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    Drug Development

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    prady
    This document outlines the process of drug development from discovery to registration. It discusses key stages including discovery, hit generation, lead generation, clinical development, and post-registration. During discovery, potential drug targets and resources are identified. Hit generation involves initial testing, preclinical development, and quality control. Lead generation focuses on further preclinical and toxicology studies, pharmacokinetics, patent strategy, and scaling up production. Clinical development consists of Phase I-III trials in humans to evaluate safety, efficacy, and obtain marketing authorization.

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    Drug Development

    Uploaded by

    prady
    619 views40 pages
    This document outlines the process of drug development from discovery to registration. It discusses key stages including discovery, hit generation, lead generation, clinical development, and post-registration. During discovery, potential drug targets and resources are identified. Hit generation involves initial testing, preclinical development, and quality control. Lead generation focuses on further preclinical and toxicology studies, pharmacokinetics, patent strategy, and scaling up production. Clinical development consists of Phase I-III trials in humans to evaluate safety, efficacy, and obtain marketing authorization.

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    This document outlines the process of drug development from discovery to registration. It discusses key stages including discovery, hit generation, lead generation, clinical development, and post-registration. During discovery, potential drug targets and resources are identified. Hit generation involves initial testing, preclinical development, and quality control. Lead generation focuses on further preclinical and toxicology studies, pharmacokinetics, patent strategy, and scaling up production. Clinical development consists of Phase I-III trials in humans to evaluate safety, efficacy, and obtain marketing authorization.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    619 views40 pages

    Drug Development

    Uploaded by

    prady
    This document outlines the process of drug development from discovery to registration. It discusses key stages including discovery, hit generation, lead generation, clinical development, and post-registration. During discovery, potential drug targets and resources are identified. Hit generation involves initial testing, preclinical development, and quality control. Lead generation focuses on further preclinical and toxicology studies, pharmacokinetics, patent strategy, and scaling up production. Clinical development consists of Phase I-III trials in humans to evaluate safety, efficacy, and obtain marketing authorization.

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    © All Rights Reserved
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    of 40
    At a glance
    Powered by AI
    The key takeaways are that drug development involves multiple stages from discovery and screening to clinical trials and approval. It also discusses different perspectives like research, quality control, and marketing authorization.

    The main stages of drug development are discovery, hit generation, lead generation, clinical development, and post registration.

    Methods used for drug discovery include high throughput screening of random samples, structure-based drug design, and the ethnobotanical approach of screening traditionally used medicinal plants.

    DRUG DEVELOPMENT

    A view on the process from the idea to


    the registered pharmaceutical

    Dr. Matthias Kreuter


    Head of Alpinia Laudanum Institute of Phytopharmaceutical
    Sciences AG Walenstadt, Switzerland

    Organisation of the presentation


    I. DISCOVERY
    Identification of target and resource

    Organisation of the presentation


    II. HIT GENERATION
    Perspectives: A) Research and Development
    B) Quality Control and Production
    C) Marketing Authorisation

    Organisation of the presentation


    III. LEAD GENERATION
    Perspectives: A) Research and Development
    B) Quality Control and Production
    C) Marketing Authorisation

    Organisation of the presentation


    IV. CLINICAL DEVELOPMENT
    Perspectives: A) Research and Development
    B) Quality Control and Production
    C) Marketing Authorisation

    Organisation of the presentation


    V. POST REGISTRATION
    Perspectives: A) Research and Development
    B) Quality Control and Production
    C) Marketing Authorisation

    I. DISCOVERY
    Identification of target and resource

    I. DISCOVERY

    Target identification
    - Area of interest in terms of drug indication ?
    - Relevant cellular or molecular targets ?
    - Appropriate assays established or to be
    developed ?
    - Available relevant literature ?
    - Patent situation in the target area ?

