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Technical Due Diligence

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Guidelines for conducting effective due diligence

Technical Due Diligence

  1. 1. Setting the Stage: Conducting Effective & Strategic Due Diligence Thomas Argentieri, Ph.D. ACI Conference Nov. 17, 2009 New York, NY
  2. 2. Introduction <ul><li>Due Diligence </li></ul><ul><li>Three Fundamental Categories: </li></ul><ul><ul><li>Technical </li></ul></ul><ul><ul><li>Commercial </li></ul></ul><ul><ul><li>Legal </li></ul></ul>
  3. 3. Introduction <ul><li>When to Start the Process?: </li></ul><ul><ul><li>Pre-Deal due diligence </li></ul></ul><ul><ul><li>Confirmatory due diligence </li></ul></ul>
  4. 4. Pre-Deal Due Diligence <ul><li>Check List: </li></ul><ul><ul><li>Is the size of the opportunity right? </li></ul></ul><ul><ul><li>Is the location (territory) right? </li></ul></ul><ul><ul><li>Is the therapeutic fit right? </li></ul></ul><ul><ul><li>Does the deal compliment your existing business? </li></ul></ul><ul><ul><li>Is enough known about competing products? </li></ul></ul><ul><ul><li>Is the appropriate sales force infrastructure in place? </li></ul></ul><ul><ul><li>Any obvious IP issues, restrictions? </li></ul></ul><ul><ul><li>Terms? </li></ul></ul>When satisfied with answers to above questions – Decision to go to full due diligence
  5. 5. … the objective … of due diligence
  6. 6. Confirmatory Due Diligence <ul><li>Objective: </li></ul><ul><ul><li>Confirm what you know </li></ul></ul><ul><ul><li>Look for reasons to kill the deal </li></ul></ul><ul><ul><li>“ You will only discover bad things at due diligence” (R. Ruffolo , Former head R&D, Wyeth ) </li></ul></ul><ul><ul><li>Should use to your advantage </li></ul></ul>
  7. 7. The Decision to Undertake Due Diligence <ul><li>What are the next steps? </li></ul><ul><ul><li>Assemble the team </li></ul></ul><ul><ul><li>Agree upon what you’re looking for/objectives </li></ul></ul><ul><ul><li>Agree upon the scope </li></ul></ul><ul><ul><li>Request the information </li></ul></ul><ul><ul><ul><li>Let the company know what you expect to see </li></ul></ul></ul><ul><ul><ul><li>Electronic? Paper? </li></ul></ul></ul><ul><ul><ul><li>Will you need laptop computers? </li></ul></ul></ul>
  8. 8. Due Diligence Team Direct costs for 1 day diligence can easily exceed $40,000-$50,000 <ul><li>On occasion, one may not have enough information to determine that it is worthwhile assembling a large team and undertaking a full diligence. </li></ul><ul><li>Send out small group of appropriate people, e.g. </li></ul><ul><ul><li>Medicinal Chemistry </li></ul></ul><ul><ul><li>Discovery </li></ul></ul><ul><ul><li>Clinical </li></ul></ul><ul><li>Ensure that specific criteria are developed to let the organization know whether or not to go to full diligence. </li></ul>Partial Diligence
  9. 9. Due Diligence Team <ul><ul><li>Appropriate disciplines to review all of the data available must be represented. </li></ul></ul><ul><ul><li>The representatives of each discipline must have sufficient experience to be able to do an effective evaluation and sufficient discipline to be able to address the task at hand in the time available. </li></ul></ul><ul><ul><li>Look for areas where synergy may be achieved. </li></ul></ul><ul><ul><ul><li>Clinical R&D, Medical Affairs and Clinical Safety. </li></ul></ul></ul><ul><ul><ul><li>Chemical Development and Manufacturing and CMC Regulatory. </li></ul></ul></ul>
  10. 10. <ul><li>Team leader </li></ul><ul><li>Discovery </li></ul><ul><li>Medicinal Chemistry </li></ul><ul><li>Toxicology </li></ul><ul><li>GLP Compliance </li></ul><ul><li>Clinical Pharmacology/PK </li></ul><ul><li>Clinical Research </li></ul><ul><li>Medical Affairs </li></ul><ul><li>Chemical Development </li></ul><ul><li>Clinical Safety </li></ul>Due Diligence Team <ul><li>Safety Systems </li></ul><ul><li>GCP Compliance </li></ul><ul><li>Biostatistics </li></ul><ul><li>Pharmaceutical Dev. </li></ul><ul><li>Manufacturing </li></ul><ul><li>Supply Chain </li></ul><ul><li>GMP Compliance </li></ul><ul><li>Regulatory Affairs </li></ul><ul><li>CMC Regulatory Affairs </li></ul>Typical DD Team Makeup (clinical asset) Preclinical Clinical Manufacturing
  11. 11. Team responsibilities: <ul><ul><li>Collection of all technical information </li></ul></ul><ul><ul><li>Assessment of all technical information </li></ul></ul><ul><ul><li>Follow up on additional data requests or clarification of data requests </li></ul></ul><ul><ul><li>Reporting out of Technical Due Diligence </li></ul></ul>Due Diligence Team
