Preclinical Safety Studies of Experimental Medicines

Size: px
Start display at page:

Download "Preclinical Safety Studies of Experimental Medicines"

Transcription

1 AOQ-Qld RRDM seminar 2 July 2008 Preclinical Safety Studies of Experimental Medicines Brian Creese

2 Introduction Seminar Outline Preclinical safety data requirements for phase 1 trials Dose selection for phase 1 trials Phase 0 trials Preclinical data requirements for later stage clinical trials and product registration

3 Drug Development Time-consuming process Requires integrated approach (CMC, preclinical, clinical, regulatory)

4

5 Preclinical Development Efficacy studies (non-glp) In vitro studies Animal disease models Mechanism of action studies Safety studies (GLP) Safety pharmacology Pharmacokinetics and metabolism Local tolerability General toxicity (single and repeated-dose) Genetic toxicity Carcinogenicity Reproductive and developmental toxicity

6 Value of Preclinical Safety Studies Dose selection in phase 1 clinical trials Based on NOAEL in preclinical safety studies Information on likely side effects Minimise risk of serious AEs in clinical trials Histopathological assessment Identifies potential target organs Toxicity endpoints not amenable to clinical investigation Carcinogenicity Genetic toxicity Reproductive toxicity

7 Aims of Preclinical Safety Studies Identification of target organs for toxicities Characterisation of dose-response relationships Determination of no-effect levels for toxicity Relationship of toxic effects to exposure Potential reversibility Mechanisms of toxicity

8 Global Harmonisation of Preclinical Study Requirements International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Government and industry representatives from USA, Europe and Japan First meeting in 1990, on-going process

9 ICH Guidelines for Preclinical Safety Testing S1 Carcinogenicity (S1A, S1B, S1C and S1C(R2)) S2 Genotoxicity (S2A and S2B, now combined into S2(R1)) S3 Toxicokinetics (S3A) and pharmacokinetics (S3B) S4 Repeated-dose toxicity (S4A) S5 Reproductive toxicity (S5A and S5B, now combined as S5(R2)) S6 Biotechnology Products S7 Safety pharmacology (S7A and S7B) S8 Immunotoxicology M3(R1) Timing of preclinical studies in relation to clinical trials

10 Preclinical Safety Studies Prior to Phase 1 Trials Safety pharmacology Toxicokinetics, pharmacokinetics and metabolism Local tolerability Acute (single-dose) toxicity Repeated-dose toxicity Genetic toxicology Effects on embryofetal development

11 Safety Pharmacology Effects on physiological systems unrelated to desired activity (i.e. unwanted effects or side-effects) Screening at high dose levels GLP compliance is required Core battery: Central nervous system Respiratory system Cardiovascular system (including QT prolongation) ICH guidelines S7A and S7B

12 Pharmacokinetics and Toxicokinetics Pharmacokinetics Absorption, distribution, metabolism and excretion Characterisation of basic pharmacokinetic parameters Doses associated with pharmacological activity Usually single-dose Toxicokinetics Assessment of systemic exposure (blood levels) in animal toxicity studies (C max and AUC) High doses, repeated dosing Same species as used in toxicity studies Usually an integral part of the toxicity study

13 Toxicokinetics Exposure data in animals should be evaluated prior to human clinical trials (ICH guideline M3) Objectives: Describe systemic exposure in animals Relationship to dose and duration of dosing Relationship between exposure and toxicity Assess clinical relevance of toxicity findings Support choice of species and treatment regimen in preclinical safety studies (ICH guideline S3A)

14 Pharmacokinetics ICH guideline M3: Further information on absorption, distribution, metabolism and excretion in animals should be made available to compare human and animal metabolic pathways. Appropriate information should usually be available by the time the Phase I (Human Pharmacology) studies have been completed.

15 Pharmacokinetics Basic pharmacokinetic studies are usually completed before phase I clinical trials In vitro studies on drug metabolism to support species selection for toxicity studies Information on plasma kinetics to determine dose frequency and toxicokinetic sampling times Understanding pharmacodynamic properties of the drug and preparation of the clinical development plan

16 Local Tolerability The evaluation of local tolerance should be performed prior to human exposure (ICH guideline M3) Animal studies using routes and formulation applicable to proposed human administration May be part of other toxicity studies

17 Acute (Single-Dose) Toxicity ICH guideline M3: The single dose (acute) toxicity for a pharmaceutical should be evaluated in two mammalian species prior to the first human exposure (Note 1). A dose escalation study is considered an acceptable alternative to the single dose design. Note 1: Refer to ICH-1 and regional guidelines ICH-1 (1991): LD 50 determination should be abandoned for pharmaceutical products

