Purification and Formulation of Biotechnological Drug Products
A.Y. 2023/2024
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.
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.
Lesson period: Second semester
Assessment methods: Esame
Assessment result: voto verbalizzato in trentesimi
Single course
This course can be attended as a single course.
Course syllabus and organization
Single session
Responsible
Lesson period
Second semester
Course syllabus
Isolation and Purification of Biotechnological Drugs
· The process of isolation and purification of biotechnological drugs: glossary and regulatory framework
· Types of "bioproducts" and their most common contaminants
· Phases of a Biotech production process:
- Downstream Bioprocessing (Recovery - Harvesting & Clarification; Purification; Polishing);
· Methods (traditional and advanced) for the isolation and purification of macromolecules of therapeutic interest:
- Continuous centrifugation;
- Orthogonal Filtration and Tangential Flow Filtration;
- Preparative Chromatography techniques (GF, IEX, HIC, RP, AC);
· Reasoned approach to process development: quality and "quality by design"
· Bacterial and viral contamination and "viral clearance"
· Verification of the notions learned: detailed design of a new process
Pharmaceutical legislation
· Regulatory sources and national and community health organization.
· Definition of medicinal product.
· Authorization for the production and marketing of medicinal products for human use.
· Centralized procedure, conditional marketing authorization and marketing authorisation under exceptional circumstances.
· Generic and biosimilar medicines.
· Dossier for obtaining marketing authorization: general information and forms.
Pharmaceutical technology
· Pharmacokinetics of the various routes of administration. Biopharmaceutical with particular reference to parenteral preparations.
· Conventional and modified drug delivery systems: generalities and mechanisms.
· Parenteral dosage forms (conventional and implants): general information, requirements.
· Inhalation and nasal drug delivery systems
· Polymer nanoparticles and liposomes
· Scaffolds for cell growth
· Water for pharmaceutical use. Containers for pharmaceutical use.
· Sterilization processes and EMA decision tree.
· The process of isolation and purification of biotechnological drugs: glossary and regulatory framework
· Types of "bioproducts" and their most common contaminants
· Phases of a Biotech production process:
- Downstream Bioprocessing (Recovery - Harvesting & Clarification; Purification; Polishing);
· Methods (traditional and advanced) for the isolation and purification of macromolecules of therapeutic interest:
- Continuous centrifugation;
- Orthogonal Filtration and Tangential Flow Filtration;
- Preparative Chromatography techniques (GF, IEX, HIC, RP, AC);
· Reasoned approach to process development: quality and "quality by design"
· Bacterial and viral contamination and "viral clearance"
· Verification of the notions learned: detailed design of a new process
Pharmaceutical legislation
· Regulatory sources and national and community health organization.
· Definition of medicinal product.
· Authorization for the production and marketing of medicinal products for human use.
· Centralized procedure, conditional marketing authorization and marketing authorisation under exceptional circumstances.
· Generic and biosimilar medicines.
· Dossier for obtaining marketing authorization: general information and forms.
Pharmaceutical technology
· Pharmacokinetics of the various routes of administration. Biopharmaceutical with particular reference to parenteral preparations.
· Conventional and modified drug delivery systems: generalities and mechanisms.
· Parenteral dosage forms (conventional and implants): general information, requirements.
· Inhalation and nasal drug delivery systems
· Polymer nanoparticles and liposomes
· Scaffolds for cell growth
· Water for pharmaceutical use. Containers for pharmaceutical use.
· Sterilization processes and EMA decision 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 and single-bench practicals.
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
"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 exam consists of two oral tests consisting of questions relating to theoretical aspects inherent to the issues addressed during the course and aimed at ascertaining the knowledge and understanding by the student, as well as the ability to discuss the topics.
Regarding the module of "Formulation of biotechnological drugs and regulatory aspects", the exam includes 3 questions concerning respectively (i) pharmacokinetic and / or biopharmaceutical aspects, (ii) formulation and technological problems of the pharmaceutical forms and (iii ) the related regulatory aspects.
To pass the "Isolation and Purification of Biotechnological Drugs" module, an oral test is also provided on the topics covered in class: the main methods (traditional and advanced) for the isolation and purification of macromolecules of therapeutic interest; the student will be asked to design / hypothesize an appropriate experimental workflow to isolate and purify biotechnological products, starting from the main chemical-physical characteristics of the biomolecules themselves.
To pass both tests, the student must achieve a grade of 18/30 in both exams.
The final grade is calculated as the average of the two individual grades.
Regarding the module of "Formulation of biotechnological drugs and regulatory aspects", the exam includes 3 questions concerning respectively (i) pharmacokinetic and / or biopharmaceutical aspects, (ii) formulation and technological problems of the pharmaceutical forms and (iii ) the related regulatory aspects.
To pass the "Isolation and Purification of Biotechnological Drugs" module, an oral test is also provided on the topics covered in class: the main methods (traditional and advanced) for the isolation and purification of macromolecules of therapeutic interest; the student will be asked to design / hypothesize an appropriate experimental workflow to isolate and purify biotechnological products, starting from the main chemical-physical characteristics of the biomolecules themselves.
To pass both tests, the student must achieve a grade of 18/30 in both exams.
The final grade is calculated as the average of the two individual grades.
Downstream processing of biopharmaceuticals
CHIM/08 - PHARMACEUTICAL CHEMISTRY
CHIM/09 - PHARMACEUTICAL AND TECHNOLOGICAL APPLICATIONS OF CHEMISTRY
CHIM/09 - PHARMACEUTICAL AND TECHNOLOGICAL APPLICATIONS OF CHEMISTRY
Lessons: 32 hours
Professor:
Altomare Alessandra Anna
Formulation of biotechnological medicinal products and Regulatory Aspects
CHIM/08 - PHARMACEUTICAL CHEMISTRY
CHIM/09 - PHARMACEUTICAL AND TECHNOLOGICAL APPLICATIONS OF CHEMISTRY
CHIM/09 - PHARMACEUTICAL AND TECHNOLOGICAL APPLICATIONS OF CHEMISTRY
Single bench laboratory practical: 16 hours
Lessons: 24 hours
Lessons: 24 hours
Shifts:
Professor:
Minghetti Paola
Turno 1
Professor:
Gennari Chiara Grazia MilenaTurno 2
Professor:
Anderluzzi GiuliaEducational website(s)