man Clinical Trials for potential high-risk medicinal products has been published now for public consultation by the SWP of the EMEA Both German competent authorities have been involved (PEI, BfArM)

24 Definition of High-Risk IMPs Monoclonal Antibodies (mab)* 1. The mab employs a new mechanism of action 2. The mab addresses a target that lacks appropriate animal models 3. The mab comprise a new type of engineered structural format NCEs 1. The NCE is new in class and employs a new mechanism of action. It is reasonable to consider that the mechanism of action might fundamentally affect clinical relevant important vital systems such as the respiratory, immune, cardiovascular, gastrointestinal tract, CNS, and other vital body systems 2. The NCE is new in class and addresses a target or pathway that lacks relevant nonclinical models. *Schneider CK, Kalinke U, and Löwer J. TGN a regulator s perspective. Nature Biotechnology 2006;24:493-6

25 When to stop Common approach From MED (minimum effective dose) to MTD (maximum tolerated dose) Nevertheless MTD not needed to be assessed in every IMP How to assess the MTD? From MID (Minimum intolerated dose) to MTD MTD => last dose level below MID Who is responsible for the stopping decision? Role of the investigator (physician) All stopping procedures and responsibilities should be clearly explained in the trial protocol

26 Dose Escalation Standard procedure Arithmetic or geometric increase Relevant factors Steepness of the slope of dose/effect and dose/toxicity relations Therapeutic range in non-clinical models Predictability (raw estimate) of the effects of the next dose step Potential pharmacodynamic effects (if any) Potential toxic effects

27 Cohort Size With larger cohorts usually more precise data can be obtained, but larger cohorts put more subjects at risk and increase the costs of clinical development programmes Common standard is an A + P design with A = 6 to 10 subjects receiving the active product and P = 2 to 4 subjects receiving placebo

28 Trial Centres for First-in-man Trials High-risk Trials: Appropriate clinical facilities Medical staff with appropriate level of training and expertise and an understanding of the IMP, its target and mechanism of action Immediate access to facilities for the treatment of medical emergencies (such as cardiac emergencies, anaphylaxis, cytokine release syndrome, convulsions, hypotension), ready availability of Intensive Care Unit facilities.

Clinical trials preclinical requirements. Clinical trials - legislation

Clinical trials preclinical requirements. Clinical trials - legislation Clinical trials preclinical requirements Mikael Andersson, PhD Senior Expert Medical Products Agency, Sweden Tallinn 9/10 2009 Clinical trials - legislation Directive 2001/20/EC Clinical trial directive

More information

Session 6 Clinical Trial Assessment Phase I Clinical Trial

Session 6 Clinical Trial Assessment Phase I Clinical Trial L1 Session 6 Clinical Trial Assessment Phase I Clinical Trial Presentation to APEC Preliminary Workshop on Review of Drug Development in Clinical Trials Celia Lourenco, PhD, Manager, Clinical Group I Office

More information

ICH Topic E 8 General Considerations for Clinical Trials. Step 5 NOTE FOR GUIDANCE ON GENERAL CONSIDERATIONS FOR CLINICAL TRIALS (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) 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 information

Overview of Phase 1 Oncology Trials of Biologic Therapeutics

Overview of Phase 1 Oncology Trials of Biologic Therapeutics Overview of Phase 1 Oncology Trials of Biologic Therapeutics Susan Jerian, MD ONCORD, Inc. February 28, 2008 February 28, 2008 Phase 1 1 Assumptions and Ground Rules The goal is regulatory approval of

More information

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE PRE-CLINICAL EVALUATION OF ANTICANCER MEDICINAL PRODUCTS

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE PRE-CLINICAL EVALUATION OF ANTICANCER MEDICINAL PRODUCTS The European Agency for the Evaluation of Medicinal Products Human Medicines Evaluation Unit London, 23 July 1998 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE PRE-CLINICAL

More information

Guidance for Industry

Guidance for Industry Guidance for Industry S9 Nonclinical Evaluation for Anticancer Pharmaceuticals U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center

