1. 1 Regulation of drug research

2. 2 What is drug research? There are two approaches: a wider and a pragmatic one The latter make a difference between „research of drugs” and „research of biologically active substances” Before we start…

3. 3 Research of drugs marketed drug product as soon as possible are taken into account, building the research on them what is necessary for registration Research of biologically substances publication, dissertation… Are not taken into account, only the rules of the „Art of academic research” What is interesting aim the drug registration/authorisation rules subject

4. 4 Consecutive phases of real drug research „molecule research” Fixing the quality of the API animal toxicology animal pharmacology dosage-form development Fixing the API manuf. technology Fixing the dosage-form manuf. technology human clinical trials registration (authorisation) Time scale (start) API = active pharmaceutical ingredient

5. 5 Can drug research be regulated at all? Its some fields by laws, directly – animal experiments: general principles and quality assurance of some studies – human clinical trials Other fields by laws only indirectly a piece of law specifies how the documentation should be compiled (e.g. listing chapters and types of experiments) and submitted for registration, but directly only by „soft law” (=guidelines)

6. 6 Research for a new drug: New API found synthesis manufacture physical and chemical quality Decomposition routes Animal experiments pharmacology toxicology Drug product development Composition (its logics) manufacture chem. and dosage-form control stability Clinical trials on humans direct regul. Dossier structure, information sheets, authorisation direct regul. „chemical dossier” indirect regul. direct regul. (GMP) „non-cinical dossier” indirect regul. direct regul. (GLP) „chem.-pharmaceutical dossier” direct regul. (GMP) indirect regul.

7. Regulation of chemical- pharmaceutical research Indirect regulation will be discussed in connection with the topic „registration, authorisation” The same for dossier structure Direct regulation: GMP: when we discuss „manufacture” 7

8. Regulation of animal experiments 8

9. 9 In many countries: Animal Protection Act Definition of „animal experiment” and „torture of animals” Killing an animal: if absolutely necessary, but in narcosis Torture of animals is forbidden Some countries: except – excirbation of goos feather (for bed-clothes) – crumming of gees or ducks (for goos liver)

10. 10 Regulation of animal experiments, 2 Before starting, you should check whether it is regulated in your country ! If regulated, is the „experimental animal” defined? (E.g.: live vertebrates) Is the purpose limited? (E.g. for drug research, other scientific and educational purposes onl y, but not for cosmetics) Is the number regulated? (E.g. the „lowest possible”) Do you need any authorisation/notification to conduct animal experiments, or it is completely free?

11. 11 A regulated quality assurance system, required for e.g. experimental toxicology in many developed countries : Good Laboratory Practice GLP

12. 12 GLP What is GLP: a quality assurance system (to be delt with in the next semester) When should GLP be applied: for all non- clinical health and environmental safety studies (including toxicology in drug research) Health and environmental safety studies: when any new substance is innovated, its further safe handling several data are needed, e.g. melting point, flashing point, toxicity, etc. !

13. 13 T hus, GLP: it is a quality assurance system dealing with the organisation and conduct of non-clinical health and environmental safety studies, including their planning, execution, control, do cumentation, archiving and the issue of their final report

14. 14 We said „new substances”. What kind of new substances applies GLP ? drugs (both human and veterinary) phyto protective agents industrial/household „chemicals”

15. 15 What „studies” are under G LP ? Physical and chemical Toxicit y (acut - chronic, reproduc t i vity, foetal, c arcinogeni city, lo cal toleranc e, toxi c okineti cs ) mutageni ci t y e kotoxi c ol o g y in aquatic and terrestrial organisms (continued)

16. 16 What „studies” are under GLP? (continued) Degradation, bioaccumulation in water, soil and air Phyto protector residues Effects on micro-climas and natural ecosystems Analytical and clinical studies if connected to any listed above (clinical: veterinary!)

17. 17 Animal experiments used for drug research… …more exactly: the non-clinical safety and efficacy studies (therapeutic benefit/risk) Are regulated by numerous guidelines („soft law”) – these will be mentioned in the part dealing with registration/authorisation!

18. 18 Next topic: Regulation of human clinical trials §

19. Recognise: In the non-clinical part we used the terms „study” or „test” or „experiment” on animals In the human clinical part the similar activity is called „trial”! This is not a play with the words! The language of the regulation would like to underline that, when a drug is used first in humans, there are many safeguard measures and we are almost sure the result will be positive or at least does not harm the subjects! 19

20. Exam topic 20

21. Regulation of drug research Direct and indirect regulation (examples, please) The role of the „soft law” Regulation of animal experiments What is GLP? When should it be applied? (Definition, types of studies and substances to be studied) 21