18 Acute Toxicity: Regional Guidelines EU USA Japan Species 2* 2 (one nonrodent) # 2 (one nonrodent) # Routes 2** 2** 1 (clinical) Days of observation * Usually mouse and rat ** Clinical route + maximum systemic exposure (IV) # Dose escalation is acceptable study design for non-rodents

19 Acute Toxicity: Changes Are Afoot Sep ICH concept paper M3(R2) The need to keep single dose toxicity studies as a fixed requirement prior to first human exposure. Nov Acute Toxicity Workshop May 2007 NC3Rs workshop report Mar Robinson et al (Reg Tox Pharmacol 50: )

20 Robinson et al (2008) A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development 18 European companies Evidence-based review 74 compounds Conclusion: Acute toxicity studies are not needed prior to first clinical trials in humans. Instead, information can be obtained from other studies, which are performed at more relevant doses for humans and are already an integral part of drug development. The conclusions have been discussed and agreed with representatives of regulatory bodies from the US, Japan and Europe.

21 Repeated-Dose Toxicity Repeated-dose toxicity studies in two mammalian species (including one non-rodent) are required to support all clinical trials (except phase 0 ) Recommended duration of repeated-dose toxicity studies is related to: Duration of proposed clinical trial Therapeutic indication Scale of the proposed trial (ICH guideline M3)

22 Duration of Repeated-Dose Toxicity Studies Equal to or longer than the duration of the proposed clinical trial (up to maximum of 6-9 months) Exception: where significant therapeutic gain has been shown, trials may be extended beyond the duration of supportive repeated dose toxicity studies on a case by case basis (ICH guideline M3)

23 Duration of Repeated-Dose Studies for Phase 1 Trials Trial duration Single dose Up to 2 weeks Up to 1 month Up to 3 months Up to 6 months > 6 months Minimum duration of animal study Rodent Non-rodent 2 weeks 2 weeks 2 weeks 2 weeks 1 month 1 month 3 months 3 months 6 months 6 months 6 months Chronic (9 mo)

24 Genetic Toxicity ICH M3 guideline: Prior to first human exposure, in vitro tests for the evaluation of mutations and chromosomal damage are generally needed ICH guideline S2(R1): Bacterial reverse gene mutation assay (Ames test) Test for chromosomal damage in mammalian cells (in vitro or in vivo) Exception: biotechnology products (ICH-S6)

25 Reproductive and Developmental Toxicity Dependent on population used in the trial: Phase 1 trials usually done in healthy males Women not of childbearing potential may also be included Women of childbearing potential (WOBCP) not usually included in early phase trials because of high level of concern regarding potential hazards associated with unintentional exposure of an embryo or fetus Regional variation in requirements for inclusion of WOCBP

26 Inclusion of Women of Child-Bearing Potential in Clinical Trials Europe and Japan (and Australia) WOCBP may be included following completion of embryofetal development studies in two species USA WOCBP may be included in early, carefully monitored studies provided appropriate precautions are taken to minimise risk (ICH M3 guideline)

27 Inclusion of WOCBP Conditions for including women of childbearing potential before developmental toxicity studies are completed (USA only): Pregnancy testing Highly effective method of birth control Entry after a confirmed menstrual period Continued testing and monitoring during the trial Informed consent must include pertinent information from related pharmaceuticals and statement of risk

28 Embryofetal Development Studies ICH guideline S5(R2): Two mammalian species (usually rats and rabbits) Dosing during organogenesis (days 6-16 in rats) Fetuses examined one day prior to parturition Endpoints include: Toxic effects in pregnant animals Embryofetal deaths Fetal growth Structural changes

29 Starting Dose in Phase 1 Trials FDA guidance document (July 2005): Based on no observed adverse effect level (NOAEL) NOAEL in each animal species converted to human equivalent dose (HED) Conversion usually based on body surface area (dose mg/m 2 ) Most appropriate animal species Usually the most sensitive, based on lowest HED Application of safety factor 10 is default value Comparison with pharmacologically active dose Based on pharmacodynamic modelling

30 Phase 0 Clinical Trials Special guidelines in Europe and USA Less stringent preclinical requirements allow early start of clinical development program Europe (and Australia) Non-clinical Safety Studies to Support Clinical Trials with a Single Microdose (June 2004). USA: Exploratory IND Studies guidance document (Jan 2006) Identified as an issue in ICH M3(R2) concept paper

31 Microdose Studies (Europe) Single dose only Microdose defined as 1/100 th of anticipated dose for pharmacological effect Maximum dose of 100 µg (0.1 mg) Endpoints: Pharmacokinetics and distribution Pharmacodynamic (receptor selectivity) Sensitive analytical techniques (PET, AMS) Suitable for comparative studies of multiple therapeutic candidates

