Academic Models of Drug Discovery: Services and Utilizing CROs

(Marcie Glicksman, Harvard NeuroDiscovery Center)

Many types of resources are needed throughout the drug discovery process (see FIG. 1)

  • Every segment of the drug discovery process can be outsourced.
  • Reasons for outsourcing
    • Lack of internal resources
    • Lack of expertise
    • Lack of proper equipment (e.g. chemistry scale-up, robotics, chemical libraries)
    • Flexibility – can accommodate needs when you have them
  • Outsourcing is a huge industry ($7-8 billion market) – many options are available.
  • Focus on the core competencies and resources you have, and use outsourcing to fill in the gaps.
  • Gold standard studies (several established specialized CRO companies available)
    • hERG channel activity (ChanTest CRO recommended – see RESOURCES)
    • preclinical toxicity
    • GLP studies
    • GMP studies

Academic resources (see ADDF Resource List)

  • Many screening facilities worldwide
  • Medicinal chemistry centers (sometimes paired with screening centers)
  • In vivo pharmacology (pharmacy schools)
  • Animal models (disease foundations, JSW, SRI, academic labs)
  • GMP synthesis

Many additional resources available on the internet (see ADDF Resource List)

  • Lists and compilations of facilities, lab equipment, etc. (e.g. SLAS directories, LabAutopedia)
  • Guides and online courses (e.g. assay guidance wiki, SLAS courses)
  • Forums, discussion groups, blogs (e.g. AAAS webinars and forums, networking sites such as LinkedIn, Lab Man blog)
  • Local state biotechnology councils (e.g. Massachusetts Biotechnology Council)

Academia-based lead discovery, two main models

  • Core, service facility – “do it yourself” shop
    • Simple IP situation (investigator-owned)
    • Usually no assay development or medicinal chemistry support – requires more time commitment
    • May have screening libraries available
    • Usually staff members maintain and run equipment, investigator develops assay and supplies assay reagents
    • May be limited to home university community
  • Collaborative
    • More complex IP situation (e.g. joint IP)
    • Possible assay development and medicinal chemistry support
    • Example: Harvard Laboratory for Drug Discovery in Neurodegeneration (LDDN)
      • For the general academic community
      • Provides small molecule libraries biased towards “drug-like” properties and likely BBB penetrance
      • Provides assay development and automation services
      • Provides medicinal chemistry support
      • Joint grants and joint IP ownership
      • Staff have industry experience

Contract research organizations (CROs) (see ADDF Resource List)

  • Types of CROs
    • Fully integrated CRO – one-stop-shop (e.g. Covance, Ricerca)
    • Specialist CRO – boutique (e.g. Cyprotex, Absorption Systems)
  • Many CRO companies worldwide, variety of cost levels
  • Most important factor in picking a CRO is experience (with expertise relevant to your project)
    • Staff experience level – ratio of Ph.D. to M.S./B.S. technicians, years of experience
    • Take advantage of their experience – interact and communicate well to get feedback
  • CRO models
    • Fee for service (FFS) – client drives the science
      • Competitive RFQs (request for quote)
      • Protocols worked out or easier chemistry
      • Intermediates, monomers, templates
      • Per compound rate
    • Full time equivalent (FTE) – client drives the science
      • Pay for a full time employee
      • With trusted partners
      • Difficult or speculative chemistry
      • Reference compounds
      • Large queues at low cost CROs
      • Do you have enough work for FTE rate?
    • Collaborations – CRO drives part or all of the science
      • May be FTE based
      • May include risk sharing
    • For some CROs, there may be reduced fees for equity sharing or milestone payments.
  • Recommendations for working with CROs
    • Talk to others for recommendations
    • Develop list of CROs with overlapping capabilities
    • Give a small FFS project to a CRO prior to making more commitment
      • Some send the same project to multiple CROs for comparison
    • Ensure good communication and updates – discuss expectations
    • Make sure you get reports that are satisfactory – agree ahead of time what the reports should look like (e.g. include supporting documentation, raw values)
    • Confidentiality agreements are standard
      • Is the CRO covered by US/WTO patent laws?
      • Proprietary processes and products need to be defined.
    • Establish a relationship with the CRO
  • Examples of outsourced CRO studies at LDDN (see RESOURCES)
    • Protein purification (Blue Sky)
    • In vitro ADME – microsomal stability, solubility (Cyprotex)
    • Pharmacokinetics (Absorption Systems)
    • Kinome profiling (Carna Biosciences)
    • Side effect profiling (Cerep, Caliper)
    • Supplemental medicinal chemistry (Aberjona)
    • In vivo efficacy models

Vendor partnerships

  • Investigators can gain access to new technology and product discounts.
  • Vendors gain marketing exposure at central academic sites (e.g. demo sites)
  • More flexibility with data sharing and publications, compared to industry.
Resources >