More information

GENERAL CONSIDERATIONS FOR CLINICAL TRIALS E8

GENERAL 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 information

Non-clinical development of biologics

Non-clinical development of biologics Aurigon Life Science GmbH Non-clinical development of biologics Requirements, challenges and case studies Committed to Life. Sigrid Messemer vet. med. M4 Seminar March 10 th 2014 Aurigon - your full service

More information

NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS

NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS

More information

Guidance for Industry

Guidance 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 information

Challenges in early clinical development of biologics

Challenges in early clinical development of biologics Challenges in early clinical development of biologics Peter Lloyd March 2011 Acknowledgements: Jennifer Sims, Phil Lowe, Sebastian Spindeldreher, Andrew Warren Protein therapeutics biologics Current generation

More information

Application for a Marketing Authorisation: Requirements and Criteria for the Assessment of QT Prolonging Potential

Application for a Marketing Authorisation: Requirements and Criteria for the Assessment of QT Prolonging Potential Application for a Marketing Authorisation: Requirements and Criteria for the Assessment of QT Prolonging Potential Bundesinstitut für Arzneimittel Dr. med. Clemens Mittmann Bundesinstitut für Arzneimittel

More information

SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS S7A

SAFETY 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 information

ICH Topic S 1 A The Need for Carcinogenicity Studies of Pharmaceuticals. Step 5

ICH 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 information

Sheffield Kidney Institute. Planning a Clinical Trial

Sheffield Kidney Institute. Planning a Clinical Trial Planning a Clinical Trial Clinical Trials Testing a new drug Ethical Issues Liability and Indemnity Trial Design Trial Protocol Statistical analysis Clinical Trials Phase I: Phase II: Phase III: Phase

More information

INTERNATIONAL 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 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 information

Biological importance of metabolites. Safety and efficacy aspects

Biological importance of metabolites. Safety and efficacy aspects Biological importance of metabolites Safety and efficacy aspects Bernard Walther Technologie Servier Biological importance of metabolites Safety testing of drug metabolites Bioanalytical strategy Structural

More information

Pharmacology skills for drug discovery. Why is pharmacology important?

Pharmacology 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 information

Guideline on similar biological medicinal products containing monoclonal antibodies non-clinical and clinical issues

Guideline on similar biological medicinal products containing monoclonal antibodies non-clinical and clinical issues 30 May 2012 EMA/CHMP/BMWP/403543/2010 Committee for Medicinal Products for Human Use (CHMP) Guideline on similar biological medicinal products containing monoclonal antibodies non-clinical and clinical

More information

4.1 Objectives of Clinical Trial Assessment

4.1 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 information

Not All Clinical Trials Are Created Equal Understanding the Different Phases

Not 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 information

WHO guideline for abbreviated licensing pathways for certain biological therapeutic products

WHO guideline for abbreviated licensing pathways for certain biological therapeutic products WHO guideline for abbreviated licensing pathways for certain biological therapeutic products - Clinical evaluation - Martina Weise, MD Federal Institute for Drugs and Medical Devices, Germany General considerations

More information

Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues

Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues 1 2 3 03 June May 2013 EMEA/CHMP/BMWP/42832/2005 Rev. 1 Committee for Medicinal Products for Human Use (CHMP) 4 5 6 7 Guideline on similar biological medicinal products containing biotechnology-derived

More information

Guideline on non-clinical and clinical development of similar biological medicinal products containing recombinant erythropoietins (Revision)

Guideline on non-clinical and clinical development of similar biological medicinal products containing recombinant erythropoietins (Revision) 18 March 2010 EMEA/CHMP/BMWP/301636/2008 Corr.* Committee for Medicinal Products for Human Use (CHMP) Guideline on non-clinical and clinical development of similar biological medicinal products containing

More information

Guidance for Industry Safety Testing of Drug Metabolites

Guidance for Industry Safety Testing of Drug Metabolites Guidance for Industry Safety Testing of Drug Metabolites U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) February 2008 Pharmacology

More information

Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues

Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues 18 December 2014 EMEA/CHMP/BMWP/42832/2005 Rev1 Committee for Medicinal Products for Human Use (CHMP) Guideline on similar biological medicinal products containing biotechnology-derived proteins as active