    I. DISCOVERY

    Resource identification
    Potential resources for novel drugs:
    - Natural organisms (plants, fungi, bacteria, animals)
    - Combinatorial chemistry
    - Structure-based drug design
    Methods for drug discovery:
    - High throughput screening of random samples (HTS):
    Including screen development, primary and
    secondary screening
    - Ethnobiological approach:
    Traditional use of natural organisms for medicines

    I. DISCOVERY

    Resource identification - Alpinia Institute


    Natural organisms, in particular plants
    Medicinal plants continue to play a significant
    role
    as a resource for the discovery of novel drugs
    (1)

    1) Balunas and Koinghorn, Life


    Sci 2005.

    I. DISCOVERY

    Resource identification - Alpinia Institute


    Natural organisms, in particular plants
    Medicinal plants continue to play a significant
    role
    as a resource for the discovery of novel drugs
    (1)
    - 52% of the drugs approved
    in the U.S. from 19812002
    them (2).

    were natural products or derived from

    - 26 plant based drugs were approved during 20002006,


    including novel-molecular based drugs (3).
    - In the future multicomponent botanical
    therapeutics will
    experience an increasing
    2) Newman, J Nat Pr 2002. 3) Saklani & Kutty, Drug Disc Today 2008. 4) Schmidt et al.,
    interest
    biomedicine
    (4).
    Nature
    Chemin
    Biol
    2007.

    I. DISCOVERY

    Method of drug discovery - Alpinia Institute


    Ethnobotanical approach
    Systematic screening of:
    - Published literature on traditional medicinal plant use
    (e.g. documented traditional healers
    experience)
    - Historical texts
    (e.g. ancient botanico-medicinal manuscripts)
    Advantages: - Preselection of potentially active
    resources
    - Promising safety profile (age-long
    experience)
    - Cost-efficient and comparatively fast

    II. HIT GENERATION


    Perspectives: A) Research and Development
    B) Quality Control and Production
    C) Marketing Authorisation

    II. HIT GENERATION


    A) RESEARCH AND DEVELOPMENT

    Process development in phytopharmacy


    Herbal raw
    material

    Extraction
    solvent
    Extract
    ion
    Miscella (Liquid raw
    extract)

    Dry
    extract
    Tablets,
    hard
    capsules

    Liquid extract,
    tincture
    Liquids,
    drops,
    ointments

    Encapsulatable
    mass
    Soft
    capsules

    II. HIT GENERATION


    A) RESEARCH AND DEVELOPMENT

    Development of the test substance


    Define:
    - Active substance (in phytopharmacy:
    native extract)
    - Dosage form
    Establish:
    marker)

    - Physico-chemical profile (active compounds,

    Investigate:

    - Pharmacology
    - Mode of action

    Prepare:

    - Patent draft

    II. HIT GENERATION


    B) QUALITY CONTROL AND PRODUCTION

    Raw material supply


    Availability of raw materials, excipients, consumables
    Herbal raw material
    - Established market product ?
    - Contract cultivation ?
    - Wild harvesting
    ?
    - Continuous availability
    Pay attention to:
    - Quality variations
    - Sustainable cultivation / harvesting
    - Biodiversity regulations
    - Existing patent and intellectual property
    rights

    II. HIT GENERATION


    B) QUALITY CONTROL AND PRODUCTION

    Identity test, controls


    Monographs in pharmacopoeias for:
    - Chemical substances
    - Herbal raw materials
    Organisation of a monograph
    Definition:
    chemical characterisation
    Characters: appearance, solubility
    Identification:
    microscopy, physico-chemical
    tests
    Tests:
    qualitative analysis
    Assay:
    quantitative analysis
    Impurities:
    chemical or microbiological impurities

    II. HIT GENERATION


    B) QUALITY CONTROL AND PRODUCTION

    In house controls
    Two standard analytical methods in phytopharmacy:
    - TLC = Thin layer chromatography

    - HPLC = High performance liquid chromatography


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    II. HIT GENERATION


    C) MARKETING AUTHORISATION PROCESS

    CTD documentation
    Common Technical
    Document:
    Harmonised format for
    applications for preparing
    marketing authorisation in the
    three ICH* regions (Europe,
    *ICH: International
    Japan,
    USA)
    conference for
    harmonisation of technical
    requirements for
    registration of
    pharmaceuticals for
    human use.