32 Exploratory IND studies (USA) Prior to traditional phase 1 IND studies Limited duration of exposure (single-dose or up to 7 days) No therapeutic or diagnostic intent Usually in healthy volunteers Study endpoints: Mechanism of action or pharmacodynamics Pharmacokinetic profile or biodistribution May include dose escalation studies with pharmacodynamic endpoint (i.e. not MTD)

33 Phase 2 Clinical Trials Additional preclinical studies will depend on design of phase 2 trials: More detailed information on preclinical pharmacokinetics Additional data on local tolerability may be required Repeated-dose toxicity studies of longer duration may also be required Genetic toxicity testing in vivo Reproductive toxicity studies (depending on geographical location and patient selection criteria) Immunotoxicity testing may be required (ICH guideline S8).

34 Phase 3 Clinical Trials Effects on fertility males and females one species, usually rats In Europe (and Australia), guidelines for duration of repeated-dose toxicity studies to support phase 3 trials are more stringent

35 Duration of Repeated-Dose Studies for Phase 3 Trials in Europe (and Australia) Trial duration Up to 2 weeks Up to 1 month Up to 3 months > 3 months Minimum duration of animal study Rodent Non-rodent 1 month 1 month 3 months 3 months 6 months 3 months 6 months Chronic (9 mo)

36 Additional Preclinical Studies to Support Marketing (Registration) Long-term ( chronic ) toxicity studies are required if clinical use is likely to exceed one month 6 months in rodents 9 months in non-rodents (FDA may require 12 months) Complete assessment of effects on reproduction and development Carcinogenicity studies in two species if cumulative lifetime exposure is > 6 months ICH guidelines S1A

37 SUMMARY Extent of preclinical safety testing is dependent on: Stage of development Duration of human exposure Target population Basic package of preclinical safety studies for phase 1 trials Reduced preclinical requirements for phase 0 trials Preclinical safety testing continues during clinical development

ICH Topic M 3 (R1) Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals. Step 5

ICH Topic M 3 (R1) Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals. Step 5 European Medicines Agency November 2000 CPMP/ICH/286/95 ICH Topic M 3 (R1) Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals Step 5 NOTE FOR GUIDANCE ON NON-CLINICAL

More information

Guidance for Industry

Guidance for Industry Guidance for Industry M3 Nonclinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals July 1997 ICH Guidance for Industry M3 Nonclinical Safety Studies for the Conduct of Human

More information

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

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

First Dose in Humans. Dr John Donohoe

First Dose in Humans. Dr John Donohoe First Dose in Humans Dr John Donohoe Clinical Trial Guidelines - ICH ICH M3 Non-clinical safety studies for the conduct of clinical trials for pharmaceuticals (Original 1996, R1 2000, R2 draft 2008) ICH

More information

ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals

ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals December 2009 EMA/CPMP/ICH/286/1995 ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals Step 5 Transmission to CHMP

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

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 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

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 guideline S9 on nonclinical evaluation for anticancer pharmaceuticals

ICH guideline S9 on nonclinical evaluation for anticancer pharmaceuticals May 2010 EMA/CHMP/ICH/646107/2008 ICH guideline S9 on nonclinical evaluation for anticancer pharmaceuticals Step 5 Transmission to CHMP December 2008 Adoption by CHMP for release for consultation December

More information

ICH Topic M 3 (R2) Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.

ICH Topic M 3 (R2) Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals. European Medicines Agency July 2008 CPMP/ICH/286/95 ICH Topic M 3 (R2) Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals Step 3 NOTE FOR

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

How Much Animal Data are Required to Move into Clinical Testing? Hilary Sheevers, PhD Aclairo October 10, 2007

How Much Animal Data are Required to Move into Clinical Testing? Hilary Sheevers, PhD Aclairo October 10, 2007 How Much Animal Data are Required to Move into Clinical Testing? Hilary Sheevers, PhD Aclairo October 10, 2007 Guidances FDA is Guidance Driven Good news: guidances are on FDA s website ICH M3 for small

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

COMMITTEE FOR HUMAN MEDICINAL PRODUCTS (CHMP) DRAFT

COMMITTEE FOR HUMAN MEDICINAL PRODUCTS (CHMP) DRAFT European Medicines Agency Pre-authorisation Evaluation of Medicines for Human Use London, 29 September 2005 Doc. Ref. EMEA/CHMP/SWP/169215/2005 COMMITTEE FOR HUMAN MEDICINAL PRODUCTS (CHMP) DRAFT GUIDELINE

