Unit MEDICINE MANUFACTURING AND REGULATORY AFFAIRS
- Course
- Industrial pharmacy
- Study-unit Code
- A003600
- Curriculum
- In all curricula
- Teacher
- Stefano Giovagnoli
- Teachers
-
- Stefano Giovagnoli
- Luana Perioli (Codocenza)
- Hours
- 48 ore - Stefano Giovagnoli
- 16 ore (Codocenza) - Luana Perioli
- CFU
- 8
- Course Regulation
- Coorte 2023
- Offered
- 2026/27
- Learning activities
- Caratterizzante
- Area
- Discipline tecnologiche normative e economico-aziendali
- Sector
- CHIM/09
- Type of study-unit
- Obbligatorio (Required)
- Type of learning activities
- Attività formativa monodisciplinare
- Language of instruction
- English
- Contents
- Concept of industry, pharmaceutical industry, and related legislative aspects. Aspects on Research and development in the production of drugs. Concepts of Quality and Quality systems Statistical approaches to the development of industrial processes and QbD Plant definition and design Industrial plant services and equipment. Pharmaceutical production plants technology transfer activity and scale up. Examples of production plants for pharmaceutical products. Continuous Manufacturing. Systems for process development
- Reference texts
- There are no reference books. The slides used for lessons and guidelines bearing regulations and protocols in use as well as information on the industrial installations described in class will be given. The student will be encouraged to investigate autonomously the topics of interest with the support of the teacher.
- Educational objectives
- The course provides a theoretical knowledge of the basic rules that the installations and industrial processes used for the production of both conventional and non-conventional medicinal forms.
The knowledge-knowledge that will be acquired by the student concerns some basic rules and approaches to deal with the productive problem- from R & D to quality control. In particular, the students will have to prove that they understand the concepts at the basis of the control and design of an industrial process from the point of view of validation. Besides, knowledge is required on the processes and systems for the production of the most common forms of conventional medicines and awareness of regulatory differences and techniques in the production of more advanced medicines such as biosimilars.
Skills- the student will acquire the ability of reasoning and decision-making in investigating the production problems depending on the type of pharmaceutical product considered. In addition, it will have to develop the ability to learn on their own the topic and industrial regulations and to address and solve case studies. - Prerequisites
- In order to ensure a sufficient level of learning, the student must have acquired knowledge of physical chemistry and Pharmaceutical Technologies. In addition, basic knowledge of formulation processes and some aspects about the methods of characterization of medicinal forms are advised. In particular, it is required a basic knowledge of the conventional pharmaceutical forms such as capsules and tablets and other solid dosage forms for oral use but also topical or parenteral. This knowledge is important for the multidisciplinary nature of the course and to the understanding of technologies applied to industrial production processes. In this regard, a study of the basic concepts and useful approaches to drug delivery is suggested. Some of these aspects will be anyway underlined at the beginning of the course.
- Teaching methods
- The course consists of classroom lectures on topics with special attention to involve the student to retrieve and evaluate the basic knowledge necessary for learning. For this purpose, it is provided that the slide of the course reference materials and guidelines. This is believed necessary given the lack of a reference text to didactic scope of the student. Both the multi-disciplinary course that the advanced level of the material that the student has available require continuous support from the teacher to verify that the student has the right level of understanding of the topics discussed. In addition, the course includes a period of continuous updating as the rapidly changing regulatory environment in the sector which is also done through the literature. To this end, a second step involves a study that will be done in the hours dedicated to support the course.
- Other information
- Support activities will be carried out after the course to develop certain aspects of the course to be agreed with the student and help the student in the activity of connection of prior knowledge and necessary learning and new knowledge gained during the course. This activity will be supported by a series of monographic seminars held by industry experts during which students will have to face and try to solve the case studies presented.
This activity will be held at the Department of Pharmaceutical Sciences - Learning verification modality
- Oral exams, consisting of questions relating to the theoretical aspects related to the topics covered during the course and, to demonstrate the student knowledge and understanding of the subjects, and the ability to expose the course contents; in particular, the students will have to demonstrate that they understand the philosophy behind standards and processes of industrial production of medicinal forms. in particular, the problems linked to the development and validation of a process that determines the characteristics of the industrial installations designed for this purpose. The reasoning skills of the student in dealing with issues concerning the production processes in the pharmaceutical industry will be evaluated. In addition, the ability of the student to investigate independently the topic will be examined.
- Extended program
- PART I
Introduction. Industry, pharmaceutical industry. Structure and organization of a pharmaceutical plant: organizational chart and key players in the pharmaceutical industry, supply chain, and organization and management.
Regulatory affairs:
1. Introduction, regulation and regulatory affairs: why the rules of the pharmaceutical and health products world are created, GxP.
2. Regulatory bodies: WHO, FDA, ECHA, EMA, HMA, AIFA, MiniSan, Geopolitics and regulatory affairs.
3. Patents. Difference between trademarks and patents, types of patents, patents relevant to the pharmaceutical sector, regulatory evolution of patents with particular reference to Italy.