    Module 1:
    Information

    Structure of the
    CTD

    Module 2:
    Summaries

    Module 3: Module 4:
    Quality
    Non clinical
    study
    reports

    Module 5:
    Clinical
    study
    reports

    II. HIT GENERATION


    C) MARKETING AUTHORISATION PROCESS

    CTD documentation
    Prepare Module 3: Quality
    - Monograph
    - Specification
    - Development report (on
    going)

    Module 1:
    Information
    Module 2:
    Summaries

    Module
    3:
    Quality

    Module 4:
    Non clinical
    study
    reports

    Module 5:
    Clinical
    study
    reports

    II. HIT GENERATION


    A) RESEARCH AND DEVELOPMENT

    Preclinical development
    In vitro profiling:
    - Biochemical assays (e.g. enzyme activity assays)
    - Cell culture assays (e.g. cancer cell lines)
    - Isolated tissue assays (e.g. mucosa model)
    In vitro toxicology:
    Investigate potential toxic effects
    in bacteria- or cell cultures

    II. HIT GENERATION


    A) RESEARCH AND DEVELOPMENT

    Working with cell cultures

    Cells are kept in liquid


    nitrogen.

    Medium and culture flasks


    for cell cultures.

    Changes of the cultivated


    cells are evaluated under
    the micro-scope after the
    addition of a test
    substance.

    Cultivation of cell
    cultures in petri-dishes or
    cell plates with the
    addition of test
    substances.

    Medium for cell cultures is


    pipetted into a culture flask.

    III. LEAD GENERATION


    Perspectives: A) Research and Development
    B) Quality Control and Production
    C) Marketing Authorisation

    III. LEAD GENERATION


    A) RESEARCH AND DEVELOPMENT

    Preclinical development
    In vivo testing

    Animal model (mouse or rat)

    Drug action:

    - Behaviour and reaction


    - Physiology
    - Histopathology

    Toxicology:

    Acute toxicity
    Subchronic toxicity
    Tissue specific toxicity
    Tolerability

    Consider ethical aspects (e.g. number and kind of


    animals used)

    III. LEAD GENERATION


    A) RESEARCH AND DEVELOPMENT

    Preclinical development (continued)


    Pharmacokinetic studies
    the drug ?
    Investigate: - Liberation
    - Absorption
    - Distribution
    - Metabolism
    - Excretion

    What does the body to

    Pharmacodynamic studies
    What does the drug to
    the body ?
    Investigate: - Physiological effects
    - Drug action
    - Relationship between drug concentration and

    III. LEAD GENERATION


    A) RESEARCH AND DEVELOPMENT

    Preclinical development (continued)


    Patent policy
    Explore the related patent environment:
    Database of the European Patent Office
    (espacencet)
    Develop a patent strategy:
    -

    Rationale
    Possibilities
    Desired strength
    Costs

    III. LEAD GENERATION


    B) QUALITY CONTROL AND PRODUCTION

    Scaling up
    Scaling up from laboratory to production size
    GMP and GLP environments
    Validation
    Conduct a process validation including various batch sizes
    Stability testing
    Conduct a stability test under different conditions of
    temperature, humidity and exposure time

    III. LEAD GENERATION


    C) MARKETING AUTHORISATION PROCESS

    CTD documentation
    Continue Module 3: Quality
    -

    Validation report
    Stability report
    Manufacturing protocol
    Development report (on
    going)
    Prepare Module 4: Non clinical
    study reports
    Module
    3:
    Quality

    Module 1:
    Information
    Module 2:
    Summaries

    Module 4: Module 5:
    Non
    Clinical
    clinical
    study
    study
    reports
    reports

    IV. CLINICAL DEVELOPMENT


    Perspectives: A) Research and Development
    B) Quality Control and Production
    C) Marketing Authorisation

    IV. CLINICAL DEVELOPMENT


    A) RESEARCH AND DEVELOPMENT

    Clinical development Linking bench to bedside


    Clinical drug studies Research in humans
    Subject to ethical concern:
    - Qualify to increase existing knowledge
    - Respect freedom of decision of volunteers
    - Involve a substantiated risk-benefit
    assessment
    The realisation of a clinical drug study has to be approved by
    an
    Independent Ethics Commitee (IEC).