More information

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) REFLECTION PAPER

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) REFLECTION PAPER European Medicines Agency London 23 April 2009 EMEA/CHMP/BMWP/102046/2006 COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) REFLECTION PAPER NON-CLINICAL AND CLINICAL DEVELOPMENT OF SIMILAR MEDICINAL

More information

Biologics: Specific Drug Safety Challenges. Violetta B. Kyburz

Biologics: Specific Drug Safety Challenges. Violetta B. Kyburz Biologics: Specific Drug Safety Challenges Violetta B. Kyburz 2012 2013 2014 Biologics: Specific Drug Safety Challenges Topics for discussion Particular issues in the preclinical development of biologics

More information

RADIOPHARMACEUTICALS BASED ON MONOCLONAL ANTIBODIES

RADIOPHARMACEUTICALS BASED ON MONOCLONAL ANTIBODIES RADIOPHARMACEUTICALS BASED ON MONOCLONAL ANTIBODIES Guideline Title Radiopharmaceuticals based on Monoclonal Antibodies Legislative basis Directives 65/65/EEC, 75/318/EEC as amended, Directive 89/343/EEC

More information

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE M3(R2)

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE M3(R2) INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE GUIDANCE ON NONCLINICAL SAFETY STUDIES FOR THE

More information

Overview of model-building strategies in population PK/PD analyses: 2002-2004 literature survey.

Overview of model-building strategies in population PK/PD analyses: 2002-2004 literature survey. Overview of model-building strategies in population PK/PD analyses: 2002-2004 literature survey. Céline Dartois, Karl Brendel, Emmanuelle Comets, Céline Laffont, Christian Laveille, Brigitte Tranchand,

More information

Guidance for Industry

Guidance for Industry Guidance for Industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals U.S. Department of Health and Human Services Food and Drug

More information

Guidance for Industry

Guidance 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 information

ICH M3 (R2) Guideline on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals

ICH M3 (R2) Guideline on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals ICH M3 (R2) Guideline on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals International Conference on Harmonisation of Technical Requirements

More information

Proof-of-Concept Studies and the End of Phase IIa Meeting with the FDA

Proof-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 information

News in Nonclinical Evaluation of Anticancer Pharmaceuticals: ICH guideline S9 and beyond

News in Nonclinical Evaluation of Anticancer Pharmaceuticals: ICH guideline S9 and beyond ews in onclinical Evaluation of Anticancer Pharmaceuticals: ICH guideline S9 and beyond Wissenschaftliche Prüfungsarbeit zur Erlangung des Titels Master of Drug Regulatory Affairs der Mathematisch-aturwissenschaftlichen

More information

Guidelines for phase 1 clinical trials. 2012 edition

Guidelines for phase 1 clinical trials. 2012 edition Guidelines for phase 1 clinical trials 2012 edition Foreword The development of new and better medicines is vital for the public health. A key step in medicines development is the transition from the laboratory

More information

CenterWatch. volunteering. clinical trial. for a. www.centerwatch.com

CenterWatch. volunteering. clinical trial. for a. www.centerwatch.com volunteering for a clinical trial www.centerwatch.com :: about this pamphlet This pamphlet provides an overview of the clinical trials process and answers frequently asked questions that many potential

More information

General toxicity study designs

General toxicity study designs General toxicity study designs Jan Willem van der Laan Section on Safety of Medicines and Teratology Centre for Biological Medicines and Medical Technology National Institute for Public Health and the

More information

BIOTECHNOLOGY OPERATIONS

BIOTECHNOLOGY OPERATIONS BIOTECHNOLOGY OPERATIONS Principles and Practices Michael J. Roy TECHNISCHE INFORMATION SBIBLIOTHEK UNIVERSITATSBIBLIOTHEK HANNOVER CRC Press TaylorStFrancis Croup Boca Raton London New York CRC Press

More information

Guidance on Investigational Medicinal Products (IMPs) and other medicinal products used in Clinical Trials

