Guidelines for drug discovery proposals

Expected standards for any proposal to the Neurobiology Task Force of the Department of Biotechnology, India, involving drug screening of synthetic or natural products.

Overview:
These guidelines are meant to improve the likelihood that projects planning to do drug screening will succeed. Good projects should be designed with the  full drug development process in mind, be aware of the competitive landscape, and should come with sufficient preliminary data to inspire confidence that the investigators will be able to carry out the project. While any given project is unlikely to be able to develop and fully characterize a new drug, it must be clear that the project is designed to accomplish a significant advance in a well-planned, stepwise portion of the overall drug development process. For example, we will not consider proposals that just aim to synthesize molecules without a thorough characterization of pharmacology. Please address all the listed points below in your application.
 


   
1. The project must be placed in context of the standard drug discovery
    pipeline:
        biological data ->
        target receptors/molecules ->
        Screens ->
        Lead compound(s) ->
        Iterative refinement /
            combinatorial chemistry /
            structure-based design  ->
        Binding screens ->
        Trials.

2. The proposal should not be designed to screen a small number of molecules. The number of proposed molecules should be commensurate with the state of the art in pharmacological drug screens, which is currently in the millions of compounds in compound libraries. Applicants are advised to plan to use such compound libraries in order to make their project reasonably competitive with the field. Any alternate approach has to be very strongly justified and a specific quantitative analysis must be made that shows how it is more likely to give results than the regular screening process.

3. The proposal must take into account the standard drug screening profile.
    It must address basic drug pharmacology
    - Toxicity and side-effects
    - Efficacy
    - Selectivity and specificity
    - Routes of administration
    - Dosage regimen
    - Prophylactic or therapeutic
    - Cellular or animal models

4. The proposal must take into account pharmacokinetics:
    * Liberation - disintegration (for solid oral forms
        {breaking down into smaller particles}),
        dispersal and dissolution
    * Absorption - How is the medication absorbed (through the skin,
        the intestine, the oral mucosa)?
    * Distribution - How does it spread through the organism?
    * Metabolism - Is the medication converted chemically
        inside the body, and into which substances. Are these active?
        Could they be toxic?
    * Excretion - How is the medication eliminated
        (through the bile, urine, breath, skin)?
        
5. The proposal must address competitive concerns.
    - Is it novel?
        - If the proposed molecules are in use or are
        known to be in development in India or internationally, the
        PI should address this and explain how their research will
        provide additional value.
    - Is it already patented?
        - If patented by others, what is the expected benefit to
        the public from the proposed research?
    - Who else is working on this system, and what is the current status:
        - what stage of trials or screening are they undertaking,
        - what existing drugs or drug candidates have been found
        - why is the current project going to improve on them?

6. Proposals to study natural products, extracts, or traditional medicine must
    specify:
    - The source (plant, animals, others; specific parts; the way it is
        collected, the region where it is collected,
        the time of the year when collected,
        genus & species determination, and any other relevant data).
    - Procedures for the preparation of the extract
    - The identity of the major component in the extract to monitor the
        'level' of 'purity' OR to determine the variations with batches
    - Substantial preliminary data to show that the extract works, in a
        strongly controlled context
    - Measures planned for detecting the active ingredient(s)
    - Measures for synthesizing the molecule(s)

7. The project should describe how the applicants plan to take lead molecules through future trails, should the outcome of the research be promising.
    Please consider the applicable section(s) of trials:
        Pre-clinical
        Clinical phase I, II and III
        Drug review.

8. Proposals that look at the action of a small number of molecules will only be considered if the study provides detailed mechanistic (rather than correlative) insights. Such proposals should only examine molecules for which such mechanistic information would substantially improve diagnosis or treatment, based on existing strong data for the applicability of the proposed molecules.