1. Supporting Irish patients and the Irish economy Development of a New Medicine Provided by the IPHA Communications Department May 2010

2. Research Activities These include: Combinatorial libraries – vast collections of novel compounds Mass screening of compounds in assay systems Molecular biology and modern genetics – role of genes in disease states Recombinant DNA technology Computer aided molecular modelling

3. Milestones in the Development Compound discovered and patent application made Submission of registration dossier to regulatory authorities Beginning of Human Trials Publication in Scientific Journal Trials in Patients Registration Research and Discovery Early Development Full Development Pre-Market Activity 0 5 8 12 15 Years * GMP = Good Manufacturing PracticeThe above shows a general representation of the development of a new medicine. Various processes may differ from country to country and between different compounds.

4. Clinical Studies Preparation of initial clinical plan. Selection of clinical study locations PHASE II Trials to determine dose ranging, safety and efficacy PHASE III Large scale trials to determine definitive safety and efficacy in patients PHASE I Human trials with healthy volunteers to test tolerability Research and Discovery Early Development Full Development Pre-Market Activity 0 5 8 12 15 Years * GMP = Good Manufacturing PracticeThe above shows a general representation of the development of a new medicine. Various processes may differ from country to country and between different compounds.

5. Toxicology Determine the effect on impregnation and implantation in animals and whether the active substance can affect the fetus Determine the reproductive effect upon future generations in animals Determine effects of medicine in animals when administered over 2 to 13 weeks(depending upon length of planned use in humans) Longer term animal studies. Does the active substance have long-term side effects? Test to determine mutagenic potential Research and Discovery Early Development Full Development Pre-Market Activity 0 5 8 12 15 Years * GMP = Good Manufacturing PracticeThe above shows a general representation of the development of a new medicine. Various processes may differ from country to country and between different compounds.

6. Pharmacokinetics / Metabolism Determination of how the medicine is absorbed, distributed, metabolised and excreted in animals Determination of the effects of the medicine on specific populations such as the elderly, different races and sexes. Determination of how the medicine is distributed, metabolised, and excreted by humans Determination of how and to what extent the medicine is absorbed by humans Final construction of the pharmacokinetic profile of the medicine Research and Discovery Early Development Full Development Pre-Market Activity 0 5 8 12 15 Years * GMP = Good Manufacturing PracticeThe above shows a general representation of the development of a new medicine. Various processes may differ from country to country and between different compounds.

7. Dosage Form Process development for large scale production of the dosage form. Testing of stability of the dosage and determination of shelf-life Pre-formulation activities – consultations with pharmacists / determination of physical and chemical properties of compound, e.g. particle size Development of clinical trial formulation Develop Market formulation based on known characteristics of medicine and patient group involved, e.g. age and condition. For example tablets, capsules, injectables or transdermal patches First dosage form for volunteer trials Process validation and production of the dosage form for launch Research and Discovery Early Development Full Development Pre-Market Activity 0 5 8 12 15 Years * GMP = Good Manufacturing PracticeThe above shows a general representation of the development of a new medicine. Various processes may differ from country to country and between different compounds.

8. Active IngredientThe therapeutically active component in a medicine's final formulation that is responsible for its physiological or pharmacological action. Batch 0 synthesis (1st non-GMP batch) Batch 4 using final method of synthesis Batch 2 of GMP Batch 5 compound produced in full scale production equipment and validation Batch 1 synthesis (1st GMP standard) Final production concept Routine production Batch 3 of GMP Research and Discovery Early Development Full Development Pre-Market Activity 0 5 8 12 15 Years * GMP = Good Manufacturing PracticeThe above shows a general representation of the development of a new medicine. Various processes may differ from country to country and between different compounds.

9. Marketing Early stage commercial assessment of the medicine taking into account medical need and existing therapies on the market Full development commercial assessment Trade Name ™ chosen for the medicine Selection of a trade name begins Marketing input to the design of clinical trials especially in the choice of comparator medicines Medicine information formulated into brochures and videos. Displays at congresses and symposia Profiling – development of comparative studies on, for example, specific patient groups and other similar medicines. Study possible applications of the medicine to other diseases Research and Discovery Early Development Full Development Pre-Market Activity 0 5 8 12 15 Years * GMP = Good Manufacturing PracticeThe above shows a general representation of the development of a new medicine. Various processes may differ from country to country and between different compounds.

10. Pharmacoeconomics Assessment of the potential impact of the new medicine on healthcare costs Compilation and publication of the pharmacoeconomic results Economic evaluation parallel to clinical trials to determine the economic value of a new medicine, e.g. cost saving and cost-effectiveness Research for the appropriate pharmacoecon-omic and quality of life parameters (linked to clinical trials Phase II) Definition of the healthcare costs caused by the disease Research and Discovery Early Development Full Development Pre-Market Activity 0 5 8 12 15 Years * GMP = Good Manufacturing PracticeThe above shows a general representation of the development of a new medicine. Various processes may differ from country to country and between different compounds.

11. Regulatory Affairs Compilation of registration dossier Application for trial authorisation to begin trials in patients (early development) Application for trial authorisation to begin trials in patients (full development) Application for trial authorisation to begin trials on healthy volunteers Formulation of medicine labelling and doctor/patient medicine information Review of registration documentation by regulatory authorities Interaction with health authorities Interaction with health authorities Interaction with health authorities Interaction with health authorities Research and Discovery Early Development Full Development Pre-Market Activity 0 5 8 12 15 Years * GMP = Good Manufacturing PracticeThe above shows a general representation of the development of a new medicine. Various processes may differ from country to country and between different compounds.

13. On average, only 1 out of 5,000 to 10,000 promising substances will survive extensive testing in the R&D phase to become approved as a quality, safe and efficient marketable product;

14. Several studies put the cost of researching and developing a new chemical entity €1,059 million;

15. Moreover around 70% of medicines that eventually reach the market do not provide sufficient return to recoup their R&D expenditure. As a consequence, the return on investment is highly dependent on a limited number of successful products.