More information

ICH guideline M3 (R2) - questions and answers

ICH guideline M3 (R2) - questions and answers May EMA/CHMP/ICH/507008/ Committee for medicinal products for human use (CHMP) ICH guideline Step 5 Transmission to CHMP for information May Release for information May 7 Westferry Circus Canary Wharf

More information

LAYOUT OF CTD COMMON TECHNICAL DOCUMENT - EU

LAYOUT OF CTD COMMON TECHNICAL DOCUMENT - EU There are five (5) modules in CTD. LAYOUT OF CTD COMMON TECHNICAL DOCUMENT - EU THESE FIVE ARE: MODULE 1 - ADMINISTRATIVE MODULE 2 OVERALL SUMMARIES MODULE 3 - QUALITY MODULE 4 NON CLINICAL STUDY REPORTS

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 Questions and Answers(R2) U.S. Department of Health and

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

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

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

ICH Topic S 3 A Toxicokinetics: A Guidance for Assessing Systemic Exposure in Toxicology Studies. Step 5

ICH Topic S 3 A Toxicokinetics: A Guidance for Assessing Systemic Exposure in Toxicology Studies. Step 5 European Medicines Agency June 1995 CPMP/ICH/384/95 ICH Topic S 3 A Toxicokinetics: A Guidance for Assessing Systemic Exposure in Toxicology Studies Step 5 NOTE FOR GUIDANCE ON TOXICOKINETICS: A GUIDANCE

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

Manual: Policies Document ID: PI013 Date Created: Jun 08 Section: Investigator No. Pages: 7 Review Date: Aug 15 Future Review Date: Aug 17

Manual: Policies Document ID: PI013 Date Created: Jun 08 Section: Investigator No. Pages: 7 Review Date: Aug 15 Future Review Date: Aug 17 P0LICYI013 PREGNANCY AND SEXUAL HEALTH POLICY Manual: Policies Document ID: PI013 Date Created: Jun 08 Section: Investigator No. Pages: 7 Review Date: Aug 15 Future Review Date: Aug 17 PURPOSE To describe

More information

Regulation (EC) n 1107/2009 -plant protection products- New data requirements for Toxicology active substances & preparations

Regulation (EC) n 1107/2009 -plant protection products- New data requirements for Toxicology active substances & preparations Regulation (EC) n 1107/2009 -plant protection products- New data requirements for Toxicology active substances & preparations Thierry Mercier French agency for food, environmental and occupational health

More information

Requirements for the First-In Clinical Trials

Requirements for the First-In Clinical Trials Requirements for the First-In In-Human Clinical Trials David R Jones (David.Jones@mhra.gsi.gov.uk) Expert Scientific Assessor (Pharmacotoxicologist), Licensing Division, Medicines and Healthcare products

More information

Safety Pharmacology. Klaus Olejniczak. Federal Institute for Drugs and Medical Devices (BfArM), Germany

Safety Pharmacology. Klaus Olejniczak. Federal Institute for Drugs and Medical Devices (BfArM), Germany Safety Pharmacology Federal Institute for Drugs and Medical Devices (BfArM), Germany SAFETY PHARMACOLOGY Scope Guideline is applied generally to New chemical and biological entities, including biotechnology-derived

More information

UK Experiences with Exploratory Clinical Trials

UK Experiences with Exploratory Clinical Trials Safeguarding public health UK Experiences with Exploratory Clinical Trials David R Jones Expert Scientific Assessor (Pharmacotoxicologist), Licensing Division, Medicines and Healthcare products Regulatory

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

GUIDELINE ON SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS (S7A) ICH S7 Expert Working Group M. Hashimoto Ph.D. Pharmacia

GUIDELINE ON SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS (S7A) ICH S7 Expert Working Group M. Hashimoto Ph.D. Pharmacia GUIDELINE ON SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS (S7A) ICH S7 Expert Working Group M. Hashimoto Ph.D. Pharmacia Efficacy Guideline on Safety Pharmacology Studies Safety ICH-CTD Definition:

More information

Clinical Trials Glossary

Clinical Trials Glossary Clinical Trials Glossary ADME: an acronym for absorption, distribution, metabolism and elimination. ADME studies determine how a drug is absorbed by the body, the chemical changes that it may undergo and

More information

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

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

More information

Introduction To Clinical Research and Drug Discovery Process

Introduction To Clinical Research and Drug Discovery Process Introduction To Clinical Research and Drug Discovery Process Drug Discovery Process Pre-clinical Development Clinical Development Drug Discovery Process Process of generating a new idea that is targeted