  12. 12. Examples of Information Requested <ul><li>Discovery </li></ul><ul><ul><li>All reports of any pharmacology studies undertaken </li></ul></ul><ul><li>Toxicology </li></ul><ul><ul><li>Status and findings of reproductive toxicology studies </li></ul></ul><ul><ul><li>hERG testing </li></ul></ul><ul><ul><li>Plans for carcinogenicity testing </li></ul></ul><ul><ul><li>Records of discussions with regulatory authorities </li></ul></ul><ul><li>Chemical Pharmaceutical Development </li></ul><ul><ul><li>Synthetic Pathways </li></ul></ul><ul><ul><li>Structural Elucidation </li></ul></ul><ul><ul><ul><li>NMR </li></ul></ul></ul><ul><ul><ul><li>Mass Spec </li></ul></ul></ul><ul><ul><ul><li>UV-Visible Spectroscopy </li></ul></ul></ul><ul><ul><li>Physicochemical Characterization </li></ul></ul><ul><ul><ul><li>Ionization constant </li></ul></ul></ul><ul><ul><ul><li>Polymorphism </li></ul></ul></ul><ul><ul><ul><li>Crystal Habit </li></ul></ul></ul><ul><ul><ul><li>Solubility Profile </li></ul></ul></ul><ul><li>Clinical R&D </li></ul><ul><ul><li>Copies of all clinical protocols including amendments </li></ul></ul><ul><ul><li>Clinical Study Reports </li></ul></ul><ul><ul><li>Clinical Data Reports </li></ul></ul><ul><ul><li>Clinical Development Plans </li></ul></ul><ul><ul><li>Case report forms should be available or retrievable for review </li></ul></ul><ul><ul><li>Minutes from advisory boards or expert panels </li></ul></ul>
  13. 13. <ul><li>Compliance/QA </li></ul><ul><ul><li>Organization charts of company </li></ul></ul><ul><ul><li>Table of contents of relevant SOPs </li></ul></ul><ul><ul><li>Service agreements with CROs </li></ul></ul><ul><ul><li>Results of Regulatory Inspections </li></ul></ul><ul><li>Regulatory Affairs </li></ul><ul><ul><li>All regulatory documents, including IND, CTX, NDA/MAA components </li></ul></ul><ul><ul><li>Draft or proposed labeling </li></ul></ul><ul><ul><li>Monitoring Reports </li></ul></ul><ul><ul><li>Audit reports </li></ul></ul><ul><li>Manufacturing </li></ul><ul><ul><li>Location of Manufacturing sites </li></ul></ul><ul><ul><li>Supply agreements </li></ul></ul><ul><ul><li>Process flow diagram </li></ul></ul><ul><ul><li>Batch Records </li></ul></ul><ul><ul><li>Critical Processing Parameters </li></ul></ul><ul><ul><li>Batch Yield </li></ul></ul><ul><ul><li>Cycle Time </li></ul></ul><ul><ul><li>Scale up experience </li></ul></ul>Examples of Information Requested
  14. 14. Product Under Development <ul><ul><li>Are all the clinical trial procedures appropriately set-up and documented? </li></ul></ul><ul><ul><li>Are the clinical methodologies appropriate? </li></ul></ul><ul><ul><ul><li>Properly sized, powered? </li></ul></ul></ul><ul><ul><ul><li>Appropriate dosages/formulation chosen? </li></ul></ul></ul><ul><ul><ul><li>Timelines reasonable? </li></ul></ul></ul><ul><ul><ul><li>Funding adequately assessed? </li></ul></ul></ul><ul><ul><li>Will the data provide the requested labeling? </li></ul></ul>Critical Questions
  15. 15. Critical Questions Marketed Product <ul><ul><li>DD requirements less onerous </li></ul></ul><ul><ul><li>Have adverse advents been properly documented and reported? </li></ul></ul><ul><ul><li>Any concerns with GMP process? </li></ul></ul><ul><ul><li>Is product currently being marketed in accordance with labeling? </li></ul></ul><ul><ul><li>Has the dossier been kept up to date? </li></ul></ul>
  16. 16. <ul><li>Lack of access to data </li></ul><ul><ul><li>Un-available, un-accessible </li></ul></ul><ul><li>Lack of access to appropriate staff </li></ul><ul><ul><li>Will there be a counterpart present for each of your staff? </li></ul></ul><ul><li>Incomplete or missing data </li></ul><ul><li>Follow-up diligence may be required </li></ul>Potential Problems
  17. 17. Other Sources of Information <ul><ul><li>Materials published by the company </li></ul></ul><ul><ul><ul><li>Annual reports, press releases, product info etc. </li></ul></ul></ul><ul><ul><li>Industry publications </li></ul></ul><ul><ul><ul><li>Script, Clinica, InVivo, Drug Market Development etc. </li></ul></ul></ul><ul><ul><li>Scientific literature </li></ul></ul><ul><ul><ul><li>How unique is the deal? </li></ul></ul></ul><ul><ul><li>Research reports from brokers, industry analysts or consulting firms </li></ul></ul><ul><ul><li>Dun & Bradstreet or Equifax reports </li></ul></ul>
  18. 18. Conclusions <ul><li>Completed critical data evaluations </li></ul><ul><li>Completed assessment of key issues </li></ul><ul><li>Circle back with key individuals </li></ul><ul><ul><li>Scientific assessment hold-up? </li></ul></ul><ul><ul><li>Clinical assessment hold-up? </li></ul></ul><ul><ul><li>Commercial assessment hold-up? </li></ul></ul><ul><li>Make recommendation to Governance body </li></ul>√ √ √ √

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