Guidance on Investigational Medicinal Products (IMPs) and other medicinal products used in Clinical Trials EUROPEAN COMMISSION ENTERPRISE AND INDUSTRY DIRECTORATE-GENERAL Consumer goods Pharmaceuticals Guidance on Investigational Medicinal Products (IMPs) and other medicinal products used in Clinical Trials

More information

Guidance for Industry Influenza: Developing Drugs for Treatment and/or Prophylaxis

Guidance for Industry Influenza: Developing Drugs for Treatment and/or Prophylaxis Guidance for Industry Influenza: Developing Drugs for Treatment and/or Prophylaxis U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER)

More information

Basic Overview of Preclinical Toxicology Animal Models

Basic Overview of Preclinical Toxicology Animal Models Basic Overview of Preclinical Toxicology Animal Models Charles D. Hebert, Ph.D., D.A.B.T. December 5, 2013 Outline Background In Vitro Toxicology In Vivo Toxicology Animal Models What is Toxicology? Background

More information

Definition of Investigational Medicinal Products (IMPs) Definition of Non Investigational Medicinal Products (NIMPs)

Definition of Investigational Medicinal Products (IMPs) Definition of Non Investigational Medicinal Products (NIMPs) EUROPEAN COMMISSION ENTERPRISE AND INDUSTRY DIRECTORATE-GENERAL Consumer goods Pharmaceuticals Definition of Investigational Medicinal Products (IMPs) Definition of Non Investigational Medicinal Products

More information

OCT Practical Aspects of Conducting Clinical Trials for Russian Innovative Companies

OCT Practical Aspects of Conducting Clinical Trials for Russian Innovative Companies OCT Practical Aspects of Conducting Clinical Trials for Russian Innovative Companies Innovative Drug Research and Development in Russia 2012 OCT: CRO in Russia, Central and Eastern Europe Russian Innovative

More information

Adocia reports positive results from phase IIa clinical study of ultra-fast acting BioChaperone Lispro

Adocia reports positive results from phase IIa clinical study of ultra-fast acting BioChaperone Lispro PRESS RELEASE Adocia reports positive results from phase IIa clinical study of ultra-fast acting BioChaperone Lispro BioChaperone Lispro is significantly faster than Humalog in type I diabetic patients;

More information

M4E(R2): The CTD Efficacy

M4E(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 information

3. Notification on the clinical trial of medicinal products for human use.

3. Notification on the clinical trial of medicinal products for human use. 3. Notification on the clinical trial of medicinal products for human use. A joint publication of the Federal Institute for Drugs and Medical Devices and the Paul Ehrlich Institute for the request to the

More information

INTERNATIONAL 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 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 information

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE. Current Step 4 version

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE. Current Step 4 version INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE THE EXTENT OF POPULATION EXPOSURE TO ASSESS CLINICAL

More information

Statistics and Pharmacokinetics in Clinical Pharmacology Studies

Statistics 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 information

Adaptive Early Phase Clinical Trials in the UK

Adaptive Early Phase Clinical Trials in the UK Adaptive Early Phase Clinical Trials in the UK Jorg Taubel Bonn, October 30 th, 2014 Dr Jorg Taubel MD 1. Adaptive Study Design One or more decision points are built into the trial design; The subsequent

More information

Overview of Drug Development: the Regulatory Process

Overview 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 information

A Peak at PK An Introduction to Pharmacokinetics

A 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 information

Longitudinal Modeling of Lung Function in Respiratory Drug Development

Longitudinal 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 information

DZIF-Product Development Unit (PDU)

DZIF-Product Development Unit (PDU) November 29, 2013 7 th International VPM Days DZIF-Product Development Unit (PDU) - DZIF-TPMO at HZI - DZIF-OSRA at PEI Thomas Hesterkamp, Helmholtz Zentrum für Infektionsforschung Support from TPMO &

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Scientific Considerations in Demonstrating Biosimilarity to a Reference Product DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and

More information

Oncology Drug Development

Oncology Drug Development Oncology Drug Development A Reviewers Personal Observations W. David McGuinn, Jr., M.S., Ph. D., D.A.B.T. 1 They Make Me Say This Disclaimer This presentation is not an official FDA guidance or policy