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

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

Clinical Epidemiology Drug Development I Preclinical Development

Clinical Epidemiology Drug Development I Preclinical Development IBE Clinical Epidemiology Drug Development I Preclinical Development Sascha Tillmanns, MSc, Medical Director s.tillmanns@online.de Clinical/Preclinical Development, SuppreMol GmbH Agenda Scope Introduction

More information

Risks and Benefits of Conducting Preclinical Studies in the Global Setting. By Mukesh Kumar, PhD, RAC and Janice Longstreth, PhD, DABT

Risks and Benefits of Conducting Preclinical Studies in the Global Setting. By Mukesh Kumar, PhD, RAC and Janice Longstreth, PhD, DABT Risks and Benefits of Conducting Preclinical Studies in the Global Setting By Mukesh Kumar, PhD, RAC and Janice Longstreth, PhD, DABT 20 December 2011 It is generally accepted that the preclinical studies

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

HYMAN, PHELPS & MCNAMARA, P.C.

HYMAN, PHELPS & MCNAMARA, P.C. J A MES R. P HE L PS PA UL M. H YMA N R OB ERT A. D ORME R S TEP HE N H. Mc N A MARA R OG ER C. T H IE S T H O MAS S CA RL E TT J EFFRE Y N. G IB BS B R IAN J. DO NA TO F R ANK J. SAS INOW SK I D IA NE

More information

LGD 6972: Glucagon Receptor Antagonist

LGD 6972: Glucagon Receptor Antagonist LGD 6972: Glucagon Receptor Antagonist Highly Potent, Orally Bioavailable, Small Molecule Glucagon Receptor Antagonist for the Treatment of Type 2 Diabetes Overview Diabetes is one of the largest and fastest

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

Challenges in the evaluation of preclinical toxicology in immuno-oncology

Challenges in the evaluation of preclinical toxicology in immuno-oncology SESSION 7: PRECLINICAL & TOXICOLOGY MODELS IN IMMUNO-ONCOLOGY Challenges in the evaluation of preclinical toxicology in immuno-oncology Belén Gracia Moneva Spanish Medicines and Healthcare Products Agency

More information

DESIGN & ENDPOINT OF PHASE I / TRANSLATIONAL RESEARCH MONDAY 7 TH JULY 2014 UZMA RAYANI CLINICAL OPERATIONS MANAGER

DESIGN & ENDPOINT OF PHASE I / TRANSLATIONAL RESEARCH MONDAY 7 TH JULY 2014 UZMA RAYANI CLINICAL OPERATIONS MANAGER DESIGN & ENDPOINT OF PHASE I / TRANSLATIONAL RESEARCH MONDAY 7 TH JULY 2014 UZMA RAYANI CLINICAL OPERATIONS MANAGER Drug Development Office 100 DRUG DEVELOPMENT AND OPERATIONAL STAFF NEW AGENTS IN CLINICAL

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

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

UNDERSTANDING THE RISK ASSESSMENT PROCESS

UNDERSTANDING THE RISK ASSESSMENT PROCESS UNDERSTANDING THE RISK ASSESSMENT PROCESS Berna Magnuson, PhD Fellow, Academy of Toxicological Sciences Presented on Behalf of The Calorie Control Council Risk Assessment for All Chemicals Natural or Synthetic

More information

Kata Bölcskei. University of Pécs Department of Pharmacology and Pharmacotherapy. Clinical trials

Kata Bölcskei. University of Pécs Department of Pharmacology and Pharmacotherapy. Clinical trials Clinical trials Kata Bölcskei University of Pécs Department of Pharmacology and Pharmacotherapy Clinical trials definition (ICH-GCP): Any investigation in human subjects intended to discover or verify

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

INITIAL INVESTIGATIONAL NEW DRUG APPLICATION. IND Title (if title being used) Serial 0000

INITIAL INVESTIGATIONAL NEW DRUG APPLICATION. IND Title (if title being used) Serial 0000 INITIAL INVESTIGATIONAL NEW DRUG APPLICATION IND Title (if title being used) Serial 0000 Name of Sponsor Investigator, MD X Professor, Department DARTHMOUTH-HITCHCOCK MEDICAL CENTER Date of Submission

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

How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14

How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14 How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14 Annankatu 18, P.O. Box 400, FI-00121 Helsinki, Finland Tel. +358 9 686180 Fax +358 9 68618210 echa.europa.eu

More information

STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: CARCINOGENICITY TESTING

STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: CARCINOGENICITY TESTING VICH GL28 (SAFETY: CARCINOGENITICY) October 2002 For implementation at Step 7 - Final STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: CARCINOGENICITY TESTING Recommended for

