Non-clinical Safety and Toxicology

Non-kliniske undersøgelser for toksicitet og bivirkninger
Course code: FMIMB1051U (previously B-8105)

Course objectives

Non-clinical safety assessment of a potential pharmaceutical represents an important part of the drug development process. Due to the recent high attrition rate seen late in development programmes this has caused an intensification and expansion of the field of safety science, the modern term for toxicology. Thus a much more integrated view is applied nowadays. This new trend will be reflected in the course.

The objective of the course is to introduce participants to non-clinical safety assessment and to give participants an insight in the requirements and the conclusions to be drawn from the results of non-clinical safety studies conducted in vivo as well as in vitro.

Target group

The course is intended for drug development professionals who need basic knowledge in safety or who need a brush-up course for continuing professional development (CPD).

Prerequisites

Applicants must meet the following criteria:

• A relevant bachelor degree or equivalent
• A minimum of 2 years of relevant job experience
• Proficiency in English

It is recommended that the courses Discovery and Development of Medicines and Pharmacology have been passed before joining this course.

Learning outcomes

On completion of the course, participants are expected to be able to:

Knowledge

• Describe the major organ systems to be examined in non-clinical safety assessment
• List some predictive toxicological biomarkers.
• Outline special conditions for assessment of the toxicological aspects of large molecules.
• Provide information on regulatory requirements for studies  used in non-clinical safety assessment and the content of application to the authorities.
• Recall in vivo reproduction in toxicology.

Skills

• Demonstrate insight and understanding of the requirements for non-clinical safety assessment in vivo as well as in vivo.
• Identify organ/tissue for the toxicity process. 
• Devise in vitro genotoxicity tests.
• Select relevant species for carcinogenicity studies in vivo.
• Provide information on factual guidelines regarding species, methodology and data handling.

Competencies

• Review and assess safety data presented for a given drug candidate
• Elucidate the mechanism of changes seen on target organ/tissue.
• Justify ADME toxicity related issue in relevant species incl. drug metabolites and toxicokinetics.
• Integrate the various safety aspects in the overall assessment for selection of drug candidates.

Contents

The course concerns investigations used in non-clinical safety assessment by identifying the "target organ/tissue" and doing the assessment. This includes testing for: genotoxicity, carcinogenicity, safety pharmacology, general toxicity and reproductive toxicity. To support the assessment, knowledge about ADME (absorption, distribution, metabolism, excretion) in relevant species is required so these aspects also are a part of the Non-Clinical Safety test battery. Studies to elucidate the mechanism of the changes seen in the target organ/tissue will also be discussed. Rationalizations of assessment experiments will be described as well as an outline of future trends.

After introduction to factual rules, methodologies and data, participants will be presented with case stories, which they have to evaluate, discuss and finally give recommendation upon in plenum.

Lecture topics:

• Where does safety science and toxicology fit in modern drug development. Chronology and project plans
• General toxicology
• Safety pharmacology
• Reproduction toxicology
• Genotoxicology
• Carcinogenicity testing
• Toxicokinetics
• Metabolism studies
• Biopharmaceuticals
• Topicals
• Biomarkers
• Safety Assessment
• Target organs and tissues
• Safety margins
• First dose in man
• The non-clinical dossier

Course materials/syllabus

Approximately 125 pages from The Textbook of Pharmaceutical Medicine, 6th edition (2010) Eds.: John Griffin and John O'Grady, Blackwell BMJ Books (exact chapters will be specified later) plus hand-outs from course presentations.

Teaching methods

Lectures in the morning with group discussions on cases, exercises and demonstrations in the afternoon. Exercises are based on case stories where students are presented with toxicological data in a stepwise manner to make their conclusions at each step

Examination and assessment

Type of examination: 2-hour written examination (anonymous).

Examination design: The purpose of the examination is to test that the examinee has a broad knowledge and comprehension of non-clinical safety studies and assessment of the findings doing drug development. The test is composed of 1 case problem and of 10 independent descriptive questions. The case problem will represent 60 % of the test; the multiple choice questions will represent 40%.
The percentage of items on the test devoted to a particular topic will roughly correspond to the emphasis given the topic in teaching of the course, and as implied in the general course objectives.

• Regular framework: 25 %
• Acute toxicity testing: 25 %
• Chronic toxicity testing: 25 %
• Genotoxicity, cancerogenicity, reproduction: 25 %

Assessment: According to the 7-point grading scale

Examiner(s): Course directors and an external examiner

Exam aids: All exam aids are allowed. Certain electronic pocket calculators are allowed

Grading

Grade 12:     The examinee:

• demonstrates a well structured presentation with a clear outline providing exact and correct answers.
• demonstrates aplomb comprehensive view
• combines convincingly the learned elements
• demonstrates with few unimportant deficits: aplomb mastering of relevant terms, principles and methods used for performing a non-clinical assessment of a drug candidate.

Grade 7:       The examinee:

• demonstrates a coherent presentation providing understandable unambiguous answers, the great majority of which should be correct.
• documents a certain overview over the learned elements
• demonstrates with minor deficits a firm knowledge of relevant terms, principles and methods used for performing a non-clinical assessment of a drug candidate.

Grade 02:     The examinee:

• demonstrates a less structured presentation with less precise answers.
• demonstrates a limited overview and the ability to combine learned elements is limited.
• demonstrates only to a limited extent and with a number of deficits capability to handle relevant terms, principles and methods used for performing a non-clinical assessment of a drug candidate.

Student workload

Preparation: 25 hours
Confrontation: 35 hours
Examination and preparation for examination: 10 hours

A total of 70 hours

Course directors

Professor Ole J. Bjerrum (MD, DMSc), Department of Pharmacology and Pharmacotherapy, The Faculty of Pharmaceutical Sciences, University of Copenhagen

Vice President Helle Northeved, DVM, Non-clinical Safety Research, H. Lundbeck

Lecturers

The list of lecturers may be subject to change

• Anders B. Lassen, H. Lundbeck
• Prof. Beatriz Lima, Lisbon University
• Dr. David Kirkland, Covance Laboratories, UK
• Flemming Højelse, H. Lundbeck
• Helle Northeved, H. Lundbeck
• Jens Thing Mortensen, LAB Research Denmark
• Kim Kristensen, Novo Nordisk
• Lars Dalgaard, H. Lundbeck
• Dr. Lorna Burns, Sequani, UK
• Nina Ostenfeldt, H. Lundbeck
• Prof. Ole J. Bjerrum, Faculty of Pharmaceutical Sciences, University of Copenhagen

Practical information

Status: Master’s level (second cycle higher education). Open for freelance students who meet the admission criteria. Compulsory for MIND students, elective for other part-time master's students at the Faculty of Pharmaceutical Sciences (subject to study board approval).

Date: 7-11 May 2012. Examination on 23 May 2012.

Application deadline: 1 March 2012. Application form.

Course credits: 2.5 ECTS credits = a student workload of approx. 70 hours

Course fee: Part-time master’s students at Faculty of Pharmaceutical Sciences DKK 7,890, freelance students DKK 9,350, freelance students from non-EU/EEA countries DKK 11,290. An additional fee of DKK 1,300 is charged for course materials and lunch. Prices may be subject to change. The Textbook of Pharmaceutical Medicine must be purchased by participants.

Course capacity: 30 participants

Language of instruction: English

Preliminary course description