More information

ICH Topic Q 5 E Comparability of Biotechnological/Biological Products

ICH Topic Q 5 E Comparability of Biotechnological/Biological Products European Medicines Agency June 2005 CPMP/ICH/5721/03 ICH Topic Q 5 E Comparability of Biotechnological/Biological Products Step 5 NOTE FOR GUIDANCE ON BIOTECHNOLOGICAL/BIOLOGICAL PRODUCTS SUBJECT TO CHANGES

More information

NATIONAL HEALTH COUNCIL RESOLUTION Nº 251, DATED 7 AUGUST 1997

NATIONAL HEALTH COUNCIL RESOLUTION Nº 251, DATED 7 AUGUST 1997 NATIONAL HEALTH COUNCIL RESOLUTION Nº 251, DATED 7 AUGUST 1997 Plenary of the National Health Council in its 15 th Special Meeting, held on 5 August 1997, in the exercise of its competencies, as set forth

More information

The Clinical Trials Process an educated patient s guide

The 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 information

Guideline for Industry

Guideline for Industry Guideline for Industry The Extent of Population Exposure to Assess Clinical Safety: For Drugs Intended for Longterm Treatment of Non-Life- Threatening Conditions ICH-E1A March 1995 GUIDELINE FOR INDUSTRY

More information

An introduction to Phase I dual-agent dose escalation trials

An introduction to Phase I dual-agent dose escalation trials An introduction to Phase I dual-agent dose escalation trials Michael Sweeting MRC Biostatistics Unit, Cambridge 13th March 2013 Outline Introduction to phase I trials Aims, objectives and key elements.

More information

QT analysis: A guide for statistical programmers. Prabhakar Munkampalli Statistical Analyst II Hyderabad, 7 th September 2012

QT analysis: A guide for statistical programmers. Prabhakar Munkampalli Statistical Analyst II Hyderabad, 7 th September 2012 QT analysis: A guide for statistical programmers Prabhakar Munkampalli Statistical Analyst II Hyderabad, 7 th September 2012 Agenda ECG ICH E14 Thorough QT/QTc study Role of Statistical Programmer References

More information

Cancer Treatments Subcommittee of PTAC Meeting held 18 September 2015. (minutes for web publishing)

Cancer Treatments Subcommittee of PTAC Meeting held 18 September 2015. (minutes for web publishing) Cancer Treatments Subcommittee of PTAC Meeting held 18 September 2015 (minutes for web publishing) Cancer Treatments Subcommittee minutes are published in accordance with the Terms of Reference for the

More information

Glossary of Clinical Trial Terms

Glossary of Clinical Trial Terms Glossary of Clinical Trial Terms ADVERSE REACTION: (Adverse Event): Also known as side effects, adverse reactions include any undesired actions or effects of the experimental drug or treatment. Experimental

More information

Rare Diseases: Common Issues in Drug Development Guidance for Industry

Rare Diseases: Common Issues in Drug Development Guidance for Industry Rare Diseases: Common Issues in Drug Development Guidance for Industry DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft

More information

CTD Dossier Preparation. Sr.Manager-Regulatory Affairs

CTD 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 information

Guidance for Industry

Guidance 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 information

Ethics and Scientific Oversight for Phase 1 Clinical Trials in Hong Kong. Sydney TANG Chairman, HKU/HA HKW IRB November 21, 2015

Ethics and Scientific Oversight for Phase 1 Clinical Trials in Hong Kong. Sydney TANG Chairman, HKU/HA HKW IRB November 21, 2015 Ethics and Scientific Oversight for Phase 1 Clinical Trials in Hong Kong Sydney TANG Chairman, HKU/HA HKW IRB November 21, 2015 Clinical Trials at HKU Phase 1 Phase II Phase III Phase IV Conducted on patient

More information

Reflection paper on clinical aspects related to tissue engineered products

Reflection paper on clinical aspects related to tissue engineered products 1 2 3 19 March 2012 EMA/CAT/CPWP/573420/2009 Committee for Advanced Therapies (CAT) 4 5 6 Reflection paper on clinical aspects related to tissue engineered products Draft Draft agreed by CPWP 7 October