More information

Preclinical Development. Biodistribution Studies in Gene Therapy

Preclinical Development. Biodistribution Studies in Gene Therapy ASGCT/ESGCT Early Phase Clinical Trials Training Course Preclinical Development Biodistribution Studies in Gene Therapy Helene Chautard, PhD Versailles. October 25 th, 2012 A unique Contract Research Organization

More information

Introduction to Drug Development Process. Proposed on May 7, Introduction to Drug Development Process

Introduction to Drug Development Process. Proposed on May 7, Introduction to Drug Development Process Introduction to Proposed on May 7, 2008 Introduction to Objectives Recognize the investigational drug success rates by stages Define pre-clinical studies Define Investigational New Drug Application Phase

More information

AKB-6548 clinical development overview early clinical studies (CI-0001 to CI-

AKB-6548 clinical development overview early clinical studies (CI-0001 to CI- AKB-6548 clinical development overview early clinical studies (CI-0001 to CI- 0004, and CI-0006) To date, AKB-6548 has been studied in 8 clinical trials across 4 separate patient populations: healthy volunteers

More information

Discovery safety assessment of drug projects can be considered in two broad areas: target-related safety and chemical related safety.

Discovery safety assessment of drug projects can be considered in two broad areas: target-related safety and chemical related safety. Toxicology Skills for Drug Discovery Why is Toxicology in Drug Discovery important? The development of novel pharmaceuticals requires non-clinical safety studies to be performed on candidate drugs. Such

More information

Clinical Research White Paper

Clinical Research White Paper September 2009 Clinical Research White Paper Understanding the Clinical Research Process The evolution from scientific hypothesis to approved and marketed medicine is a lengthy and arduous process that

More information

Plasma Drug Concentration Time Profile Plotting Data

Plasma Drug Concentration Time Profile Plotting Data UNIT 2 PHARMACOKINETICS-BASIC CONSIDERATIONS Plasma Drug Concentration Time Profile Plotting Data S. SANGEETHA., M.PHARM., (Ph.d) Department of Pharmaceutics SRM College of Pharmacy SRM University INTRODUCTION

More information

Guideline on non-clinical local tolerance testing of medicinal products Draft

Guideline on non-clinical local tolerance testing of medicinal products Draft 1 2 3 25 April 2014 EMA/CHMP/SWP/ Committee for Medicinal Products for Human Use (CHMP) 4 5 6 7 8 Guideline on non-clinical local tolerance testing of medicinal products Draft Agreed by Safety Working

More information

STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: CARCINOGENICITY TESTING

STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: CARCINOGENICITY TESTING VICH GL28 (SAFETY: CARCINOGENITICY) Revision (at Step 9) February 2005 For implementation at Step 7 STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: CARCINOGENICITY TESTING

More information

THE ASEAN COMMON TECHNICAL DOSSIER (ACTD) FOR THE REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE PART III: NONCLINICAL DOCUMENT

THE ASEAN COMMON TECHNICAL DOSSIER (ACTD) FOR THE REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE PART III: NONCLINICAL DOCUMENT THE ASEAN COMMON TECHNICAL DOSSIER (ACTD) FOR THE REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE PART III: NONCLINICAL DOCUMENT PREAMBLE THE ASEAN COMMON TECHNICAL DOSSIER (ACTD) FOR THE REGISTRATION OF

More information

Introductory overview of medicines development process. Markku Toivonen

Introductory overview of medicines development process. Markku Toivonen Introductory overview of medicines development process Markku Toivonen June 2014 Contents What is medical research? Evidence-based medicine Life cycle of drug development WHAT IS MEDICAL RESEARCH? How

More information

Biologics and Manufacturing Changes

Biologics and Manufacturing Changes Biologics and Manufacturing Changes Richard M. Lewis, PhD and Mary Ellen Cosenza, PhD, DABT, RAC 24 Historically, biological products were defined by the process that produced them. Biochemical methods

More information

HOW DO I GET MY COMPOUND INTO PHASE I?

HOW DO I GET MY COMPOUND INTO PHASE I? HOW DO I GET MY COMPOUND INTO PHASE I? Considerations For Program Design: Various Scenarios And Approaches By Dr. Scott E. Boley and Greg Ruppert PREFACE The primary challenge for pharmaceutical and biotechnology

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

PART B: METHODS FOR THE DETERMINATION OF TOXICITY AND OTHER HEALTH EFFECTS GENERAL INTRODUCTION: PART B

PART B: METHODS FOR THE DETERMINATION OF TOXICITY AND OTHER HEALTH EFFECTS GENERAL INTRODUCTION: PART B PART B: METHODS FOR THE DETERMINATION OF TOXICITY AND OTHER HEALTH EFFECTS GENERAL INTRODUCTION: PART B A. EXPLANATORY NOTE For the purpose of this General Introduction the following nymbering applies:

More information

PRECLINICAL SAFETY EVALUATION OF BIOTECHNOLOGY-DERIVED PHARMACEUTICALS S6(R1)

PRECLINICAL SAFETY EVALUATION OF BIOTECHNOLOGY-DERIVED PHARMACEUTICALS S6(R1) INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE PRECLINICAL SAFETY EVALUATION OF BIOTECHNOLOGY-DERIVED

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

Preclinical Development to IND: Drugs and Vaccines

Preclinical Development to IND: Drugs and Vaccines Preclinical Development to IND: Drugs and Vaccines Maralee McVean, PhD Vice President, Pharmacology and Toxicology Services PreClinical Research Services, Inc. maralee.mcvean@preclinicalresearch.com Overview

More information

Non Clinical Development for ATMP: In Vivo Study Requirements and Strategy in Absence of Relevant Models. Swissmedic

Non Clinical Development for ATMP: In Vivo Study Requirements and Strategy in Absence of Relevant Models. Swissmedic Non Clinical Development for ATMP: In Vivo Study Requirements and Strategy in Absence of Relevant Models Swissmedic Overview 1. Swiss Regulatory Basis for GT/GMO Products and TpPs 2. General Strategies

More information

From The Lab To Your Medicine Cabinet:

From The Lab To Your Medicine Cabinet: From The Lab To Your Medicine Cabinet: A Pharmaceutical Drug s Journey Presented by: Dr. Steven Hansel Sr. Director; Pfizer Moderated by: Sam Gilchrist Ph.D. Candidate; UBC The Drug Development Process

More information

Non-Rodent Selection in Pharmaceutical Toxicology

Non-Rodent Selection in Pharmaceutical Toxicology Non-Rodent Selection in Pharmaceutical Toxicology A Points to Consider document, developed by the ABPI in conjunction with the UK Home Office DAVID SMITH Animal Research & Welfare Advisory Group PAUL TRENNERY

More information

ICH Topic E 5 (R1) Ethnic Factors in the Acceptability of Foreign Clinical Data. Step 5

ICH Topic E 5 (R1) Ethnic Factors in the Acceptability of Foreign Clinical Data. Step 5 European Medicines Agency September 1998 CPMP/ICH/289/95 ICH Topic E 5 (R1) Ethnic Factors in the Acceptability of Foreign Clinical Data Step 5 NOTE FOR GUIDANCE ON ETHNIC FACTORS IN THE ACCEPTABILITY

More information

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) DRAFT GUIDELINE ON FIXED COMBINATION MEDICINAL PRODUCTS

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) DRAFT GUIDELINE ON FIXED COMBINATION MEDICINAL PRODUCTS European Medicines Agency London, 21 February 2008 Doc. Ref. CPMP/EWP/240/95 Rev. 1 COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) DRAFT GUIDELINE ON FIXED COMBINATION MEDICINAL PRODUCTS DRAFT AGREED

More information

REQUIREMENT AND GUIDELINES ON CLINICAL TRIALS FOR IMPORT AND MANUFACTURE OF NEW DRUG.

REQUIREMENT AND GUIDELINES ON CLINICAL TRIALS FOR IMPORT AND MANUFACTURE OF NEW DRUG. 549 2 [SCHEDULE Y REQUIREMENT AND GUIDELINES ON CLINICAL TRIALS FOR IMPORT AND MANUFACTURE OF NEW DRUG. 1. Clinical Trials. 1.1. Nature of trials. - The clinical trials required to be carried out in the

More information

TOXICITY AND GENOTOXICITY STUDIES

TOXICITY AND GENOTOXICITY STUDIES TOXICITY AND GENOTOXICITY STUDIES 1.0 Acute Toxicity Studies 1.1 Acute Toxicity and Toxicokinetic Study in Rat and Mice In order to determine LD 50 (cut-off) of test item, animals are dosed with one or

More information

Antibody-Drug Conjugates:

Antibody-Drug Conjugates: Antibody-Drug Conjugates: what are the data telling us? A retrospective review with emphasis on human starting dose Haleh Saber, Ph.D. Supervisory Pharmacologist Office of Hematology and Oncology Products

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

To view this booklet online, please visit PacificBioLabs.com.

