Fasi di realizzazione del farmaco (Creating medicines)
The path to a new medicine is long and demanding, typically requiring 10 to 12 years and an investment of approximately 600 – 700 millionEuros. The entire process requires an immense amount of effort with a great deal of risk. According to the Pharmaceutical Research and Manufacturers of America, for every 5,000 potential medicines tested, on average, only five are tested in patients, and only one of the five is approved for patient use.
The Medicines Discovery and Development process begins by determining the diseases for which to find a treatment and ends with the filing and launching of the New Medicine.
Technology and computer-aided techniques are used to identify and understand disease targets; leads are generated and synthesised with the aim to selecting the Best Candidate.
Before testing in humans, a range of preclinical tasks are undertaken to study all aspects of the candidate, evaluate pharmacokinetic and safety as well as to characterize the Active Product Ingredient (API) and design a Drug Delivery System (DDS).
Key is the First Time in Humans (PhaseI). Early clinical trials and ongoing non-clinical studies continue to test and refine the drug and to prove the hypothesis about how it will act in people.
Studies proceed from healthy volunteers to patients (PhaseII) suffering from the disease.
Phase III studies are conducted to fully establish efficacy while continuing to evaluate safety; these are large studies that typically involve thousands of patients in centres worldwide and may require years of effort.
Industrialisation meanwhile is taking place to make available the New Medicine for the launch and market.
During the course the different stages of the Medicines Discovery and Development both pre-clinical and clinical process – from early research to launching a new product in markets will be presented. (see the below course outline).
For each stage critical aspects will be discussed in depth with cases studies to exemplify how specific issues has been tackled and solved and enabling technologies applied.
1. Determining which Disease to Investigate - The R&D process begins by determining the diseases for which we wish to find a treatment (disease selection). Then, in order to arrive at a new medicine, we must identify potential drug targets in the body (target selection).
• Disease Selection; Disease Areas; Family Selection
2. Identifying Genes Associated with Disease - Technology and computer-aided techniques are used to identify and understand disease targets.
• Genetic Technologies; Gene Sequencing; SNP Mapping; Pharmacogenetics
3. Finding Potential Leads - Once a target has been identified, chemists synthesise compounds which interact with the target. This is called lead generation.
There are three approaches to lead generation:
1. Modify the structure of a known drug
2. Randomly screen an already existing store of compounds against a target of interest
3. Synthesise novel compounds based on knowledge of which chemical structures will most likely interact with the target of interest.
• High Throughput; Lead Optimisation
4. Selecting the Best Candidate - The lead candidate selected for further development must possess the characteristics required for clinical and commercial success.
• Selection Criteria - The multi-disciplinary teams that make candidate selections must answer numerous questions, such as:
Which compounds are likely to be most effective?
a. What are the projected dose range and easiest method of delivery?
b. Which compounds are easy to manufacture on a large scale?
c. What return on investment will be generated: Can the compound meet
or surpass the market standards?
• Tests; Modifying the Lead; Scaled-up Synthesis
5. Studying All Aspects of the Candidate - Before testing a new medicine in humans, a range of preclinical tasks is undertaken.
• Preclinical Tasks; Further Studies; Chemistry; Pharmaceutical Development
6. Special topics - Biopharmaceutics of Oral Drug Delivery - Key drivers and challenges. (GI tract physiology, physical-chemical properties of the API, delivery systems and role of in vitro dissolution tools); In silico and in-vitro/in-vivo prediction. Understanding cause of attrition
7. Testing for the First Time in Humans - Early clinical trials and ongoing non-clinical studies continue to test and refine the drug and to prove the hypothesis about how it will act in people.
• Phase I Trials; Proof of Concept
8. Progressing to Final Testing - Studies proceed from healthy volunteers to patients suffering from the disease.
• Phase II Trials
9. Conducting Final Testing - Phase III studies are large studies that typically involve thousands of patients in centres worldwide and may require years of effort. It is these studies that fully establish efficacy while continuing to evaluate safety.
• Larger-Scale Testing Phase III trials; Preparing for Registration; Making the Product; Preparing the Product
10. Filing and Launching the New Medicine - A dossier is submitted to the regulatory authorities, asking for approval to market the new drug. Once approval is granted, the drug is launched.
• File; Preparing for Market; Launch
11. Managing a Medicine's Lifecycle - After a new medicine is launched, safety monitoring continues, and further management of the product's lifecycle looks toward finding other potential uses for the drug.
• Post-Marketing Surveillance; Uses and Value
Il corso si terrà, dal 27 novembre al 15 gennaio 2016, presso le Aule della Sede dello IUSS (Palazzo del Broletto, Piazza della Vittoria n. 15); le lezioni di novembre si terranno nell’Aula 1-17, quelle di dicembre nell’Aula 1-14.
Le indicazioni bibliografiche saranno comunicate a inizio corso.
Gennaio 2016 (da definire).
Semestre: Semestre I
Anno accademico: 2015-2016