More information

Current version dated 5 March 2012

Current version dated 5 March 2012 M3(R2) Implementation Working Group M3(R2) Guideline: Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals Questions & Answers

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-derived Products Center for

More information

EUROPEAN COMMISSION ENTERPRISE DIRECTORATE-GENERAL. Brussels, ENTR/CT 1. Revision 1

EUROPEAN COMMISSION ENTERPRISE DIRECTORATE-GENERAL. Brussels, ENTR/CT 1. Revision 1 EUROPEAN COMMISSION ENTERPRISE DIRECTORATE-GENERAL Single market : management & legislation for consumer goods Pharmaceuticals : regulatory framework and market authorisations Brussels, ENTR/CT 1 Revision

More information

Guidance for Industry Migraine: Developing Drugs for Acute Treatment

Guidance for Industry Migraine: Developing Drugs for Acute Treatment Guidance for Industry Migraine: Developing Drugs for Acute Treatment DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft

More information

EUROPEAN COMMISSION ENTERPRISE DIRECTORATE-GENERAL. Brussels, ENTR/F2/BL D(2003) CT 1 Revision 2

EUROPEAN COMMISSION ENTERPRISE DIRECTORATE-GENERAL. Brussels, ENTR/F2/BL D(2003) CT 1 Revision 2 EUROPEAN COMMISSION ENTERPRISE DIRECTORATE-GENERAL Single market : management & legislation for consumer goods Pharmaceuticals : regulatory framework and market authorisations Brussels, ENTR/F2/BL D(2003)

More information

The Promise and Challenge of Adaptive Design in Oncology Trials

The Promise and Challenge of Adaptive Design in Oncology Trials THE POWER OFx Experts. Experience. Execution. The Promise and Challenge of Adaptive Design in Oncology Trials Clinical oncology trials are more complex and time consuming than those in any other therapeutic

More information

Early Drug Discovery and Development Guidelines: For Academic Researchers, Collaborators, and Start-up Companies

Early Drug Discovery and Development Guidelines: For Academic Researchers, Collaborators, and Start-up Companies 1 of 46 7/26/2013 11:44 PM NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. Sittampalam GS, Gal-Edd N, Arkin M, et al., editors. Assay Guidance Manual [Internet].

More information

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE S7B

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE S7B INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE THE NON-CLINICAL EVALUATION OF THE POTENTIAL FOR

More information

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP)

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) The European Agency for the Evaluation of Medicinal Products Evaluation of Medicines for Human Use London, 18 December 2002 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE

More information

General Principles for the Safety Assessment of Excipients

General Principles for the Safety Assessment of Excipients General Principles for the Safety Assessment of Excipients General Characteristics of the Pharmaceutical Excipients Classification of excipients The Safety Assessment of Pharmaceutical Excipients : how

More information

Challenges in the Regulation of Pediatric Clinical Trials

Challenges in the Regulation of Pediatric Clinical Trials Challenges in the Regulation of Pediatric Clinical Trials Wilson W. Bryan, M.D. FDA / CBER / OCTGT wilson.bryan@fda.hhs.gov National Institutes of Health Recombinant DNA Advisory Committee (RAC) Meeting

More information

Adaptive and Innovative Study Designs to Accelerate Drug Development from First-In- Human to First-In-Patient

Adaptive and Innovative Study Designs to Accelerate Drug Development from First-In- Human to First-In-Patient Adaptive and Innovative Study Designs to Accelerate Drug Development from First-In- Human to First-In-Patient Michelle L. Combs, PhD Vice President, Clinical Pharmacology Sciences Definition of Adaptive

More information

Scientific Challenges for Development of Biosimilar Monoclonal Antibodies. Rafiqul Islam Director, Global Bioanalytical Services Celerion