To view this booklet online, please visit PacificBioLabs.com. To view this booklet online, please visit PacificBioLabs.com. Preclinical Toxicology Points To Consider in Program Design PACIFIC BIOLABS YOUR PARTNER FOR PRECLINICAL SAFETY TESTING As The Service Leader

More information

Guideline on repeated dose toxicity

Guideline on repeated dose toxicity 18 March 2010 CPMP/SWP/1042/99 Rev 1 Corr* Committee for Human Medicinal Products (CHMP) Guideline on repeated dose toxicity Draft Agreed by Safety Working Party May - December 2007 Adoption by CHMP for

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

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

ICH guideline S6 (R1) preclinical safety evaluation of biotechnology-derived pharmaceuticals

ICH guideline S6 (R1) preclinical safety evaluation of biotechnology-derived pharmaceuticals June 2011 EMA/CHMP/ICH/731268/1998 Committee for medicinal products for human use (CHMP) ICH guideline S6 (R1) preclinical safety evaluation of biotechnology-derived pharmaceuticals Step 5 Part I (Parent

More information

Request for Proposal. Class D Oligonucleotide CpG ODN D35. IND-enabling preclinical package

Request for Proposal. Class D Oligonucleotide CpG ODN D35. IND-enabling preclinical package Request for Proposal Class D Oligonucleotide CpG ODN D35 IND-enabling preclinical package Dated: October 20, 2015 Page 1 TABLE OF CONTENTS 1. PURPOSE... 3 2. RFP INSTRUCTIONS... 3 3. DNDi OVERVIEW... 6

More information

3 major considerations of this testing: medical uses/needs for substance commercial potential feasibility for mass production (manufacturing costs)

3 major considerations of this testing: medical uses/needs for substance commercial potential feasibility for mass production (manufacturing costs) FDA Protocol for Drug Development 1. Preclinical Testing starts with the discovery of a new molecule FDA issues a 17 year exclusive patent to produce/market that molecule More recently, companies patent

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

Risk Assessment in Chemical Food Safety. Dept. of Food Safety and Zoonoses (FOS) http://www.who.int/foodsafety/en/

Risk Assessment in Chemical Food Safety. Dept. of Food Safety and Zoonoses (FOS) http://www.who.int/foodsafety/en/ Risk Assessment in Chemical Food Safety Dept. of Food Safety and Zoonoses (FOS) http://www.who.int/foodsafety/en/ Risk Analysis Paradigm Internationally Scientific data analysis Risk Assessment WHO & FAO

More information

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) REPLACEMENT OF ANIMAL STUDIES BY IN VITRO MODELS

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) REPLACEMENT OF ANIMAL STUDIES BY IN VITRO MODELS The European Agency for the Evaluation of Medicinal Products Human Medicines Evaluation Unit London, 19 February 1997 CPMP/SWP/728/95 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) REPLACEMENT OF

More information

1/14/2014. The Drug Development Process and Design of Clinical Trials. Clinical Trial Design Guidance. Regulatory Definitions

1/14/2014. The Drug Development Process and Design of Clinical Trials. Clinical Trial Design Guidance. Regulatory Definitions The Drug Development Process and Design of Clinical Trials Darlene Kitterman, MBA Director, Investigator Support & Integration Services January 15, 2014 Clinical Trial Design Guidance Clinical Trial: a

More information

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP)

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) European Medicines Agency Evaluation of Medicines for Human Use London, 23 March 2006 EMEA/CHMP/203927/2005 COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) GUIDELINE ON RISK ASSESSMENT OF MEDICINAL

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

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP)

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) European Medicines Agency Evaluation of Medicines for Human Use London, 22 February 2006 EMEA/CHMP/BMWP/31329/2005 COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) ANNEX TO GUIDELINE ON SIMILAR BIOLOGICAL

More information

Chapter 5: ACUTE, SUBACUTE AND CHRONIC TOXICITY IN ANIMALS. Year III Pharm.D Dr. V. Chitra

Chapter 5: ACUTE, SUBACUTE AND CHRONIC TOXICITY IN ANIMALS. Year III Pharm.D Dr. V. Chitra Chapter 5: ACUTE, SUBACUTE AND CHRONIC TOXICITY IN ANIMALS Year III Pharm.D Dr. V. Chitra INTRODUCTION A drug is a single substance or mixture of substances used for diagnosis, treatment, mitigation or

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

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

Guidance on dose level selection for regulatory general toxicology studies for pharmaceuticals

Guidance on dose level selection for regulatory general toxicology studies for pharmaceuticals Guidance on dose level selection for regulatory general toxicology studies for pharmaceuticals The 3Rs: Replacement refers to methods that replace or avoid the use of animals in areas where animals would

More information

Risk Assessment of Pesticides Residue by JMPR - To set ADI and ARfD-

Risk Assessment of Pesticides Residue by JMPR - To set ADI and ARfD- The FAO Regional Training Course: Strengthening Capacity of Data Collection and Generation for Food Safety Risk Analysis Support to Capacity Building and Implementation of International Safety Standards

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