4. Definition of drug and medicinal product, industrial medicinal product, Legislative Decree 219/2006 (consolidated); definitions of API and Pharma and their regulatory aspects. API, DMF, EDMF, ASMF, Pharmaceuticals; Common Technical Document (CTD), e-CTD, Marketing Authorization (MA) and its types and procedure. Manufacturing Authorization (MA).
5. Quality, qualifications, validations, QS (PQS), QC, QA, deviations, CAPA, Fordism, Toyotism.
6. Standards and guidelines, Quality, internal rules, external rules, ALCOA, data integrity, ISO, EN, UNI
GMP, EU GMP, cGMP, ICH.
7. Quality by Design and its application, concepts of risk and hazard, Risk Management and Quality Risk Management, risk assessment in QbD, Risk Assessment.
Technology Transfer and R&D.
The role of R&D in drug development, notes on patenting, phases of drug development, process organization. Chemical phase (drug discovery), Preclinical phase (development) - preclinical pharmacokinetics, toxicokinetics, Ames test, Flint test. Clinical dose estimation, allometric equations, and the concept of maximum recommended starting dose (MRSA). Clinical phases. Clinical trial design: blinding. New approaches to the clinical phase: Proof of concept and adaptive design.
Process development in technology transfer: Application of QbD, Risk Assessment and Design of Experiments (DOE), PAT (Process Analytical Technology). Quality concepts: target product profile (QTPP), critical quality attributes (CQA), critical process parameters (CPP), and critical material attributes (CMA) and their significance in process development.
Statistical methods in process development: basic concepts, ANOVA and statistical tests, application of DOE methods and models, factorial designs, and RSM. Practical examples.
PART II (GENERAL PLANT ENGINEERING)
Typology and classification of industrial plants. Types of plants. Design of a pharmaceutical plant. Structure and flow diagrams. Organization and types of services. Compartmentalization and isolation strategies. Classification of workspaces: ventilated, air-conditioned, dehumidified, sterile. Air conditioning and air distribution systems. Dehumidification, liquid and solid-phase adsorbers. Cleanroom concepts and validation. Differential pressure. Airlocks and air flows. Air quality, classification and filtration of HVAC systems. Types of filters, HEPA and UHEPA filters, abatement systems, and exhaust air processing. Air quality control and validation tests. Development of a production plant: technology transfer concepts, scale-up methods, and pilot plants. Management of materials, spaces, and personnel. Centralized services and systems. Water and plumbing systems. Industrial water supply and proper wastewater disposal (Divo 152/99). Types of water for the pharmaceutical industry. Softening. Deionization with resins (double and mixed flow), continuous electrodeionization. UV disinfection. Distillation: single-effect, multiple-effect, and thermocompression evaporators (Ponzini), capillary distillers. Reverse osmosis. Ultrapure water, microfiltration, ultrafiltration. Water for injections. Thermal and steam production systems. Steam production and distribution systems. Compressed air production systems. Uses of compressed air. Compressed air production and distribution systems. Refrigeration systems. Refrigeration systems, refrigeration machines. Production of high-temperature refrigeration. Uses of industrial refrigeration: freeze-drying process, industrial freeze-dryers, freeze-drying, and production of depot forms.
Sterilization systems: Dry heat sterilization: forced-air drying cabinet. Moist heat sterilization. Sterilization using ionizing radiation methods. Chemical sterilization, areas of application, products used. Gas or vapor sterilization: ethylene oxide. Autoclaves: steam autoclave, vertical autoclave, horizontal autoclave with water shower. Autoclave sterilization phases.
PART III (PHARMACEUTICAL PLANTS AND PRODUCTION)
Liquid and solid formulation production plants:
Packaging lines for freeze-dried products. Solid formulation plants: Parenteral product plants: special requirements for plant structure and filling and primary packaging systems. Preparation of pharmaceutical powders. Preparation of solid, liquid, and semisolid formulations. Liquid and solid formulation filling lines. Capsule and tablet plants. Tablet production. Tablet coating. Packaging - blistering and packaging line. Capsule production. Hard gelatin capsules: uses, industrial preparation, capsule types and closure systems. Capsule filling lines for powders and liquids. Soft gelatin capsules: preparation methods. Packaging lines. Plants for the production of dry and inhalable powders. Spray dryers and spray freeze-dryers.
CM-ready technologies: continuous fluid bed, 3D printing, and feeding systems (hot melt extrusion).
From traditional to continuous production. Concepts and examples. RTD models, material tracing, and architecture. Batch definition and regulations in CM. Control strategies and technologies for real-time tracking and monitoring and finished product QC. Basic concepts and applications of AI in R&D for continuous production systems. - Obiettivi Agenda 2030 per lo sviluppo sostenibile
- health and well-being