Scientific Challenges for Development of Biosimilar Monoclonal Antibodies. Rafiqul Islam Director, Global Bioanalytical Services Celerion Scientific Challenges for Development of Biosimilar Monoclonal Antibodies Rafiqul Islam Director, Global Bioanalytical Services Celerion Presentation outline Biosimilars Definitions and Concepts Regulatory

More information

Guidance for Industry

Guidance 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 information

Regulatory Pathways for Licensure and Use of Ebola Virus Vaccines During the Current Outbreak FDA Perspective

Regulatory Pathways for Licensure and Use of Ebola Virus Vaccines During the Current Outbreak FDA Perspective Regulatory Pathways for Licensure and Use of Ebola Virus Vaccines During the Current Outbreak FDA Perspective Office of Vaccines Research and Review Center for Biologics Evaluation and Research U.S. Food

More information

Humulin (LY041001) Page 1 of 1

Humulin (LY041001) Page 1 of 1 (LY041001) These clinical study results are supplied for informational purposes only in the interests of scientific disclosure. They are not intended to substitute for the FDA-approved package insert or

More information

Medicine Safety Glossary

Medicine Safety Glossary The following definitions are provided as a resource to supplement the information provided in the Medicine Safety Education section of the Pfizer.com Web site; they are not intended as a comprehensive

More information

Bayesian Phase I/II clinical trials in Oncology

Bayesian Phase I/II clinical trials in Oncology Bayesian Phase I/II clinical trials in Oncology Pierre Mancini, Sandrine Micallef, Pierre Colin Séminaire JEM-SFES - 26 Janvier 2012 Outline Oncology phase I trials Limitations of traditional phase I designs

More information

Guideline on similar biological medicinal products containing interferon beta

Guideline on similar biological medicinal products containing interferon beta 1 2 3 15 December 2011 EMA/CHMP/BMWP/652000/2010 Committee for Medicinal Products for Human Use (CHMP) 4 5 6 Guideline on similar biological medicinal products containing interferon beta 7 Draft Draft

More information

Guideline on similar biological medicinal products containing interferon beta

Guideline on similar biological medicinal products containing interferon beta 21 February 2013 EMA/CHMP/BMWP/652000/2010 Committee for Medicinal Products for Human Use (CHMP) Guideline on similar biological medicinal products containing interferon beta Draft Agreed by BMWP June

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Exposure-Response Relationships Study Design, Data Analysis, and Regulatory Applications U.S. Department of Health and Human Services Food and Drug Administration Center for Drug

More information

Summary of the risk management plan (RMP) for Ofev (nintedanib)

Summary of the risk management plan (RMP) for Ofev (nintedanib) EMA/738120/2014 Summary of the risk management plan (RMP) for Ofev (nintedanib) This is a summary of the risk management plan (RMP) for Ofev, which details the measures to be taken in order to ensure that

More information

Achieving Regulatory Success: Areas of focus for biotechnology companies. Michael J. Schlosser, PhD, DABT April 21, 2013

Achieving Regulatory Success: Areas of focus for biotechnology companies. Michael J. Schlosser, PhD, DABT April 21, 2013 Achieving Regulatory Success: Areas of focus for biotechnology companies Michael J. Schlosser, PhD, DABT April 21, 2013 Regulatory Success Outline Regulatory Initiatives Regulatory Science Pre-Regulatory

More information

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE E11

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE E11 INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE CLINICAL INVESTIGATION OF MEDICINAL PRODUCTS IN

More information

New Drug Application (NDA) Checklist

New Drug Application (NDA) Checklist New Drug Application (NDA) Checklist New Drug Applications (NDA) are very complex and detailed. It is difficult to know whether a company has included all of the information that is required by the applicable

More information

Clinical Trial Design. Sponsored by Center for Cancer Research National Cancer Institute

Clinical Trial Design. Sponsored by Center for Cancer Research National Cancer Institute Clinical Trial Design Sponsored by Center for Cancer Research National Cancer Institute Overview Clinical research is research conducted on human beings (or on material of human origin such as tissues,

More information

Careers in Biostatistics and Clinical SAS Programming An Overview for the Uninitiated Justina M. Flavin, Independent Consultant, San Diego, CA

Careers 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 information