Purification and formulation of biotechnological drug products

A.Y. 2020/2021
Overall hours
Learning objectives
The course is intended to cover principles and general requirements for the development of biotechnological medicinal products from the isolation and the purification of the active substances to the formulation of pharmaceutical dose forms. References are made to the quality assays, compendial and not, to characterize active substances and dosage forms. Regulatory aspects relevant to production and marketing are also addressed.
Expected learning outcomes
At the end of the course, the student will acquire principles required to design biotechnological medicinal products, based on the specific properties of the active substance and the therapeutic requirements. Starting from the main chemical-physical characteristics of the molecules, the student will be able to propose the most suitable methods to produce, isolate and purify the related drug substances under sterile conditions according to the Good Manufacturing Practices.
Thanks to the knowledge and understanding acquired, the student will be able to individuate the criticisms and to define an appropriate control strategy in the attempt to satisfy the Regulatory Agencies' requirements.
Course syllabus and organization

Single session

Lesson period
Second semester
Course syllabus
· The process of isolation and purification of biotechnological drugs: glossary and regulatory framework
· Types of bioproducts and their most common contaminants
· Rational approach to process development I: old and new experimental approaches
· Rational approach to process development II: old and new technologies
· Rational approach to process development III: quality and quality by design
· Basic principles of biotech industrial filtration
· Bacterial and viral contamination and viral clearance
· Verification of the concepts learned: detailed drawing of a new process
· Notions of business administration in the biotech production field
Pharmaceutical Legislation
· Definition of medicinal product
· Manufacturing authorization for human medicinal products and marketing authorization procedures. Introduction to the centralised procedure, conditional marketing authorization and marketing authorisation under exceptional circumstances
· Requested data from EMA for biotechnological medicinal products.
· European Medicines Agency (EMA) and Agenzia Italiana del Farmaco (AIFA).
· Generic medicines and biosimilars.
Pharmaceutical Technology
· In-depth analysis of pharmacokinetics and biopharmaceutical aspects of the routes of administration.
· Modified drug delivery systems: rational and formulative approaches.
· Parenteral dosage forms: rational and formulative approaches.
· Inhalation and nasal drug delivery systems.
· Non-conventional drug delivery systems: nanoparticles and liposomes.
· Scaffolds for tissue engineering
· Water for pharmaceutical use.
· Containers and closures
· Sterilization process and EMA decisional tree.
Prerequisites for admission
Fundamentals on general and inorganic chemistry, stoichiometry, organic chemistry, analytic chemistry and physiological. Due to the multidisciplinary of the course, knowledge in physiology and pharmacology are required. Moreover, the basic concepts of pharmaceutical technologies are needed, even if main points will be discussed throughout the course.
Teaching methods
Lectures in classes.
Teaching Resources
Teaching material presented during the lessons (constituting the topics of the exam) will be available in pdf format on the Ariel portal of Unimi.
"Legislazione Farmaceutica" di P. Minghetti e M. Marchetti, CEA, 9 edizione
"Principi di tecnologie farmaceutiche" di P. Colombo et al, CEA; 2 edizione
Assessment methods and Criteria
The course exam consists of an oral and written test. The students will be evaluated based on their capacity to answer theoretical questions and to discuss the topics dealt during the course.
Regarding "Formulation of biotechnological medicinal products and regulatory aspects", the oral exam is articulated in three questions on (i) PK and biopharmaceutics (ii) formulation and relative technologies and (iii) regulatory aspects. The exam on "Isolation and purification of biotechnological drugs" consists of a written test which is related to the topics covered in class and is articulated in several points with exercises and open-ended questions with a final grade out of 30/30. The written test lasts 120 minutes. To pass the exam, the student must reach a score of 18/30.
The final grade will be calculated as the weighted average of the two exam grades.
Downstream processing of biopharmaceuticals
CHIM/08 - PHARMACEUTICAL CHEMISTRY - University credits: 0
Lessons: 32 hours
Formulation of biotechnological medicinal products and Regulatory Aspects
CHIM/08 - PHARMACEUTICAL CHEMISTRY - University credits: 0
Lessons: 32 hours
Professor: Minghetti Paola