    IV. CLINICAL DEVELOPMENT


    A) RESEARCH AND DEVELOPMENT

    Clinical development Linking bench to bedside


    Phase I studies

    20 to 30 healthy volunteers
    Investigate:

    Example:
    Dose titration - first application in
    humans

    - Safety and tolerability


    - Pharmacokinetics
    - Pharmacodynamics

    Dosage
    (mg)

    toxic
    therapeut
    ic
    subtherape
    utic
    Treatment
    groups

    IV. CLINICAL DEVELOPMENT


    A) RESEARCH AND DEVELOPMENT

    Clinical development Linking bench to bedside


    (continued)
    Phase II studies

    100 to 500 patient volunteers


    Investigate:

    Safety and tolerability


    Pharmacokinetics
    Pharmacodynamics
    Efficiency
    Dosage to effect

    relationship
    Study design: - Dosage comparison
    Antitumor drugs: Combination of Phase I and II at an early
    stage of drug development is possible.

    IV. CLINICAL DEVELOPMENT


    A) RESEARCH AND DEVELOPMENT

    Overall aim of Phase III: Risk-benefit


    evaluation
    Phase III studies are pivotal studies = outcome is crucial for
    the decision taking of the regulatory authorities.

    IV. CLINICAL DEVELOPMENT


    B) QUALITY CONTROL AND PRODUCTION

    Clinical samples
    Production
    I, II, III)

    - Provide appropriate sample quantities (Phase


    - Define sample shipment logistics

    Quality control
    - Prepare complete batch release
    documentation
    - Define short and long term storage of
    samples
    GMP and GLP environments

    IV. CLINICAL DEVELOPMENT


    C) MARKETING AUTHORISATION PROCESS

    CTD documentation
    - Prepare Modules:
    Module 1:
    Information
    1: Administrative information
    2: CTD summaries
    Module 2:
    5: Clinical study reports
    Summaries

    - Compile the whole CTD


    Module 3: Module 4:
    Quality
    Non clinical
    study
    Regulatory Authorities
    reports

    Module 5:
    Clinical
    study
    reports

    - Submit the completed CTD


    - File a New Drug Application with EMEA (Europe) or FDA
    (USA)

    V. POST REGISTRATION
    Perspectives: A) Research and Development
    B) Quality Control and Production
    C) Marketing Authorisation

    V. POST REGISTRATION
    A) RESEARCH AND DEVELOPMENT

    Clinical development after marketing


    Phase IV studies

    Post marketing testing

    Investigate specific questions within the frame of the


    approved indication:
    - Expanded benefit-risk-profile
    - Combination with other drugs
    - Optimization (e.g. dosage, application)
    E.g.: The worldwide use of the approved drug might lead to
    the occurrence of very rare side effects.
    Reason for expanded epidemiologic
    studies

    V. POST REGISTRATION
    B) PRODUCTION & QC / C) MARKETING AUTHORISATION

    Production and quality control


    Manufacture- Manufacturing of the product
    - Controls acc. to the established batch release
    process
    GMP and GLP environments

    Marketing authorisation process


    Approval
    Authorities

    - Drug is approved for marketing by the

    Summary
    I.

    DISCOVERY
    Identify target and resource

    II. HIT GENERATION


    Develop process and test substance
    Conduct in vitro testing
    III. LEAD GENERATION
    Conduct in vivo testing
    Pharmacokinetic and pharmacodynamic
    studies
    IV. CLINICAL DEVELOPMENT
    Human trials Phase I, II, III
    V. POST REGISTRATION
    Human trials Phase IV

    Thank you for your attention !

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