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Regulation of drug research

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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…

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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

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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

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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)

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Research for a new drug:New API found• synthesis• manufacture• physical and chemical quality• Decomposition routesAnimal experiments• pharmacology• toxicologyDrug 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.

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”

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Regulation of animal experiments

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Regulation of animal experiments

In many countries: Animal Protection ActDefinition 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)

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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 only, 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?

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A regulated quality assurance system, required for e.g. experimental toxicology in many developed

countries:

Good Laboratory Practice GLP

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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.!

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Thus, 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, documentation, archiving and the issue of their final report

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We said „new substances”. What kind of new substances applies

GLP?

• drugs (both human and veterinary)

• phyto protective agents

• industrial/household „chemicals”

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What „studies” are under GLP?

• Physical and chemical• Toxicity (acut - chronic, reproductivity, foetal,

carcinogenicity, local tolerance, toxicokinetics)

• mutagenicity• ekotoxicology in aquatic and terrestrial

organisms(continued)

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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!)

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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!

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Next topic:Regulation of human clinical trials

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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!

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Exam topic

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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)

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