Chemical Process Development and Production of Active Pharmaceutical Ingredients (API)

Course code: FMIMM1141U (Previously M-8114)

Course objectives

The development of a safe and efficient manufacturing process of an active pharmaceutical ingredient (API or bulk drug substance) is a substantial undertaking. A successful endeavour requires solving problems within synthetic organic, physical organic, analytical and environmental chemistry, engineering, and economics. An understanding of chemical development and the particular challenges during each phase is the primary focus of this course. A combination of theory and practice using fresh examples from industry and the literature will create the foundation for solid decision-making skills and an understanding of the trade terminology.

Target group

The course is intended for MIND students and other drug development professionals with contact to chemical process development.

A typical participant’s background is one of the following:

• MIND student
• Process Chemist at the start of their industrial career
• Scientist from Drug Discovery
• Project Manager

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 necessary to understand a basic level of chemistry.

Expected learning outcomes

Upon successful completion of the course, participants are expected to:

Knowledge

• be familiar with the terms, principles and methods used in developing a chemical process from discovery to routine manufacturing.

Skills

• be able to discuss different aspects and solutions to problems in a broad range covering scale-up, organization, planning, process monitoring, validation, life cycle management, registration, resource consumption, environmental and safety issues.

Competencies

• Closely interact with specialists and work as project leader where process development is a part of the project.
• Identify and explain common risks and problems in process development
• Compute and critically apply various process metrics

Contents

All relevant subjects related to the chemical process development of biologically active compounds used as pharmaceuticals will be discussed. The course will begin with the discovery synthesis and end with the full-scale production process. 

Basic conventions terms and definitions will be discussed. Focus will be placed on scale-up, process optimization, yield considerations, purification, validation, registration, and regulatory approval for new processes.

Various strategies to achieve a safer, more economical, and defensible process will be covered. Other topics to be covered include: Design of Experiments, route scouting, telescoping, 2nd generation processes, process monitoring, selection of appropriate in-process controls, process analytical technology (PAT), thermogravimetric analysis, reaction calorimetry, and differential scanning calorimetry.

Special topics are catalysis and stereochemistry

Further subjects are quality assurance, GLP and GMP considerations, Quality-by Design (QbD), environmental considerations, life cycle management, emission limits and monitoring, resource consumption and CO2-emission, safety, hazard and operability, risk assessment and handling excessive reaction conditions.

Course materials/syllabus

The syllabus corresponds to about 200 pages in the textbook Practical Process Research and Development by Neal G. Anderson, Academic Press Inc., U.S., 2000. (ISBN 0-12-059475-7). In addition, 2-3 case studies reported in current journal articles will be subject to analysis.   Lecture materials will be provided as handouts.  Purchase of the textbook is optional; however, process chemists will find the text highly useful in their daily work.

Teaching methods

Lectures, workshops, discussion in plenum, and problem solving of real-life examples.

Lectures are based upon a combination of selected material from the textbook, scientific papers and the lecturers own work and experiences.  The workshops encourage the participants to actively propose solutions to challenges that often occur during process development, based on relevant examples found in the current literature.

Examination and assessment

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

Examination design: The examination consists of a multiple choice test and of 1-2 literate problems based on a case story.

Examiner(s): Course director and external examiner.

Examination aids: All examination aids are allowed incl. certain calculators.

Assessment: According to the 7-point grading scale.

Grade 12
Excellent: A well structured presentation with a clear outline providing exact and correct answers. The examinee demonstrates aplomb comprehensive view and combines convincingly the learned elements. The examinee demonstrates with few unimportant deficits: Aplomb mastering of relevant terms, principles and methods used for developing a process from discovery to production.

Grade 7
Good: A coherent presentation providing understandable unambiguous answers. The great majority of which should be correct. The examinee documents a certain overview over the learned elements and with minor deficits demonstrates a firm knowledge of relevant terms, principles and methods used for developing a process from discovery to production.

Grade 02
Sufficient: A less structured presentation with less precise answers. The overview is limited and the ability to combine learned elements is limited. The examinee only to a limited extent and with a number of deficits demonstrates capability to handle relevant terms, principles and methods used for developing a process from discovery to production.

Student workload

Preparation: 48 hours
Confrontation: 28 hours
Examination and preparation hereof: 6 hours
A total of 82 hours.

Course directors

Professor Fredrik Björkling, PhD (chem.), Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen

Head of Section Michael Mealy, PhD, H. Lundbeck A/S

Lecturers

List of lecturers may be subject to change.

• Anders Buur, H. Lundbeck A/S
• Claus Ulrich Jessen, Novo Nordisk A/S
• Lisbeth Kværnø, H. Lundbeck A/S
• Michael J. Mealy, H. Lundbeck A/S
• Hans Petersen, H. Lundbeck A/S
• Michael Bech Sommer, Zacco A/S
• Niels Østergaard, Cheminova A/S

Practical information

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

Date: 21–25 November 2011. Examination on the last day of the course.

Application deadline: 1 September 2011. Closed for applications.

Course credits: 3 ECTS credits = a student workload of approx. 82 hours

Course fee: Part-time master’s students at Faculty of Pharmaceutical Sciences DKK 8,950, freelance students DKK 10,700, freelance students from non-EU/EEA countries DKK 13,550. An additional fee of DKK 1,350 will be charged for course materials and lunch. Prices may be subject to change.

The textbook must be purchased by the student (approx. DKK 500).

Course capacity: 32 participants.

Language of instruction: English.

Approved by the MIND/MPRA Study Board 26 August 2010.